History of Changes for Study: NCT05310084

Study Identification


Unique Protocol ID:	C4591030
Brief Title:	Safety and Immunogenicity of BNT162b2 Coadministered With SIIV in Adults 18 Through 64 Years of Age
Official Title:	A PHASE 3, RANDOMIZED, OBSERVER-BLIND TRIAL TO EVALUATE THE SAFETY AND IMMUNOGENICITY OF BNT162b2 WHEN COADMINISTERED WITH SEASONAL INACTIVATED INFLUENZA VACCINE (SIIV) IN ADULTS 18 THROUGH 64 YEARS OF AGE
Secondary IDs:

Study Status


Record Verification:	October 2023
Overall Status:	Completed
Study Start:	April 20, 2022
Primary Completion:	October 5, 2022 [Actual]
Study Completion:	October 5, 2022 [Actual]

First Submitted:	March 25, 2022
First Submitted that Met QC Criteria:	March 25, 2022
First Posted:	April 4, 2022 [Actual]

Last Update Submitted that Met QC Criteria:
Last Update Posted:	October 30, 2023 [Actual]

Sponsor/Collaborators


Sponsor:	BioNTech SE
Responsible Party:	Sponsor
Collaborators:	Pfizer

Study Description

Brief Summary:

This study will assess the safety and immunogenicity of a fourth dose (booster) of BNT162b2 when coadministered with SIIV compared to separate administration of the vaccines when given 1 month apart (SIIV followed by BNT162b2), in participants who have received 3 prior doses of 30 µg BNT162b2, with the third dose being at least 90 days before Visit 1 (Day 1).

Healthy adults 18 through 64 years of age will be randomized 1:1 to either the co-administration group, or the separate administration group
The duration of the study for each participant will be approximately 2 months
There are 3 scheduled study visits each about 1 month apart
The study will be conducted in New Zealand and Australia.

Detailed Description:

Study Design


Study Type:	Interventional
Primary Purpose:	Prevention
Study Phase:	Phase 3
Interventional Study Model:	Parallel Assignment
Number of Arms:	2
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:	Randomized
Enrollment:	1134 [Actual]

Arms and Interventions

Arms	Assigned Interventions
Experimental: Coadministration Group BNT162b2 and SIIV followed by placebo a month later	Biological: BNT162b2 Intramuscular injection Placebo Saline intramuscular injection Biological: Seasonal Inactivated Influenza Vaccine SIIV intramuscular injection
Experimental: Separate Administration Group Placebo and SIIV followed by BNT162b2 a month later	Biological: BNT162b2 Intramuscular injection Placebo Saline intramuscular injection Biological: Seasonal Inactivated Influenza Vaccine SIIV intramuscular injection

Outcome Measures

[See Results Section.]


Primary Outcome Measures:
1.	Percentage of Participants With Local Reactions Within 7 Days After Vaccination 1 [ Time Frame: Within 7 Days After Vaccination 1 ] Local reactions included redness, swelling, and pain at the injection site occurring at the BNT162b2 or placebo injection site. Local reactions were recorded by participants in an electronic diary (e-diary). Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 centimeter (cm) and graded as mild: greater than (>) 2.0 to 5.0 cm, moderate: >5.0 to 10.0 cm, severe: >10.0 cm, and potentially life threatening (Grade 4): necrosis or exfoliative dermatitis. Pain at injection site was graded as mild: did not interfere with daily activity, moderate: interfered with daily activity, severe: prevented daily activity, and potentially life threatening (Grade 4): emergency room visit or hospitalization for severe pain. Exact 2-sided confidence interval (CI), based on the Clopper and Pearson method was used.
2.	Percentage of Participants With Local Reactions Within 7 Days After Vaccination 2 [ Time Frame: Within 7 Days After Vaccination 2 ] Local reactions included redness, swelling, and pain at the injection site occurring at the BNT162b2 or placebo injection site. Local reactions were recorded by participants in an e-diary. Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 cm and graded as mild: greater than >2.0 to 5.0 cm, moderate: >5.0 to 10.0 cm, severe: >10.0 cm, and potentially life threatening (Grade 4): necrosis or exfoliative dermatitis. Pain at injection site was graded as mild: did not interfere with daily activity, moderate: interfered with daily activity, severe: prevented daily activity, and potentially life threatening (Grade 4): emergency room visit or hospitalization for severe pain. Exact 2-sided CI, based on the Clopper and Pearson method was used.
3.	Percentage of Participants With Systemic Events Within 7 Days After Vaccination 1 [ Time Frame: Within 7 Days After Vaccination 1 ] Systemic events included fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain recorded by participants in an e-diary. Fever was defined as temperature: >=38.0 degrees (deg) Celsius (C), and categorized as: >=38.0 to 38.4 deg C, >38.4 to 38.9 deg C, >38.9 to 40.0 deg C, and >40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain, and new or worsened joint pain were graded as mild: did not interfere with activity, moderate: some interference with activity, and severe: prevented daily routine activity. Vomiting graded as mild: 1 to 2 times in 24 hours(h), moderate: >2 times in 24h, severe: required intravenous hydration, and grade 4: emergency room (ER) visit or hospitalization for hypotensive shock. Diarrhea graded as mild: 2 to 3 loose stools in 24h, moderate: 4 to 5 loose stools in 24h, severe: 6 or more loose stools in 24h, and grade 4: ER visit or hospitalization for severe diarrhea.
4.	Percentage of Participants With Systemic Events Within 7 Days After Vaccination 2 [ Time Frame: Within 7 Days After Vaccination 2 ] Systemic events included fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain recorded by participants in an e-diary. Fever was defined as temperature: >=38.0 deg C, and categorized as: >=38.0 to 38.4 deg C, >38.4 to 38.9 deg C, >38.9 to 40.0 deg C, and >40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain, and new or worsened joint pain were graded as mild: did not interfere with activity, moderate: some interference with activity, and severe: prevented daily routine activity. Vomiting graded as mild: 1 to 2 times in 24h, moderate: >2 times in 24h, severe: required intravenous hydration, and grade 4: ER visit or hospitalization for hypotensive shock. Diarrhea graded as mild: 2 to 3 loose stools in 24h, moderate: 4 to 5 loose stools in 24h, severe: 6 or more loose stools in 24h, and grade 4: ER visit or hospitalization for severe diarrhea. Exact 2-sided CI, based on Clopper and Pearson method used.
5.	Percentage of Participants With Adverse Events Within 1 Month After Vaccination 1 [ Time Frame: Within 1 month after Vaccination 1 ] An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Exact 2-sided CI was calculated using the Clopper and Pearson method.
6.	Percentage of Participants With Adverse Events Within 1 Month After Vaccination 2 [ Time Frame: Within 1 month after Vaccination 2 ] An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Exact 2-sided CI was calculated using the Clopper and Pearson method.
7.	Percentage of Participants With Serious Adverse Events Within 1 Month After Vaccination 1 [ Time Frame: Within 1 Month After Vaccination 1 ] An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Exact 2-sided CI was calculated using the Clopper and Pearson method. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial/prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; or that was considered to be an important medical event.
8.	Percentage of Participants With Serious Adverse Events Within 1 Month After Vaccination 2 [ Time Frame: Within 1 Month After Vaccination 2 ] An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Exact 2-sided CI was calculated using the Clopper and Pearson method. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial/prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; or that was considered to be an important medical event.
9.	Geometric Mean Ratio (GMR) Based on Geometric Mean Concentration (GMC) of Full-Length S-binding Immunoglobulin G (IgG) at 1 Month After BNT162b2 Vaccination [ Time Frame: 1 Month After BNT162b2 vaccination ] GMCs of full-length S-binding IgG level for the coadministration group and separate administration group were reported in this outcome measure in descriptive data section. GMC and the 2-sided 95% CI were calculated by exponentiating the LSMeans of the concentrations and the corresponding CIs based on analysis of logarithmically transformed assay results using a linear regression model with terms of vaccine group, age group, and the corresponding baseline assay results (log scale). Assay results below the LLOQ were set to 0.5*LLOQ. Geometric mean ratio (GMR) was reported in the statistical analysis section and was calculated as ratio of GMCs in the coadministration group to the separate administration group. Here, "Number of participants analyzed" signifies number of participants evaluable for this outcome measure.
10.	Geometric Mean Ratio (GMR) Based on Geometric Mean Titer (GMT) of Strain-Specific Hemagglutination Inhibition (HAI) at 1 Month After SIIV Vaccination [ Time Frame: 1 Month After SIIV vaccination ] GMTs of strain-specific HAI titers for the coadministration group and separate administration group were reported in this outcome measure in descriptive data section. GMTs and the 2-sided 95% CIs were calculated by exponentiating the LSMeans of the titers and the corresponding CIs based on analysis of logarithmically transformed assay results using a linear regression model with terms of vaccine group, age group, and the corresponding baseline assay results (log scale). Assay results below the LLOQ were set to 0.5*LLOQ, and results above the ULOQ were set to ULOQ+1. Geometric mean ratio (GMR) was reported in the statistical analysis section and was calculated as ratio of GMT in the coadministration group to the separate administration group. Here, "Number of participants analyzed" signifies number of participants evaluable for this outcome measure.
Secondary Outcome Measures:
1.	Geometric Mean Concentration (GMC) of Full-Length S-binding IgG Levels Before Vaccination and 1 Month After BNT162b2 Vaccination [ Time Frame: Before BNT162b2 vaccination, and 1 month After BNT162b2 vaccination ] GMCs were calculated by exponentiating the mean logarithm of the concentrations and the corresponding CIs (based on the Student's t-distribution). Assay results below the lower limit of quantitation (LLOQ) were set to 0.5*LLOQ. Here, "Number of participants analyzed" signifies number of participants evaluable for this outcome measure''.
2.	Geometric Mean Fold Rise (GMFR) of Full-Length S-binding IgG Levels From Before Vaccination to 1 Month After BNT162b2 Vaccination [ Time Frame: From before BNT162b2 vaccination to 1 month After BNT162b2 vaccination ] GMFR was defined as ratio of the geometric mean concentration of IgG at 1 month after BNT162b2 vaccination to the geometric mean concentration of IgG before BNT162b2 vaccination. GMFRs were calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the Student's t-distribution). Assay results below the LLOQ were set to 0.5*LLOQ. Here, "Number of participants analyzed" signifies number of participants evaluable for this outcome measure''.
3.	Geometric Mean Titer (GMT) of SARS-CoV-2 Neutralizing Titers Before Vaccination and 1 Month After BNT162b2 Vaccination [ Time Frame: Before BNT162b2 vaccination, and 1 month after BNT162b2 vaccination ]
4.	Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Neutralizing Titers From Before Vaccination to 1 Month After BNT162b2 Vaccination [ Time Frame: From before BNT162b2 vaccination to 1 month after BNT162b2 vaccination ] SARS-CoV-2 neutralization assay (reference strain) (for a subset of approximately 200 participants).

