The classic website will no longer be available as of June 25, 2024. Please use the modernized ClinicalTrials.gov.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety and Immunogenicity of a Live-attenuated Universal Flu Vaccine Followed by an Inactivated Universal Flu Vaccine

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03300050
Recruitment Status : Completed
First Posted : October 3, 2017
Results First Posted : February 21, 2021
Last Update Posted : February 21, 2021
Sponsor:
Collaborators:
Icahn School of Medicine at Mount Sinai
Children's Hospital Medical Center, Cincinnati
Duke University
The Emmes Company, LLC
GlaxoSmithKline
Information provided by (Responsible Party):
PATH

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Prevention
Conditions Influenza
Vaccine
Interventions Biological: cH8/1N1 LAIV
Biological: AS03-adjuvanted cH5/1N1 IIV
Biological: cH5/1N1 IIV
Biological: AS03-adjuvanted cH8/1N1 IIV
Biological: Normal saline
Biological: Phosphate buffered saline (PBS)
Enrollment 65
Recruitment Details Participants were recruited from the community and enrolled at Cincinnati Children's Hospital Medical Center (Cincinnati, OH, USA) and the Duke Early Phase Clinical Research Unit (Durham, NC, USA) between October 10, 2017, and November 27, 2017.
Pre-assignment Details Participants were randomly assigned in a 4:3:1:3:2 ratio to one of five treatment groups. Randomization was blocked (block size 13) and stratified by site. Participants received two sequential study vaccinations, an initial priming dose on Day 1 followed by a booster dose on Day 85.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description Participants received 0.5 mL chimeric H8/1N1 live-attenuated influenza virus vaccine (cH8/1N1 LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03 (Adjuvant System 03)-adjuvanted chimeric H5/1N1 inactivated influenza virus vaccine (cH5/1N1 IIV) administered as an intramuscular injection on Day 85. Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85. Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85. Participants received 0.5 mL AS03-adjuvanted chimeric H8/1N1 inactivated influenza vaccine (cH8/1N1 IIV) administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85. Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Period Title: Overall Study
Started 20 15 5 16 10
Received Treatment 19 14 3 15 10
Received All Scheduled Treatments 16 13 2 15 10
Completed 17 13 2 15 9
Not Completed 3 2 3 1 1
Reason Not Completed
Lost to Follow-up             2             1             0             0             1
Withdrawal by Subject             1             1             1             0             0
Death             0             0             1             0             0
Not Eligible at Randomization             0             0             1             1             0
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo Total
Hide Arm/Group Description Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85. Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85. Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85. Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85. Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85. Total of all reporting groups
Overall Number of Baseline Participants 20 15 5 16 10 66
Hide Baseline Analysis Population Description
All enrolled participants
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 20 participants 15 participants 5 participants 16 participants 10 participants 66 participants
29.9  (5.3) 27.5  (5.9) 25.0  (3.7) 30.3  (5.5) 29.3  (4.6) 28.9  (5.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 15 participants 5 participants 16 participants 10 participants 66 participants
Female
14
  70.0%
10
  66.7%
2
  40.0%
10
  62.5%
5
  50.0%
41
  62.1%
Male
6
  30.0%
5
  33.3%
3
  60.0%
6
  37.5%
5
  50.0%
25
  37.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 15 participants 5 participants 16 participants 10 participants 66 participants
Hispanic or Latino
0
   0.0%
2
  13.3%
1
  20.0%
0
   0.0%
0
   0.0%
3
   4.5%
Not Hispanic or Latino
20
 100.0%
13
  86.7%
4
  80.0%
16
 100.0%
10
 100.0%
63
  95.5%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 15 participants 5 participants 16 participants 10 participants 66 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
1
  20.0%
0
   0.0%
0
   0.0%
1
   1.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
15
  75.0%
10
  66.7%
4
  80.0%
14
  87.5%
7
  70.0%
50
  75.8%
White
5
  25.0%
3
  20.0%
0
   0.0%
2
  12.5%
3
  30.0%
13
  19.7%
More than one race
0
   0.0%
1
   6.7%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.5%
Unknown or Not Reported
0
   0.0%
1
   6.7%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.5%
1.Primary Outcome
Title Number of Participants With Solicited Local Reactions Within 7 Days Following Each Vaccination
Hide Description

Solicited adverse events were assessed by study staff for 60 minutes after each vaccination and and then by study participants daily for 7 days on a a diary card.

Solicited local reactions included:

  • Post LAIV dose: nasal congestion, rhinorrhea;
  • Post IIV dose: pain, redness, swelling.
Time Frame 7 days after each vaccination (Days 1-8 and Days 85-92)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received the priming dose and booster dose
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Measure Type: Count of Participants
Unit of Measure: Participants
Post Prime Dose Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
Any Local Reacton
10
  52.6%
2
  14.3%
0
   0.0%
11
  73.3%
1
  10.0%
Nasal Congestion
4
  21.1%
1
   7.1%
0
   0.0%
 NA [1]  NA [1] 
Rhinorrhea
8
  42.1%
2
  14.3%
0
   0.0%
 NA [1]  NA [1] 
Pain NA [2]  NA [2]  NA [2] 
11
  73.3%
1
  10.0%
Redness NA [2]  NA [2]  NA [2] 
1
   6.7%
0
   0.0%
Swelling NA [2]  NA [2]  NA [2] 
1
   6.7%
0
   0.0%
Post Booster Dose Number Analyzed 16 participants 13 participants 2 participants 15 participants 10 participants
Any Local Reacton
10
  62.5%
1
   7.7%
0
   0.0%
8
  53.3%
0
   0.0%
Nasal Congestion NA [1]  NA [1]  NA [1]  NA [1]  NA [1] 
Rhinorrhea NA [1]  NA [1]  NA [1]  NA [1]  NA [1] 
Pain
10
  62.5%
1
   7.7%
0
   0.0%
8
  53.3%
0
   0.0%
Redness
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Swelling
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Reaction not applicable for intramuscular injection
[2]
Reaction not applicable for intranasal administration
2.Primary Outcome
Title Number of Participants With Solicited General Reactions Within 7 Days Following Each Vaccination
Hide Description

Solicited adverse events were assessed by study staff for 60 minutes after each vaccination and and then by study participants daily for 7 days on a a diary card.

Solicited general reactions included:

  • abdominal pain
  • arthralgia
  • cough
  • diarrhea
  • fatigue
  • fever
  • headache
  • myalgia
  • nausea
  • shivering
  • sore throat
  • vomiting
  • wheezing
Time Frame 7 days after each vaccination (Days 1-8 and Days 85-92)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received the priming dose and booster dose
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Measure Type: Count of Participants
Unit of Measure: Participants
Post Prime Dose: Any General Reaction Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
13
  68.4%
8
  57.1%
1
  33.3%
10
  66.7%
4
  40.0%
Post Prime Dose: Fever Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Post Prime Dose: Shivering Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
3
  15.8%
0
   0.0%
0
   0.0%
1
   6.7%
0
   0.0%
Post Prime Dose: Fatigue Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
3
  15.8%
4
  28.6%
0
   0.0%
6
  40.0%
3
  30.0%
Post Prime Dose: Headache Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
7
  36.8%
4
  28.6%
1
  33.3%
6
  40.0%
2
  20.0%
Post Prime Dose: Myalgia Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
4
  21.1%
2
  14.3%
0
   0.0%
6
  40.0%
0
   0.0%
Post Prime Dose: Arthralgia Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
0
   0.0%
3
  21.4%
0
   0.0%
2
  13.3%
0
   0.0%
Post Prime Dose: Nausea Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
3
  15.8%
3
  21.4%
0
   0.0%
0
   0.0%
1
  10.0%
Post Prime Dose: Vomiting Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
1
   5.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Post Prime Dose: Abdominal Pain Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
2
  10.5%
2
  14.3%
0
   0.0%
2
  13.3%
2
  20.0%
Post Prime Dose: Diarrhea Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
0
   0.0%
0
   0.0%
0
   0.0%
2
  13.3%
1
  10.0%
Post Prime Dose: Sore Throat Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
2
  10.5%
1
   7.1%
0
   0.0%
0
   0.0%
0
   0.0%
Post Prime Dose: Cough Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
4
  21.1%
0
   0.0%
0
   0.0%
1
   6.7%
0
   0.0%
Post Prime Dose: Wheezing Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Post Booster Dose: Any General Reaction Number Analyzed 16 participants 13 participants 2 participants 15 participants 10 participants
10
  62.5%
5
  38.5%
0
   0.0%
5
  33.3%
1
  10.0%
Post Booster Dose : Fever Number Analyzed 16 participants 13 participants 2 participants 15 participants 10 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Post Booster Dose: Shivering Number Analyzed 16 participants 13 participants 2 participants 15 participants 10 participants
2
  12.5%
2
  15.4%
0
   0.0%
1
   6.7%
0
   0.0%
Post Booster Dose: Fatigue Number Analyzed 16 participants 13 participants 2 participants 15 participants 10 participants
8
  50.0%
3
  23.1%
0
   0.0%
2
  13.3%
1
  10.0%
Post Booster Dose : Headache Number Analyzed 16 participants 13 participants 2 participants 15 participants 10 participants
4
  25.0%
4
  30.8%
0
   0.0%
0
   0.0%
1
  10.0%
Post Booster Dose: Myalgia Number Analyzed 16 participants 13 participants 2 participants 15 participants 10 participants
5
  31.3%
1
   7.7%
0
   0.0%
1
   6.7%
0
   0.0%
Post Booster Dose: Arthralgia Number Analyzed 16 participants 13 participants 2 participants 15 participants 10 participants
4
  25.0%
2
  15.4%
0
   0.0%
0
   0.0%
0
   0.0%
Post Booster Dose: Nausea Number Analyzed 16 participants 13 participants 2 participants 15 participants 10 participants
3
  18.8%
2
  15.4%
0
   0.0%
0
   0.0%
0
   0.0%
Post Booster Dose: Vomiting Number Analyzed 16 participants 13 participants 2 participants 15 participants 10 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Post Booster Dose: Abdominal Pain Number Analyzed 16 participants 13 participants 2 participants 15 participants 10 participants
2
  12.5%
1
   7.7%
0
   0.0%
1
   6.7%
0
   0.0%
Post Booster Dose: Diarrhea Number Analyzed 16 participants 13 participants 2 participants 15 participants 10 participants
0
   0.0%
1
   7.7%
0
   0.0%
0
   0.0%
0
   0.0%
Post Booster Dose: Sore Throat Number Analyzed 16 participants 13 participants 2 participants 15 participants 10 participants
3
  18.8%
2
  15.4%
0
   0.0%
0
   0.0%
0
   0.0%
Post Booster Dose: Cough Number Analyzed 16 participants 13 participants 2 participants 15 participants 10 participants
1
   6.3%
1
   7.7%
0
   0.0%
1
   6.7%
0
   0.0%
Post Booster Dose: Wheezing Number Analyzed 16 participants 13 participants 2 participants 15 participants 10 participants
0
   0.0%
1
   7.7%
0
   0.0%
0
   0.0%
0
   0.0%
3.Primary Outcome
Title Number of Participants With Unsolicited Adverse Events Within 28 Days Following Any Vaccination
Hide Description

Unsolicited adverse events (AEs) are any AEs reported spontaneously by the participant, observed by the study personnel during study visits or those identified during review of medical records or source documents, such as diary cards. Participants were asked to record any unsolicited symptoms or other illness description in their diary card during the 28 days after each vaccination.

All AEs, including clinical laboratory test results, were assessed by a study clinician and the study subject (as applicable) to quantify severity using a protocol-defined grading system as mild (mild symptoms, easily tolerated, not interfering with daily activities), moderate (causing some interference with daily activity), or severe (severe symptoms that prevent normal every day activities).

The investigator assessed the relationship between study vaccines and the occurrence of each AE using clinical judgment.
Time Frame 28 days after each vaccination (Days 1 to 28 and Days 85 to 113)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one study vaccination
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Measure Type: Count of Participants
Unit of Measure: Participants
Any adverse events
10
  52.6%
8
  57.1%
1
  33.3%
6
  40.0%
5
  50.0%
AEs related to study vaccine
5
  26.3%
2
  14.3%
0
   0.0%
1
   6.7%
0
   0.0%
Mild adverse events
6
  31.6%
3
  21.4%
0
   0.0%
3
  20.0%
3
  30.0%
Mild AEs related to study vaccine
5
  26.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Moderate adverse events
3
  15.8%
4
  28.6%
1
  33.3%
3
  20.0%
2
  20.0%
Moderate AEs related to study vaccine
0
   0.0%
2
  14.3%
0
   0.0%
1
   6.7%
0
   0.0%
Severe adverse events
1
   5.3%
1
   7.1%
0
   0.0%
0
   0.0%
0
   0.0%
Severe AEs related to study vaccine
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
4.Primary Outcome
Title Number of Participants With Grade 2 or Higher Hematological and Biochemical Laboratory Abnormalities From Day 8 to Day 113
Hide Description

Hematological and biochemical parameters assessed included hemoglobin, platelets, red blood cells, white blood cells (WBC), absolute neutrophil count (ANC), lymphocytes, monocytes, eosinophils, basophils, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, blood urea nitrogen (BUN) and BUN-to-creatinine ratio.

Grading of laboratory parameters was based on the FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials as Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (severe), or Grade 4 (Potentially life-threatening).

Grade 2 or higher:

  • BUN: > 26 mg/dL
  • Creatinine: > 1.7 mg/dL
  • ALT, AST: > 2.5 × upper limit of normal (ULN)
  • Hemoglobin: < 11.0 g/dL (females) or < 12.5 g/dL (males) or change from baseline > 1.5 g/dL
  • WBC: > 15,000 cell/mm³ or < 2,500 cell/mm³
  • Lymphocytes: < 750 cell/mm³
  • ANC: < 1,500 cell/mm³
  • Eosinophils: > 1,500 cell/mm³
  • Platelets: < 125,000 cell/mm³
Time Frame Days 8, 29, 85, 92, and 113
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one study vaccination
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Measure Type: Count of Participants
Unit of Measure: Participants
Hemoglobin
0
   0.0%
2
  14.3%
0
   0.0%
3
  20.0%
1
  10.0%
Hemoglobin change from baseline
3
  15.8%
1
   7.1%
2
  66.7%
3
  20.0%
0
   0.0%
Platelets
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White blood cell count
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Absolute neutrophil count
5
  26.3%
1
   7.1%
0
   0.0%
3
  20.0%
0
   0.0%
Lymphocytes
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Basophils
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Monocytes
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Eosinophils
1
   5.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Red blood cells
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Creatinine
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Blood urea nitrogen
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
BUN to creatinine ratio
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Alanine aminotransferase
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asparate aminotransferase
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
5.Primary Outcome
Title Number of Participants With a Medically Attended Event (MAE), Laboratory-Confirmed Influenza-like Illness (LC-ILI), Potential Immune-mediated Disease (pIMD), or Serious Adverse Event (SAE) up to Day 113
Hide Description

An MAE is an event for which the participant received medical attention such as hospitalization, an emergency room visit, or a visit to or from medical personnel.

pIMDs are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology.

