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Trial record 1 of 1 for:    VAC18193RSV2001
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A Study of an Ad26.RSV.preF-based Regimen in the Prevention of Reverse Transcriptase Polymerase Chain Reaction (RT-PCR)-Confirmed Respiratory Syncytial Virus (RSV)-Mediated Lower Respiratory Tract Disease in Adults Aged 65 Years and Older (CYPRESS)

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ClinicalTrials.gov Identifier: NCT03982199
Recruitment Status : Terminated (The study was terminated early by the sponsor due to strategic reprioritization reasons.)
First Posted : June 11, 2019
Results First Posted : July 24, 2023
Last Update Posted : May 16, 2024
Sponsor:
Information provided by (Responsible Party):
Janssen Vaccines & Prevention B.V.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Prevention
Conditions Respiratory Syncytial Viruses
Respiratory Tract Diseases
Interventions Biological: RSV Vaccine
Biological: Placebo
Enrollment 5815
Recruitment Details  
Pre-assignment Details Participants in the main cohort who did not enter the re-vaccination subcohorts continued in the main cohort up to Day 1095. Hence, the assessments for both main cohorts and re-vaccination subcohorts were conducted in parallel until Day 1095 (end of main cohort).
Arm/Group Title Arm 1: Main Cohort: Group 1: Ad26.RSV.preF and RSV preF Protein (Protein Mixture) Arm 2: Main Cohort: Group 2: Placebo Arm 3: Revaccination (ReVacc) Subcohort 1A: Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 4: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein Mixture Arm 5: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein + Ad26.RSV.PreF Alone Arm 6: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein + RSV preF Protein Alone Arm 7: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 8: ReVacc Subcohort 1B: Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 9: ReVacc Subcohort 2B:Placebo to Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 10: ReVacc Subcohort 2B: Placebo to Ad26.RSV.preF/RSV preF Protein + Ad26.RSV.preF Arm 11: ReVacc Subcohort 2B: Placebo to Ad26.RSV.preF/RSV preF Protein + RSV preF Protein Alone Arm 12: ReVacc Subcohort 2B: Placebo to Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 13: ReVacc Subcohort 1C: Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 14: ReVacc Subcohort 2C: Placebo to Ad26.RSV.preF/RSV preF Protein (Protein Mixture)
Hide Arm/Group Description Adult participants aged greater than or equal to (>=) 65 years received a single intramuscular (IM) injection of adenovirus serotype 26 respiratory syncytial virus pre-fusion conformation stabilized F-protein (Ad26.RSV.preF) 1*10^11 viral particles (vp) and RSV preF protein 150 micrograms (mcg) (protein mixture) on Day 1. Participants were divided into revaccination subcohorts: 1A, 1B, and 1C. Participants further received revaccination with the Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) at 1 (Subcohort 1A), 2 (Subcohort 1B), and 3 (Subcohort 1C) years, respectively after the first vaccination on Day 1. Participants who were not re-vaccinated continued in the main cohort and were followed up for safety assessments until Day 1095. Adult participants aged >=65 years received a single IM injection of placebo on Day 1. Participants were divided into revaccination subcohorts: 2A, 2B, and 2C. Participants further received revaccination with Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) at 1 (Subcohort 2A), 2 (Subcohort 2B), and 3 (Subcohort 2C) years, respectively after the first vaccination on Day 1. Participants in subcohorts 2A and 2B were additionally re-randomised in three groups at Year 3 and Year 4, respectively, to receive either Ad26.RSV.preF 1*10^11 vp alone, RSV preF protein 150 mcg alone or the Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture). Participants who were not re-vaccinated continued in the main cohort and were followed up for safety assessments until Day 1095. Eligible participants who received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 1 in the main cohort entered the revaccination subcohort 1A and received IM injection of the protein mixture at the same dose level on Day 365. Participants were then followed up for safety assessments till Day 730. Eligible participants who received IM injection of placebo on Day 1 in the main study cohort entered the revaccination subcohort and received Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 365. Participants were then followed up for safety assessments till Day 730. Eligible participants who received IM injection of placebo on Day 1 in the main cohort followed by Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 365 in the revaccination subcohort further received Ad26.RSV.preF 1*10^11 vp alone as IM injection on Day 730. Participants were then followed up for safety assessments till Day 1095. Eligible participants who received IM injection of placebo on Day 1 in the main cohort followed by Ad26.RSV.preF 1*10^11 vp and RSV preF protein (protein mixture) on Day 365 in the revaccination subcohort further received RSV preF protein 150 mcg alone as IM injection on Day 730. Participants were then followed up for safety assessments till Day 1095. Eligible participants who received IM injection of placebo on Day 1 in the main study cohort entered the revaccination subcohort and received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 365 and 730. Participants were then followed up for safety assessments till Day 1095. Eligible participants who received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 1 in the main cohort entered the revaccination subcohort and received the protein mixture at the same dose level on Day 730. Participants were then followed up for safety assessments till Day 1095. Eligible participants who received IM injection of placebo on Day 1 in the main cohort entered the revaccination subcohort and received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 730. Participants were then followed up for safety assessments till Day 1095. Eligible participants who received IM injection of placebo on Day 1 in the main cohort entered the revaccination subcohort and received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 730 followed by Ad26.RSV.preF 1*10^11 vp alone on Day 1095. Participants were then followed up for safety assessments till Day 1460. Eligible participants who received IM injection of placebo on Day 1 in the main cohort entered the revaccination subcohort and received IM injection Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 730 followed by RSV preF protein 150 mcg alone on Day 1095. Participants were then followed up for safety assessments till Day 1460. Eligible participants who received IM injection of placebo on Day 1 in the main cohort entered the revaccination subcohort and received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Days 730 and Day 1095. Participants were then followed up for safety assessments till Day 1460. Eligible participants who received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 1 in the main cohort entered the revaccination subcohort and received the protein mixture at the same dose level on Day 1095. Participants were then followed up for safety assessments till Day 1460. Eligible participants who received IM injection of placebo on Day 1 in the main cohort entered the revaccination subcohort and received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 1095. Participants were then followed up for safety assessments till Day 1460.
Period Title: Main Cohorts (Day 1 up to Day 1095)
Started 2909 2906 0 0 0 0 0 0 0 0 0 0 0 0
Vaccinated 2891 2891 0 0 0 0 0 0 0 0 0 0 0 0
Completed 1875 1897 0 0 0 0 0 0 0 0 0 0 0 0
Not Completed 1034 1009 0 0 0 0 0 0 0 0 0 0 0 0
Reason Not Completed
Lost to Follow-up             152             159             0             0             0             0             0             0             0             0             0             0             0             0
Physician Decision             39             33             0             0             0             0             0             0             0             0             0             0             0             0
Withdrawal by Subject             514             503             0             0             0             0             0             0             0             0             0             0             0             0
Adverse Event             12             14             0             0             0             0             0             0             0             0             0             0             0             0
Technical Problems             10             8             0             0             0             0             0             0             0             0             0             0             0             0
Death             39             38             0             0             0             0             0             0             0             0             0             0             0             0
Site terminated by Sponsor             26             21             0             0             0             0             0             0             0             0             0             0             0             0
Study Terminated by Sponsor             129             117             0             0             0             0             0             0             0             0             0             0             0             0
Other             80             83             0             0             0             0             0             0             0             0             0             0             0             0
Randomized but not vaccinated             18             15             0             0             0             0             0             0             0             0             0             0             0             0
Protocol Violation             4             7             0             0             0             0             0             0             0             0             0             0             0             0
Initiated prohibited medication             11             11             0             0             0             0             0             0             0             0             0             0             0             0
Period Title: Revacc Subcohorts (From Day 365 to 730)
Started 0 0 120 126 0 0 0 0 0 0 0 0 0 0
Completed 0 0 94 102 0 0 0 0 0 0 0 0 0 0
Not Completed 0 0 26 24 0 0 0 0 0 0 0 0 0 0
Reason Not Completed
Other             0             0             0             3             0             0             0             0             0             0             0             0             0             0
Site terminated by Sponsor             0             0             1             0             0             0             0             0             0             0             0             0             0             0