Eligibility


Minimum Age:	18 Years
Maximum Age:	64 Years
Sex:	All
Gender Based:
Accepts Healthy Volunteers:	Yes
Criteria:	Inclusion Criteria: Participants 18 through 64 years of age, inclusive, at the time of consent. Are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures. Adults determined by clinical assessment, including medical history and clinical judgment, to be eligible for the study, including adults with preexisting stable disease, defined as disease not requiring significant change in therapy in the previous 6 weeks or hospitalization for worsening disease within 12 weeks before receipt of study intervention. Have received 3 prior doses of 30 µg BNT162b2, with the third dose being at least 90 days before Visit 1 (Day 1). Documented confirmation of prior BNT162b2 receipt must be obtained prior to randomization. Capable of giving personal signed informed consent, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol. Exclusion Criteria: Other medical or psychiatric condition, including recent (within the past year) or active suicidal ideation/behavior, or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study. Allergy to egg proteins (egg or egg products) or chicken proteins. History of Guillain-Barré syndrome. History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s). A positive SARS-CoV-2 test result (either by NAAT or rapid antigen test) within 28 days of Visit 1 (Day 1). Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination. Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection. Women who are pregnant or breastfeeding. Vaccination with any influenza vaccine <6 months before study intervention administration, or planned receipt of any licensed or investigational nonstudy influenza vaccine during study participation. Individuals who receive treatment with radiotherapy or immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids (if systemic corticosteroids are administered for ≥14 days at a dose of ≥20 mg/day of prednisone or equivalent), eg, for COPD, or planned receipt throughout the study. Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted. Receipt of blood/plasma products or immunoglobulin, from 60 days before study intervention administration or planned receipt throughout the study. Receipt of any passive antibody therapy specific to COVID-19 from 90 days before study intervention administration or planned receipt throughout the study. Prior receipt of any COVID-19 vaccine other than BNT162b2 or receipt of more than 3 prior doses of BNT162b2. Participation in other studies involving study intervention within 28 days prior to study entry and/or during study participation. Investigator site staff or Pfizer/BioNTech employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.

Contacts/Locations


Study Officials:	Pfizer CT.gov Call Center Study Director Pfizer
Locations:	Australia, New South Wales
	Northern Beaches Clinical Research Brookvale, New South Wales, Australia, 2100
	Australian Clinical Research Network Sydney, New South Wales, Australia, NSW 2035
	Westmead Hospital Westmead, New South Wales, Australia, 2145
	Australia, Queensland
	Paratus Clinical Research Brisbane Albion, Queensland, Australia, 4010
	AusTrials - Wellers Hill Wellers Hill, Queensland, Australia, 4121
	Australia, Victoria
	Emeritus Research Camberwell, Victoria, Australia, 3124
	Barwon Health Geelong, Victoria, Australia, 3220
	New Zealand
	Southern Clinical Trials Waitemata Ltd Auckland, New Zealand, 0626
	Aotearoa Clinical Trials Auckland, New Zealand, 2025
	Middlemore Clinical Trials Auckland, New Zealand, 2025
	Southern Clinical Trials Tasman Nelson, New Zealand, 7011
	Capital, Coast and Hutt Valley District - Wellington Regional Hospital Wellington, New Zealand, 6021
	P3 Research - Wellington Wellington, New Zealand, 6021
	New Zealand, Auckland
	New Zealand Clinical Research (Auckland) Grafton, Auckland, New Zealand, 1010
	Optimal Clinical Trials Grafton, Auckland, New Zealand, 1010
	Southern Clinical Trials Totara New Lynn, Auckland, New Zealand, 0600
	New Zealand, BAY OF Plenty
	Lakeland Clinical Trials Culloden Papamoa Beach, BAY OF Plenty, New Zealand, 3118
	Pacific Clinical Research Network - Rotorua Rotorua, BAY OF Plenty, New Zealand, 3010
	P3 Research - Tauranga Tauranga, BAY OF Plenty, New Zealand, 3110
	New Zealand, Canterbury
	New Zealand Clinical Research (Christchurch) Christchurch, Canterbury, New Zealand, 8011
	Pacific Clinical Research Network - Forte Christchurch, Canterbury, New Zealand, 8013
	New Zealand, Hawke's BAY
	P3 Research - Hawke's Bay Havelock North, Hawke's BAY, New Zealand, 4130
	New Zealand, Manawatu-wanganui
	P3 Research - Palmerston North Palmerston North, Manawatu-wanganui, New Zealand, 4414
	New Zealand, Waikato
	Lakeland Clinical Trials Waikato Hamilton, Waikato, New Zealand, 3200
	New Zealand, Wellington
	P3 Research - Kapiti Paraparaumu, Wellington, New Zealand, 5032
	Lakeland Clinical Trials Wellington Upper Hutt, Wellington, New Zealand, 5018

References


Citations:
Links:	URL: https://pmiform.com/clinical-trial-info-request?StudyID=C4591030 Description: To obtain contact information for a study center near you, click here.
Available IPD/Information:

Document Section


	Study Protocol Document Date: March 9, 2022 Uploaded: 09/28/2023 11:09 File Name: Prot_000.pdf
	Statistical Analysis Plan Document Date: October 20, 2022 Uploaded: 09/28/2023 11:09 File Name: SAP_001.pdf

Study Results

Participant Flow

Recruitment Details

A total of 1165 participants were screened, out of which 31 were screen failures and 1134 were randomized into the study.