LC-ILI is defined as at least 1 systemic symptom (fever or myalgia) AND at least 1 respiratory symptom (cough or sore throat), confirmed by polymerase chain reaction (PCR) assay.

An SAE is an AE that met any of the following:

  • Death
  • Life threatening
  • Required inpatient hospitalization or prolongation of existing hospitalization
  • Results in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions
  • Results in congenital anomaly/birth defect
  • An important medical event that may jeopardize the well-being of the subject or require medical or surgical intervention to prevent an above outcome.
Time Frame Through Day 113 (28 days post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one study vaccination
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Measure Type: Count of Participants
Unit of Measure: Participants
SAEs
0
   0.0%
0
   0.0%
1
  33.3%
0
   0.0%
0
   0.0%
MAEs
6
  31.6%
2
  14.3%
0
   0.0%
3
  20.0%
1
  10.0%
LC-ILIs
0
   0.0%
0
   0.0%
1
  33.3%
0
   0.0%
0
   0.0%
pIMDs
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
6.Secondary Outcome
Title Number of Participants With Any Grade 2 or Higher Hematological and Biochemical Laboratory Abnormalities From Month 9 to Month 15
Hide Description

Hematological and biochemical parameters assessed included hemoglobin, platelets, red blood cells, white blood cells (WBC), absolute neutrophil count (ANC), lymphocytes, monocytes, eosinophils, basophils, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, blood urea nitrogen (BUN) and BUN-to-creatinine ratio.

Grading of laboratory parameters was based on the FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials as Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (severe), or Grade 4 (Potentially life-threatening).

Grade 2 or higher:

  • BUN: > 26 mg/dL
  • Creatinine: > 1.7 mg/dL
  • ALT, AST: > 2.5 × upper limit of normal (ULN)
  • Hemoglobin: < 11.0 g/dL (females) or < 12.5 g/dL (males) or change from baseline > 1.5 g/dL
  • WBC: > 15,000 cell/mm³ or < 2,500 cell/mm³
  • Lymphocytes: < 750 cell/mm³
  • ANC: < 1,500 cell/mm³
  • Eosinophils: > 1,500 cell/mm³
  • Platelets: < 125,000 cell/mm³
Time Frame Month 9 (6 months post-dose 2) and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one study vaccination
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Measure Type: Count of Participants
Unit of Measure: Participants
Hemoglobin
0
   0.0%
1
   7.1%
0
   0.0%
2
  13.3%
0
   0.0%
Hemoglobin change from baseline
0
   0.0%
1
   7.1%
1
  33.3%
2
  13.3%
0
   0.0%
Platelets
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White blood cell count
1
   5.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Absolute neutrophil count
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Lymphocytes
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Basophils
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Monocytes
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Eosinophils
1
   5.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Red blood cells
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Creatinine
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Blood urea nitrogen
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
BUN to creatinine ratio
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Alanine aminotransferase
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asparate aminotransferase
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
7.Secondary Outcome
Title Number of Participants With a Medically Attended Event (MAE), Laboratory-Confirmed Influenza-like Illness (LC-ILI), Potential Immune-mediated Disease (pIMD), or Serious Adverse Event (SAE) up to End of Study
Hide Description

An MAE is an event for which the participant received medical attention such as hospitalization, an emergency room visit, or a visit to or from medical personnel.

pIMDs are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology.

LC-ILI is defined as at least 1 systemic symptom (fever or myalgia) AND at least 1 respiratory symptom (cough or sore throat), confirmed by PCR assay.

An SAE is an AE that met any of the following:

  • Death
  • Life threatening
  • Required inpatient hospitalization or prolongation of existing hospitalization
  • Resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions
  • Resulted in congenital anomaly/birth defect
  • An important medical event that may jeopardize the well-being of the subject or require medical or surgical intervention to prevent an above outcome.
Time Frame From first dose to end of study, 588 days (21 months; 18 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one study vaccination
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Measure Type: Count of Participants
Unit of Measure: Participants
SAEs
0
   0.0%
0
   0.0%
1
  33.3%
0
   0.0%
2
  20.0%
MAEs
7
  36.8%
4
  28.6%
0
   0.0%
4
  26.7%
4
  40.0%
LC-ILIs
1
   5.3%
1
   7.1%
1
  33.3%
0
   0.0%
0
   0.0%
pIMDs
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
8.Secondary Outcome
Title Number of Participants in Groups 1, 2, and 3 With Detectable Influenza A Virus in Nasal and Oropharyngeal Swabs on Days 1 to 5
Hide Description To detect viral shedding participants who received LAIV vaccine or intranasal sterile saline as the prime dose had nasal and oropharyngeal swabs collected on Days 1 to 5. Influenza type A virus ribonucleic acid (RNA) was detected using reverse transcription polymerase chain reaction (RT-PCR).
Time Frame Days 1 to 5
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received LAIV (Groups 1, 2, and 3) with evaluable samples
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3
Measure Type: Count of Participants
Unit of Measure: Participants
Overall
7
  36.8%
8
  57.1%
0
   0.0%
Day 2
7
  36.8%
4
  28.6%
0
   0.0%
Day 3
1
   5.3%
1
   7.1%
0
   0.0%
Day 4
0
   0.0%
0
   0.0%
0
   0.0%
Day 5
0
   0.0%
3
  21.4%
0
   0.0%
9.Secondary Outcome
Title Number of Participants in Groups 1, 2, and 3 With Viable Vaccine Virus in Cell Culture Through 5 Days Post-vaccination
Hide Description To study virus infectivity, nasal and oropharyngeal swab specimens that tested influenza A positive by RT-PCR were further tested for viability of virus in Madin Darby canine kidney (MDCK) cell culture and stained with monoclonal antibody specific to the cH8/1N1 LAIV virus to confirm detected virus is of vaccine origin.
Time Frame Days 1 to 5
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received LAIV (Groups 1, 2, and 3) and tested positive for influenza A virus by RT-PCR at any time during the 5 days post LAIV dose and with evaluable samples
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 7 7 0
Measure Type: Count of Participants
Unit of Measure: Participants
Overall Number Analyzed 7 participants 7 participants 0 participants
0
   0.0%
0
   0.0%
Day 2 Number Analyzed 7 participants 3 participants 0 participants
0
   0.0%
0
   0.0%
Day 3 Number Analyzed 1 participants 1 participants 0 participants
0
   0.0%
0
   0.0%
Day 4 Number Analyzed 0 participants 0 participants 0 participants
Day 5 Number Analyzed 0 participants 3 participants 0 participants
0
   0.0%
10.Secondary Outcome
Title Percentage of Participants With Serum Anti-H1 Hemagglutinin Stalk Immunoglobulin G Antibody Seropositivity
Hide Description

Anti-H1 hemagglutinin (HA) stalk immunoglobulin G (IgG) was quantified using an enzyme-linked immunosorbent assay (ELISA).

The ELISA measured IgG antibodies against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]) .

Titers are expressed as ELISA units (EU) per mL and were calculated on the basis of an internal standard to which units were arbitrarily assigned. Seropositivity rate was defined as the percentage of participants with an antibody titer of at least the cut-off for the assay; ≥ 65.3 EU/mL.
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), Month 9 (6 months post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Measure Type: Number
Unit of Measure: percentage of participants
Baseline (pre-vaccination) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
100 100 100 100 100
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
100 100 100 100 100
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
100 100 100 100 100
Month 9 (6 months post-dose 2) Number Analyzed 15 participants 13 participants 2 participants 14 participants 9 participants
100 100 100 100 100
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
100 100 100 100 100
11.Secondary Outcome
Title Geometric Mean Titer of Serum Anti-H1 Hemagglutinin Stalk IgG Antibodies
Hide Description

Anti-H1 hemagglutinin stalk immunoglobulin G (IgG) was quantified using an enzyme-linked immunosorbent assay (ELISA).

The ELISA measured IgG antibodies against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]) .

Titers are expressed as ELISA units (EU) per mL and were calculated on the basis of an internal standard to which units were arbitrarily assigned. The lower limit of quantitation (LLOQ) for the assay was 65.3 EU/mL.
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), Month 9 (6 months post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Geometric Mean (95% Confidence Interval)
Unit of Measure: EU/mL
Baseline (pre-vaccination) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
11503
(7698 to 17187)
10213
(6559 to 15903)
12966
(2459 to 68377)
12028
(6658 to 21729)
8615
(5517 to 13453)
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
11337
(7790 to 16499)
10347
(6810 to 15721)
11832
(2593 to 53992)
84207
(63756 to 111219)
7975
(5317 to 11961)
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
62238
(44507 to 87034)
22073
(14577 to 33423)
10628 [1] 
(NA to 5749922)
62992
(46931 to 84549)
9226
(5791 to 14696)
Month 9 (6 months post-dose 2) Number Analyzed 15 participants 13 participants 2 participants 14 participants 9 participants
19955
(13334 to 29863)
10846
(7108 to 16549)
8364 [1] 
(NA to 12544501)
31228
(21153 to 46101)
7043
(4019 to 12345)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
16046
(10632 to 24218)
13470
(8300 to 21860)
16195
27323
(17736 to 42092)
6825
(4132 to 11272)
[1]
< LLOQ (65.3 EU/mL)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 2: cH8/1N1 LAIV and cH5/1N1 IIV
Comments Comparison of Anti-H1 HA-stalk IgG (Serum) Humoral Response: Adjusted Geometric Mean Titer (GMT) Ratio 28 Days Post-Boost Dose
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 2.73
Confidence Interval (2-Sided) 95%
1.73 to 4.29
Estimation Comments GMT ratio computed after fitting an analysis of covariance (ANCOVA) model on the log10 transformed titers, including vaccine group as fixed effect and the pre-vaccination titer as covariate.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
Comments Comparison of Anti-H1 HA-stalk IgG (Serum) Humoral Response: Adjusted GMT Ratio 28 Days Post-Boost Dose
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9411
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 1.06
Confidence Interval (2-Sided) 95%
0.68 to 1.66
Estimation Comments GMT ratio computed after fitting an analysis of covariance (ANCOVA) model on the log10 transformed titers, including vaccine group as fixed effect and the pre-vaccination titer as covariate.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Group 2: cH8/1N1 LAIV and cH5/1N1 IIV, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
Comments Comparison of Anti-H1 HA-stalk IgG (Serum) Humoral Response: Adjusted GMT Ratio 28 Days Post-Boost Dose
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 0.39
Confidence Interval (2-Sided) 95%
0.24 to 0.62
Estimation Comments GMT ratio computed after fitting an analysis of covariance (ANCOVA) model on the log10 transformed titers, including vaccine group as fixed effect and the pre-vaccination titer as covariate.
12.Secondary Outcome
Title Percentage of Participants With a ≥ 4-fold Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk IgG Antibodies
Hide Description

Anti-H1 hemagglutinin stalk immunoglobulin G (IgG) was quantified using an enzyme-linked immunosorbent assay (ELISA).

The ELISA measured IgG antibodies against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]) .
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), Month 9 (6 months post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
0.0
(0.0 to 17.6)
0.0
(0.0 to 23.2)
0.0
(0.0 to 70.8)
80.0
(51.9 to 95.7)
0.0
(0.0 to 30.8)
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
75.0
(47.6 to 92.7)
15.4
(1.9 to 45.4)
0.0
(0.0 to 84.2)
57.1
(28.9 to 82.3)
0.0
(0.0 to 30.8)
Month 9 (6 months post-dose 2) Number Analyzed 15 participants 13 participants 2 participants 14 participants 9 participants
6.7
(0.2 to 31.9)
0.0
(0.0 to 24.7)
0.0
(0.0 to 84.2)
21.4
(4.7 to 50.8)
0.0
(0.0 to 33.6)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
7.1
(0.2 to 33.9)
15.4
(1.9 to 45.4)
0.0
23.1
(5.0 to 53.8)
0.0
(0.0 to 30.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 2: cH8/1N1 LAIV and cH5/1N1 IIV
Comments Comparison of Anti-H1 HA-stalk IgG (Serum) Humoral Response: Seroresponse (≥4-fold) Rate 28 Days Post-Boost Dose
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0025
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 59.6
Confidence Interval (2-Sided) 95%
23.59 to 81.02
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
Comments Comparison of Anti-H1 HA-stalk IgG (Serum) Humoral Response: Seroresponse (≥4-fold) Rate 28 Days Post-Boost Dose
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4421
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 17.9
Confidence Interval (2-Sided) 95%
-16.24 to 49.00
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Group 2: cH8/1N1 LAIV and cH5/1N1 IIV, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
Comments Comparison of Anti-H1 HA-stalk IgG (Serum) Humoral Response: Seroresponse (≥4-fold) Rate 28 Days Post-Boost Dose
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0461
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -41.8
Confidence Interval (2-Sided) 95%
-68.75 to -4.80
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Percentage of Participants With a ≥ 10-fold Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk IgG Antibodies
Hide Description

Anti-H1 hemagglutinin stalk immunoglobulin G (IgG) was quantified using an enzyme-linked immunosorbent assay (ELISA).

The ELISA measured IgG antibodies against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]) .
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), Month 9 (6 months post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
0.0
(0.0 to 17.6)
0.0
(0.0 to 23.2)
0.0
(0.0 to 70.8)
33.3
(11.8 to 61.6)
0.0
(0.0 to 30.8)
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
25.0
(7.3 to 52.4)
0.0
(0.0 to 24.7)
0.0
(0.0 to 84.2)
14.3
(1.8 to 42.8)
0.0
(0.0 to 30.8)
Month 9 (6 months post-dose 2) Number Analyzed 15 participants 13 participants 2 participants 14 participants 9 participants
0.0
(0.0 to 21.8)
0.0
(0.0 to 24.7)
0.0
(0.0 to 84.2)
0.0
(0.0 to 23.2)
0.0
(0.0 to 33.6)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
0.0
(0.0 to 23.2)
0.0
(0.0 to 24.7)
0.0
0.0
(0.0 to 24.7)
0.0
(0.0 to 30.8)
14.Secondary Outcome
Title Mean Geometric Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk IgG Antibodies
Hide Description

Anti-H1 hemagglutinin stalk immunoglobulin G (IgG) was quantified using an enzyme-linked immunosorbent assay (ELISA).

The ELISA measured IgG antibodies against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]).