Death             0             0             1             0             0             0             0             0             0             0             0             0             0             0
Withdrawal by Subject             0             0             21             18             0             0             0             0             0             0             0             0             0             0
Physician Decision             0             0             0             1             0             0             0             0             0             0             0             0             0             0
Lost to Follow-up             0             0             3             2             0             0             0             0             0             0             0             0             0             0
Period Title: Revacc Subcohorts (From Day 730 to 1095)
Started 0 0 0 0 28 28 28 137 149 0 0 0 0 0
Completed 0 0 0 0 28 24 28 127 3 0 0 0 0 0
Not Completed 0 0 0 0 0 4 0 10 146 0 0 0 0 0
Reason Not Completed
Other             0             0             0             0             0             0             0             0             5             0             0             0             0             0
Study Terminated by Sponsor             0             0             0             0             0             0             0             0             107             0             0             0             0             0
Site terminated by Sponsor             0             0             0             0             0             0             0             0             3             0             0             0             0             0
Death             0             0             0             0             0             0             0             0             2             0             0             0             0             0
Adverse Event             0             0             0             0             0             0             0             0             2             0             0             0             0             0
Withdrawal by Subject             0             0             0             0             0             3             0             7             20             0             0             0             0             0
Physician Decision             0             0             0             0             0             0             0             0             3             0             0             0             0             0
Lost to Follow-up             0             0             0             0             0             1             0             3             4             0             0             0             0             0
Period Title: Revacc Subcohort (From Day 1095 to 1460)
Started 0 0 0 0 0 0 0 0 0 37 37 37 131 119
Completed 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Not Completed 0 0 0 0 0 0 0 0 0 37 37 37 131 119
Reason Not Completed
Study Terminated by Sponsor             0             0             0             0             0             0             0             0             0             36             36             35             125             114
Site terminated by Sponsor             0             0             0             0             0             0             0             0             0             1             0             0             0             0
Death             0             0             0             0             0             0             0             0             0             0             0             0             0             1
Withdrawal by Subject             0             0             0             0             0             0             0             0             0             0             1             2             4             0
Physician Decision             0             0             0             0             0             0             0             0             0             0             0             0             0             1
Lost to Follow-up             0             0             0             0             0             0             0             0             0             0             0             0             1             3
Other             0             0             0             0             0             0             0             0             0             0             0             0             1             0
Arm/Group Title Arm 1: Main Cohort: Group 1: Ad26.RSV.preF and RSV preF Protein (Protein Mixture) Arm 2: Main Cohort: Group 2: Placebo Total
Hide Arm/Group Description Adult participants aged greater than or equal to (>=) 65 years received a single intramuscular (IM) injection of adenovirus serotype 26 respiratory syncytial virus pre-fusion conformation stabilized F-protein (Ad26.RSV.preF) 1*10^11 viral particles (vp) and RSV preF protein 150 micrograms (mcg) (protein mixture) on Day 1. Participants were divided into revaccination subcohorts: 1A, 1B, and 1C. Participants further received revaccination with the Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) at 1 (Subcohort 1A), 2 (Subcohort 1B), and 3 (Subcohort 1C) years, respectively after the first vaccination on Day 1. Participants who were not re-vaccinated continued in the main cohort and were followed up for safety assessments until Day 1095. Adult participants aged >=65 years received a single IM injection of placebo on Day 1. Participants were divided into revaccination subcohorts: 2A, 2B, and 2C. Participants further received revaccination with Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) at 1 (Subcohort 2A), 2 (Subcohort 2B), and 3 (Subcohort 2C) years, respectively after the first vaccination on Day 1. Participants in subcohorts 2A and 2B were additionally re-randomised in three groups at Year 3 and Year 4, respectively, to receive either Ad26.RSV.preF 1*10^11 vp alone, RSV preF protein 150 mcg alone or the Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture). Participants who were not re-vaccinated continued in the main cohort and were followed up for safety assessments until Day 1095. Total of all reporting groups
Overall Number of Baseline Participants 2891 2891 5782
Hide Baseline Analysis Population Description
The Full Analysis Set (FAS) included all randomized participants with a documented vaccine administration, regardless of the occurrence of protocol deviations.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 2891 participants 2891 participants 5782 participants
71.7  (5.37) 71.6  (5.38) 71.7  (5.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2891 participants 2891 participants 5782 participants
Female
1639
  56.7%
1694
  58.6%
3333
  57.6%
Male
1252
  43.3%
1197
  41.4%
2449
  42.4%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2891 participants 2891 participants 5782 participants
Hispanic or Latino
85
   2.9%
97
   3.4%
182
   3.1%
Not Hispanic or Latino
2778
  96.1%
2773
  95.9%
5551
  96.0%
Unknown or Not Reported
28
   1.0%
21
   0.7%
49
   0.8%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2891 participants 2891 participants 5782 participants
American Indian or Alaska Native
8
   0.3%
9
   0.3%
17
   0.3%
Asian
15
   0.5%
17
   0.6%
32
   0.6%
Native Hawaiian or Other Pacific Islander
16
   0.6%
5
   0.2%
21
   0.4%
Black or African American
169
   5.8%
148
   5.1%
317
   5.5%
White
2658
  91.9%
2690
  93.0%
5348
  92.5%
More than one race
9
   0.3%
14
   0.5%
23
   0.4%
Unknown or Not Reported
16
   0.6%
8
   0.3%
24
   0.4%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
UNITED STATES Number Analyzed 2891 participants 2891 participants 5782 participants
2891
 100.0%
2891
 100.0%
5782
 100.0%
1.Primary Outcome
Title Number of Participants With First Occurrence of Reverse Transcriptase Polymerase Chain Reaction (RT-PCR)-Confirmed Respiratory Syncytial Virus (RSV) Mediated Lower Respiratory Tract Disease (LRTD)
Hide Description Number of participants with first occurrence of RT-PCR-confirmed RSV mediated LRTD according to case definition-1, 2 and 3 were reported. Case definition 1 was defined as having a new onset or worsening in 3 or more symptoms of lower respiratory tract infection (LRTI) ; Case definition 2 was defined as having a new onset or worsening in greater than or equal to (>=) 2 symptoms of LRTI; and Case definition 3 was defined as having a new onset or worsening in >=2 OR >=1 symptoms of LRTI with >=1 systemic symptoms. Systemic symptoms (fatigue/malaise and fever/feverishness) and symptoms of LRTI (cough, shortness of breath, sputum production, wheezing and tachypnea) were collected via the RiiQ. RiiQ symptom scale was a 13-items questionnaire rated on a 4-point scale. Each symptom was rated on a scale of 0 to 3 where 0=None, 1=Mild, 2=Moderate, and 3=Severe. Higher scores indicated greater severity. The total LRTD symptom score was calculated as the mean of the LRTD symptom scores.
Time Frame From screening (Day 1) up to 9 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Per-protocol Efficacy (PPE) population included all randomized and vaccinated participants excluding participants with major protocol deviations expecting to impact the efficacy outcomes. Any participant with an RT-PCR-confirmed RSV-mediated acute respiratory infection (ARI) with onset within 14 days after vaccination and participants who discontinued within 14 days after vaccination were excluded from the PPE population.
Arm/Group Title Arm 1: Main Cohort: Group 1: Ad26.RSV.preF and RSV preF Protein (Protein Mixture) Arm 2: Main Cohort: Group 2: Placebo
Hide Arm/Group Description:
Adult participants aged greater than or equal to (>=) 65 years received a single intramuscular (IM) injection of adenovirus serotype 26 respiratory syncytial virus pre-fusion conformation stabilized F-protein (Ad26.RSV.preF) 1*10^11 viral particles (vp) and RSV preF protein 150 micrograms (mcg) (protein mixture) on Day 1. Participants were divided into revaccination subcohorts: 1A, 1B, and 1C. Participants further received revaccination with the Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) at 1 (Subcohort 1A), 2 (Subcohort 1B), and 3 (Subcohort 1C) years, respectively after the first vaccination on Day 1. Participants who were not re-vaccinated continued in the main cohort and were followed up for safety assessments until Day 1095.
Adult participants aged >=65 years received a single IM injection of placebo on Day 1. Participants were divided into revaccination subcohorts: 2A, 2B, and 2C. Participants further received revaccination with Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) at 1 (Subcohort 2A), 2 (Subcohort 2B), and 3 (Subcohort 2C) years, respectively after the first vaccination on Day 1. Participants in subcohorts 2A and 2B were additionally re-randomised in three groups at Year 3 and Year 4, respectively, to receive either Ad26.RSV.preF 1*10^11 vp alone, RSV preF protein 150 mcg alone or the Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture). Participants who were not re-vaccinated continued in the main cohort and were followed up for safety assessments until Day 1095.