Pre-assignment Details

Arm/Group Title	Coadministration Group	Separate Administration Group
Arm/Group Description	Participants were randomized to receive 30 microgram (mcg) intramuscular (IM) injection of BNT162b2 vaccine along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and IM injection of Placebo 1 month later (Visit 2).	Participants were randomized to receive an intramuscular (IM) injection of Placebo along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and 30 mcg IM injection of BNT162b2 vaccine 1 month later (Visit 2).

Period Title: Overall Study
Started	568	566
Vaccinated	564	564
Completed	560	555
Not Completed	8	11
Reason Not Completed
Withdrawal by Subject	2	3
Participant availability	0	4
Lost to Follow-up	1	1
Adverse Event	1	1
Randomized but not vaccinated	4	2

Baseline Characteristics


Arm/Group Title		Coadministration Group	Separate Administration Group	Total
Arm/Group Description		Participants were randomized to receive 30 microgram (mcg) intramuscular (IM) injection of BNT162b2 vaccine along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and IM injection of Placebo 1 month later (Visit 2).	Participants were randomized to receive an intramuscular (IM) injection of Placebo along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and 30 mcg IM injection of BNT162b2 vaccine 1 month later (Visit 2).	Total of all reporting groups
Overall Number of Baseline Participants		564	564	1128
Baseline Analysis Population Description
Age, Continuous Mean (Standard Deviation) Unit of measure: Years	Number Analyzed	564 Participants	564 Participants	1128 Participants
		39.7(13.20)	39.8(13.52)	39.7(13.35)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	564 Participants	564 Participants	1128 Participants
	Female	356 63.12%	361 64.01%	717 63.56%
	Male	208 36.88%	203 35.99%	411 36.44%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	564 Participants	564 Participants	1128 Participants
	Hispanic or Latino	5 0.89%	9 1.6%	14 1.24%
	Not Hispanic or Latino	539 95.57%	537 95.21%	1076 95.39%
	Unknown or Not Reported	20 3.55%	18 3.19%	38 3.37%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	564 Participants	564 Participants	1128 Participants
	American Indian or Alaska Native	0 0%	0 0%	0 0%
	Asian	73 12.94%	66 11.7%	139 12.32%
	Native Hawaiian or Other Pacific Islander	26 4.61%	36 6.38%	62 5.5%
	Black or African American	1 0.18%	2 0.35%	3 0.27%
	White	446 79.08%	439 77.84%	885 78.46%
	More than one race	1 0.18%	10 1.77%	11 0.98%
	Unknown or Not Reported	17 3.01%	11 1.95%	28 2.48%

Outcome Measures

1. Primary Outcome:

Title

Percentage of Participants With Local Reactions Within 7 Days After Vaccination 1

Description

Local reactions included redness, swelling, and pain at the injection site occurring at the BNT162b2 or placebo injection site. Local reactions were recorded by participants in an electronic diary (e-diary). Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 centimeter (cm) and graded as mild: greater than (>) 2.0 to 5.0 cm, moderate: >5.0 to 10.0 cm, severe: >10.0 cm, and potentially life threatening (Grade 4): necrosis or exfoliative dermatitis. Pain at injection site was graded as mild: did not interfere with daily activity, moderate: interfered with daily activity, severe: prevented daily activity, and potentially life threatening (Grade 4): emergency room visit or hospitalization for severe pain. Exact 2-sided confidence interval (CI), based on the Clopper and Pearson method was used.

Time Frame

Within 7 Days After Vaccination 1

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received any of the study intervention. Here, ''Number of participants analyzed'' signifies number of participants evaluable and "Number Analyzed" (n) signifies number of participants evaluable for specified rows for this outcome measure.


Arm/Group Title		Coadministration Group	Separate Administration Group
Arm/Group Description		Participants were randomized to receive 30 microgram (mcg) intramuscular (IM) injection of BNT162b2 vaccine along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and IM injection of Placebo 1 month later (Visit 2).	Participants were randomized to receive an intramuscular (IM) injection of Placebo along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and 30 mcg IM injection of BNT162b2 vaccine 1 month later (Visit 2).
Overall Number of Participants Analyzed		564	563
Number (95% Confidence Interval) Unit of Measure: Percentage of participants
Redness: Any	Number Analyzed	Participants	Participants
Redness: Any		7.6(5.6 to 10.1)	0.5(0.1 to 1.6)
Redness: Mild	Number Analyzed	Participants	Participants
Redness: Mild		6.2(4.4 to 8.5)	0.5(0.1 to 1.6)
Redness: Moderate	Number Analyzed	Participants	Participants
Redness: Moderate		1.2(0.5 to 2.5)	0(0.0 to 0.7)
Redness: Severe	Number Analyzed	Participants	Participants
Redness: Severe		0.2(0.0 to 1.0)	0(0.0 to 0.7)
Redness: Grade 4	Number Analyzed	Participants	Participants
Redness: Grade 4		0(0.0 to 0.7)	0(0 to 0.7)
Swelling: Any	Number Analyzed	Participants	Participants
Swelling: Any		9.2(7.0 to 11.9)	1.1(0.4 to 2.3)
Swelling: Mild	Number Analyzed	Participants	Participants
Swelling: Mild		6.2(4.4 to 8.5)	0.4(0.0 to 1.3)
Swelling: Moderate	Number Analyzed	Participants	Participants
Swelling: Moderate		3.0(1.8 to 4.8)	0.7(0.2 to 1.8)
Swelling: Severe	Number Analyzed	Participants	Participants
Swelling: Severe		0(0.0 to 0.7)	0(0.0 to 0.7)
Swelling: Grade 4	Number Analyzed	Participants	Participants
Swelling: Grade 4		0(0.0 to 0.7)	0(0.0 to 0.7)
Pain at the injection site: Any	Number Analyzed	Participants	Participants
Pain at the injection site: Any		86.2(83.0 to 88.9)	13.9(11.1 to 17.0)
Pain at the injection site: Mild	Number Analyzed	Participants	Participants
Pain at the injection site: Mild		66.3(62.2 to 70.2)	13.5(10.8 to 16.6)
Pain at the injection site: Moderate	Number Analyzed	Participants	Participants
Pain at the injection site: Moderate		19.9(16.6 to 23.4)	0.4(0.0 to 1.3)
Pain at the injection site: Severe	Number Analyzed	Participants	Participants
Pain at the injection site: Severe		0(0.0 to 0.7)	0(0.0 to 0.7)
Pain at the injection site: Grade 4	Number Analyzed	Participants	Participants
Pain at the injection site: Grade 4		0(0.0 to 0.7)	0(0.0 to 0.7)

2. Primary Outcome:

Title

Percentage of Participants With Local Reactions Within 7 Days After Vaccination 2

Description

Local reactions included redness, swelling, and pain at the injection site occurring at the BNT162b2 or placebo injection site. Local reactions were recorded by participants in an e-diary. Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 cm and graded as mild: greater than >2.0 to 5.0 cm, moderate: >5.0 to 10.0 cm, severe: >10.0 cm, and potentially life threatening (Grade 4): necrosis or exfoliative dermatitis. Pain at injection site was graded as mild: did not interfere with daily activity, moderate: interfered with daily activity, severe: prevented daily activity, and potentially life threatening (Grade 4): emergency room visit or hospitalization for severe pain. Exact 2-sided CI, based on the Clopper and Pearson method was used.

Time Frame

Within 7 Days After Vaccination 2

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received any of the study intervention. Here, "Number of participants analyzed" signifies number of participants evaluable for this outcome measure.