Mean geometric increase represents the fold-rise in antibody titer from baseline to each post-baseline time point (ratio of post-baseline titer to Baseline titer).
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), Month 9 (6 months post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Geometric Mean (95% Confidence Interval)
Unit of Measure: fold-rise
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
1.0
(0.9 to 1.0)
1.0
(0.9 to 1.1)
0.9
(0.8 to 1.1)
7.0
(4.3 to 11.4)
0.9
(0.9 to 1.0)
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
5.8
(3.8 to 8.8)
2.2
(1.6 to 3.2)
1.0
(0.3 to 3.7)
4.9
(3.2 to 7.5)
1.1
(0.8 to 1.4)
Month 9 (6 months post-dose 2) Number Analyzed 15 participants 13 participants 2 participants 14 participants 9 participants
1.8
(1.4 to 2.3)
1.1
(0.9 to 1.4)
0.8
(0.6 to 1.1)
2.4
(1.7 to 3.5)
0.8
(0.6 to 1.2)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
1.5
(1.1 to 1.9)
1.4
(0.9 to 2.0)
0.8
2.1
(1.5 to 3.0)
0.8
(0.6 to 1.1)
15.Secondary Outcome
Title Percentage of Participants With Serum Anti-H1 Hemagglutinin Stalk Immunoglobulin A Antibody Seropositivity
Hide Description

Anti-H1 hemagglutinin stalk immunoglobulin A (IgA) was quantified using an enzyme-linked immunosorbent assay (ELISA).

The ELISA measured IgA antibodies against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]) .

Seropositivity rate was defined as the percentage of participants with an antibody titer of at least the cut-off for the assay; ≥ 1:100.
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Measure Type: Number
Unit of Measure: percentage of participants
Baseline (pre-vaccination) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
100 100 100 100 100
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
100 100 100 100 100
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
100 100 100 100 100
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
100 100 100 100 100
16.Secondary Outcome
Title Geometric Mean Titer of Serum Anti-H1 Hemagglutinin Stalk IgA Antibodies
Hide Description

Anti-H1 hemagglutinin stalk immunoglobulin A (IgA) was quantified using an enzyme-linked immunosorbent assay (ELISA).

The ELISA measured IgA antibodies against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]) .
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Geometric Mean (95% Confidence Interval)
Unit of Measure: titer
Baseline (pre-vaccination) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
5815
(3281 to 10306)
3536
(1831 to 6826)
6935
(2425 to 19834)
3408
(1765 to 6580)
2887
(1754 to 4753)
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
6070
(3585 to 10277)
4781
(2230 to 10249)
7824
(1280 to 47812)
15919
(8635 to 29347)
3163
(1698 to 5893)
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
23595
(15414 to 36116)
11095
(5304 to 23210)
7571
(371 to 154530)
18079
(10319 to 31677)
2818
(1797 to 4417)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
10267
(5724 to 18417)
8460
(3625 to 19745)
5740
11856
(5992 to 23458)
2765
(1546 to 4945)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 2: cH8/1N1 LAIV and cH5/1N1 IIV
Comments Comparison of Anti-H1 HA-stalk IgA (Serum) Humoral Response: Adjusted GMT Ratio 28 Days Post-Boost Dose
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1665
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 1.71
Confidence Interval (2-Sided) 95%
0.84 to 3.48
Estimation Comments GMT ratio computed after fitting an analysis of covariance (ANCOVA) model on the log10 transformed titers, including vaccine group as fixed effect and the pre-vaccination titer as covariate.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Group 2: cH8/1N1 LAIV and cH5/1N1 IIV, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
Comments Comparison of Anti-H1 HA-stalk IgA (Serum) Humoral Response: Adjusted GMT Ratio 28 Days Post-Boost Dose
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9377
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 1.10
Confidence Interval (2-Sided) 95%
0.55 to 2.20
Estimation Comments GMT ratio computed after fitting an analysis of covariance (ANCOVA) model on the log10 transformed titers, including vaccine group as fixed effect and the pre-vaccination titer as covariate.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Group 2: cH8/1N1 LAIV and cH5/1N1 IIV, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
Comments Comparison of Anti-H1 HA-stalk IgG (Serum) Humoral Response: Adjusted GMT Ratio 28 Days Post-Boost Dose
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3088
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 0.64
Confidence Interval (2-Sided) 95%
0.31 to 1.33
Estimation Comments GMT ratio computed after fitting an analysis of covariance (ANCOVA) model on the log10 transformed titers, including vaccine group as fixed effect and the pre-vaccination titer as covariate.
17.Secondary Outcome
Title Percentage of Participants With a ≥ 4-fold Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk IgA Antibodies
Hide Description

Anti-H1 hemagglutinin stalk immunoglobulin A (IgA) was quantified using an enzyme-linked immunosorbent assay (ELISA).

The ELISA measured IgA antibodies against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]) .
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
0.0
(0.0 to 17.6)
7.1
(0.2 to 33.9)
0.0
(0.0 to 70.8)
53.3
(26.6 to 78.7)
0.0
(0.0 to 30.8)
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
62.5
(35.4 to 84.8)
46.2
(19.2 to 74.9)
0.0
(0.0 to 84.2)
64.3
(35.1 to 87.2)
0.0
(0.0 to 30.8)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
14.3
(1.8 to 42.8)
23.1
(5.0 to 53.8)
0.0
46.2
(19.2 to 74.9)
0.0
(0.0 to 30.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 2: cH8/1N1 LAIV and cH5/1N1 IIV
Comments Comparison of Anti-H1 HA-stalk IgG (Serum) Humoral Response: Seroresponse (≥4-fold) Rate 28 Days Post-Boost Dose
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4667
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 16.3
Confidence Interval (2-Sided) 95%
-19.85 to 48.88
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
Comments Comparison of Anti-H1 HA-stalk IgG (Serum) Humoral Response: Seroresponse (≥4-fold) Rate 28 Days Post-Boost Dose
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.9999
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -1.8
Confidence Interval (2-Sided) 95%
-34.76 to 32.17
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Group 2: cH8/1N1 LAIV and cH5/1N1 IIV, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
Comments Comparison of Anti-H1 HA-stalk IgG (Serum) Humoral Response: Seroresponse (≥4-fold) Rate 28 Days Post-Boost Dose
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4495
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -18.1
Confidence Interval (2-Sided) 95%
-51.15 to 19.37
Estimation Comments [Not Specified]
18.Secondary Outcome
Title Percentage of Participants With a ≥ 10-fold Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk IgA Antibodies
Hide Description

Anti-H1 hemagglutinin stalk immunoglobulin A (IgA) was quantified using an enzyme-linked immunosorbent assay (ELISA).

The ELISA measured IgA antibodies against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]) .
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
0.0
(0.0 to 17.6)
0.0
(0.0 to 23.2)
0.0
(0.0 to 70.8)
26.7
(7.8 to 55.1)
0.0
(0.0 to 30.8)
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
18.8
(4.0 to 45.6)
15.4
(1.9 to 45.4)
0.0
(0.0 to 84.2)
28.6
(8.4 to 58.1)
0.0
(0.0 to 30.8)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
0.0
(0.0 to 23.2)
0.0
(0.0 to 24.7)
0.0
7.7
(0.2 to 36.0)
0.0
(0.0 to 30.8)
19.Secondary Outcome
Title Mean Geometric Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk IgA Antibodies
Hide Description

Anti-H1 hemagglutinin stalk immunoglobulin A (IgA) was quantified using an enzyme-linked immunosorbent assay (ELISA).

The ELISA measured IgA antibodies against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]) .

Mean geometric increase represents the fold-rise in antibody titer from baseline to each post-baseline time point (ratio of post-baseline titer to Baseline titer).
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Geometric Mean (95% Confidence Interval)
Unit of Measure: fold-rise
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
1.0
(0.9 to 1.2)
1.4
(1.0 to 1.8)
1.1
(0.5 to 2.7)
4.7
(2.6 to 8.5)
1.1
(0.9 to 1.4)
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
4.8
(2.9 to 7.9)
3.4
(2.0 to 5.6)
0.9
(0.0 to 18.9)
5.0
(2.8 to 9.1)
1.0
(0.8 to 1.2)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
1.8
(1.2 to 2.7)
2.6
(1.7 to 3.8)
0.6
3.1
(1.6 to 5.9)
1.0
(0.7 to 1.3)
20.Secondary Outcome
Title Percentage of Participants With Serum Anti-H1 Hemagglutinin Stalk Neutralizing Antibody Seropositivity
Hide Description

Anti H1 hemagglutinin stalk neutralizing antibodies were quantified using a microneutralization (MN) assay using a virus that expresses a chimeric hemagglutinin that contains an exotic HA head domain (strain A/mallard/Sweden/81/2002 [H6N1]) and the H1 stalk domain (strain A/California/04/2009 [H1N1pandemic]) and an exotic neuraminidase, N5, for which humans are generally naïve (strain: A/mallard/Sweden/86/2003 [H12N5]).

Seropositivity rate was defined as the percentage of participants with an antibody titer of ≥ 1:10.
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Measure Type: Number
Unit of Measure: percentage of participants
Baseline (pre-vaccination) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
100 100 100 100 100
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
100 100 100 100 100
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
100 100 100 100 100
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
100 100 100 100 100
21.Secondary Outcome
Title Geometric Mean Titer of Serum Anti-H1 Hemagglutinin Stalk Neutralizing Antibodies
Hide Description Anti H1 hemagglutinin stalk neutralizing antibodies were quantified using a microneutralization (MN) assay using a virus that expresses a chimeric hemagglutinin that contains an exotic HA head domain (strain A/mallard/Sweden/81/2002 ([H6N1]) and the H1 stalk domain (strain A/California/04/2009 ([H1N1pandemic]) and an exotic neuraminidase, N5, for which humans are generally naïve (strain: A/mallard/Sweden/86/2003 [H12N5]). The LLOQ for the assay was 1:10.
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Geometric Mean (95% Confidence Interval)
Unit of Measure: titer
Baseline (pre-vaccination) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
48
(34 to 67)
49
(29 to 83)
63 [1] 
(NA to 881)
58
(36 to 93)
43
(25 to 74)
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
48
(32 to 72)
38
(23 to 62)
50 [1] 
(NA to 368)
111
(74 to 166)
40
(24 to 67)
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
153
(103 to 277)
94
(56 to 157)
40 [1] 
(NA to 267306)
138
(96 to 197)
37
(24 to 58)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
62
(41 to 96)
58
(35 to 96)
80
99
(62 to 158)
40
(25 to 64)
[1]
< LLOQ (1:10)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 2: cH8/1N1 LAIV and cH5/1N1 IIV
Comments Comparison of Anti-H1 HA-stalk MN (Serum) Assay: Adjusted GMT Ratio 28 Days Post-Boost Dose
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0928
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 1.61
Confidence Interval (2-Sided) 95%
0.94 to 2.77
Estimation Comments GMT ratio computed after fitting an analysis of covariance (ANCOVA) model on the log10 transformed titers, including vaccine group as fixed effect and the pre-vaccination titer as covariate.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
Comments Comparison of Anti-H1 HA-stalk MN (Serum) Assay: Adjusted GMT Ratio 28 Days Post-Boost Dose
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4198
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 1.32
Confidence Interval (2-Sided) 95%
0.77 to 2.26
Estimation Comments GMT ratio computed after fitting an analysis of covariance (ANCOVA) model on the log10 transformed titers, including vaccine group as fixed effect and the pre-vaccination titer as covariate.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Group 2: cH8/1N1 LAIV and cH5/1N1 IIV, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
Comments Comparison of Anti-H1 HA-stalk MN (Serum) Assay: Adjusted GMT Ratio 28 Days Post-Boost Dose
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6754
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 0.82
Confidence Interval (2-Sided) 95%
0.47 to 1.45
Estimation Comments GMT ratio computed after fitting an analysis of covariance (ANCOVA) model on the log10 transformed titers, including vaccine group as fixed effect and the pre-vaccination titer as covariate.
22.Secondary Outcome
Title Percentage of Participants With a ≥ 4-fold Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk Neutralizing Antibodies
Hide Description Anti H1 hemagglutinin stalk neutralizing antibodies were quantified using a microneutralization (MN) assay using a virus that expresses a chimeric hemagglutinin that contains an exotic HA head domain (strain A/mallard/Sweden/81/2002 ([H6N1]) and the H1 stalk domain (strain A/California/04/2009 ([H1N1pandemic]) and an exotic neuraminidase, N5, for which humans are generally naïve (strain: A/mallard/Sweden/86/2003 [H12N5]).
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
5.3
(0.1 to 26.0)
0.0
(0.0 to 23.2)
0.0
(0.0 to 70.8)
20.0
(4.3 to 48.1)
0.0
(0.0 to 30.8)
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
50.0
(24.7 to 75.3)
30.8
(9.1 to 61.4)
0.0
(0.0 to 84.2)
35.7
(12.8 to 64.9)
0.0
(0.0 to 30.8)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
7.1
(0.2 to 33.9)
15.4
(1.9 to 45.4)
0.0
15.4
(1.9 to 45.4)
0.0
(0.0 to 30.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 2: cH8/1N1 LAIV and cH5/1N1 IIV
Comments Comparison of Anti-H1 HA-stalk MN (Serum) Assay: Seroresponse (>4-Fold) Rate 28 Days Post-Boost Dose
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4515
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 19.2
Confidence Interval (2-Sided) 95%
-17.19 to 50.49
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
Comments Comparison of Anti-H1 HA-stalk MN (Serum) Assay: Seroresponse (>4-Fold) Rate 28 Days Post-Boost Dose
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4837
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 14.3
Confidence Interval (2-Sided) 95%
-21.22 to 46.19
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Group 2: cH8/1N1 LAIV and cH5/1N1 IIV, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
Comments Comparison of Anti-H1 HA-stalk MN (Serum) Assay: Seroresponse (>4-Fold) Rate 28 Days Post-Boost Dose
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.9999
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -4.9
Confidence Interval (2-Sided) 95%
-38.80 to 30.46
Estimation Comments [Not Specified]
23.Secondary Outcome
Title Percentage of Participants With a ≥ 10-fold Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk Neutralizing Antibodies
Hide Description Anti H1 hemagglutinin stalk neutralizing antibodies were quantified using a microneutralization (MN) assay using a virus that expresses a chimeric hemagglutinin that contains an exotic HA head domain (strain A/mallard/Sweden/81/2002 ([H6N1]) and the H1 stalk domain (strain A/California/04/2009 ([H1N1pandemic]) and an exotic neuraminidase, N5, for which humans are generally naïve (strain: A/mallard/Sweden/86/2003 [H12N5]).
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
0.0
(0.0 to 17.6)
0.0
(0.0 to 23.2)
0.0
(0.0 to 70.8)
0.0
(0.0 to 21.8)
0.0
(0.0 to 30.8)
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
6.3
(0.2 to 30.2)
0.0
(0.0 to 24.7)
0.0
(0.0 to 84.2)
0.0
(0.0 to 23.2)
0.0
(0.0 to 30.8)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
0.0
(0.0 to 23.2)
0.0
(0.0 to 24.7)
0.0
0.0
(0.0 to 24.7)
0.0
(0.0 to 30.8)
24.Secondary Outcome
Title Mean Geometric Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk Neutralizing Antibodies
Hide Description

Anti H1 hemagglutinin stalk neutralizing antibodies were quantified using a microneutralization (MN) assay using a virus that expresses a chimeric hemagglutinin that contains an exotic HA head domain (strain A/mallard/Sweden/81/2002 [H6N1]) and the H1 stalk domain (strain A/California/04/2009 [H1N1pandemic]) and an exotic neuraminidase, N5, for which humans are generally naïve (strain: A/mallard/Sweden/86/2003 [H12N5]).