Overall Number of Participants Analyzed 2791 2801
Measure Type: Count of Participants
Unit of Measure: Participants
Case Definition-1
6
   0.2%
30
   1.1%
Case Definition-2
10
   0.4%
40
   1.4%
Case Definition-3
13
   0.5%
43
   1.5%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm 1: Main Cohort: Group 1: Ad26.RSV.preF and RSV preF Protein (Protein Mixture), Arm 2: Main Cohort: Group 2: Placebo
Comments Case Definition 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00004
Comments [Not Specified]
Method Poisson regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Event Rate
Estimated Value 80.0
Confidence Interval (2-Sided) 94.211%
52.2 to 92.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Arm 1: Main Cohort: Group 1: Ad26.RSV.preF and RSV preF Protein (Protein Mixture), Arm 2: Main Cohort: Group 2: Placebo
Comments Case Definition 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00001
Comments [Not Specified]
Method Poisson regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Event Rate
Estimated Value 75.0
Confidence Interval (2-Sided) 94.211%
50.1 to 88.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Arm 1: Main Cohort: Group 1: Ad26.RSV.preF and RSV preF Protein (Protein Mixture), Arm 2: Main Cohort: Group 2: Placebo
Comments Case Definition 3
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00004
Comments [Not Specified]
Method Poisson regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Event Rate
Estimated Value 69.8
Confidence Interval (2-Sided) 94.211%
43.7 to 84.7
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Main Cohorts: Number of Participants With Any RT-PCR-confirmed RSV Disease
Hide Description Number of participants with any RT-PCR-confirmed RSV disease were reported. The analysis was based on poisson regression model.
Time Frame From screening (Day 1) up to 9 months
Hide Outcome Measure Data
Hide Analysis Population Description
The PPE population included all randomized and vaccinated participants excluding participants with major protocol deviations expecting to impact the efficacy outcomes. Any participant with an RT-PCR-confirmed RSV-mediated ARI with onset within 14 days after vaccination and participants who discontinued within 14 days after vaccination were excluded from the PPE population.
Arm/Group Title Arm 1: Main Cohort: Group 1: Ad26.RSV.preF and RSV preF Protein (Protein Mixture) Arm 2: Main Cohort: Group 2: Placebo
Hide Arm/Group Description:
Adult participants aged greater than or equal to (>=) 65 years received a single intramuscular (IM) injection of adenovirus serotype 26 respiratory syncytial virus pre-fusion conformation stabilized F-protein (Ad26.RSV.preF) 1*10^11 viral particles (vp) and RSV preF protein 150 micrograms (mcg) (protein mixture) on Day 1. Participants were divided into revaccination subcohorts: 1A, 1B, and 1C. Participants further received revaccination with the Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) at 1 (Subcohort 1A), 2 (Subcohort 1B), and 3 (Subcohort 1C) years, respectively after the first vaccination on Day 1. Participants who were not re-vaccinated continued in the main cohort and were followed up for safety assessments until Day 1095.
Adult participants aged >=65 years received a single IM injection of placebo on Day 1. Participants were divided into revaccination subcohorts: 2A, 2B, and 2C. Participants further received revaccination with Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) at 1 (Subcohort 2A), 2 (Subcohort 2B), and 3 (Subcohort 2C) years, respectively after the first vaccination on Day 1. Participants in subcohorts 2A and 2B were additionally re-randomised in three groups at Year 3 and Year 4, respectively, to receive either Ad26.RSV.preF 1*10^11 vp alone, RSV preF protein 150 mcg alone or the Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture). Participants who were not re-vaccinated continued in the main cohort and were followed up for safety assessments until Day 1095.
Overall Number of Participants Analyzed 2791 2801
Measure Type: Count of Participants
Unit of Measure: Participants
13
   0.5%
43
   1.5%
3.Secondary Outcome
Title Main Cohorts: Respiratory Syncytial Virus (RSV) A2 Strain Neutralization Antibody Titers
Hide Description RSV A2 strain neutralizing antibody titers of the vaccine-induced immune response was assessed through virus neutralization assay.
Time Frame Days 15, 85, 169, 365
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol Immunogenicity (PPI) population included all randomized and vaccinated participants who were part of the immunogenicity subset and for whom immunogenicity data were available. Here, 'N' (number of participants analyzed) signifies participants who were evaluable for this outcome measure and 'n' (participants analyzed) signifies the participants evaluable at specified timepoints.
Arm/Group Title Arm 1: Main Cohort: Group 1: Ad26.RSV.preF and RSV preF Protein (Protein Mixture) Arm 2: Main Cohort: Group 2: Placebo
Hide Arm/Group Description:
Adult participants aged greater than or equal to (>=) 65 years received a single intramuscular (IM) injection of adenovirus serotype 26 respiratory syncytial virus pre-fusion conformation stabilized F-protein (Ad26.RSV.preF) 1*10^11 viral particles (vp) and RSV preF protein 150 micrograms (mcg) (protein mixture) on Day 1. Participants were divided into revaccination subcohorts: 1A, 1B, and 1C. Participants further received revaccination with the Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) at 1 (Subcohort 1A), 2 (Subcohort 1B), and 3 (Subcohort 1C) years, respectively after the first vaccination on Day 1. Participants who were not re-vaccinated continued in the main cohort and were followed up for safety assessments until Day 1095.
Adult participants aged >=65 years received a single IM injection of placebo on Day 1. Participants were divided into revaccination subcohorts: 2A, 2B, and 2C. Participants further received revaccination with Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) at 1 (Subcohort 2A), 2 (Subcohort 2B), and 3 (Subcohort 2C) years, respectively after the first vaccination on Day 1. Participants in subcohorts 2A and 2B were additionally re-randomised in three groups at Year 3 and Year 4, respectively, to receive either Ad26.RSV.preF 1*10^11 vp alone, RSV preF protein 150 mcg alone or the Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture). Participants who were not re-vaccinated continued in the main cohort and were followed up for safety assessments until Day 1095.
Overall Number of Participants Analyzed 95 96
Geometric Mean (95% Confidence Interval)
Unit of Measure: Titers
Day 15 Number Analyzed 95 participants 91 participants
6761
(5478 to 8346)
516
(443 to 602)
Day 85 Number Analyzed 94 participants 96 participants
4963
(4053 to 6077)
602
(528 to 687)
Day 169 Number Analyzed 94 participants 93 participants
3057
(2523 to 3703)
552
(489 to 623)
Day 365 Number Analyzed 81 participants 72 participants
1546
(1235 to 1936)
341
(284 to 409)
4.Secondary Outcome
Title Revaccination Subcohorts: Respiratory Syncytial Virus (RSV) A2 Strain Neutralization Antibody Titers
Hide Description RSV A2 strain neutralizing antibody titers of the vaccine-induced immune response was assessed through virus neutralization assay.
Time Frame Days 15, 365, 379, 393, 449, 730, 737, 744, 758
Hide Outcome Measure Data
Hide Analysis Population Description
PPI set: all randomized and vaccinated participants who were part of immunogenicity subset and for whom immunogenicity data were available. 'N' (number of participants analyzed): participants evaluable for this outcome measure, 'n' (participants analyzed): participants evaluable at specified timepoints and 'n (number analyzed)=0' signifies that none of participants were available for the assessment at specified timepoints. This outcome measure was planned to be analyzed for specified arms only.
Arm/Group Title Arm 3: Revaccination (ReVacc) Subcohort 1A: Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 4: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein Mixture Arm 5: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein + Ad26.RSV.PreF Alone Arm 6: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein + RSV preF Protein Alone Arm 7: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein (Protein Mixture)
Hide Arm/Group Description:
Eligible participants who received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 1 in the main cohort entered the revaccination subcohort 1A and received IM injection of the protein mixture at the same dose level on Day 365. Participants were then followed up for safety assessments till Day 730.
Eligible participants who received IM injection of placebo on Day 1 in the main study cohort entered the revaccination subcohort and received Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 365. Participants were then followed up for safety assessments till Day 730.
Eligible participants who received IM injection of placebo on Day 1 in the main cohort followed by Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 365 in the revaccination subcohort further received Ad26.RSV.preF 1*10^11 vp alone as IM injection on Day 730. Participants were then followed up for safety assessments till Day 1095.
Eligible participants who received IM injection of placebo on Day 1 in the main cohort followed by Ad26.RSV.preF 1*10^11 vp and RSV preF protein (protein mixture) on Day 365 in the revaccination subcohort further received RSV preF protein 150 mcg alone as IM injection on Day 730. Participants were then followed up for safety assessments till Day 1095.
Eligible participants who received IM injection of placebo on Day 1 in the main study cohort entered the revaccination subcohort and received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 365 and 730. Participants were then followed up for safety assessments till Day 1095.