Arm/Group Title	Coadministration Group	Separate Administration Group
Arm/Group Description	Participants were randomized to receive 30 microgram (mcg) intramuscular (IM) injection of BNT162b2 vaccine along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and IM injection of Placebo 1 month later (Visit 2).	Participants were randomized to receive an intramuscular (IM) injection of Placebo along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and 30 mcg IM injection of BNT162b2 vaccine 1 month later (Visit 2).
Overall Number of Participants Analyzed	557	553
Number (95% Confidence Interval) Unit of Measure: Percentage of participants
Redness: Any	0.2(0.0 to 1.0)	4.7(3.1 to 6.8)
Redness: Mild	0.2(0.0 to 1.0)	4.3(2.8 to 6.4)
Redness: Moderate	0(0.0 to 0.7)	0.4(0.0 to 1.3)
Redness: Severe	0(0.0 to 0.7)	0(0.0 to 0.7)
Redness: Grade 4	0(0.0 to 0.7)	0(0.0 to 0.7)
Swelling: Any	0.4(0.0 to 1.3)	8.9(6.6 to 11.5)
Swelling: Mild	0.4(0.0 to 1.3)	5.8(4.0 to 8.1)
Swelling: Moderate	0(0.0 to 0.7)	3.1(1.8 to 4.9)
Swelling: Severe	0(0.0 to 0.7)	0(0.0 to 0.7)
Swelling: Grade 4	0(0.0 to 0.7)	0(0.0 to 0.7)
Pain at the injection site: Any	6.6(4.7 to 9.0)	84.4(81.2 to 87.4)
Pain at the injection site: Mild	6.3(4.4 to 8.6)	61.7(57.5 to 65.7)
Pain at the injection site: Moderate	0.4(0.0 to 1.3)	22.4(19.0 to 26.1)
Pain at the injection site: Severe	0(0.0 to 0.7)	0.4(0.0 to 1.3)
Pain at the injection site: Grade 4	0(0.0 to 0.7)	0(0.0 to 0.7)

3. Primary Outcome:

Title

Percentage of Participants With Systemic Events Within 7 Days After Vaccination 1

Description

Systemic events included fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain recorded by participants in an e-diary. Fever was defined as temperature: >=38.0 degrees (deg) Celsius (C), and categorized as: >=38.0 to 38.4 deg C, >38.4 to 38.9 deg C, >38.9 to 40.0 deg C, and >40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain, and new or worsened joint pain were graded as mild: did not interfere with activity, moderate: some interference with activity, and severe: prevented daily routine activity. Vomiting graded as mild: 1 to 2 times in 24 hours(h), moderate: >2 times in 24h, severe: required intravenous hydration, and grade 4: emergency room (ER) visit or hospitalization for hypotensive shock. Diarrhea graded as mild: 2 to 3 loose stools in 24h, moderate: 4 to 5 loose stools in 24h, severe: 6 or more loose stools in 24h, and grade 4: ER visit or hospitalization for severe diarrhea.

Time Frame

Within 7 Days After Vaccination 1

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received any of the study intervention. Here, "Number of participants analyzed" signifies number of participants evaluable and "Number Analyzed" (n) signifies number of participants evaluable for specified rows for this outcome measure.


Arm/Group Title		Coadministration Group	Separate Administration Group
Arm/Group Description		Participants were randomized to receive 30 microgram (mcg) intramuscular (IM) injection of BNT162b2 vaccine along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and IM injection of Placebo 1 month later (Visit 2).	Participants were randomized to receive an intramuscular (IM) injection of Placebo along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and 30 mcg IM injection of BNT162b2 vaccine 1 month later (Visit 2).
Overall Number of Participants Analyzed		564	563
Number (95% Confidence Interval) Unit of Measure: Percentage of participants
Fever: >=38.0 deg C	Number Analyzed	Participants	Participants
Fever: >=38.0 deg C		2.0(1.0 to 3.5)	1.1(0.4 to 2.3)
Fever: >=38.0 deg C to 38.4 deg C	Number Analyzed	Participants	Participants
Fever: >=38.0 deg C to 38.4 deg C		1.2(0.5 to 2.5)	0.4(0.0 to 1.3)
Fever: >38.4 deg C to 38.9 deg C	Number Analyzed	Participants	Participants
Fever: >38.4 deg C to 38.9 deg C		0.4(0.0 to 1.3)	0.4(0.0 to 1.3)
Fever: >38.9 deg C to 40.0 deg C	Number Analyzed	Participants	Participants
Fever: >38.9 deg C to 40.0 deg C		0.4(0.0 to 1.3)	0.4(0.0 to 1.3)
Fever: >40.0 deg C	Number Analyzed	Participants	Participants
Fever: >40.0 deg C		0.0(0.0 to 0.7)	0.0(0.0 to 0.7)
Fatigue: Any	Number Analyzed	Participants	Participants
Fatigue: Any		64.0(59.9 to 68.0)	42.1(38.0 to 46.3)
Fatigue: Mild	Number Analyzed	Participants	Participants
Fatigue: Mild		31.9(28.1 to 35.9)	24.7(21.2 to 28.5)
Fatigue: Moderate	Number Analyzed	Participants	Participants
Fatigue: Moderate		30.9(27.1 to 34.8)	16.3(13.4 to 19.7)
Fatigue: Severe	Number Analyzed	Participants	Participants
Fatigue: Severe		1.2(0.5 to 2.5)	1.1(0.4 to 2.3)
Fatigue: Grade 4	Number Analyzed	Participants	Participants
Fatigue: Grade 4		0(0.0 to 0.7)	0(0.0 to 0.7)
Headache: Any	Number Analyzed	Participants	Participants
Headache: Any		47.2(43.0 to 51.4)	34.3(30.4 to 38.4)
Headache: Mild	Number Analyzed	Participants	Participants
Headache: Mild		28.2(24.5 to 32.1)	23.3(19.9 to 27.0)
Headache: Moderate	Number Analyzed	Participants	Participants
Headache: Moderate		17.9(14.8 to 21.3)	10.3(7.9 to 13.1)
Headache: Severe	Number Analyzed	Participants	Participants
Headache: Severe		1.1(0.4 to 2.3)	0.7(0.2 to 1.8)
Headache: Grade 4	Number Analyzed	Participants	Participants
Headache: Grade 4		0(0.0 to 0.7)	0(0.0 to 0.7)
Chills: Any	Number Analyzed	Participants	Participants
Chills: Any		19.9(16.6 to 23.4)	6.2(4.4 to 8.6)
Chills: Mild	Number Analyzed	Participants	Participants
Chills: Mild		12.9(10.3 to 16.0)	4.3(2.8 to 6.3)
Chills: Moderate	Number Analyzed	Participants	Participants
Chills: Moderate		6.0(4.2 to 8.3)	1.6(0.7 to 3.0)
Chills: Severe	Number Analyzed	Participants	Participants
Chills: Severe		0.9(0.3 to 2.1)	0.4(0.0 to 1.3)
Chills: Grade 4	Number Analyzed	Participants	Participants
Chills: Grade 4		0(0.0 to 0.7)	0(0.0 to 0.7)
Vomiting: Any	Number Analyzed	Participants	Participants
Vomiting: Any		2.7(1.5 to 4.3)	0.9(0.3 to 2.1)
Vomiting: Mild	Number Analyzed	Participants	Participants
Vomiting: Mild		2.3(1.2 to 3.9)	0.7(0.2 to 1.8)
Vomiting: Moderate	Number Analyzed	Participants	Participants
Vomiting: Moderate		0.4(0.0 to 1.3)	0.2(0.0 to 1.0)
Vomiting: Severe	Number Analyzed	Participants	Participants
Vomiting: Severe		0(0.0 to 0.7)	0(0.0 to 0.7)
Vomiting: Grade 4	Number Analyzed	Participants	Participants
Vomiting: Grade 4		0(0.0 to 0.7)	0(0.0 to 0.7)
Diarrhea: Any	Number Analyzed	Participants	Participants
Diarrhea: Any		11.5(9.0 to 14.5)	10.1(7.8 to 12.9)
Diarrhea: Mild	Number Analyzed	Participants	Participants
Diarrhea: Mild		9.9(7.6 to 12.7)	8.9(6.7 to 11.6)
Diarrhea: Moderate	Number Analyzed	Participants	Participants
Diarrhea: Moderate		1.4(0.6 to 2.8)	1.2(0.5 to 2.5)
Diarrhea: Severe	Number Analyzed	Participants	Participants
Diarrhea: Severe		0.2(0.0 to 1.0)	0(0.0 to 0.7)
Diarrhea: Grade 4	Number Analyzed	Participants	Participants
Diarrhea: Grade 4		0(0.0 to 0.7)	0(0.0 to 0.7)
New or worsened muscle pain: Any	Number Analyzed	Participants	Participants
New or worsened muscle pain: Any		27.7(24.0 to 31.6)	11.4(8.9 to 14.3)
New or worsened muscle pain: Mild	Number Analyzed	Participants	Participants
New or worsened muscle pain: Mild		15.8(12.9 to 19.1)	6.2(4.4 to 8.6)
New or worsened muscle pain: Moderate	Number Analyzed	Participants	Participants
New or worsened muscle pain: Moderate		11.3(8.8 to 14.3)	5.0(3.3 to 7.1)
New or worsened muscle pain: Severe	Number Analyzed	Participants	Participants
New or worsened muscle pain: Severe		0.5(0.1 to 1.5)	0.2(0.0 to 1.0)
New or worsened muscle pain: Grade 4	Number Analyzed	Participants	Participants
New or worsened muscle pain: Grade 4		0(0.0 to 0.7)	0(0.0 to 0.7)
New or worsened joint pain: Any	Number Analyzed	Participants	Participants
New or worsened joint pain: Any		15.1(12.2 to 18.3)	5.3(3.6 to 7.5)
New or worsened joint pain: Mild	Number Analyzed	Participants	Participants
New or worsened joint pain: Mild		10.3(7.9 to 13.1)	2.7(1.5 to 4.4)
New or worsened joint pain: Moderate	Number Analyzed	Participants	Participants
New or worsened joint pain: Moderate		4.8(3.2 to 6.9)	2.7(1.5 to 4.4)
New or worsened joint pain: Severe	Number Analyzed	Participants	Participants
New or worsened joint pain: Severe		0(0.0 to 0.7)	0(0.0 to 0.7)
New or worsened joint pain: Grade 4	Number Analyzed	Participants	Participants
New or worsened joint pain: Grade 4		0(0.0 to 0.7)	0(0.0 to 0.7)