Mean geometric increase represents the fold-rise in antibody titer from baseline to each post-baseline time point (ratio of post-baseline titer to Baseline titer).
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Geometric Mean (95% Confidence Interval)
Unit of Measure: fold-rise
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
1.0
(0.8 to 1.3)
0.8
(0.6 to 1.0)
0.8
(0.3 to 2.1)
1.9
(1.5 to 2.5)
0.9
(0.6 to 1.3)
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
3.4
(2.2 to 5.2)
2.1
(1.4 to 3.1)
0.7
(0.0 to 57.8)
2.2
(1.6 to 3.0)
0.9
(0.7 to 1.1)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
1.2
(0.9 to 1.6)
1.3
(0.9 to 1.9)
0.5
1.5
(1.1 to 2.2)
0.9
(0.6 to 1.4)
25.Secondary Outcome
Title Serum Antibody-dependent Cell-mediated Cytotoxicity (ADCC) to the H1 Hemagglutinin Stalk
Hide Description

Antibody-dependent cell-mediated cytotoxicity (ADCC) is an immune response leading to lysis of antibody-coated target cells by immune effector cells and is triggered by the interaction between the Fc portion of an antibody and Fc-gamma receptors expressed on immune effector cells.

This bioluminescent assay measured antibodies to a chimeric hemagglutinin (H6 head domain and H1 stalk domain) virus that mediate ADCC activity via the Fc-receptor. ADCC activity was measured in relative luciferase units (RLU) for serial dilutions of serum samples using a plate reader.

ADCC activity was expressed by the area under the curve (AUC) of luminescence (RLU) per serial dilution (X-fold serial dilutions).
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Median (95% Confidence Interval)
Unit of Measure: RLU * dilution factor
Baseline (pre-vaccination) Number Analyzed 19 participants 12 participants 3 participants 15 participants 10 participants
321389
(91992 to 581362)
200649
(30810 to 542237)
486775
(173346 to 566708)
331849
(227546 to 558058)
109178
(38622 to 239985)
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 13 participants 3 participants 15 participants 10 participants
322530
(70776 to 432268)
183017
(88548 to 457200)
693225
(104524 to 807975)
869805
(606000 to 1327125)
103919
(32655 to 241028)
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
1334738
(875063 to 1801500)
366815
(188478 to 795829)
474913
(175000 to 774825)
863811
(524405 to 1521176)
65371
(28729 to 307257)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
334076
(132771 to 767038)
353639
(74637 to 840500)
708455
(708455 to 708455)
508248
(368035 to 979896)
130882
(47973 to 310940)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 2: cH8/1N1 LAIV and cH5/1N1 IIV
Comments Comparison of Serum cH6/1 - ADCC Activity: AUC at 28 Days Post-Boost
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0031
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 2.93
Confidence Interval (2-Sided) 95%
1.56 to 7.49
Estimation Comments Based on log10 AUC, using the Hodges-Lehmann location parameter difference back-transformed to the original scale.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
Comments Comparison of Serum cH6/1 - ADCC Activity: AUC at 28 Days Post-Boost
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2048
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 1.25
Confidence Interval (2-Sided) 95%
0.73 to 2.23
Estimation Comments Based on log10 AUC, using the Hodges-Lehmann location parameter difference back-transformed to the original scale.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Group 2: cH8/1N1 LAIV and cH5/1N1 IIV, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
Comments Comparison of Serum cH6/1 - ADCC Activity: AUC at 28 Days Post-Boost
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0392
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 0.43
Confidence Interval (2-Sided) 95%
0.18 to 1.00
Estimation Comments [Not Specified]
26.Secondary Outcome
Title Fold-Increase From Baseline in Serum ADCC to the H1 Hemagglutinin Stalk
Hide Description

Antibody-dependent cell-mediated cytotoxicity (ADCC) is an immune response leading to lysis of antibody-coated target cells by immune effector cells and is triggered by the interaction between the Fc portion of an antibody and Fc-gamma receptors expressed on immune effector cells.

This bioluminescent assay measured antibodies to a chimeric hemagglutinin (H6 head domain and H1 stalk domain) virus that mediate ADCC activity via the Fc-receptor. ADCC activity was measured by the area under the curve (AUC) of luminescence per serial dilution.
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at Baseline and each time point. The-per protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 12 3 15 10
Median (95% Confidence Interval)
Unit of Measure: fold-increase
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 12 participants 3 participants 15 participants 10 participants
0.9
(0.77 to 1.00)
1.1
(0.90 to 1.35)
1.2
(0.60 to 1.66)
2.4
(1.29 to 4.59)
1.0
(0.58 to 1.18)
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 12 participants 2 participants 14 participants 10 participants
3.6
(2.22 to 14.36)
3.8
(1.33 to 18202.00)
1.2
(1.01 to 1.37)
2.3
(1.49 to 4.78)
1.0
(0.51 to 1.59)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 12 participants 1 participants 13 participants 10 participants
1.8
(0.67 to 5.20)
1.8
(0.79 to 4.27)
1.25
(1.25 to 1.25)
1.9
(0.82 to 2.12)
0.9
(0.76 to 1.69)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 2: cH8/1N1 LAIV and cH5/1N1 IIV
Comments Comparison of Serum cH6/1 - ADCC Activity: Fold Increase in AUC at 28 Days Post-Boost
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8243
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 1.16
Confidence Interval (2-Sided) 95%
0.14 to 4.95
Estimation Comments Based on the Hodges-Lehmann location parameter difference on the log scale then back-transformed to the original scale.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
Comments Comparison of Serum cH6/1 - ADCC Activity: Fold Increase in AUC at 28 Days Post-Boost
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2530
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 1.74
Confidence Interval (2-Sided) 95%
0.67 to 6.06
Estimation Comments Based on the Hodges-Lehmann location parameter difference on the log scale then back-transformed to the original scale.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Group 2: cH8/1N1 LAIV and cH5/1N1 IIV, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
Comments Comparison of Serum cH6/1 - ADCC Activity: Fold Increase in AUC at 28 Days Post-Boost
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5654
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 1.83
Confidence Interval (2-Sided) 95%
0.47 to 39.92
Estimation Comments Based on the Hodges-Lehmann location parameter difference on the log scale then back-transformed to the original scale.
27.Secondary Outcome
Title Percentage of Participants With a ≥ 4-fold Increase From Baseline in Serum ADCC to the H1 Hemagglutinin Stalk
Hide Description

Antibody-dependent cell-mediated cytotoxicity (ADCC) is an immune response leading to lysis of antibody-coated target cells by immune effector cells and is triggered by the interaction between the Fc portion of an antibody and Fc-gamma receptors expressed on immune effector cells.

This bioluminescent assay measured antibodies to a chimeric hemagglutinin (H6 head domain and H1 stalk domain) virus that mediate ADCC activity via the Fc-receptor. ADCC activity was measured by the area under the curve (AUC) of luminescence per serial dilution.
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at Baseline and each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 12 3 15 10
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 12 participants 3 participants 15 participants 10 participants
0.0
(0.0 to 17.6)
8.3
(0.2 to 38.5)
0.0
(0.0 to 70.8)
26.7
(7.8 to 55.1)
10.0
(0.3 to 44.5)
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 12 participants 2 participants 14 participants 10 participants
50.0
(24.7 to 75.3)
45.5
(16.7 to 76.6)
0.0
(0.0 to 84.2)
42.9
(17.7 to 71.1)
10.0
(0.3 to 44.5)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 12 participants 1 participants 13 participants 10 participants
28.6
(8.4 to 58.1)
27.3
(6.0 to 61.0)
0.0
15.4
(1.9 to 45.4)
0.0
(0.0 to 30.8)
28.Secondary Outcome
Title Percentage of Participants With a ≥ 10-fold Increase From Baseline in Serum ADCC to the H1 Hemagglutinin Stalk
Hide Description

Antibody-dependent cell-mediated cytotoxicity (ADCC) is an immune response leading to lysis of antibody-coated target cells by immune effector cells and is triggered by the interaction between the Fc portion of an antibody and Fc-gamma receptors expressed on immune effector cells.

This bioluminescent assay measured antibodies to a chimeric hemagglutinin (H6 head domain and H1 stalk domain) virus that mediate ADCC activity via the Fc-receptor. ADCC activity was measured by the area under the curve (AUC) of luminescence per serial dilution.
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at Baseline and each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 12 3 15 10
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 12 participants 3 participants 15 participants 10 participants
0.0
(0.0 to 17.6)
8.3
(0.2 to 38.5)
0.
(0.0 to 70.8)
13.3
(1.7 to 40.5)
0.0
(0.0 to 30.8)
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 12 participants 2 participants 14 participants 10 participants
31.3
(11.0 to 58.7)
45.5
(16.7 to 76.6)
0.0
(0.0 to 84.2)
14.3
(1.8 to 42.8)
0.0
(0.0 to 30.8)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 12 participants 1 participants 13 participants 10 participants
14.3
(1.8 to 42.8)
18.2
(2.3 to 51.8)
0.0
7.7
(0.2 to 36.0)
0.0
(0.0 to 30.8)
29.Secondary Outcome
Title Percentage of Participants With Anti-H1 Hemagglutinin Stalk Salivary IgG Antibody Seropositivity
Hide Description

Anti-H1 hemagglutinin stalk immunoglobulin G (IgG) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA).

The ELISA measured IgG antibodies in saliva against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]).

Seropositivity rate was defined as the percentage of participants with an antibody titer of at least the cut-off for the assay; ≥ 1:10.
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 18 13 3 15 9
Measure Type: Number
Unit of Measure: percentage of participants
Baseline (pre-vaccination) Number Analyzed 18 participants 13 participants 3 participants 15 participants 9 participants
94.4 84.6 66.7 86.7 88.9
Month 1 (28 days post-dose 1) Number Analyzed 18 participants 13 participants 3 participants 15 participants 8 participants
94.4 84.6 100 100 87.5
Month 4 (28 days post-dose 2) Number Analyzed 15 participants 12 participants 2 participants 14 participants 9 participants
100 100 100 100 88.9
Month 15 (12 months post-dose 2) Number Analyzed 13 participants 12 participants 1 participants 12 participants 9 participants
100 91.7 100 100 88.9
30.Secondary Outcome
Title Geometric Mean Titer of Anti-H1 Hemagglutinin Stalk Salivary IgG Antibodies
Hide Description

Anti-H1 hemagglutinin stalk immunoglobulin G (IgG) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA).

The ELISA measured IgG antibodies against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]). The LLOQ for the assay was 1:10.
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 18 13 3 15 9
Geometric Mean (95% Confidence Interval)
Unit of Measure: titer
Baseline (pre-vaccination) Number Analyzed 18 participants 13 participants 3 participants 15 participants 9 participants
40
(24 to 65)
43
(18 to 103)
21 [1] 
(NA to 520)
55
(24 to 123)
45
(17 to 121)
Month 1 (28 days post-dose 1) Number Analyzed 18 participants 13 participants 3 participants 15 participants 8 participants
31
(21 to 48)
40
(18 to 91)
42
(14 to 130)
155
(67 to 356)
36
(11 to 114)
Month 4 (28 days post-dose 2) Number Analyzed 15 participants 12 participants 2 participants 14 participants 9 participants
161
(102 to 254)
131
(49 to 346)
15 [1] 
(NA to 1153)
233
(117 to 462)
61
(16 to 224)
Month 15 (12 months post-dose 2) Number Analyzed 13 participants 12 participants 1 participants 12 participants 9 participants
67
(32 to 142)
51
(22 to 114)
35
168
(76 to 372)
43
(16 to 119)
[1]
< LLOQ (1:10)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 2: cH8/1N1 LAIV and cH5/1N1 IIV
Comments Comparison of Anti-H1 HA-stalk IgG (Saliva), Mucosal Response: Adjusted GMT Ratio 28 Days Post-Boost Dose
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8830
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 1.21
Confidence Interval (2-Sided) 95%
0.45 to 3.27
Estimation Comments GMT ratio computed after fitting an analysis of covariance (ANCOVA) model on the log10 transformed titers, including vaccine group as fixed effect and the pre-vaccination titer as covariate.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
Comments Comparison of Anti-H1 HA-stalk IgG (Saliva), Mucosal Response: Adjusted GMT Ratio 28 Days Post-Boost Dose
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9238
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 0.86
Confidence Interval (2-Sided) 95%
0.33 to 2.26
Estimation Comments GMT ratio computed after fitting an analysis of covariance (ANCOVA) model on the log10 transformed titers, including vaccine group as fixed effect and the pre-vaccination titer as covariate.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Group 2: cH8/1N1 LAIV and cH5/1N1 IIV, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
Comments Comparison of Anti-H1 HA-stalk IgG (Saliva), Mucosal Response: Adjusted GMT Ratio 28 Days Post-Boost Dose
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6926
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 0.71
Confidence Interval (2-Sided) 95%
0.26 to 1.97
Estimation Comments GMT ratio computed after fitting an analysis of covariance (ANCOVA) model on the log10 transformed titers, including vaccine group as fixed effect and the pre-vaccination titer as covariate.
31.Secondary Outcome
Title Percentage of Participants With a ≥ 4-fold Increase From Baseline in Anti-H1 Hemagglutinin Stalk Salivary IgG
Hide Description

Anti-H1 hemagglutinin stalk immunoglobulin G (IgG) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA).

The ELISA measured IgG antibodies in saliva against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]).
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 18 13 3 15 9
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 1 (28 days post-dose 1) Number Analyzed 18 participants 13 participants 3 participants 15 participants 8 participants
0.0
(0.0 to 19.5)
7.7
(0.2 to 36.0)
33.3
(0.8 to 90.6)
40.0
(16.3 to 67.7)
0.0
(0.0 to 36.9)
Month 4 (28 days post-dose 2) Number Analyzed 15 participants 12 participants 2 participants 14 participants 9 participants
53.3
(26.6 to 78.7)
41.7
(15.2 to 72.3)
0.0
(0.0 to 84.2)
57.1
(28.9 to 82.3)
12.5
(0.3 to 52.7)
Month 15 (12 months post-dose 2) Number Analyzed 13 participants 12 participants 1 participants 12 participants 9 participants
23.1
(5.0 to 53.8)
9.1
(0.2 to 41.3)
0.0
33.3
(9.9 to 65.1)
0.0
(0.0 to 36.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 2: cH8/1N1 LAIV and cH5/1N1 IIV
Comments Comparison of Anti-H1 HA-stalk IgG (Saliva), Mucosal Response: Seroresponse (≥4-fold) Rate 28 Days Post-Boost Dose
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7036
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 11.7
Confidence Interval (2-Sided) 95%
-25.72 to 45.82
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
Comments Comparison of Anti-H1 HA-stalk IgG (Saliva), Mucosal Response: Seroresponse (≥4-fold) Rate 28 Days Post-Boost Dose
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.9999
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -3.8
Confidence Interval (2-Sided) 95%
-37.90 to 31.31
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Group 2: cH8/1N1 LAIV and cH5/1N1 IIV, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
Comments Comparison of Anti-H1 HA-stalk IgG (Saliva), Mucosal Response: Seroresponse (≥4-fold) Rate 28 Days Post-Boost Dose
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6951
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -15.5
Confidence Interval (2-Sided) 95%
-49.56 to 22.79
Estimation Comments [Not Specified]
32.Secondary Outcome
Title Percentage of Participants With a ≥ 10-fold Increase From Baseline in Anti-H1 Hemagglutinin Stalk Salivary IgG
Hide Description

Anti-H1 hemagglutinin stalk immunoglobulin G (IgG) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA).