Overall Number of Participants Analyzed 117 120 26 28 27
Geometric Mean (95% Confidence Interval)
Unit of Measure: Titers
Day 15 Number Analyzed 111 participants 116 participants 26 participants 24 participants 27 participants
5508
(4695 to 6460)
421
(374 to 475)
357
(281 to 454)
361
(291 to 448)
487
(383 to 620)
Day 365 Number Analyzed 117 participants 120 participants 25 participants 28 participants 27 participants
1451
(1275 to 1651)
402
(354 to 456)
308
(241 to 392)
342
(264 to 444)
435
(348 to 544)
Day 379 Number Analyzed 90 participants 100 participants 23 participants 24 participants 20 participants
2075
(1779 to 2420)
5416
(4462 to 6573)
4289
(2739 to 6717)
6117
(4194 to 8922)
5114
(3161 to 8275)
Day 393 Number Analyzed 97 participants 99 participants 22 participants 20 participants 24 participants
2098
(1760 to 2501)
4821
(3982 to 5836)
4487
(3200 to 6291)
5008
(3272 to 7664)
4078
(2524 to 6589)
Day 449 Number Analyzed 109 participants 105 participants 22 participants 24 participants 26 participants
2491
(2183 to 2841)
4136
(3483 to 4912)
3186
(2290 to 4433)
4194
(3108 to 5659)
3553
(2557 to 4935)
Day 730 Number Analyzed 0 participants 76 participants 24 participants 25 participants 25 participants
2260
(1914 to 2669)
1795
(1319 to 2443)
2486
(1827 to 3382)
2491
(1859 to 3338)
Day 737 Number Analyzed 0 participants 0 participants 21 participants 23 participants 22 participants
2073
(1415 to 3036)
2677
(2125 to 3373)
3116
(2303 to 4215)
Day 744 Number Analyzed 0 participants 0 participants 19 participants 19 participants 21 participants
2542
(1721 to 3753)
3115
(2453 to 3954)
3812
(2772 to 5242)
Day 758 Number Analyzed 0 participants 0 participants 15 participants 16 participants 21 participants
2263
(1423 to 3598)
3631
(2601 to 5067)
3668
(2714 to 4958)
5.Secondary Outcome
Title Revaccination Subcohorts: Geometric Mean Titers (GMTs) of Prefusion F-protein (Pre-F) A Antibodies as Assessed by Enzyme-linked Immunosorbent Assay (ELISA)
Hide Description GMTs of preF-A antibodies after the administration of Ad26.RSV.preF-based vaccine as assessed by ELISA were reported.
Time Frame Day 15: Arms 3 to 7,13 and 14; Days 365, 379, 393, 449, 533: Arms 3 to 7; Day 730: Arms 4 to 7; Days 737, 744, 758: Arms 5 to 7; Day 1095, 1109: Arms 13 and 14
Hide Outcome Measure Data
Hide Analysis Population Description
PPI set: all randomized and vaccinated participants who were part of immunogenicity subset and for whom immunogenicity data were available. 'N' (number of participants analyzed): participants evaluable for this outcome measure, 'n' (participants analyzed): participants evaluable at specified timepoints and 'n (number analyzed)=0' signifies that none of participants were available for the assessment at specified timepoints. This outcome measure was planned to be analyzed for specified arms only.
Arm/Group Title Arm 3: Revaccination (ReVacc) Subcohort 1A: Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 4: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein Mixture Arm 5: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein + Ad26.RSV.PreF Alone Arm 6: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein + RSV preF Protein Alone Arm 7: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 13: ReVacc Subcohort 1C: Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 14: ReVacc Subcohort 2C: Placebo to Ad26.RSV.preF/RSV preF Protein (Protein Mixture)
Hide Arm/Group Description:
Eligible participants who received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 1 in the main cohort entered the revaccination subcohort 1A and received IM injection of the protein mixture at the same dose level on Day 365. Participants were then followed up for safety assessments till Day 730.
Eligible participants who received IM injection of placebo on Day 1 in the main study cohort entered the revaccination subcohort and received Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 365. Participants were then followed up for safety assessments till Day 730.
Eligible participants who received IM injection of placebo on Day 1 in the main cohort followed by Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 365 in the revaccination subcohort further received Ad26.RSV.preF 1*10^11 vp alone as IM injection on Day 730. Participants were then followed up for safety assessments till Day 1095.
Eligible participants who received IM injection of placebo on Day 1 in the main cohort followed by Ad26.RSV.preF 1*10^11 vp and RSV preF protein (protein mixture) on Day 365 in the revaccination subcohort further received RSV preF protein 150 mcg alone as IM injection on Day 730. Participants were then followed up for safety assessments till Day 1095.
Eligible participants who received IM injection of placebo on Day 1 in the main study cohort entered the revaccination subcohort and received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 365 and 730. Participants were then followed up for safety assessments till Day 1095.
Eligible participants who received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 1 in the main cohort entered the revaccination subcohort and received the protein mixture at the same dose level on Day 1095. Participants were then followed up for safety assessments till Day 1460.
Eligible participants who received IM injection of placebo on Day 1 in the main cohort entered the revaccination subcohort and received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 1095. Participants were then followed up for safety assessments till Day 1460.
Overall Number of Participants Analyzed 117 120 26 28 27 127 114
Geometric Mean (95% Confidence Interval)
Unit of Measure: Titers
Day 15 Number Analyzed 111 participants 116 participants 26 participants 24 participants 27 participants 125 participants 112 participants
4091
(3540 to 4728)
301
(269 to 336)
258
(203 to 328)
282
(228 to 349)
391
(307 to 497)
4195
(3685 to 4776)
279
(238 to 326)
Day 365 Number Analyzed 117 participants 120 participants 25 participants 28 participants 27 participants 0 participants 0 participants
1003
(901 to 1117)
325
(293 to 361)
259
(200 to 335)
317
(259 to 388)
358
(291 to 440)
Day 379 Number Analyzed 90 participants 100 participants 23 participants 24 participants 20 participants 0 participants 0 participants
1688
(1487 to 1917)
4402
(3807 to 5089)
3642
(2582 to 5136)
4827
(3545 to 6572)
4290
(3069 to 5996)
Day 393 Number Analyzed 97 participants 99 participants 22 participants 20 participants 24 participants 0 participants 0 participants
1757
(1549 to 1994)
3793
(3265 to 4405)
3408
(2578 to 4505)
4341
(3072 to 6134)
3541
(2473 to 5070)
Day 449 Number Analyzed 109 participants 105 participants 22 participants 24 participants 26 participants 0 participants 0 participants
1534
(1376 to 1710)
2513
(2172 to 2908)
2227
(1671 to 2968)
2999
(2254 to 3991)
2129
(1509 to 3002)
Day 533 Number Analyzed 95 participants 99 participants 20 participants 24 participants 25 participants 0 participants 0 participants
1430
(1287 to 1590)
1818
(1585 to 2086)
1605
(1132 to 2275)
1835
(1429 to 2358)
1783
(1350 to 2355)
Day 730 Number Analyzed 0 participants 75 participants 24 participants 25 participants 25 participants 0 participants 0 participants
1270
(1112 to 1451)
992
(767 to 1283)
1467
(1182 to 1822)
1379
(1099 to 1732)
Day 737 Number Analyzed 0 participants 0 participants 21 participants 23 participants 22 participants 0 participants 0 participants
1138
(850 to 1524)
1779
(1510 to 2096)
1674
(1348 to 2077)
Day 744 Number Analyzed 0 participants 0 participants 19 participants 19 participants 21 participants 0 participants 0 participants
1352
(1111 to 1644)
2001
(1619 to 2473)
2181
(1714 to 2774)
Day 758 Number Analyzed 0 participants 0 participants 15 participants 16 participants 21 participants 0 participants 0 participants
1436
(1049 to 1964)
2331
(1786 to 3043)
2131
(1666 to 2726)
Day 1095 Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 127 participants 114 participants
825
(743 to 917)
317
(276 to 363)
Day 1109 Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 108 participants 96 participants
2152
(1923 to 2407)
3736
(3196 to 4367)
6.Secondary Outcome
Title Revaccination Subcohort 2A: T-cell Interferon (IFN) Gamma Responses to RSV F Protein Peptides Analyzed by Enzyme-linked Immunospot Assay (ELISpot)
Hide Description T-cell IFN gamma responses to RSV F protein specific peptides as measured by ELISpot assay were reported. RSV F protein specific T-cell IFN gamma ELISpot responses were measured as counts of spot forming cells per million peripheral blood mononuclear cells (SFC/10^6 PBMCs).
Time Frame Days 730, 744, 758
Hide Outcome Measure Data
Hide Analysis Population Description
PPI population included all randomized and vaccinated participants who were part of the immuno subset and for whom immunogenicity data were available. Here, 'N' (Overall number of participants analyzed) signifies participants who were evaluable for this outcome measure. Here, 'n' signifies participants evaluable for specified timepoints. This outcome measure was planned to be analyzed for specified arms only.
Arm/Group Title Arm 5: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein + Ad26.RSV.PreF Alone Arm 6: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein + RSV preF Protein Alone Arm 7: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein (Protein Mixture)
Hide Arm/Group Description:
Eligible participants who received IM injection of placebo on Day 1 in the main cohort followed by Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 365 in the revaccination subcohort further received Ad26.RSV.preF 1*10^11 vp alone as IM injection on Day 730. Participants were then followed up for safety assessments till Day 1095.