4. Primary Outcome:

Title

Percentage of Participants With Systemic Events Within 7 Days After Vaccination 2

Description

Systemic events included fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain recorded by participants in an e-diary. Fever was defined as temperature: >=38.0 deg C, and categorized as: >=38.0 to 38.4 deg C, >38.4 to 38.9 deg C, >38.9 to 40.0 deg C, and >40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain, and new or worsened joint pain were graded as mild: did not interfere with activity, moderate: some interference with activity, and severe: prevented daily routine activity. Vomiting graded as mild: 1 to 2 times in 24h, moderate: >2 times in 24h, severe: required intravenous hydration, and grade 4: ER visit or hospitalization for hypotensive shock. Diarrhea graded as mild: 2 to 3 loose stools in 24h, moderate: 4 to 5 loose stools in 24h, severe: 6 or more loose stools in 24h, and grade 4: ER visit or hospitalization for severe diarrhea. Exact 2-sided CI, based on Clopper and Pearson method used.

Time Frame

Within 7 Days After Vaccination 2

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Coadministration Group	Separate Administration Group
Arm/Group Description	Participants were randomized to receive 30 microgram (mcg) intramuscular (IM) injection of BNT162b2 vaccine along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and IM injection of Placebo 1 month later (Visit 2).	Participants were randomized to receive an intramuscular (IM) injection of Placebo along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and 30 mcg IM injection of BNT162b2 vaccine 1 month later (Visit 2).
Overall Number of Participants Analyzed	557	553
Number (95% Confidence Interval) Unit of Measure: Percentage of participants
Fever: >=38.0 deg C	1.1(0.4 to 2.3)	1.6(0.7 to 3.1)
Fever: >=38.0 deg C to 38.4 deg C	0.5(0.1 to 1.6)	1.1(0.4 to 2.3)
Fever: >38.4 deg C to 38.9 deg C	0.5(0.1 to 1.6)	0.5(0.1 to 1.6)
Fever: >38.9 deg C to 40.0 deg C	0(0.0 to 0.7)	0(0.0 to 0.7)
Fever: >40.0 deg C	0.(0.0 to 0.7)	0(0.0 to 0.7)
Fatigue: Any	21.7(18.4 to 25.4)	50.8(46.6 to 55.1)
Fatigue: Mild	12.4(9.8 to 15.4)	27.3(23.6 to 31.2)
Fatigue: Moderate	8.6(6.4 to 11.3)	22.1(18.7 to 25.8)
Fatigue: Severe	0.7(0.2 to 1.8)	1.4(0.6 to 2.8)
Fatigue: Grade 4	0(0.0 to 0.7)	0(0.0 to 0.7)
Headache: Any	20.8(17.5 to 24.4)	37.8(33.7 to 42.0)
Headache: Mild	13.1(10.4 to 16.2)	25.0(21.4 to 28.8)
Headache: Moderate	7.5(5.5 to 10.1)	12.1(9.5 to 15.1)
Headache: Severe	0.2(0.0 to 1.0)	0.7(0.2 to 1.8)
Headache: Grade 4	0(0.0 to 0.7)	0(0.0 to 0.7)
Chills: Any	3.4(2.1 to 5.3)	13.4(10.7 to 16.5)
Chills: Mild	2.3(1.2 to 4.0)	8.5(6.3 to 11.1)
Chills: Moderate	1.1(0.4 to 2.3)	4.7(3.1 to 6.8)
Chills: Severe	0(0.0 to 0.7)	0.2(0.0 to 1.0)
Chills: Grade 4	0(0.0 to 0.7)	0(0.0 to 0.7)
Vomiting: Any	1.1(0.4 to 2.3)	2.4(1.3 to 4.0)
Vomiting: Mild	0.7(0.2 to 1.8)	1.8(0.9 to 3.3)
Vomiting: Moderate	0.4(0.0 to 1.3)	0.5(0.1 to 1.6)
Vomiting: Severe	0(0.0 to 0.7)	0(0.0 to 0.7)
Vomiting: Grade 4	0(0.0 to 0.7)	0(0.0 to 0.7)
Diarrhea: Any	4.5(2.9 to 6.6)	6.5(4.6 to 8.9)
Diarrhea: Mild	3.8(2.3 to 5.7)	5.2(3.5 to 7.4)
Diarrhea: Moderate	0.7(0.2 to 1.8)	0.9(0.3 to 2.1)
Diarrhea: Severe	0(0.0 to 0.7)	0.4(0.0 to 1.3)
Diarrhea: Grade 4	0(0.0 to 0.7)	0(0.0 to 0.7)
New or worsened muscle pain: Any	5.2(3.5 to 7.4)	23.5(20.0 to 27.3)
New or worsened muscle pain: Mild	2.7(1.5 to 4.4)	12.8(10.2 to 15.9)
New or worsened muscle pain: Moderate	2.5(1.4 to 4.2)	10.5(8.1 to 13.3)
New or worsened muscle pain: Severe	0(0.0 to 0.7)	0.2(0.0 to 1.0)
New or worsened muscle pain: Grade 4	0(0.0 to 0.7)	0(0.0 to 0.7)
New or worsened joint pain: Any	3.4(2.1 to 5.3)	9.8(7.4 to 12.5)
New or worsened joint pain: Mild	2.0(1.0 to 3.5)	5.6(3.8 to 7.9)
New or worsened joint pain: Moderate	1.4(0.6 to 2.8)	4.2(2.7 to 6.2)
New or worsened joint pain: Severe	0(0.0 to 0.7)	0(0.0 to 0.7)
New or worsened joint pain: Grade 4	0(0.0 to 0.7)	0(0.0 to 0.7)

Quality Control Review Comment provided by the National Library of Medicine:

Information within the measure appears inconsistent.