The ELISA measured IgG antibodies in saliva against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]).
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 18 13 3 15 9
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 1 (28 days post-dose 1) Number Analyzed 18 participants 13 participants 3 participants 15 participants 8 participants
0.0
(0.0 to 19.5)
7.7
(0.2 to 36.0)
0.0
(0.0 to 70.8)
13.3
(1.7 to 40.5)
0.0
(0.0 to 36.9)
Month 4 (28 days post-dose 2) Number Analyzed 15 participants 12 participants 2 participants 14 participants 9 participants
20.0
(4.3 to 48.1)
16.7
(2.1 to 48.4)
0.0
(0.0 to 84.2)
21.4
(4.7 to 50.8)
12.5
(0.3 to 52.7)
Month 15 (12 months post-dose 2) Number Analyzed 13 participants 12 participants 1 participants 12 participants 9 participants
7.7
(0.2 to 36.0)
0.0
(0.0 to 28.5)
0.0
25.0
(5.5 to 57.2)
0.0
(0.0 to 36.9)
33.Secondary Outcome
Title Mean Geometric Increase of Anti-H1 Hemagglutinin Stalk Salivary IgG Antibodies
Hide Description

Anti-H1 hemagglutinin stalk immunoglobulin G (IgG) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA).

The ELISA measured IgG antibodies in saliva against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]).

Mean geometric increase represents the fold-rise in antibody titer from baseline to each post-baseline time point (ratio of post-baseline titer to Baseline titer).
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 18 13 3 15 9
Geometric Mean (95% Confidence Interval)
Unit of Measure: fold-rise
Month 1 (28 days post-dose 1) Number Analyzed 18 participants 13 participants 3 participants 15 participants 8 participants
0.7
(0.5 to 1.1)
0.9
(0.5 to 1.7)
2.0
(0.1 to 51.6)
2.8
(1.2 to 6.7)
0.8
(0.4 to 1.4)
Month 4 (28 days post-dose 2) Number Analyzed 15 participants 12 participants 2 participants 14 participants 9 participants
4.0
(2.2 to 7.3)
3.4
(1.6 to 6.9)
1.2
(0.0 to 1145.6)
3.6
(1.5 to 8.4)
1.6
(0.5 to 5.2)
Month 15 (12 months post-dose 2) Number Analyzed 13 participants 12 participants 1 participants 12 participants 9 participants
2.0
(1.0 to 4.0)
1.5
(0.9 to 2.6)
1.2
2.8
(0.9 to 9.1)
0.8
(0.4 to 1.7)
34.Secondary Outcome
Title Percentage of Participants With Anti-H1 Hemagglutinin Stalk Secretory IgA Antibody Seropositivity in Saliva
Hide Description

Anti-H1 hemagglutinin stalk secretory immunoglobulin A (IgA) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA).

The ELISA measured secretory IgA antibodies antibodies (actively secreted in the mucosa) against the H1 stalk domain in saliva using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]).

Seropositivity rate was defined as the percentage of participants with an antibody titer of at least the cut-off for the assay; ≥ 1:4.
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Measure Type: Number
Unit of Measure: percentage of participants
Baseline (pre-vaccination) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
100 100 100 100 100
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 13 participants 2 participants 14 participants 9 participants
100 100 100 100 100
Month 4 (28 days post-dose 2) Number Analyzed 15 participants 12 participants 2 participants 9 participants 9 participants
100 100 100 100 100
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 12 participants 1 participants 12 participants 10 participants
100 100 100 100 100
35.Secondary Outcome
Title Geometric Mean Titer of Anti-H1 Hemagglutinin Stalk Secretory IgA Antibodies in Saliva
Hide Description

Anti-H1 hemagglutinin stalk secretory immunoglobulin A (IgA) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA).

The ELISA measured secretory IgA antibodies antibodies (actively secreted in the mucosa) against the H1 stalk domain in saliva using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]). The LLOQ for the assay was 1:4.
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Geometric Mean (95% Confidence Interval)
Unit of Measure: titer
Baseline (pre-vaccination) Number Analyzed 19 participants 14 participants 3 participants 14 participants 8 participants
86
(52 to 143)
102
(55 to 190)
58
(10 to 323)
221
(148 to 330)
155
(75 to 332)
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 13 participants 2 participants 14 participants 9 participants
80
(48 to 133)
118
(72 to 193)
77 [1] 
(NA to 604449)
191
(95 to 381)
119
(46 to 308)
Month 4 (28 days post-dose 2) Number Analyzed 15 participants 12 participants 2 participants 14 participants 9 participants
93
(52 to 166)
136
(86 to 213)
47 [1] 
(NA to 11552)
201
(116 to 347)
115
(41 to 324)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 12 participants 1 participants 12 participants 10 participants
97
(42 to 224)
109
(56 to 213)
87
190
(115 to 314)
105
(37 to 294)
[1]
< LLOQ (1:4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 2: cH8/1N1 LAIV and cH5/1N1 IIV
Comments Comparison of Anti-H1 HA-stalk Secretory IgA (Saliva), Mucosal Response: Adjusted GMT Ratio 28 Days post-Boost Dose
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3203
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 0.65
Confidence Interval (2-Sided) 95%
0.32 to 1.33
Estimation Comments GMT ratio computed after fitting an analysis of covariance (ANCOVA) model on the log10 transformed titers, including vaccine group as fixed effect and the pre-vaccination titer as covariate.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
Comments Comparison of Anti-H1 HA-stalk Secretory IgA (Saliva), Mucosal Response: Adjusted GMT Ratio 28 Days post-Boost Dose
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5009
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 0.72
Confidence Interval (2-Sided) 95%
0.35 to 1.47
Estimation Comments GMT ratio computed after fitting an analysis of covariance (ANCOVA) model on the log10 transformed titers, including vaccine group as fixed effect and the pre-vaccination titer as covariate.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Group 2: cH8/1N1 LAIV and cH5/1N1 IIV, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
Comments Comparison of Anti-H1 HA-stalk Secretory IgA (Saliva), Mucosal Response: Adjusted GMT Ratio 28 Days post-Boost Dose
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9542
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 1.10
Confidence Interval (2-Sided) 95%
0.51 to 2.37
Estimation Comments GMT ratio computed after fitting an analysis of covariance (ANCOVA) model on the log10 transformed titers, including vaccine group as fixed effect and the pre-vaccination titer as covariate.
36.Secondary Outcome
Title Percentage of Participants With a ≥ 4-fold Increase From Baseline in Anti-H1 Hemagglutinin Stalk Secretory IgA Antibodies in Saliva
Hide Description

Anti-H1 hemagglutinin stalk secretory immunoglobulin A (IgA) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA).

The ELISA measured secretory IgA antibodies (actively secreted in the mucosa) against the H1 stalk domain in saliva by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]).
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 14 8
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 13 participants 2 participants 14 participants 8 participants
0.0
(0.0 to 17.6)
0.0
(0.0 to 24.7)
0.0
(0.0 to 84.2)
0.0
(0.0 to 24.7)
0.0
(0.0 to 36.9)
Month 4 (28 days post-dose 2) Number Analyzed 15 participants 12 participants 2 participants 14 participants 8 participants
6.7
(0.2 to 31.9)
8.3
(0.2 to 38.5)
0.0
(0.0 to 84.2)
0.0
(0.0 to 23.2)
0.0
(0.0 to 41.0)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 12 participants 1 participants 12 participants 8 participants
28.6
(8.4 to 58.1)
0.0
(0.0 to 26.5)
0.0
0.0
(0.0 to 26.5)
12.5
(0.3 to 52.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 2: cH8/1N1 LAIV and cH5/1N1 IIV
Comments Comparison of Anti-H1 HA-stalk Secretory IgA (Saliva), Mucosal Response: Seroresponse (≥4-fold) Rate 28 Days post-Boost Dose
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.9999
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -1.7
Confidence Interval (2-Sided) 95%
-30.62 to 23.79
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
Comments Comparison of Anti-H1 HA-stalk Secretory IgA (Saliva), Mucosal Response: Seroresponse (≥4-fold) Rate 28 Days post-Boost Dose
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.9999
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 6.7
Confidence Interval (2-Sided) 95%
-16.24 to 30.34
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Group 2: cH8/1N1 LAIV and cH5/1N1 IIV, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
Comments Comparison of Anti-H1 HA-stalk Secretory IgA (Saliva), Mucosal Response: Seroresponse (≥4-fold) Rate 28 Days post-Boost Dose
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4615
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 8.3
Confidence Interval (2-Sided) 95%
-19.94 to 36.04
Estimation Comments [Not Specified]
37.Secondary Outcome
Title Percentage of Participants With a ≥ 10-fold Increase From Baseline in Anti-H1 Hemagglutinin Stalk Secretory IgA Antibodies in Saliva
Hide Description

Anti-H1 hemagglutinin stalk secretory immunoglobulin A (IgA) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA).

The ELISA measured secretory IgA antibodies (actively secreted in the mucosa) against the H1 stalk domain in saliva by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]).
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 14 8
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 13 participants 2 participants 14 participants 8 participants
0.0
(0.0 to 17.6)
0.0
(0.0 to 24.7)
0.0
(0.0 to 84.2)
0.0
(0.0 to 24.7)
0.0
(0.0 to 36.9)
Month 4 (28 days post-dose 2) Number Analyzed 15 participants 12 participants 2 participants 14 participants 8 participants
6.7
(0.2 to 31.9)
0.0
(0.0 to 26.5)
0.0
(0.0 to 84.2)
0.0
(0.0 to 23.2)
0.0
(0.0 to 41.0)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 12 participants 1 participants 12 participants 8 participants
14.3
(1.8 to 42.8)
0.0
(0.0 to 26.5)
0.0
0.0
(0.0 to 26.5)
0.0
(0.0 to 36.9)
38.Secondary Outcome
Title Mean Geometric Increase From Baseline in Anti-H1 Hemagglutinin Stalk Secretory IgA in Saliva
Hide Description

Anti-H1 hemagglutinin stalk secretory immunoglobulin A (IgA) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA).

The ELISA measured secretory IgA antibodies antibodies (actively secreted in the mucosa) against the H1 stalk domain in saliva using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]).

Mean geometric increase represents the fold-rise in antibody titer from Baseline to each post-baseline time point (ratio of post-baseline titer to Baseline titer).
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 14 8
Geometric Mean (95% Confidence Interval)
Unit of Measure: fold-rise
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 13 participants 2 participants 14 participants 8 participants
0.9
(0.6 to 1.4)
1.1
(0.7 to 1.7)
1.3
(1.1 to 1.6)
0.8
(0.4 to 1.4)
0.7
(0.3 to 1.7)
Month 4 (28 days post-dose 2) Number Analyzed 15 participants 12 participants 2 participants 14 participants 8 participants
0.9
(0.5 to 1.6)
1.4
(0.9 to 2.3)
1.1
(0.3 to 5.0)
0.9
(0.6 to 1.3)
0.6
(0.3 to 1.2)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 12 participants 1 participants 12 participants 8 participants
1.1
(0.5 to 2.7)
1.1
(0.6 to 2.3)
1.6
0.9
(0.7 to 1.3)
0.7
(0.2 to 2.3)
39.Secondary Outcome
Title Percentage of Participants With Anti-H1 Hemagglutinin Stalk Total IgA Antibody Seropositivity in Saliva
Hide Description

Anti-H1 hemagglutinin stalk total immunoglobulin A (IgA) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA).

The ELISA measured total IgA antibodies antibodies (secreted through active and passive transfer processes in the mucosa) against the H1 stalk domain in saliva using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]).

Seropositivity rate was defined as the percentage of participants with an antibody titer of at least the cut-off for the assay; ≥ 1:10.
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 17 14 2 12 9
Measure Type: Number
Unit of Measure: percentage of participants
Baseline (pre-vaccination) Number Analyzed 17 participants 14 participants 2 participants 11 participants 7 participants
100 100 100 100 100
Month 1 (28 days post-dose 1) Number Analyzed 16 participants 14 participants 2 participants 12 participants 8 participants
100 100 100 100 100
Month 4 (28 days post-dose 2) Number Analyzed 13 participants 13 participants 1 participants 12 participants 9 participants
100 100 100 100 100
Month 15 (12 months post-dose 2) Number Analyzed 10 participants 13 participants 1 participants 11 participants 9 participants
100 100 100 100 100
40.Secondary Outcome
Title Geometric Mean Titer of Anti-H1 Hemagglutinin Stalk Total IgA Antibodies in Saliva
Hide Description

Anti-H1 hemagglutinin stalk total immunoglobulin A (IgA) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA).

The ELISA measured total IgA antibodies antibodies (secreted through active and passive transfer processes in the mucosa) against the H1 stalk domain in saliva using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]). The LLOQ for the assay was 1:10.
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 17 14 2 12 9
Geometric Mean (95% Confidence Interval)
Unit of Measure: titer
Baseline (pre-vaccination) Number Analyzed 17 participants 14 participants 2 participants 11 participants 7 participants
364
(175 to 758)
487
(259 to 916)
317 [1] 
(NA to NA)
792
(420 to 1494)
541
(252 to 1162)
Month 1 (28 days post-dose 1) Number Analyzed 16 participants 14 participants 2 participants 12 participants 8 participants
369
(198 to 687)
685
(408 to 1148)
280 [2] 
(NA to NA)
849
(477 to 1509)
321
(81 to 1265)
Month 4 (28 days post-dose 2) Number Analyzed 13 participants 13 participants 1 participants 12 participants 9 participants
625
(265 to 1477)
543
(269 to 1094)
39
1149
(662 to 1995)
672
(204 to 2210)
Month 15 (12 months post-dose 2) Number Analyzed 10 participants 13 participants 1 participants 11 participants 9 participants
353
(152 to 823)
527
(330 to 843)
239
966
(507 to 1838)
401
(116 to 1390)
[1]
< LLOQ (1:10), 2.181^12
[2]
< LLOQ (1:10), 3.7115^9
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 2: cH8/1N1 LAIV and cH5/1N1 IIV
Comments Comparison of Anti-H1 HA-stalk Total IgA (Saliva), Mucosal Response: Adjusted GMT Ratio 28 Days Post-Boost Dose
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9164
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 1.20
Confidence Interval (2-Sided) 95%
0.38 to 3.80
Estimation Comments GMT ratio computed after fitting an analysis of covariance (ANCOVA) model on the log10 transformed titers, including vaccine group as fixed effect and the pre-vaccination titer as covariate.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
Comments Comparison of Anti-H1 HA-stalk Total IgA (Saliva), Mucosal Response: Adjusted GMT Ratio 28 Days Post-Boost Dose
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8642
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 0.76
Confidence Interval (2-Sided) 95%
0.21 to 2.79
Estimation Comments GMT ratio computed after fitting an analysis of covariance (ANCOVA) model on the log10 transformed titers, including vaccine group as fixed effect and the pre-vaccination titer as covariate.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Group 2: cH8/1N1 LAIV and cH5/1N1 IIV, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
Comments Comparison of Anti-H1 HA-stalk Total IgA (Saliva), Mucosal Response: Adjusted GMT Ratio 28 Days Post-Boost Dose
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6545
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 0.63
Confidence Interval (2-Sided) 95%
0.18 to 2.27
Estimation Comments GMT ratio computed after fitting an analysis of covariance (ANCOVA) model on the log10 transformed titers, including vaccine group as fixed effect and the pre-vaccination titer as covariate.
41.Secondary Outcome
Title Percentage of Participants With a ≥ 4-fold Increase From Baseline in Anti-H1 Hemagglutinin Stalk Total IgA Antibodies in Saliva
Hide Description

Anti-H1 hemagglutinin stalk total immunoglobulin A (IgA) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA).