Eligible participants who received IM injection of placebo on Day 1 in the main cohort followed by Ad26.RSV.preF 1*10^11 vp and RSV preF protein (protein mixture) on Day 365 in the revaccination subcohort further received RSV preF protein 150 mcg alone as IM injection on Day 730. Participants were then followed up for safety assessments till Day 1095.
Eligible participants who received IM injection of placebo on Day 1 in the main study cohort entered the revaccination subcohort and received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 365 and 730. Participants were then followed up for safety assessments till Day 1095.
Overall Number of Participants Analyzed 12 24 16
Median (Full Range)
Unit of Measure: SFC/10^6 PBMCs
Day 730 Number Analyzed 12 participants 24 participants 16 participants
129
(34 to 320)
198
(34 to 1035)
168
(34 to 795)
Day 744 Number Analyzed 11 participants 18 participants 15 participants
402
(105 to 1420)
498
(130 to 2269)
405
(34 to 3104)
Day 758 Number Analyzed 8 participants 12 participants 12 participants
278
(84 to 443)
484
(196 to 1375)
277
(34 to 1253)
7.Secondary Outcome
Title Main Cohorts: T-cell Interferon (IFN) Gamma Responses to RSV F Protein Peptides Analyzed by Enzyme-linked Immunospot Assay (ELISpot)
Hide Description T-cell IFN gamma responses to RSV F protein specific peptides as measured by ELISpot assay were reported. RSV F protein specific T-cell IFN gamma ELISpot responses were measured as counts of spot forming cells per million peripheral blood mononuclear cells (SFC/10^6 PBMCs).
Time Frame Days 15, 85, 169, 365, 533
Hide Outcome Measure Data
Hide Analysis Population Description
PPI population included all randomized and vaccinated participants who were part of the immuno subset and for whom immunogenicity data were available. Here, 'N' (number of participants analyzed) signifies participants who were evaluable for this outcome measure. Here, 'n' signifies participants evaluable for specified timepoints.
Arm/Group Title Arm 1: Main Cohort: Group 1: Ad26.RSV.preF and RSV preF Protein (Protein Mixture) Arm 2: Main Cohort: Group 2: Placebo
Hide Arm/Group Description:
Adult participants aged greater than or equal to (>=) 65 years received a single intramuscular (IM) injection of adenovirus serotype 26 respiratory syncytial virus pre-fusion conformation stabilized F-protein (Ad26.RSV.preF) 1*10^11 viral particles (vp) and RSV preF protein 150 micrograms (mcg) (protein mixture) on Day 1. Participants were divided into revaccination subcohorts: 1A, 1B, and 1C. Participants further received revaccination with the Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) at 1 (Subcohort 1A), 2 (Subcohort 1B), and 3 (Subcohort 1C) years, respectively after the first vaccination on Day 1. Participants who were not re-vaccinated continued in the main cohort and were followed up for safety assessments until Day 1095.
Adult participants aged >=65 years received a single IM injection of placebo on Day 1. Participants were divided into revaccination subcohorts: 2A, 2B, and 2C. Participants further received revaccination with Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) at 1 (Subcohort 2A), 2 (Subcohort 2B), and 3 (Subcohort 2C) years, respectively after the first vaccination on Day 1. Participants in subcohorts 2A and 2B were additionally re-randomised in three groups at Year 3 and Year 4, respectively, to receive either Ad26.RSV.preF 1*10^11 vp alone, RSV preF protein 150 mcg alone or the Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture). Participants who were not re-vaccinated continued in the main cohort and were followed up for safety assessments until Day 1095.
Overall Number of Participants Analyzed 91 87
Median (Full Range)
Unit of Measure: SFC/10^6 PBMCs
Day 15 Number Analyzed 76 participants 76 participants
444
(279 to 641)
34
(34 to 34)
Day 85 Number Analyzed 90 participants 87 participants
274
(173 to 471)
34
(34 to 34)
Day 169 Number Analyzed 91 participants 87 participants
201
(123 to 324)
34
(34 to 34)
Day 365 Number Analyzed 75 participants 66 participants
182
(110 to 297)
34
(34 to 34)
Day 533 Number Analyzed 59 participants 56 participants
143
(96 to 238)
34
(34 to 74)
8.Secondary Outcome
Title Main Cohorts: Number of Participants With Solicited Local Adverse Events (AEs) up to 7 Days After First Vaccination
Hide Description An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Solicited local AEs were precisely defined events that participants were specifically asked about and which were noted by participants in the diary. Solicited local AEs included erythema, swelling/induration, and pain/tenderness. Per protocol, all solicited local AEs were considered as related to intervention.
Time Frame Up to Day 8 (7 days after first vaccination on Day 1)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety subset included all participants that consented to the collection of AEs (solicited AEs for up to 7 days after vaccination and unsolicited AEs for 28 days after vaccination). Here, 'N' (number of participants analyzed) signifies participants who were evaluable for this outcome measure.
Arm/Group Title Arm 1: Main Cohort: Group 1: Ad26.RSV.preF and RSV preF Protein (Protein Mixture) Arm 2: Main Cohort: Group 2: Placebo
Hide Arm/Group Description:
Adult participants aged greater than or equal to (>=) 65 years received a single intramuscular (IM) injection of adenovirus serotype 26 respiratory syncytial virus pre-fusion conformation stabilized F-protein (Ad26.RSV.preF) 1*10^11 viral particles (vp) and RSV preF protein 150 micrograms (mcg) (protein mixture) on Day 1. Participants were divided into revaccination subcohorts: 1A, 1B, and 1C. Participants further received revaccination with the Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) at 1 (Subcohort 1A), 2 (Subcohort 1B), and 3 (Subcohort 1C) years, respectively after the first vaccination on Day 1. Participants who were not re-vaccinated continued in the main cohort and were followed up for safety assessments until Day 1095.
Adult participants aged >=65 years received a single IM injection of placebo on Day 1. Participants were divided into revaccination subcohorts: 2A, 2B, and 2C. Participants further received revaccination with Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) at 1 (Subcohort 2A), 2 (Subcohort 2B), and 3 (Subcohort 2C) years, respectively after the first vaccination on Day 1. Participants in subcohorts 2A and 2B were additionally re-randomised in three groups at Year 3 and Year 4, respectively, to receive either Ad26.RSV.preF 1*10^11 vp alone, RSV preF protein 150 mcg alone or the Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture). Participants who were not re-vaccinated continued in the main cohort and were followed up for safety assessments until Day 1095.
Overall Number of Participants Analyzed 341 334
Measure Type: Count of Participants
Unit of Measure: Participants
132
  38.7%
29
   8.7%
9.Secondary Outcome
Title Main Cohorts: Number of Participants With Solicited Systemic AEs up to 7 Days After First Vaccination
Hide Description An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Solicited systemic AEs included fatigue, headache, myalgia, arthralgia, and fever (defined as an endogenous elevation of body temperature >=38.0°C, as recorded in at least one measurement).
Time Frame Up to Day 8 (7 days after first vaccination on Day 1)
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Hide Analysis Population Description
The safety subset included all participants that consented to the collection of AEs (solicited AEs for up to 7 days after vaccination and unsolicited AEs for 28 days after vaccination). Here, 'N' (number of participants analyzed) signifies participants who were evaluable for this outcome measure.
Arm/Group Title Arm 1: Main Cohort: Group 1: Ad26.RSV.preF and RSV preF Protein (Protein Mixture) Arm 2: Main Cohort: Group 2: Placebo
Hide Arm/Group Description:
Adult participants aged greater than or equal to (>=) 65 years received a single intramuscular (IM) injection of adenovirus serotype 26 respiratory syncytial virus pre-fusion conformation stabilized F-protein (Ad26.RSV.preF) 1*10^11 viral particles (vp) and RSV preF protein 150 micrograms (mcg) (protein mixture) on Day 1. Participants were divided into revaccination subcohorts: 1A, 1B, and 1C. Participants further received revaccination with the Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) at 1 (Subcohort 1A), 2 (Subcohort 1B), and 3 (Subcohort 1C) years, respectively after the first vaccination on Day 1. Participants who were not re-vaccinated continued in the main cohort and were followed up for safety assessments until Day 1095.
Adult participants aged >=65 years received a single IM injection of placebo on Day 1. Participants were divided into revaccination subcohorts: 2A, 2B, and 2C. Participants further received revaccination with Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) at 1 (Subcohort 2A), 2 (Subcohort 2B), and 3 (Subcohort 2C) years, respectively after the first vaccination on Day 1. Participants in subcohorts 2A and 2B were additionally re-randomised in three groups at Year 3 and Year 4, respectively, to receive either Ad26.RSV.preF 1*10^11 vp alone, RSV preF protein 150 mcg alone or the Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture). Participants who were not re-vaccinated continued in the main cohort and were followed up for safety assessments until Day 1095.