5. Primary Outcome:

Title

Percentage of Participants With Adverse Events Within 1 Month After Vaccination 1

Description

Time Frame

Within 1 month after Vaccination 1

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received any of the study intervention.


Arm/Group Title	Coadministration Group	Separate Administration Group
Arm/Group Description	Participants were randomized to receive 30 microgram (mcg) intramuscular (IM) injection of BNT162b2 vaccine along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and IM injection of Placebo 1 month later (Visit 2).	Participants were randomized to receive an intramuscular (IM) injection of Placebo along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and 30 mcg IM injection of BNT162b2 vaccine 1 month later (Visit 2).
Overall Number of Participants Analyzed	564	564
Number (95% Confidence Interval) Unit of Measure: Percentage of participants	31.6(27.7 to 35.6)	30.5(26.7 to 34.5)

6. Primary Outcome:

Title

Percentage of Participants With Adverse Events Within 1 Month After Vaccination 2

Description

Time Frame

Within 1 month after Vaccination 2

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received any of the study intervention. Here, "Number of participants analyzed" signifies number of participants evaluable for this outcome measure''.


Arm/Group Title	Coadministration Group	Separate Administration Group
Arm/Group Description	Participants were randomized to receive 30 microgram (mcg) intramuscular (IM) injection of BNT162b2 vaccine along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and IM injection of Placebo 1 month later (Visit 2).	Participants were randomized to receive an intramuscular (IM) injection of Placebo along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and 30 mcg IM injection of BNT162b2 vaccine 1 month later (Visit 2).
Overall Number of Participants Analyzed	562	557
Number (95% Confidence Interval) Unit of Measure: Percentage of participants	29.0(25.3 to 32.9)	25.1(21.6 to 29.0)

7. Primary Outcome:

Title

Percentage of Participants With Serious Adverse Events Within 1 Month After Vaccination 1

Description

An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Exact 2-sided CI was calculated using the Clopper and Pearson method. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial/prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; or that was considered to be an important medical event.

Time Frame

Within 1 Month After Vaccination 1

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received any of the study intervention.


Arm/Group Title	Coadministration Group	Separate Administration Group
Arm/Group Description	Participants were randomized to receive 30 microgram (mcg) intramuscular (IM) injection of BNT162b2 vaccine along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and IM injection of Placebo 1 month later (Visit 2).	Participants were randomized to receive an intramuscular (IM) injection of Placebo along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and 30 mcg IM injection of BNT162b2 vaccine 1 month later (Visit 2).
Overall Number of Participants Analyzed	564	564
Number (95% Confidence Interval) Unit of Measure: Percentage of participants	0.4(0.0 to 1.3)	0.2(0.0 to 1.0)

8. Primary Outcome:

Title

Percentage of Participants With Serious Adverse Events Within 1 Month After Vaccination 2

Description

Time Frame

Within 1 Month After Vaccination 2

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received any of the study intervention. Here, "Number of participants analyzed" signifies number of participants evaluable for this outcome measure''.


Arm/Group Title	Coadministration Group	Separate Administration Group
Arm/Group Description	Participants were randomized to receive 30 microgram (mcg) intramuscular (IM) injection of BNT162b2 vaccine along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and IM injection of Placebo 1 month later (Visit 2).	Participants were randomized to receive an intramuscular (IM) injection of Placebo along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and 30 mcg IM injection of BNT162b2 vaccine 1 month later (Visit 2).
Overall Number of Participants Analyzed	562	557
Number (95% Confidence Interval) Unit of Measure: Percentage of participants	0.5(0.1 to 1.6)	0.7(0.2 to 1.8)

9. Primary Outcome:

Title

Geometric Mean Ratio (GMR) Based on Geometric Mean Concentration (GMC) of Full-Length S-binding Immunoglobulin G (IgG) at 1 Month After BNT162b2 Vaccination

Description

GMCs of full-length S-binding IgG level for the coadministration group and separate administration group were reported in this outcome measure in descriptive data section. GMC and the 2-sided 95% CI were calculated by exponentiating the LSMeans of the concentrations and the corresponding CIs based on analysis of logarithmically transformed assay results using a linear regression model with terms of vaccine group, age group, and the corresponding baseline assay results (log scale). Assay results below the LLOQ were set to 0.5*LLOQ. Geometric mean ratio (GMR) was reported in the statistical analysis section and was calculated as ratio of GMCs in the coadministration group to the separate administration group. Here, "Number of participants analyzed" signifies number of participants evaluable for this outcome measure.

Time Frame

1 Month After BNT162b2 vaccination

Outcome Measure Data

Analysis Population Description

Evaluable BNT162b2 immunogenicity population: Eligible participants who received all vaccinations(Vax) at Visit1(V1) (coadministration group) or all Vax at V1 and V2 (separate administration group) as randomized, had at least 1 valid full-length S-binding IgG result from blood sample collected 28 to 42 days after BNT162b2 vax, had no reported COVID-19/new SARS-CoV-2 infection after V1 through 1 month after BNT162b2 vax, and had no other important protocol deviations as determined by clinician.


Arm/Group Title	Coadministration Group	Separate Administration Group
Arm/Group Description	Participants were randomized to receive 30 microgram (mcg) intramuscular (IM) injection of BNT162b2 vaccine along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and IM injection of Placebo 1 month later (Visit 2).	Participants were randomized to receive an intramuscular (IM) injection of Placebo along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and 30 mcg IM injection of BNT162b2 vaccine 1 month later (Visit 2).
Overall Number of Participants Analyzed	499	413
Geometric Mean (95% Confidence Interval) Unit of Measure: Units per millilitre (U/mL)	13767.8(13110.0 to 14458.6)	16644.5(15774.7 to 17562.3)

Statistical Analysis 1


Statistical Analysis Overview	Comparison Group Selection	Coadministration Group, Separate Administration Group
	Comments	[Not specified]
	Type of Statistical Test	Non-Inferiority
	Comments	Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (coadministration group to separate-administration group) was greater than 0.67.


Method of Estimation	Estimation Parameter	GMR
	Estimated Value	0.83
	Confidence Interval	(2-sided) 95% 0.77 to 0.89
	Estimation Comments	GMRs and 95% CIs were calculated by exponentiating LSmeans difference of logarithms of concentrations (coadmin group-separate admin group), corresponding CIs based on analysis of log transformed assay results using a linear regression model.

10. Primary Outcome:

Title

Geometric Mean Ratio (GMR) Based on Geometric Mean Titer (GMT) of Strain-Specific Hemagglutination Inhibition (HAI) at 1 Month After SIIV Vaccination

Description

GMTs of strain-specific HAI titers for the coadministration group and separate administration group were reported in this outcome measure in descriptive data section. GMTs and the 2-sided 95% CIs were calculated by exponentiating the LSMeans of the titers and the corresponding CIs based on analysis of logarithmically transformed assay results using a linear regression model with terms of vaccine group, age group, and the corresponding baseline assay results (log scale). Assay results below the LLOQ were set to 0.5*LLOQ, and results above the ULOQ were set to ULOQ+1. Geometric mean ratio (GMR) was reported in the statistical analysis section and was calculated as ratio of GMT in the coadministration group to the separate administration group. Here, "Number of participants analyzed" signifies number of participants evaluable for this outcome measure.

Time Frame

1 Month After SIIV vaccination

Outcome Measure Data

Analysis Population Description

Evaluable SIIV immunogenicity population: participants who received all vaccinations at Visit 1 as randomized, had at least 1 valid and determinate HAI titer result from the blood sample collected 28 to 42 days after SIIV, and had no other important protocol deviations as determined by the clinician. Here, "Number of participants analyzed" signifies number of participants evaluable and "Number Analyzed" (n) signifies number of participants evaluable for specified rows for this outcome measure.