The ELISA measured total IgA antibodies antibodies (secreted through active and passive transfer processes in the mucosa) against the H1 stalk domain in saliva using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]).
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 17 14 2 11 7
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 1 (28 days post-dose 1) Number Analyzed 16 participants 14 participants 2 participants 11 participants 7 participants
12.5
(1.6 to 38.3)
7.1
(0.2 to 33.9)
0.0
(0.0 to 84.2)
11.1
(0.3 to 48.2)
14.3
(0.4 to 57.9)
Month 4 (28 days post-dose 2) Number Analyzed 13 participants 13 participants 1 participants 11 participants 7 participants
30.8
(9.1 to 61.4)
23.1
(5.0 to 53.8)
0.0
0.0
(0.0 to 30.8)
0.0
(0.0 to 45.9)
Month 15 (12 months post-dose 2) Number Analyzed 10 participants 13 participants 0 participants 11 participants 7 participants
30.0
(6.7 to 65.2)
23.1
(5.0 to 53.8)
0.0
(0.0 to 30.8)
16.7
(0.4 to 64.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 2: cH8/1N1 LAIV and cH5/1N1 IIV
Comments Comparison of Anti-H1 HA-stalk Total IgA (Saliva), Mucosal Response: Seroresponse (>4-Fold) Rate 28 Days Post-Boost Dose
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.9999
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 7.7
Confidence Interval (2-Sided) 95%
-27.10 to 40.96
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
Comments Comparison of Anti-H1 HA-stalk Total IgA (Saliva), Mucosal Response: Seroresponse (≥4-fold) Rate 28 Days Post-Boost Dose
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1045
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 30.8
Confidence Interval (2-Sided) 95%
-1.76 to 58.19
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Group 2: cH8/1N1 LAIV and cH5/1N1 IIV, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
Comments Comparison of Anti-H1 HA-stalk Total IgA (Saliva), Mucosal Response: Seroresponse (≥4-fold) Rate 28 Days Post-Boost Dose
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2292
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 23.1
Confidence Interval (2-Sided) 95%
-8.62 to 50.86
Estimation Comments [Not Specified]
42.Secondary Outcome
Title Percentage of Participants With a ≥ 10-fold Increase From Baseline in Anti-H1 Hemagglutinin Stalk Total IgA Antibodies in Saliva
Hide Description

Anti-H1 hemagglutinin stalk total immunoglobulin A (IgA) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA).

The ELISA measured total IgA antibodies antibodies (secreted through active and passive transfer processes in the mucosa) against the H1 stalk domain in saliva using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]).
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 17 14 2 11 7
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 1 (28 days post-dose 1) Number Analyzed 16 participants 14 participants 2 participants 11 participants 7 participants
6.3
(0.2 to 30.2)
0.0
(0.0 to 23.2)
0.0
(0.0 to 84.2)
0.0
(0.0 to 33.6)
0.0
(0.0 to 41.0)
Month 4 (28 days post-dose 2) Number Analyzed 13 participants 13 participants 1 participants 11 participants 7 participants
7.7
(0.2 to 36.0)
7.7
(0.2 to 36.0)
0.0
0.0
(0.0 to 30.8)
0.0
(0.0 to 45.9)
Month 15 (12 months post-dose 2) Number Analyzed 10 participants 13 participants 0 participants 11 participants 7 participants
10.0
(0.3 to 44.5)
0.0
(0.0 to 24.7)
0.0
(0.0 to 30.8)
0.0
(0.0 to 45.9)
43.Secondary Outcome
Title Mean Geometric Increase From Baseline in Anti-H1 Hemagglutinin Stalk Total IgA Antibodies in Saliva
Hide Description

Anti-H1 hemagglutinin stalk total immunoglobulin A (IgA) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA).

The ELISA measured total IgA antibodies (secreted through active and passive transfer processes in the mucosa) against the H1 stalk domain in saliva using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]).

Mean geometric increase represents the fold-rise in antibody titer from baseline to each post-baseline time point (ratio of post-baseline titer to Baseline titer).
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 17 14 2 11 7
Geometric Mean (95% Confidence Interval)
Unit of Measure: fold-rise
Month 1 (28 days post-dose 1) Number Analyzed 16 participants 14 participants 2 participants 11 participants 7 participants
1.1
(0.6 to 2.2)
1.4
(0.8 to 2.5)
0.9
(0.0 to 458.5)
0.7
(0.4 to 1.4)
0.6
(0.2 to 2.4)
Month 4 (28 days post-dose 2) Number Analyzed 13 participants 13 participants 1 participants 11 participants 7 participants
1.7
(0.6 to 4.6)
1.2
(0.5 to 3.2)
0.7
1.1
(0.7 to 1.8)
0.9
(0.3 to 2.8)
Month 15 (12 months post-dose 2) Number Analyzed 10 participants 13 participants 0 participants 11 participants 7 participants
1.2
(0.3 to 5.0)
1.2
(0.6 to 2.3)
0.9
(0.5 to 1.6)
0.8
(0.2 to 2.8)
44.Secondary Outcome
Title Percentage of Participants With Serum Anti-H2 Full-length Hemagglutinin IgG Antibody Seropositivity
Hide Description

To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin, subtype H2, of which the stalk domain shares about 78% amino acid identity with the H1 vaccine stalk domain.

Anti-H2 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on A/mallard/Netherlands/5/1999 (H2N9) HA.

Titers are expressed as ELISA units (EU) per mL and were calculated on the basis of an internal standard to which units were arbitrarily assigned. Seropositivity rate was defined as the percentage of participants with an antibody titer of at least the cut-off for the assay; ≥ 22.
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Measure Type: Number
Unit of Measure: percentage of participants
Baseline (pre-vaccination) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
100 100 100 100 100
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
100 100 100 100 100
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
100 100 100 100 100
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
100 100 100 100 100
45.Secondary Outcome
Title Geometric Mean Titer of Serum Anti-H2 Full-length Hemagglutinin IgG Antibodies
Hide Description

To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin, subtype H2, of which the stalk domain shares about 78% amino acid identity with the H1 vaccine stalk domain.

Anti-H2 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on A/mallard/Netherlands/5/1999 (H2N9) HA. Titers are expressed as ELISA units (EU) per mL and were calculated on the basis of an internal standard to which units were arbitrarily assigned.
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Geometric Mean (95% Confidence Interval)
Unit of Measure: EU/mL
Baseline (pre-vaccination) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
6973
(4596 to 10578)
6027
(3882 to 9357)
7354
(4095 to 13206)
7554
(4005 to 14249)
5597
(3569 to 8776)
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
7079
(4720 to 10616)
6324
(4106 to 9740)
6757
(4149 to 11002)
67191
(50322 to 89715)
4971
(3179 to 7774)
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
39171
(26079 to 58833)
13584
(8684 to 21250)
8348
(1232 to 56577)
41005
(28395 to 59213)
5493
(3326 to 9072)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
13289
(8311 to 21250)
10682
(6480 to 17609)
12289
26453
(15699 to 44576)
6283
(3643 to 10836)
46.Secondary Outcome
Title Percentage of Participants With a ≥ 4-fold Increase From Baseline in Serum Anti-H2 Full-length Hemagglutinin IgG Antibodies
Hide Description

To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin, subtype H2, of which the stalk domain shares about 78% amino acid identity with the H1 vaccine stalk domain.

Anti-H2 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on A/mallard/Netherlands/5/1999 (H2N9) HA.
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
0.0
(0.0 to 17.6)
0.0
(0.0 to 23.2)
0.0
(0.0 to 70.8)
80.0
(51.9 to 95.7)
0.0
(0.0 to 30.8)
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
68.8
(41.3 to 89.0)
7.7
(0.2 to 36.0)
0.0
(0.0 to 84.2)
71.4
(41.9 to 91.6)
0.0
(0.0 to 30.8)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
0.0
(0.0 to 23.2)
7.7
(0.2 to 36.0)
0.0
46.2
(19.2 to 74.9)
0.0
(0.0 to 30.8)
47.Secondary Outcome
Title Percentage of Participants With a ≥ 10-fold Increase From Baseline in Serum Anti-H2 Full-length Hemagglutinin IgG Antibodies
Hide Description

To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin, subtype H2, of which the stalk domain shares about 78% amino acid identity with the H1 vaccine stalk domain.

Anti-H2 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on A/mallard/Netherlands/5/1999 (H2N9) HA.
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
0.0
(0.0 to 17.6)
0.0
(0.0 to 23.2)
0.0
(0.0 to 70.8)
53.3
(26.6 to 78.7)
0.0
(0.0 to 30.8)
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
25.0
(7.3 to 52.4)
0.0
(0.0 to 24.7)
0.0
(0.0 to 84.2)
14.3
(1.8 to 42.8)
0.0
(0.0 to 30.8)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
0.0
(0.0 to 23.2)
7.7
(0.2 to 36.0)
0.0
0.0
(0.0 to 24.7)
0.0
(0.0 to 30.8)
48.Secondary Outcome
Title Mean Geometric Increase of Serum Anti-H2 Full-length Hemagglutinin IgG Antibodies
Hide Description

To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin, subtype H2, of which the stalk domain shares about 78% amino acid identity with the H1 vaccine stalk domain.

Anti-H2 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on A/mallard/Netherlands/5/1999 (H2N9) HA.

Mean geometric increase represents the fold-rise in antibody titer from Baseline to each post-baseline time point (ratio of post-baseline titer to Baseline titer).
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Geometric Mean (95% Confidence Interval)
Unit of Measure: fold-rise
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
1.0
(1.0 to 1.1)
1.0
(1.0 to 1.1)
0.9
(0.8 to 1.1)
8.9
(5.2 to 15.1)
0.9
(0.8 to 1.0)
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
5.8
(4.0 to 8.5)
2.2
(1.7 to 2.9)
1.1
(0.6 to 1.9)
5.1
(3.2 to 8.1)
1.0
(0.8 to 1.2)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
2.0
(1.7 to 2.3)
1.8
(1.2 to 2.6)
1.3
3.3
(2.2 to 5.0)
1.1
(0.9 to 1.4)
49.Secondary Outcome
Title Percentage of Participants With Serum Anti-H9 Full-length Hemagglutinin IgG Antibody Seropositivity
Hide Description

To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin, subtype H9, the stalk domain of which shares about 59% amino acid identity with the H1 vaccine stalk domain.

Anti-H9 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on Strain A/chicken/Hong Kong/G9/1997 (H9N2) HA. Titers are expressed as ELISA units (EU) per mL and were calculated on the basis of an internal standard to which units were arbitrarily assigned.

Seropositivity rate was defined as the percentage of participants with an antibody titer of at least the cut-off for the assay; ≥ 31.
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Measure Type: Number
Unit of Measure: percentage of participants
Baseline (pre-vaccination) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
100 100 100 100 100
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
100 100 100 100 100
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
100 100 100 100 100
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
100 100 100 100 100
50.Secondary Outcome
Title Geometric Mean Titer of Serum Anti-H9 Full-length Hemagglutinin IgG Antibodies
Hide Description

To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin, subtype H9, the stalk domain of which shares about 59% amino acid identity with the H1 vaccine stalk domain.

Anti-H9 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on Strain A/chicken/Hong Kong/G9/1997 (H9N2) HA. Titers are expressed as ELISA units (EU) per mL and were calculated on the basis of an internal standard to which units were arbitrarily assigned. The LLOQ for the assay was 31 EU/mL.
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Geometric Mean (95% Confidence Interval)
Unit of Measure: EU/mL
Baseline (pre-vaccination) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
10613
(7193 to 15660)
8703
(5569 to 13603)
13257
(2295 to 76571)
10436
(5654 to 19261)
7981
(5204 to 12240)
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
10610
(7246 to 15536)
8683
(5540 to 13611)
11641
(2239 to 60530)
37478
(24971 to 56248)
7477
(5076 to 11013)
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
40587
(26113 to 63083)
16410
(10647 to 25291)
11081 [1] 
(NA to 18410906)
41113
(26860 to 62931)
8244
(5491 to 12377)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
16809
(10261 to 27536)
12271
(7422 to 20287)
17996
24041
(14625 to 39519)
7593
(4697 to 12275)
[1]
< LLOQ (31 EU/mL)
51.Secondary Outcome
Title Percentage of Participants With a ≥ 4-fold Increase From Baseline in Serum Anti-H9 Full-length Hemagglutinin IgG Antibodies
Hide Description

To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin, subtype H9, the stalk domain of which shares about 59% amino acid identity with the H1 vaccine stalk domain.

Anti-H9 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on Strain A/chicken/Hong Kong/G9/1997 (H9N2) HA.
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
0.0
(0.0 to 17.6)
0.0
(0.0 to 23.2)
0.0
(0.0 to 70.8)
40.0
(16.3 to 67.7)
0.0
(0.0 to 30.8)
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
37.5
(15.2 to 64.6)
7.7
(0.2 to 36.0)
0.0
(0.0 to 84.2)
50.0
(23.0 to 77.0)
0.0
(0.0 to 30.8)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
7.1
(0.2 to 33.9)
7.7
(0.2 to 36.0)
0.0
23.1
(5.0 to 53.8)
0.0
(0.0 to 30.8)
52.Secondary Outcome
Title Percentage of Participants With a ≥ 10-fold Increase From Baseline in Serum Anti-H9 Full-length Hemagglutinin IgG Antibodies
Hide Description

To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin, subtype H9, the stalk domain of which shares about 59% amino acid identity with the H1 vaccine stalk domain.