Overall Number of Participants Analyzed 341 334
Measure Type: Count of Participants
Unit of Measure: Participants
143
  41.9%
58
  17.4%
10.Secondary Outcome
Title Main Cohorts: Number of Participants With Unsolicited AEs up to 28 Days After First Vaccination
Hide Description An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Unsolicited adverse events included all adverse events for which the participant is not specifically questioned in the participant diary.
Time Frame Up to Day 29 (28 days after first vaccination on Day 1)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety subset included all participants that consented to the collection of AEs (solicited AEs for up to 7 days after vaccination and unsolicited AEs for 28 days after vaccination).
Arm/Group Title Arm 1: Main Cohort: Group 1: Ad26.RSV.preF and RSV preF Protein (Protein Mixture) Arm 2: Main Cohort: Group 2: Placebo
Hide Arm/Group Description:
Adult participants aged greater than or equal to (>=) 65 years received a single intramuscular (IM) injection of adenovirus serotype 26 respiratory syncytial virus pre-fusion conformation stabilized F-protein (Ad26.RSV.preF) 1*10^11 viral particles (vp) and RSV preF protein 150 micrograms (mcg) (protein mixture) on Day 1. Participants were divided into revaccination subcohorts: 1A, 1B, and 1C. Participants further received revaccination with the Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) at 1 (Subcohort 1A), 2 (Subcohort 1B), and 3 (Subcohort 1C) years, respectively after the first vaccination on Day 1. Participants who were not re-vaccinated continued in the main cohort and were followed up for safety assessments until Day 1095.
Adult participants aged >=65 years received a single IM injection of placebo on Day 1. Participants were divided into revaccination subcohorts: 2A, 2B, and 2C. Participants further received revaccination with Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) at 1 (Subcohort 2A), 2 (Subcohort 2B), and 3 (Subcohort 2C) years, respectively after the first vaccination on Day 1. Participants in subcohorts 2A and 2B were additionally re-randomised in three groups at Year 3 and Year 4, respectively, to receive either Ad26.RSV.preF 1*10^11 vp alone, RSV preF protein 150 mcg alone or the Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture). Participants who were not re-vaccinated continued in the main cohort and were followed up for safety assessments until Day 1095.
Overall Number of Participants Analyzed 348 347
Measure Type: Count of Participants
Unit of Measure: Participants
58
  16.7%
50
  14.4%
11.Secondary Outcome
Title Revaccination Subcohorts: Number of Participants With Solicited Local AEs 7 Days After Re-vaccination up to 1, 2 and 3 Years
Hide Description Number of participants with solicited local AEs 7 days after re-vaccination at 1, 2 and 3 years were reported. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Solicited local AEs were precisely defined events that participants were specifically asked about and which were noted by participants in the diary. Solicited local AEs included erythema, swelling/induration, and pain/tenderness. Per protocol, all solicited local AEs were considered as related to intervention.
Time Frame Arms 3,4: 7 days after revacc at 1 year (up to Day 372); Arm 5,6,7,8,9: 7 days after revacc at 2 years (up to Day 737); Arms 10,11,12,13,14: 7 days after revacc at 3 year (up to Day 1102)
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Hide Analysis Population Description
The Full Analysis Set (FAS) included all randomized participants with a documented vaccine administration, regardless of the occurrence of protocol deviations. Here, 'N' (number of participants analyzed) signifies participants who were evaluable for this outcome measure.
Arm/Group Title Arm 3: Revaccination (ReVacc) Subcohort 1A: Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 4: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein Mixture Arm 5: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein + Ad26.RSV.PreF Alone Arm 6: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein + RSV preF Protein Alone Arm 7: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 8: ReVacc Subcohort 1B: Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 9: ReVacc Subcohort 2B:Placebo to Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 10: ReVacc Subcohort 2B: Placebo to Ad26.RSV.preF/RSV preF Protein + Ad26.RSV.preF Arm 11: ReVacc Subcohort 2B: Placebo to Ad26.RSV.preF/RSV preF Protein + RSV preF Protein Alone Arm 12: ReVacc Subcohort 2B: Placebo to Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 13: ReVacc Subcohort 1C: Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 14: ReVacc Subcohort 2C: Placebo to Ad26.RSV.preF/RSV preF Protein (Protein Mixture)
Hide Arm/Group Description:
Eligible participants who received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 1 in the main cohort entered the revaccination subcohort 1A and received IM injection of the protein mixture at the same dose level on Day 365. Participants were then followed up for safety assessments till Day 730.
Eligible participants who received IM injection of placebo on Day 1 in the main study cohort entered the revaccination subcohort and received Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 365. Participants were then followed up for safety assessments till Day 730.
Eligible participants who received IM injection of placebo on Day 1 in the main cohort followed by Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 365 in the revaccination subcohort further received Ad26.RSV.preF 1*10^11 vp alone as IM injection on Day 730. Participants were then followed up for safety assessments till Day 1095.
Eligible participants who received IM injection of placebo on Day 1 in the main cohort followed by Ad26.RSV.preF 1*10^11 vp and RSV preF protein (protein mixture) on Day 365 in the revaccination subcohort further received RSV preF protein 150 mcg alone as IM injection on Day 730. Participants were then followed up for safety assessments till Day 1095.
Eligible participants who received IM injection of placebo on Day 1 in the main study cohort entered the revaccination subcohort and received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 365 and 730. Participants were then followed up for safety assessments till Day 1095.
Eligible participants who received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 1 in the main cohort entered the revaccination subcohort and received the protein mixture at the same dose level on Day 730. Participants were then followed up for safety assessments till Day 1095.
Eligible participants who received IM injection of placebo on Day 1 in the main cohort entered the revaccination subcohort and received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 730. Participants were then followed up for safety assessments till Day 1095.
Eligible participants who received IM injection of placebo on Day 1 in the main cohort entered the revaccination subcohort and received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 730 followed by Ad26.RSV.preF 1*10^11 vp alone on Day 1095. Participants were then followed up for safety assessments till Day 1460.
Eligible participants who received IM injection of placebo on Day 1 in the main cohort entered the revaccination subcohort and received IM injection Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 730 followed by RSV preF protein 150 mcg alone on Day 1095. Participants were then followed up for safety assessments till Day 1460.
Eligible participants who received IM injection of placebo on Day 1 in the main cohort entered the revaccination subcohort and received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Days 730 and Day 1095. Participants were then followed up for safety assessments till Day 1460.
Eligible participants who received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 1 in the main cohort entered the revaccination subcohort and received the protein mixture at the same dose level on Day 1095. Participants were then followed up for safety assessments till Day 1460.
Eligible participants who received IM injection of placebo on Day 1 in the main cohort entered the revaccination subcohort and received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 1095. Participants were then followed up for safety assessments till Day 1460.
Overall Number of Participants Analyzed 119 126 28 27 28 137 149 37 36 37 131 118
Measure Type: Count of Participants
Unit of Measure: Participants
37
  31.1%
31
  24.6%
9
  32.1%
18
  66.7%
12
  42.9%
97
  70.8%
81
  54.4%
26
  70.3%
17
  47.2%
29
  78.4%
93
  71.0%
64
  54.2%
12.Secondary Outcome
Title Revaccination Subcohorts: Number of Participants With Solicited Systemic AEs 7 Days After Re-vaccination up to 1, 2 and 3 Years
Hide Description Number of participants with solicited systemic AEs 7 days after re-vaccination up to 1, 2 and 3 years were reported. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Solicited systemic AEs included fatigue, headache, myalgia, arthralgia, and fever (defined as an endogenous elevation of body temperature >=38.0°C, as recorded in at least one measurement).
Time Frame Arms 3,4: 7 days after revacc at 1 year (up to Day 372); Arm 5,6,7,8,9: 7 days after revacc at 2 years (up to Day 737); Arms 10,11,12,13,14: 7 days after revacc at 3 year (up to Day 1102)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized participants with a documented vaccine administration, regardless of the occurrence of protocol deviations. Here, 'N' (number of participants analyzed) signifies participants who were evaluable for this outcome measure.
Arm/Group Title Arm 3: Revaccination (ReVacc) Subcohort 1A: Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 4: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein Mixture Arm 5: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein + Ad26.RSV.PreF Alone Arm 6: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein + RSV preF Protein Alone Arm 7: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 8: ReVacc Subcohort 1B: Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 9: ReVacc Subcohort 2B:Placebo to Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 10: ReVacc Subcohort 2B: Placebo to Ad26.RSV.preF/RSV preF Protein + Ad26.RSV.preF Arm 11: ReVacc Subcohort 2B: Placebo to Ad26.RSV.preF/RSV preF Protein + RSV preF Protein Alone Arm 12: ReVacc Subcohort 2B: Placebo to Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 13: ReVacc Subcohort 1C: Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 14: ReVacc Subcohort 2C: Placebo to Ad26.RSV.preF/RSV preF Protein (Protein Mixture)
Hide Arm/Group Description:
Eligible participants who received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 1 in the main cohort entered the revaccination subcohort 1A and received IM injection of the protein mixture at the same dose level on Day 365. Participants were then followed up for safety assessments till Day 730.