Arm/Group Title		Coadministration Group	Separate Administration Group
Arm/Group Description		Participants were randomized to receive 30 microgram (mcg) intramuscular (IM) injection of BNT162b2 vaccine along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and IM injection of Placebo 1 month later (Visit 2).	Participants were randomized to receive an intramuscular (IM) injection of Placebo along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and 30 mcg IM injection of BNT162b2 vaccine 1 month later (Visit 2).
Overall Number of Participants Analyzed		515	484
Geometric Mean (95% Confidence Interval) Unit of Measure: Titer
B/Austria	Number Analyzed	Participants	Participants
B/Austria		80.1(71.7 to 89.6)	89.7(80.0 to 100.7)
B/Phuket	Number Analyzed	Participants	Participants
B/Phuket		81.3(74.4 to 88.9)	81.3(74.2 to 89.2)
H1N1 A/Victoria	Number Analyzed	Participants	Participants
H1N1 A/Victoria		301.7(273.1 to 333.4)	316.5(285.5 to 350.9)
H3N2 A/Darwin	Number Analyzed	Participants	Participants
H3N2 A/Darwin		226.8(207.2 to 248.3)	235.6(214.6 to 258.7)

Statistical Analysis 1


Statistical Analysis Overview	Comparison Group Selection	Coadministration Group, Separate Administration Group
	Comments	B/Austria
	Type of Statistical Test	Non-Inferiority
	Comments	Noninferiority was declared for an influenza strain if the lower bound of the 2-sided 95% CI for the GMR (coadministration group to separate administration group) was greater than 0.67


Method of Estimation	Estimation Parameter	Geometric Mean Ratio
	Estimated Value	0.89
	Confidence Interval	(2-sided) 95% 0.77 to 1.04
	Estimation Comments	GMRs and 95% CIs were calculated by exponentiating LSmeans difference of logarithms of titers (coadministration group-separate administration group), corresponding CIs based on analysis of log transformed assay results using a linear regression model

Statistical Analysis 2


Statistical Analysis Overview	Comparison Group Selection	Coadministration Group, Separate Administration Group
	Comments	B/Phuket
	Type of Statistical Test	Non-Inferiority
	Comments	Noninferiority was declared for an influenza strain if the lower bound of the 2-sided 95% CI for the GMR (coadministration group to separate administration group) was greater than 0.67.


Method of Estimation	Estimation Parameter	GMR
	Estimated Value	1.00
	Confidence Interval	(2-sided) 95% 0.89 to 1.13
	Estimation Comments	GMRs and 95% CIs were calculated by exponentiating LSmeans difference of logarithms of titers (coadministration group-separate administration group), corresponding CIs based on analysis of log transformed assay results using a linear regression model

Statistical Analysis 3


Statistical Analysis Overview	Comparison Group Selection	Coadministration Group, Separate Administration Group
	Comments	H1N1 A/Victoria
	Type of Statistical Test	Non-Inferiority
	Comments	Noninferiority was declared for an influenza strain if the lower bound of the 2-sided 95% CI for the GMR (coadministration group to separate administration group) was greater than 0.67.


Method of Estimation	Estimation Parameter	GMR
	Estimated Value	0.95
	Confidence Interval	(2-sided) 95% 0.83 to 1.09
	Estimation Comments	GMRs and 95% CIs were calculated by exponentiating LSmeans difference of logarithms of titers (coadministration group-separate administration group), corresponding CIs based on analysis of log transformed assay results using a linear regression model

Statistical Analysis 4


Statistical Analysis Overview	Comparison Group Selection	Coadministration Group, Separate Administration Group
	Comments	H3N2 A/Darwin
	Type of Statistical Test	Non-Inferiority
	Comments	Noninferiority was declared for an influenza strain if the lower bound of the 2-sided 95% CI for the GMR (coadministration group to separate administration group) was greater than 0.67.


Method of Estimation	Estimation Parameter	GMR
	Estimated Value	0.96
	Confidence Interval	(2-sided) 95% 0.85 to 1.09
	Estimation Comments	GMRs and 95% CIs were calculated by exponentiating LSmeans difference of logarithms of titers (coadministration group-separate administration group), corresponding CIs based on analysis of log transformed assay results using a linear regression model

11. Secondary Outcome:

Title

Geometric Mean Concentration (GMC) of Full-Length S-binding IgG Levels Before Vaccination and 1 Month After BNT162b2 Vaccination

Description

GMCs were calculated by exponentiating the mean logarithm of the concentrations and the corresponding CIs (based on the Student's t-distribution). Assay results below the lower limit of quantitation (LLOQ) were set to 0.5*LLOQ. Here, "Number of participants analyzed" signifies number of participants evaluable for this outcome measure''.

Time Frame

Before BNT162b2 vaccination, and 1 month After BNT162b2 vaccination

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Coadministration Group	Separate Administration Group
Arm/Group Description	Participants were randomized to receive 30 microgram (mcg) intramuscular (IM) injection of BNT162b2 vaccine along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and IM injection of Placebo 1 month later (Visit 2).	Participants were randomized to receive an intramuscular (IM) injection of Placebo along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and 30 mcg IM injection of BNT162b2 vaccine 1 month later (Visit 2).
Overall Number of Participants Analyzed	499	413
Geometric Mean (95% Confidence Interval) Unit of Measure: Units per millilitre (U/mL)
Before BNT162b2 Vaccination	5520.3(5034.7 to 6052.8)	5272.3(4704.3 to 5909.0)
1 Month After BNT162b2 Vaccination	13806.5(12838.9 to 14847.0)	16254.6(15035.5 to 17572.5)

12. Secondary Outcome:

Title

Geometric Mean Fold Rise (GMFR) of Full-Length S-binding IgG Levels From Before Vaccination to 1 Month After BNT162b2 Vaccination

Description

GMFR was defined as ratio of the geometric mean concentration of IgG at 1 month after BNT162b2 vaccination to the geometric mean concentration of IgG before BNT162b2 vaccination. GMFRs were calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the Student's t-distribution). Assay results below the LLOQ were set to 0.5*LLOQ. Here, "Number of participants analyzed" signifies number of participants evaluable for this outcome measure''.

Time Frame

From before BNT162b2 vaccination to 1 month After BNT162b2 vaccination

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Coadministration Group	Separate Administration Group
Arm/Group Description	Participants were randomized to receive 30 microgram (mcg) intramuscular (IM) injection of BNT162b2 vaccine along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and IM injection of Placebo 1 month later (Visit 2).	Participants were randomized to receive an intramuscular (IM) injection of Placebo along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and 30 mcg IM injection of BNT162b2 vaccine 1 month later (Visit 2).
Overall Number of Participants Analyzed	499	413
Geometric Mean (95% Confidence Interval) Unit of Measure: Fold rise	2.5(2.4 to 2.7)	3.1(2.9 to 3.3)

13. Secondary Outcome:


Title	Geometric Mean Titer (GMT) of SARS-CoV-2 Neutralizing Titers Before Vaccination and 1 Month After BNT162b2 Vaccination
Description
Time Frame	Before BNT162b2 vaccination, and 1 month after BNT162b2 vaccination
Anticipated Reporting Date	July 2024
Outcome Measure Data Not Reported

14. Secondary Outcome:


Title	Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Neutralizing Titers From Before Vaccination to 1 Month After BNT162b2 Vaccination
Description	SARS-CoV-2 neutralization assay (reference strain) (for a subset of approximately 200 participants).
Time Frame	From before BNT162b2 vaccination to 1 month after BNT162b2 vaccination
Anticipated Reporting Date	July 2024
Outcome Measure Data Not Reported

Adverse Events


Time Frame	AEs and SAEs: From Day 1 (Visit 1) to 1 month after last dose of study vaccine (approximately 2 months after Visit 1 [Day1]); Local reactions (at the BNT162b2/placebo injection site) and systemic events: Within 7 days after each vaccination
Adverse Event Reporting Description	An AE may be categorized as serious in 1 participant and non-serious in another participant, or 1 participant may experience both serious and non-serious AE during the study. Safety population included all participants who received any of the study intervention. AEs included events collected in electronic diary (local and systemic reactions; systematic assessment) and events collected on case report form at each visit (non-systematic assessment).