Anti-H9 full-length(ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on Strain A/chicken/Hong Kong/G9/1997 (H9N2) HA.
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
0.0
(0.0 to 17.6)
0.0
(0.0 to 23.2)
0.0
(0.0 to 70.8)
6.7
(0.2 to 31.9)
0.0
(0.0 to 30.8)
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
6.3
(0.2 to 30.2)
0.0
(0.0 to 24.7)
0.0
(0.0 to 84.2)
7.1
(0.2 to 33.9)
0.0
(0.0 to 30.8)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
0.0
(0.0 to 23.2)
0.0
(0.0 to 24.7)
0.0
0.0
(0.0 to 24.7)
0.0
(0.0 to 30.8)
53.Secondary Outcome
Title Mean Geometric Increase of Serum Anti-H9 Full-length Hemagglutinin IgG Antibodies
Hide Description

To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin, subtype H9, the stalk domain of which shares about 59% amino acid identity with the H1 vaccine stalk domain.

Anti-H9 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on Strain A/chicken/Hong Kong/G9/1997 (H9N2) HA.

Mean geometric increase represents the fold-rise in antibody titer from Baseline to each post-baseline time point (ratio of post-baseline titer to Baseline titer).
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Geometric Mean (95% Confidence Interval)
Unit of Measure: fold-rise
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
1.0
(0.9 to 1.1)
1.0
(0.9 to 1.1)
0.9
(0.7 to 1.1)
3.6
(2.4 to 5.5)
0.9
(0.9 to 1.0)
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
3.8
(2.6 to 5.6)
1.9
(1.4 to 2.6)
0.9
(0.2 to 4.0)
3.7
(2.4 to 5.8)
1.0
(0.8 to 1.3)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
1.5
(1.2 to 2.0)
1.5
(1.0 to 2.1)
0.7
2.2
(1.6 to 3.2)
1.0
(0.7 to 1.4)
54.Secondary Outcome
Title Percentage of Participants With Serum Anti-H18 Full-length Hemagglutinin IgG Antibody Seropositivity
Hide Description

To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin distantly related to the currently circulating influenza A/H1 viruses, subtype H18, the stalk domain of which shares about 65% amino acid identity with the H1 vaccine stalk domain.

Anti-H18 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on Strain A/flat-faced bat/Peru/033/10 (H18N11) HA. Titers are expressed as ELISA units (EU) per mL and were calculated on the basis of an internal standard to which units were arbitrarily assigned.

Seropositivity rate was defined as the percentage of participants with an antibody titer of at least the cut-off for the assay; ≥ 42.3.
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Measure Type: Number
Unit of Measure: percentage of participants
Baseline (pre-vaccination) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
100 100 100 100 100
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
100 100 100 100 100
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
100 100 100 100 100
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
100 100 100 100 100
55.Secondary Outcome
Title Geometric Mean Titer of Serum Anti-H18 Full-length Hemagglutinin IgG Antibodies
Hide Description

To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin distantly related to the currently circulating influenza A/H1 viruses, H18, the stalk domain of which shares about 65% amino acid identity with the H1 vaccine stalk domain.

Anti-H18 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on Strain A/flat-faced bat/Peru/033/10 (H18N11) HA. Titers are expressed as ELISA units (EU) per mL and were calculated on the basis of an internal standard to which units were arbitrarily assigned.
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Geometric Mean (95% Confidence Interval)
Unit of Measure: EU/mL
Baseline (pre-vaccination) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
5764
(3981 to 8345)
5266
(3463 to 8007)
6142
(2841 to 13276)
7585
(3822 to 15052)
5315
(3444 to 8201)
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
6030
(4181 to 8696)
5463
(3560 to 8384)
5238
(2788 to 9843)
30197
(19699 to 46292)
4977
(3279 to 7553)
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
25400
(17546 to 36770)
9965
(6757 to 14695)
5178
(297 to 90261)
30254
(20266 to 45165)
5702
(3692 to 8807)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
8478
(5693 to 12626)
6403
(4299 to 9538)
6783
14577
(9190 to 23121)
4747
(2993 to 7531)
56.Secondary Outcome
Title Percentage of Participants With a ≥ 4-fold Increase From Baseline in Serum Anti-H18 Full-length Hemagglutinin IgG Antibodies
Hide Description

To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin distantly related to the currently circulating influenza A/H1 viruses, subtype H18, the stalk domain of which shares about 65% amino acid identity with the H1 vaccine stalk domain.

Anti-H18 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on Strain A/flat-faced bat/Peru/033/10 (H18N11) HA.
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
0.0
(0.0 to 17.6)
0.0
(0.0 to 23.2)
0.0
(0.0 to 70.8)
40.0
(16.3 to 67.7)
0.0
(0.0 to 30.8)
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
50.0
(24.7 to 75.3)
15.4
(1.9 to 45.4)
0.0
(0.0 to 84.2)
50.0
(23.0 to 77.0)
0.0
(0.0 to 30.8)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
0.0
(0.0 to 23.2)
7.7
(0.2 to 36.0)
0.0
23.1
(5.0 to 53.8)
0.0
(0.0 to 30.8)
57.Secondary Outcome
Title Percentage of Participants With a ≥ 10-fold Increase From Baseline in Serum Anti-H18 Full-length Hemagglutinin IgG Antibodies
Hide Description

To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin distantly related to the currently circulating influenza A/H1 viruses, subtype H18, the stalk domain of which shares about 65% amino acid identity with the H1 vaccine stalk domain.

Anti-H18 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on Strain A/flat-faced bat/Peru/033/10 (H18N11) HA.
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
0.0
(0.0 to 17.6)
0.0
(0.0 to 23.2)
0.0
(0.0 to 70.8)
13.3
(1.7 to 40.5)
0.0
(0.0 to 30.8)
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
25.0
(7.3 to 52.4)
0.0
(0.0 to 24.7)
0.0
(0.0 to 84.2)
14.3
(1.8 to 42.8)
0.0
(0.0 to 30.8)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
0.0
(0.0 to 23.2)
0.0
(0.0 to 24.7)
0.0
0.0
(0.0 to 24.7)
0.0
(0.0 to 30.8)
58.Secondary Outcome
Title Mean Geometric Increase of Serum Anti-H18 Full-length Hemagglutinin IgG Antibodies
Hide Description

To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin distantly related to the currently circulating influenza A/H1 viruses, subtype H18, the stalk domain of which shares about 65% amino acid identity with the H1 vaccine stalk domain.

Anti-H18 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on Strain A/flat-faced bat/Peru/033/10 (H18N11) HA.

Mean geometric increase represents the fold-rise in antibody titer from Baseline to each post-baseline time point (ratio of post-baseline titer to Baseline titer).
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Geometric Mean (95% Confidence Interval)
Unit of Measure: fold-rise
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
1.0
(1.0 to 1.1)
1.0
(1.0 to 1.1)
0.9
(0.7 to 1.1)
4.0
(2.5 to 6.3)
0.9
(0.9 to 1.0)
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
4.5
(3.1 to 6.7)
2.0
(1.5 to 2.6)
0.9
(0.3 to 2.3)
3.8
(2.4 to 6.0)
1.1
(0.9 to 1.3)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
1.4
(1.1 to 1.8)
1.3
(0.9 to 1.8)
0.9
1.8
(1.2 to 2.8)
0.9
(0.7 to 1.1)
59.Secondary Outcome
Title Percentage of Participants With Serum Anti-Human H1N1 Virus Neutralizing Antibody Seropositivity
Hide Description

This assay was performed to measure the neutralizing potential of antibodies against the currently circulating human H1N1 isolate which is similar to the stalk used in study vaccines.

Anti-human H1N1 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using Strain A/Singapore/GP1908/2015 (IVR-180).

Seropositivity rate was defined as the percentage of participants with an antibody titer of ≥ 1:10.
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Measure Type: Number
Unit of Measure: percentage of participants
Baseline (pre-vaccination) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
100 100 100 100 100
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
100 100 100 100 100
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
100 100 100 100 100
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
100 100 100 100 100
60.Secondary Outcome
Title Geometric Mean Titer of Serum Anti-Human H1N1 Virus Neutralizing Antibodies
Hide Description

This assay was performed to measure the neutralizing potential of antibodies against the currently circulating human H1N1 isolate which is similar to the stalk used in study vaccines.

Anti-human H1N1 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using Strain A/Singapore/GP1908/2015 (IVR-180). The LLOQ for the assay was 1:10.
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Geometric Mean (95% Confidence Interval)
Unit of Measure: titer
Baseline (pre-vaccination) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
149
(79 to 279)
108
(46 to 253)
63 [1] 
(NA to 881)
84
(47 to 148)
98
(38 to 259)
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
172
(89 to 332)
113
(45 to 285)
50 [1] 
(NA to 368)
175
(98 to 313)
80
(27 to 233)
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
217
(129 to 365)
129
(56 to 301)
40 [1] 
(NA to 267306)
226
(129 to 396)
106
(38 to 294)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
113
(54 to 239)
129
(48 to 347)
80
136
(75 to 247)
130
(54 to 312)
[1]
< LLOQ (1:10)
61.Secondary Outcome
Title Percentage of Participants With a ≥ 4-fold Increase in Serum Anti-Human H1N1 Virus Neutralizing Antibodies
Hide Description

This assay was performed to measure the neutralizing potential of antibodies against the currently circulating human H1N1 isolate which is similar to the stalk used in study vaccines.

Anti-human H1N1 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using Strain A/Singapore/GP1908/2015 (IVR-180).
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
5.3
(0.1 to 26.0)
0.0
(0.0 to 23.2)
0.0
(0.0 to 70.8)
20.0
(4.3 to 48.1)
0.0
(0.0 to 30.8)
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
25.0
(7.3 to 52.4)
7.7
(0.2 to 36.0)
0.0
(0.0 to 84.2)
28.6
(8.4 to 58.1)
10.0
(0.3 to 44.5)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
0.0
(0.0 to 23.2)
7.7
(0.2 to 36.0)
0.0
15.4
(1.9 to 45.4)
10.0
(0.3 to 44.5)
62.Secondary Outcome
Title Percentage of Participants With a ≥ 10-fold Increase From Baseline in Serum Anti-Human H1N1 Virus Neutralizing Antibodies
Hide Description

This assay was performed to measure the neutralizing potential of antibodies against the currently circulating human H1N1 isolate which is similar to the stalk used in study vaccines.

Anti-human H1N1 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using Strain A/Singapore/GP1908/2015 (IVR-180).
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
0.0
(0.0 to 17.6)
0.0
(0.0 to 23.2)
0.0
(0.0 to 70.8)
0.0
(0.0 to 21.8)
0.0
(0.0 to 30.8)
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
6.3
(0.2 to 30.2)
0.0
(0.0 to 24.7)
0.0
(0.0 to 84.2)
7.1
(0.2 to 33.9)
0.0
(0.0 to 30.8)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
0.0
(0.0 to 23.2)
0.0
(0.0 to 24.7)
0.0
0.0
(0.0 to 24.7)
0.0
(0.0 to 30.8)
63.Secondary Outcome
Title Mean Geometric Increase of Serum Anti-Human H1N1 Virus Neutralizing Antibodies
Hide Description

This assay was performed to measure the neutralizing potential of antibodies against the currently circulating human H1N1 isolate which is similar to the stalk used in study vaccines.

Anti-human H1N1 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using Strain A/Singapore/GP1908/2015 (IVR-180).

Mean geometric increase represents the fold-rise in antibody titer from Baseline to each post-baseline time point (ratio of post-baseline titer to Baseline titer).
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Geometric Mean (95% Confidence Interval)
Unit of Measure: fold-rise
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
1.2
(0.9 to 1.5)
1.1
(0.9 to 1.3)
0.8
(0.3 to 2.1)
2.1
(1.4 to 3.0)
0.8
(0.6 to 1.1)
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
1.8
(1.1 to 2.8)
1.3
(0.9 to 1.8)
1.0 [1] 
(NA to NA)
2.4
(1.6 to 3.6)
1.1
(0.6 to 1.8)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
1.0
(0.7 to 1.3)
1.3
(0.9 to 1.9)
1.0
1.6
(1.0 to 2.5)
1.3
(0.7 to 2.4)
[1]
Confidence interval could not be calculated as the variance was zero
64.Secondary Outcome
Title Percentage of Participants With Serum Anti-Avian-Swine H1N1 Virus Neutralizing Antibody Seropositivity
Hide Description

This assay was performed to measure the neutralizing potential of cross-reactive antibodies to a Group 1 influenza against an H1N1 virus isolate that currently circulates in animals and is antigenically different from current human isolates.

Anti-avian-swine H1N1 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using Strain A/Swine/Jiangsu/40/2011 (asH1N1).

Seropositivity rate was defined as the percentage of participants with an antibody titer of ≥ 1:10.
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Measure Type: Number
Unit of Measure: percentage of participants
Baseline (pre-vaccination) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
100 100 100 100 100
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
100 100 100 100 100
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
100 100 100 100 100
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
100 100 100 100 100
65.Secondary Outcome
Title Geometric Mean Titer of Serum Anti-Avian-Swine H1N1 Virus Neutralizing Antibodies
Hide Description

This assay was performed to measure the neutralizing potential of cross-reactive antibodies to a Group 1 influenza against an H1N1 virus isolate that currently circulates in animals and is antigenically different from current human isolates.

Anti-avian-swine H1N1 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using Strain A/Swine/Jiangsu/40/2011 (asH1N1). The LLOQ for the assay was 1:10.
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Geometric Mean (95% Confidence Interval)
Unit of Measure: titer
Baseline (pre-vaccination) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
54
(35 to 83)
46
(26 to 84)
63 [1] 
(NA to 881)
73
(42 to 128)
61
(26 to 142)
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
56
(34 to 90)
54
(29 to 100)
63 [1] 
(NA to 881)
127
(79 to 204)
46
(20 to 106)
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
141
(95 to 207)
72
(40 to 130)
40 [1] 
(NA to 267306)
195
(131 to 290)
57
(25 to 128)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
69
(42 to 114)
58
(31 to 109)
80
94
(61 to 143)
70
(34 to 145)
[1]
< LLOQ (1:10)
66.Secondary Outcome
Title Percentage of Participants With a ≥ 4-fold Increase in Serum Anti-Avian-Swine H1N1 Virus Neutralizing Antibodies
Hide Description

This assay was performed to measure the neutralizing potential of cross-reactive antibodies to a Group 1 influenza against an H1N1 virus isolate that currently circulates in animals and is antigenically different from current human isolates.