Eligible participants who received IM injection of placebo on Day 1 in the main study cohort entered the revaccination subcohort and received Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 365. Participants were then followed up for safety assessments till Day 730.
Eligible participants who received IM injection of placebo on Day 1 in the main cohort followed by Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 365 in the revaccination subcohort further received Ad26.RSV.preF 1*10^11 vp alone as IM injection on Day 730. Participants were then followed up for safety assessments till Day 1095.
Eligible participants who received IM injection of placebo on Day 1 in the main cohort followed by Ad26.RSV.preF 1*10^11 vp and RSV preF protein (protein mixture) on Day 365 in the revaccination subcohort further received RSV preF protein 150 mcg alone as IM injection on Day 730. Participants were then followed up for safety assessments till Day 1095.
Eligible participants who received IM injection of placebo on Day 1 in the main study cohort entered the revaccination subcohort and received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 365 and 730. Participants were then followed up for safety assessments till Day 1095.
Eligible participants who received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 1 in the main cohort entered the revaccination subcohort and received the protein mixture at the same dose level on Day 730. Participants were then followed up for safety assessments till Day 1095.
Eligible participants who received IM injection of placebo on Day 1 in the main cohort entered the revaccination subcohort and received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 730. Participants were then followed up for safety assessments till Day 1095.
Eligible participants who received IM injection of placebo on Day 1 in the main cohort entered the revaccination subcohort and received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 730 followed by Ad26.RSV.preF 1*10^11 vp alone on Day 1095. Participants were then followed up for safety assessments till Day 1460.
Eligible participants who received IM injection of placebo on Day 1 in the main cohort entered the revaccination subcohort and received IM injection Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 730 followed by RSV preF protein 150 mcg alone on Day 1095. Participants were then followed up for safety assessments till Day 1460.
Eligible participants who received IM injection of placebo on Day 1 in the main cohort entered the revaccination subcohort and received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Days 730 and Day 1095. Participants were then followed up for safety assessments till Day 1460.
Eligible participants who received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 1 in the main cohort entered the revaccination subcohort and received the protein mixture at the same dose level on Day 1095. Participants were then followed up for safety assessments till Day 1460.
Eligible participants who received IM injection of placebo on Day 1 in the main cohort entered the revaccination subcohort and received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 1095. Participants were then followed up for safety assessments till Day 1460.
Overall Number of Participants Analyzed 119 126 28 27 28 137 149 37 36 37 131 118
Measure Type: Count of Participants
Unit of Measure: Participants
35
  29.4%
36
  28.6%
7
  25.0%
15
  55.6%
10
  35.7%
79
  57.7%
85
  57.0%
16
  43.2%
12
  33.3%
25
  67.6%
80
  61.1%
70
  59.3%
13.Secondary Outcome
Title Revaccination Subcohorts: Number of Participants With Unsolicited AEs 28 Days After Re-vaccination up to 1, 2 and 3 Years
Hide Description An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Unsolicited adverse events included all adverse events for which the participant is not specifically questioned in the participant diary.
Time Frame Arms 3,4: 28 days after revacc at 1 year (up to Day 393); Arms 5,6,7,8,9: 28 days after revacc at 2 years (up to Day 758); Arms 10,11,12,13,14: 28 days after revaccination at 3 year (up to Day 1123)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized participants with a documented vaccine administration, regardless of the occurrence of protocol deviations.
Arm/Group Title Arm 3: Revaccination (ReVacc) Subcohort 1A: Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 4: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein Mixture Arm 5: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein + Ad26.RSV.PreF Alone Arm 6: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein + RSV preF Protein Alone Arm 7: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 8: ReVacc Subcohort 1B: Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 9: ReVacc Subcohort 2B:Placebo to Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 10: ReVacc Subcohort 2B: Placebo to Ad26.RSV.preF/RSV preF Protein + Ad26.RSV.preF Arm 11: ReVacc Subcohort 2B: Placebo to Ad26.RSV.preF/RSV preF Protein + RSV preF Protein Alone Arm 12: ReVacc Subcohort 2B: Placebo to Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 13: ReVacc Subcohort 1C: Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 14: ReVacc Subcohort 2C: Placebo to Ad26.RSV.preF/RSV preF Protein (Protein Mixture)
Hide Arm/Group Description:
Eligible participants who received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 1 in the main cohort entered the revaccination subcohort 1A and received IM injection of the protein mixture at the same dose level on Day 365. Participants were then followed up for safety assessments till Day 730.
Eligible participants who received IM injection of placebo on Day 1 in the main study cohort entered the revaccination subcohort and received Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 365. Participants were then followed up for safety assessments till Day 730.
Eligible participants who received IM injection of placebo on Day 1 in the main cohort followed by Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 365 in the revaccination subcohort further received Ad26.RSV.preF 1*10^11 vp alone as IM injection on Day 730. Participants were then followed up for safety assessments till Day 1095.
Eligible participants who received IM injection of placebo on Day 1 in the main cohort followed by Ad26.RSV.preF 1*10^11 vp and RSV preF protein (protein mixture) on Day 365 in the revaccination subcohort further received RSV preF protein 150 mcg alone as IM injection on Day 730. Participants were then followed up for safety assessments till Day 1095.
Eligible participants who received IM injection of placebo on Day 1 in the main study cohort entered the revaccination subcohort and received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 365 and 730. Participants were then followed up for safety assessments till Day 1095.
Eligible participants who received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 1 in the main cohort entered the revaccination subcohort and received the protein mixture at the same dose level on Day 730. Participants were then followed up for safety assessments till Day 1095.
Eligible participants who received IM injection of placebo on Day 1 in the main cohort entered the revaccination subcohort and received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 730. Participants were then followed up for safety assessments till Day 1095.
Eligible participants who received IM injection of placebo on Day 1 in the main cohort entered the revaccination subcohort and received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 730 followed by Ad26.RSV.preF 1*10^11 vp alone on Day 1095. Participants were then followed up for safety assessments till Day 1460.
Eligible participants who received IM injection of placebo on Day 1 in the main cohort entered the revaccination subcohort and received IM injection Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 730 followed by RSV preF protein 150 mcg alone on Day 1095. Participants were then followed up for safety assessments till Day 1460.
Eligible participants who received IM injection of placebo on Day 1 in the main cohort entered the revaccination subcohort and received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Days 730 and Day 1095. Participants were then followed up for safety assessments till Day 1460.
Eligible participants who received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 1 in the main cohort entered the revaccination subcohort and received the protein mixture at the same dose level on Day 1095. Participants were then followed up for safety assessments till Day 1460.
Eligible participants who received IM injection of placebo on Day 1 in the main cohort entered the revaccination subcohort and received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 1095. Participants were then followed up for safety assessments till Day 1460.
Overall Number of Participants Analyzed 120 126 28 28 28 137 149 37 37 37 131 119
Measure Type: Count of Participants
Unit of Measure: Participants
6
   5.0%
10
   7.9%
4
  14.3%
5
  17.9%
8
  28.6%
12
   8.8%
16
  10.7%
4
  10.8%
3
   8.1%
4
  10.8%
11
   8.4%
10
   8.4%
14.Secondary Outcome
Title Revaccination Subcohorts: Number of Participants With Adverse Events of Special Interests (AESI)
Hide Description Number of participants with AESIs were reported. An AE was any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Thrombosis with thrombocytopenia syndrome (TTS) was considered as an AESI.
Time Frame Arms 3,4: 6 months after revacc at 1 year (up to Day 547); Arm 5,6,7,8,9: 6 months after revacc at 2 years (up to Day 912); Arms 10,11,12,13,14: 6 months after revacc at 3 year (up to Day 1277)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized participants with a documented vaccine administration, regardless of the occurrence of protocol deviations.
Arm/Group Title Arm 3: Revaccination (ReVacc) Subcohort 1A: Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 4: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein Mixture Arm 5: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein + Ad26.RSV.PreF Alone Arm 6: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein + RSV preF Protein Alone Arm 7: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 8: ReVacc Subcohort 1B: Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 9: ReVacc Subcohort 2B:Placebo to Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 10: ReVacc Subcohort 2B: Placebo to Ad26.RSV.preF/RSV preF Protein + Ad26.RSV.preF Arm 11: ReVacc Subcohort 2B: Placebo to Ad26.RSV.preF/RSV preF Protein + RSV preF Protein Alone Arm 12: ReVacc Subcohort 2B: Placebo to Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 13: ReVacc Subcohort 1C: Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 14: ReVacc Subcohort 2C: Placebo to Ad26.RSV.preF/RSV preF Protein (Protein Mixture)
Hide Arm/Group Description:
Eligible participants who received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 1 in the main cohort entered the revaccination subcohort 1A and received IM injection of the protein mixture at the same dose level on Day 365. Participants were then followed up for safety assessments till Day 730.