Arm/Group Title	Coadministration Group (Visit 1)	Coadministration Group (Visit 2)	Separate Administration Group (Visit 1)	Separate Administration Group (Visit 2)
Arm/Group Description	Participants were randomized to receive 30 microgram (mcg) intramuscular (IM) injection of BNT162b2 vaccine along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and IM injection of Placebo 1 month later (Visit 2).	Participants were randomized to receive 30 microgram (mcg) intramuscular (IM) injection of BNT162b2 vaccine along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and IM injection of Placebo 1 month later (Visit 2).	Participants were randomized to receive an intramuscular (IM) injection of Placebo along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and 30 mcg IM injection of BNT162b2 vaccine 1 month later (Visit 2).	Participants were randomized to receive an intramuscular (IM) injection of Placebo along with IM injection of Seasonal Inactivated Influenza Vaccine (SIIV) on Day 1 (Visit 1), and 30 mcg IM injection of BNT162b2 vaccine 1 month later (Visit 2).
All-Cause Mortality
	Coadministration Group (Visit 1)	Coadministration Group (Visit 2)	Separate Administration Group (Visit 1)	Separate Administration Group (Visit 2)
	Affected / At Risk (%)	Affected / At Risk (%)	Affected / At Risk (%)	Affected / At Risk (%)
Total	0 / 564 (0%)	0 / 562 (0%)	0 / 564 (0%)	0 / 557 (0%)
Serious Adverse Events
	Coadministration Group (Visit 1)	Coadministration Group (Visit 2)	Separate Administration Group (Visit 1)	Separate Administration Group (Visit 2)
	Affected / At Risk (%)	Affected / At Risk (%)	Affected / At Risk (%)	Affected / At Risk (%)
Total	2 / 564 (0.35%)	3 / 562 (0.53%)	1 / 564 (0.18%)	4 / 557 (0.72%)
Cardiac disorders
Atrial fibrillation ^{∗ A}	0 / 564 (0%)	0 / 562 (0%)	0 / 564 (0%)	1 / 557 (0.18%)
Gastrointestinal disorders
Intestinal perforation ^{∗ A}	0 / 564 (0%)	1 / 562 (0.18%)	0 / 564 (0%)	0 / 557 (0%)
Infections and infestations
Abscess limb ^{∗ A}	0 / 564 (0%)	0 / 562 (0%)	1 / 564 (0.18%)	0 / 557 (0%)
Wound infection ^{∗ A}	1 / 564 (0.18%)	0 / 562 (0%)	0 / 564 (0%)	0 / 557 (0%)
Injury, poisoning and procedural complications
Concussion ^{∗ A}	0 / 564 (0%)	0 / 562 (0%)	0 / 564 (0%)	1 / 557 (0.18%)
Ligament sprain ^{∗ A}	0 / 564 (0%)	0 / 562 (0%)	0 / 564 (0%)	1 / 557 (0.18%)
Pneumocephalus ^{∗ A}	0 / 564 (0%)	0 / 562 (0%)	0 / 564 (0%)	1 / 557 (0.18%)
Skull fracture ^{∗ A}	0 / 564 (0%)	0 / 562 (0%)	0 / 564 (0%)	1 / 557 (0.18%)
Musculoskeletal and connective tissue disorders
Costochondritis ^{∗ A}	0 / 564 (0%)	1 / 562 (0.18%)	0 / 564 (0%)	0 / 557 (0%)
Musculoskeletal chest pain ^{∗ A}	1 / 564 (0.18%)	0 / 562 (0%)	0 / 564 (0%)	1 / 557 (0.18%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma stage II ^{∗ A}	0 / 564 (0%)	1 / 562 (0.18%)	0 / 564 (0%)	0 / 557 (0%)
∗Indicates events were collected by non-systematic methods. ATerm from vocabulary, MedDRA v25.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	1%
	Coadministration Group (Visit 1)	Coadministration Group (Visit 2)	Separate Administration Group (Visit 1)	Separate Administration Group (Visit 2)
	Affected / At Risk (%)	Affected / At Risk (%)	Affected / At Risk (%)	Affected / At Risk (%)
Total	532 / 564 (94.33%)	261 / 562 (46.44%)	364 / 564 (64.54%)	502 / 557 (90.13%)
Gastrointestinal disorders
Diarrhoea ^{† A}	65 / 564 (11.52%)	25 / 562 (4.45%)	57 / 564 (10.11%)	36 / 557 (6.46%)
Vomiting ^{† A}	15 / 564 (2.66%)	6 / 562 (1.07%)	5 / 564 (0.89%)	13 / 557 (2.33%)
General disorders
Chills ^{† A}	112 / 564 (19.86%)	19 / 562 (3.38%)	35 / 564 (6.21%)	74 / 557 (13.29%)
Fatigue ^{† A}	361 / 564 (64.01%)	121 / 562 (21.53%)	237 / 564 (42.02%)	281 / 557 (50.45%)
Influenza like illness ^{∗ A}	9 / 564 (1.6%)	9 / 562 (1.6%)	12 / 564 (2.13%)	7 / 557 (1.26%)
Injection site erythema ^{† A}	43 / 564 (7.62%)	1 / 562 (0.18%)	3 / 564 (0.53%)	26 / 557 (4.67%)
Injection site pain ^{† A}	486 / 564 (86.17%)	37 / 562 (6.58%)	78 / 564 (13.83%)	467 / 557 (83.84%)
Injection site pain ^{∗ A}	16 / 564 (2.84%)	1 / 562 (0.18%)	14 / 564 (2.48%)	1 / 557 (0.18%)
Injection site swelling ^{† A}	52 / 564 (9.22%)	2 / 562 (0.36%)	6 / 564 (1.06%)	49 / 557 (8.8%)
Pyrexia ^{† A}	11 / 564 (1.95%)	6 / 562 (1.07%)	6 / 564 (1.06%)	9 / 557 (1.62%)
Infections and infestations
COVID-19 ^{∗ A}	46 / 564 (8.16%)	63 / 562 (11.21%)	56 / 564 (9.93%)	48 / 557 (8.62%)
Gastroenteritis ^{∗ A}	8 / 564 (1.42%)	6 / 562 (1.07%)	7 / 564 (1.24%)	5 / 557 (0.9%)
Upper respiratory tract infection ^{∗ A}	27 / 564 (4.79%)	31 / 562 (5.52%)	24 / 564 (4.26%)	22 / 557 (3.95%)
Viral upper respiratory tract infection ^{∗ A}	4 / 564 (0.71%)	6 / 562 (1.07%)	6 / 564 (1.06%)	7 / 557 (1.26%)
Nervous system disorders
Headache ^{† A}	266 / 564 (47.16%)	116 / 562 (20.64%)	193 / 564 (34.22%)	209 / 557 (37.52%)
†Indicates events were collected by systematic assessment. ∗Indicates events were collected by non-systematic methods. ATerm from vocabulary, MedDRA v25.1

Limitations and Caveats


The evolving nature of the pandemic has required serology work to be focused on newly emerging strains as a matter of urgent priority, which has delayed serology work on earlier trials. Hence data is not yet available for all serology outcome measures.

More Information


Certain Agreements:
Principal Investigators are NOT employed by the organization sponsoring the study. There IS an agreement between the Principal Investigator and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact:
Name/Official Title:	Pfizer ClinicalTrials.gov Call Center
Organization:	Pfizer Inc.
Phone:	1-800-718-1021
Email:	ClinicalTrials.gov_Inquiries@pfizer.com