Anti-avian-swine H1N1 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using Strain A/Swine/Jiangsu/40/2011 (asH1N1).
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
0.0
(0.0 to 17.6)
7.1
(0.2 to 33.9)
0.0
(0.0 to 70.8)
20.0
(4.3 to 48.1)
0.0
(0.0 to 30.8)
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
37.5
(15.2 to 64.6)
7.7
(0.2 to 36.0)
0.0
(0.0 to 84.2)
28.6
(8.4 to 58.1)
0.0
(0.0 to 30.8)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
14.3
(1.8 to 42.8)
15.4
(1.9 to 45.4)
0.0
7.7
(0.2 to 36.0)
0.0
(0.0 to 30.8)
67.Secondary Outcome
Title Percentage of Participants With a ≥ 10-fold Increase in Serum Anti-Avian-Swine H1N1 Virus Neutralizing Antibodies
Hide Description

This assay was performed to measure the neutralizing potential of cross-reactive antibodies to a Group 1 influenza against an H1N1 virus isolate that currently circulates in animals and is antigenically different from current human isolates.

Anti-avian-swine H1N1 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using Strain A/Swine/Jiangsu/40/2011 (asH1N1).
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
0.0
(0.0 to 17.6)
0.0
(0.0 to 23.2)
0.0
(0.0 to 70.8)
0.0
(0.0 to 21.8)
0.0
(0.0 to 30.8)
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
0.0
(0.0 to 20.6)
0.0
(0.0 to 24.7)
0.0
(0.0 to 84.2)
0.0
(0.0 to 23.2)
0.0
(0.0 to 30.8)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
0.0
(0.0 to 23.2)
0.0
(0.0 to 24.7)
0.0
0.0
(0.0 to 24.7)
0.0
(0.0 to 30.8)
68.Secondary Outcome
Title Mean Geometric Increase From Baseline in Serum Anti-Avian-Swine H1N1 Virus Neutralizing Antibodies
Hide Description

This assay was performed to measure the neutralizing potential of cross-reactive antibodies to a Group 1 influenza against an H1N1 virus isolate that currently circulates in animals and is antigenically different from current human isolates.

Anti-avian-swine H1N1 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using Strain A/Swine/Jiangsu/40/2011 (asH1N1).

Mean geometric increase represents the fold-rise in antibody titer from Baseline to each post-baseline time point (ratio of post-baseline titer to Baseline titer).
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Geometric Mean (95% Confidence Interval)
Unit of Measure: fold-rise
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
1.0
(0.8 to 1.3)
1.2
(0.8 to 1.7)
1.0 [1] 
(NA to NA)
1.7
(1.3 to 2.4)
0.8
(0.6 to 1.0)
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
2.8
(1.8 to 4.3)
1.6
(1.1 to 2.3)
1.0 [1] 
(NA to NA)
2.4
(1.7 to 3.5)
0.9
(0.7 to 1.2)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
1.4
(1.0 to 2.0)
1.3
(0.8 to 2.0)
1.0
1.3
(0.9 to 1.8)
1.1
(0.8 to 1.7)
[1]
Confidence interval could not be calculated as the variance was zero
69.Secondary Outcome
Title Percentage of Participants With Serum Anti-H5N8 Virus Neutralizing Antibody Seropositivity
Hide Description

This assay was performed to measure the induction of antibodies reactive against the head domain of a group 1 influenza virus with a heterosubtypic hemagglutinin from a recent avian influenza virus. Anti-H5N8 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using a reverse genetics (RG) reassortant virus based on Puerto Rico (PR)/8 for 6 genes with 2 surface proteins: HA and neuraminidase (NA) from A/Gyrfalcon/Washington/41088-6/2014 (H5N8).

Seropositivity rate was defined as the percentage of participants with an antibody titer of ≥ 1:10.
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Measure Type: Number
Unit of Measure: percentage of participants
Baseline (pre-vaccination) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
100 100 100 100 100
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
100 100 100 100 100
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
100 100 100 100 100
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
100 100 100 100 100
70.Secondary Outcome
Title Geometric Mean Titer of Serum Anti-H5N8 Virus Neutralizing Antibodies
Hide Description This assay was performed to measure the induction of antibodies reactive against the head domain of a group 1 influenza virus with a heterosubtypic hemagglutinin from a recent avian influenza virus. Anti-H5N8 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using a reverse genetics (RG) reassortant virus based on PR8 for 6 genes with 2 surface proteins: HA and NA from A/Gyrfalcon/Washington/41088-6/2014 (H5N8). The LLOQ for the assay was 1:10.
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Geometric Mean (95% Confidence Interval)
Unit of Measure: titer
Baseline (pre-vaccination) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
37
(29 to 48)
30
(23 to 38)
40 [1] 
(NA to 224)
35
(26 to 47)
28
(22 to 37)
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
36
(27 to 47)
27
(21 to 35)
50 [1] 
(NA to 699)
55
(40 to 76)
26
(20 to 34)
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
62
(43 to 88)
47
(37 to 60)
57 [1] 
(NA to 30902821)
66
(49 to 88)
30
(20 to 46)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
42
(29 to 61)
34
(25 to 46)
20
55
(38 to 80)
30
(20 to 46)
[1]
< LLOQ (1:10)
71.Secondary Outcome
Title Percentage of Participants With a ≥ 4-fold Increase in Serum Anti-H5N8 Virus Neutralizing Antibodies
Hide Description This assay was performed to measure the induction of antibodies reactive against the head domain of a group 1 influenza virus with a heterosubtypic hemagglutinin from a recent avian influenza virus. Anti-H5N8 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using a reverse genetics (RG) reassortant virus based on PR8 for 6 genes with 2 surface proteins: HA and NA from A/Gyrfalcon/Washington/41088-6/2014 (H5N8).
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
0.0
(0.0 to 17.6)
0.0
(0.0 to 23.2)
0.0
(0.0 to 70.8)
6.7
(0.2 to 31.9)
0.0
(0.0 to 30.8)
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
12.5
(1.6 to 38.3)
15.4
(1.9 to 45.4)
0.0
(0.0 to 84.2)
14.3
(1.8 to 42.8)
0.0
(0.0 to 30.8)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
0.0
(0.0 to 23.2)
15.4
(1.9 to 45.4)
0.0
0.0
(0.0 to 24.7)
0.0
(0.0 to 30.8)
72.Secondary Outcome
Title Percentage of Participants With a ≥ 10-fold Increase in Serum Anti-H5N8 Virus Neutralizing Antibodies
Hide Description This assay was performed to measure the induction of antibodies reactive against the head domain of a group 1 influenza virus with a heterosubtypic hemagglutinin from a recent avian influenza virus. Anti-H5N8 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using a reverse genetics (RG) reassortant virus based on PR8 for 6 genes with 2 surface proteins: HA and NA from A/Gyrfalcon/Washington/41088-6/2014 (H5N8).
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
0.0
(0.0 to 17.6)
0.0
(0.0 to 23.2)
0.0
(0.0 to 70.8)
0.0
(0.0 to 21.8)
0.0
(0.0 to 30.8)
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
0.0
(0.0 to 20.6)
0.0
(0.0 to 24.7)
0.0
(0.0 to 84.2)
0.0
(0.0 to 23.2)
0.0
(0.0 to 30.8)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
0.0
(0.0 to 23.2)
0.0
(0.0 to 24.7)
0.0
0.0
(0.0 to 24.7)
0.0
(0.0 to 30.8)
73.Secondary Outcome
Title Mean Geometric Increase From Baseline in Serum Anti-H5N8 Virus Neutralizing Antibodies
Hide Description

This assay was performed to measure the induction of antibodies reactive against the head domain of a group 1 influenza virus with a heterosubtypic hemagglutinin from a recent avian influenza virus. Anti-H5N8 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using a reverse genetics (RG) reassortant virus based on PR8 for 6 genes with 2 surface proteins: HA and NA from A/Gyrfalcon/Washington/41088-6/2014 (H5N8).

Mean geometric increase represents the fold-rise in antibody titer from Baseline to each post-baseline time point (ratio of post-baseline titer to Baseline titer).
Time Frame Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description:
Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.
Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Number of Participants Analyzed 19 14 3 15 10
Geometric Mean (95% Confidence Interval)
Unit of Measure: fold-rise
Month 1 (28 days post-dose 1) Number Analyzed 19 participants 14 participants 3 participants 15 participants 10 participants
1.0
(0.8 to 1.1)
0.9
(0.8 to 1.0)
1.3
(0.5 to 3.4)
1.6
(1.3 to 2.0)
0.9
(0.8 to 1.1)
Month 4 (28 days post-dose 2) Number Analyzed 16 participants 13 participants 2 participants 14 participants 10 participants
1.8
(1.3 to 2.3)
1.6
(1.2 to 2.2)
1.4
(0.0 to 115.6)
1.9
(1.5 to 2.4)
1.1
(0.7 to 1.5)
Month 15 (12 months post-dose 2) Number Analyzed 14 participants 13 participants 1 participants 13 participants 10 participants
1.1
(0.8 to 1.4)
1.2
(0.8 to 1.8)
1.0
1.5
(1.2 to 1.9)
1.1
(0.8 to 1.4)
Time Frame All-cause mortality and serious adverse events were recorded through the end of study, 588 days (21 months). Other adverse events were collected through 28 days after each vaccination (Days 1 to 28 and Days 85 to 113)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Hide Arm/Group Description Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85. Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85. Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85. Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85. Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
All-Cause Mortality
Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/19 (0.00%)   0/14 (0.00%)   1/3 (33.33%)   0/15 (0.00%)   0/10 (0.00%) 
Hide Serious Adverse Events
Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/19 (0.00%)   0/14 (0.00%)   1/3 (33.33%)   0/15 (0.00%)   2/10 (20.00%) 
Gastrointestinal disorders           
Upper gastrointestinal haemorrhage † 1  0/19 (0.00%)  0/14 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  1/10 (10.00%) 
Injury, poisoning and procedural complications           
Road traffic accident † 1  0/19 (0.00%)  0/14 (0.00%)  1/3 (33.33%)  0/15 (0.00%)  0/10 (0.00%) 
Pregnancy, puerperium and perinatal conditions           
Abortion spontaneous † 1  0/19 (0.00%)  0/14 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  1/10 (10.00%) 
1
Term from vocabulary, MedDRA
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Group 3: Placebo Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Group 5: Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   10/19 (52.63%)   8/14 (57.14%)   1/3 (33.33%)   6/15 (40.00%)   5/10 (50.00%) 
Blood and lymphatic system disorders           
Lymph node pain † 1  1/19 (5.26%)  0/14 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/10 (0.00%) 
Lymphadenopathy † 1  1/19 (5.26%)  0/14 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/10 (0.00%) 
Eye disorders           
Photophobia † 1  1/19 (5.26%)  0/14 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/10 (0.00%) 
Vision blurred † 1  1/19 (5.26%)  0/14 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/10 (0.00%) 
Gastrointestinal disorders           
Toothache † 1  1/19 (5.26%)  0/14 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/10 (0.00%) 
Vomiting † 1  0/19 (0.00%)  0/14 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  1/10 (10.00%) 
General disorders           
Chest pain † 1  0/19 (0.00%)  0/14 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  1/10 (10.00%) 
Infections and infestations           
Bacterial vaginosis † 1  0/19 (0.00%)  1/14 (7.14%)  0/3 (0.00%)  1/15 (6.67%)  0/10 (0.00%) 
Cervicitis † 1  1/19 (5.26%)  0/14 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/10 (0.00%) 
Gastroenteritis † 1  1/19 (5.26%)  1/14 (7.14%)  0/3 (0.00%)  0/15 (0.00%)  0/10 (0.00%) 
Gastroenteritis viral † 1  1/19 (5.26%)  1/14 (7.14%)  0/3 (0.00%)  0/15 (0.00%)  0/10 (0.00%) 
Respiratory tract infection viral † 1  0/19 (0.00%)  1/14 (7.14%)  0/3 (0.00%)  0/15 (0.00%)  0/10 (0.00%) 
Upper respiratory tract infection † 1  1/19 (5.26%)  2/14 (14.29%)  0/3 (0.00%)  2/15 (13.33%)  0/10 (0.00%) 
Viral upper respiratory tract infection † 1  0/19 (0.00%)  2/14 (14.29%)  0/3 (0.00%)  0/15 (0.00%)  0/10 (0.00%) 
Injury, poisoning and procedural complications           
Foot fracture † 1  0/19 (0.00%)  0/14 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  1/10 (10.00%) 
Musculoskeletal and connective tissue disorders           
Arthralgia † 1  0/19 (0.00%)  1/14 (7.14%)  0/3 (0.00%)  0/15 (0.00%)  0/10 (0.00%) 
Back pain † 1  1/19 (5.26%)  0/14 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/10 (0.00%) 
Musculoskeletal pain † 1  0/19 (0.00%)  0/14 (0.00%)  1/3 (33.33%)  0/15 (0.00%)  0/10 (0.00%) 
Myalgia † 1  1/19 (5.26%)  1/14 (7.14%)  0/3 (0.00%)  0/15 (0.00%)  1/10 (10.00%) 
Nervous system disorders           
Headache † 1  1/19 (5.26%)  0/14 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/10 (0.00%) 
Presyncope † 1  0/19 (0.00%)  0/14 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/10 (0.00%) 
Reproductive system and breast disorders           
Vulvovaginal pruritis † 1  1/19 (5.26%)  0/14 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/10 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Cough † 1  1/19 (5.26%)  0/14 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/10 (0.00%) 
Epistaxis † 1  2/19 (10.53%)  2/14 (14.29%)  0/3 (0.00%)  0/15 (0.00%)  0/10 (0.00%) 
Nasal congestion † 1  1/19 (5.26%)  0/14 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/10 (0.00%) 
Nasal discomfort † 1  1/19 (5.26%)  0/14 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/10 (0.00%) 
Nasal mucosal disorder † 1  0/19 (0.00%)  1/14 (7.14%)  0/3 (0.00%)  0/15 (0.00%)  0/10 (0.00%) 
Oropharyngeal pain † 1  1/19 (5.26%)  0/14 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  2/10 (20.00%) 
Pharyngeal erythema † 1  1/19 (5.26%)  0/14 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/10 (0.00%) 
Rhinitis allergic † 1  1/19 (5.26%)  0/14 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/10 (0.00%) 
Rhinorrhoea † 1  0/19 (0.00%)  0/14 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/10 (0.00%) 
Skin and subcutaneous tissue disorders           
Dermatitis contact † 1  0/19 (0.00%)  1/14 (7.14%)  0/3 (0.00%)  1/15 (6.67%)  0/10 (0.00%) 
Erythema † 1  0/19 (0.00%)  1/14 (7.14%)  0/3 (0.00%)  0/15 (0.00%)  0/10 (0.00%) 
Hyperhidrosis † 1  1/19 (5.26%)  1/14 (7.14%)  0/3 (0.00%)  0/15 (0.00%)  0/10 (0.00%) 
Pruritis † 1  1/19 (5.26%)  0/14 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/10 (0.00%) 
1
Term from vocabulary, MedDRA
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Jorge Flores, MD
Organization: PATH
Phone: (202) 822-0033
EMail: jeflores@path.org
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: PATH
ClinicalTrials.gov Identifier: NCT03300050    
Other Study ID Numbers: CVIA 057 (1082166-1)
First Submitted: September 28, 2017
First Posted: October 3, 2017
Results First Submitted: November 17, 2020
Results First Posted: February 21, 2021
Last Update Posted: February 21, 2021