Eligible participants who received IM injection of placebo on Day 1 in the main study cohort entered the revaccination subcohort and received Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 365. Participants were then followed up for safety assessments till Day 730.
Eligible participants who received IM injection of placebo on Day 1 in the main cohort followed by Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 365 in the revaccination subcohort further received Ad26.RSV.preF 1*10^11 vp alone as IM injection on Day 730. Participants were then followed up for safety assessments till Day 1095.
Eligible participants who received IM injection of placebo on Day 1 in the main cohort followed by Ad26.RSV.preF 1*10^11 vp and RSV preF protein (protein mixture) on Day 365 in the revaccination subcohort further received RSV preF protein 150 mcg alone as IM injection on Day 730. Participants were then followed up for safety assessments till Day 1095.
Eligible participants who received IM injection of placebo on Day 1 in the main study cohort entered the revaccination subcohort and received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 365 and 730. Participants were then followed up for safety assessments till Day 1095.
Eligible participants who received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 1 in the main cohort entered the revaccination subcohort and received the protein mixture at the same dose level on Day 730. Participants were then followed up for safety assessments till Day 1095.
Eligible participants who received IM injection of placebo on Day 1 in the main cohort entered the revaccination subcohort and received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 730. Participants were then followed up for safety assessments till Day 1095.
Eligible participants who received IM injection of placebo on Day 1 in the main cohort entered the revaccination subcohort and received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 730 followed by Ad26.RSV.preF 1*10^11 vp alone on Day 1095. Participants were then followed up for safety assessments till Day 1460.
Eligible participants who received IM injection of placebo on Day 1 in the main cohort entered the revaccination subcohort and received IM injection Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 730 followed by RSV preF protein 150 mcg alone on Day 1095. Participants were then followed up for safety assessments till Day 1460.
Eligible participants who received IM injection of placebo on Day 1 in the main cohort entered the revaccination subcohort and received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Days 730 and Day 1095. Participants were then followed up for safety assessments till Day 1460.
Eligible participants who received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 1 in the main cohort entered the revaccination subcohort and received the protein mixture at the same dose level on Day 1095. Participants were then followed up for safety assessments till Day 1460.
Eligible participants who received IM injection of placebo on Day 1 in the main cohort entered the revaccination subcohort and received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 1095. Participants were then followed up for safety assessments till Day 1460.
Overall Number of Participants Analyzed 120 126 28 28 28 137 149 37 37 37 131 119
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
15.Secondary Outcome
Title Main Cohorts:Number of Participants With Serious Adverse Events (SAEs)
Hide Description An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect; suspected transmission of any infectious agent via a medicinal product or medically important. For participants who were not revaccinated only SAEs associated with ARIs and complications related to ARIs that classify as SAEs, SAEs classified as related, SAEs resulting in death, and (S)AEs resulting in study discontinuation or from procedures and non-investigational (concomitant) Janssen products were collected.
Time Frame From Day 1 up to Day 1095
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized participants with a documented vaccine administration, regardless of the occurrence of protocol deviations.
Arm/Group Title Arm 1: Main Cohort: Group 1: Ad26.RSV.preF and RSV preF Protein (Protein Mixture) Arm 2: Main Cohort: Group 2: Placebo
Hide Arm/Group Description:
Adult participants aged greater than or equal to (>=) 65 years received a single intramuscular (IM) injection of adenovirus serotype 26 respiratory syncytial virus pre-fusion conformation stabilized F-protein (Ad26.RSV.preF) 1*10^11 viral particles (vp) and RSV preF protein 150 micrograms (mcg) (protein mixture) on Day 1. Participants were divided into revaccination subcohorts: 1A, 1B, and 1C. Participants further received revaccination with the Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) at 1 (Subcohort 1A), 2 (Subcohort 1B), and 3 (Subcohort 1C) years, respectively after the first vaccination on Day 1. Participants who were not re-vaccinated continued in the main cohort and were followed up for safety assessments until Day 1095.
Adult participants aged >=65 years received a single IM injection of placebo on Day 1. Participants were divided into revaccination subcohorts: 2A, 2B, and 2C. Participants further received revaccination with Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) at 1 (Subcohort 2A), 2 (Subcohort 2B), and 3 (Subcohort 2C) years, respectively after the first vaccination on Day 1. Participants in subcohorts 2A and 2B were additionally re-randomised in three groups at Year 3 and Year 4, respectively, to receive either Ad26.RSV.preF 1*10^11 vp alone, RSV preF protein 150 mcg alone or the Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture). Participants who were not re-vaccinated continued in the main cohort and were followed up for safety assessments until Day 1095.
Overall Number of Participants Analyzed 2891 2891
Measure Type: Count of Participants
Unit of Measure: Participants
203
   7.0%
196
   6.8%
16.Secondary Outcome
Title Revaccination Subcohorts: Number of Participants With Serious Adverse Events (SAEs)
Hide Description An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect; suspected transmission of any infectious agent via a medicinal product or medically important.
Time Frame Arms 3,4: 6 months after revacc at 1 year (up to Day 547); Arm 5,6,7,8,9: 6 months after revacc at 2 years (up to Day 912); Arms 10,11,12,13,14: 6 months after revacc at 3 year (up to Day 1277)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized participants with a documented vaccine administration, regardless of the occurrence of protocol deviations.
Arm/Group Title Arm 3: Revaccination (ReVacc) Subcohort 1A: Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 4: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein Mixture Arm 5: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein + Ad26.RSV.PreF Alone Arm 6: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein + RSV preF Protein Alone Arm 7: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 8: ReVacc Subcohort 1B: Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 9: ReVacc Subcohort 2B:Placebo to Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 10: ReVacc Subcohort 2B: Placebo to Ad26.RSV.preF/RSV preF Protein + Ad26.RSV.preF Arm 11: ReVacc Subcohort 2B: Placebo to Ad26.RSV.preF/RSV preF Protein + RSV preF Protein Alone Arm 12: ReVacc Subcohort 2B: Placebo to Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 13: ReVacc Subcohort 1C: Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 14: ReVacc Subcohort 2C: Placebo to Ad26.RSV.preF/RSV preF Protein (Protein Mixture)
Hide Arm/Group Description:
Eligible participants who received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 1 in the main cohort entered the revaccination subcohort 1A and received IM injection of the protein mixture at the same dose level on Day 365. Participants were then followed up for safety assessments till Day 730.
Eligible participants who received IM injection of placebo on Day 1 in the main study cohort entered the revaccination subcohort and received Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 365. Participants were then followed up for safety assessments till Day 730.
Eligible participants who received IM injection of placebo on Day 1 in the main cohort followed by Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 365 in the revaccination subcohort further received Ad26.RSV.preF 1*10^11 vp alone as IM injection on Day 730. Participants were then followed up for safety assessments till Day 1095.
Eligible participants who received IM injection of placebo on Day 1 in the main cohort followed by Ad26.RSV.preF 1*10^11 vp and RSV preF protein (protein mixture) on Day 365 in the revaccination subcohort further received RSV preF protein 150 mcg alone as IM injection on Day 730. Participants were then followed up for safety assessments till Day 1095.
Eligible participants who received IM injection of placebo on Day 1 in the main study cohort entered the revaccination subcohort and received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 365 and 730. Participants were then followed up for safety assessments till Day 1095.
Eligible participants who received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 1 in the main cohort entered the revaccination subcohort and received the protein mixture at the same dose level on Day 730. Participants were then followed up for safety assessments till Day 1095.
Eligible participants who received IM injection of placebo on Day 1 in the main cohort entered the revaccination subcohort and received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 730. Participants were then followed up for safety assessments till Day 1095.
Eligible participants who received IM injection of placebo on Day 1 in the main cohort entered the revaccination subcohort and received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 730 followed by Ad26.RSV.preF 1*10^11 vp alone on Day 1095. Participants were then followed up for safety assessments till Day 1460.
Eligible participants who received IM injection of placebo on Day 1 in the main cohort entered the revaccination subcohort and received IM injection Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 730 followed by RSV preF protein 150 mcg alone on Day 1095. Participants were then followed up for safety assessments till Day 1460.
Eligible participants who received IM injection of placebo on Day 1 in the main cohort entered the revaccination subcohort and received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Days 730 and Day 1095. Participants were then followed up for safety assessments till Day 1460.
Eligible participants who received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 1 in the main cohort entered the revaccination subcohort and received the protein mixture at the same dose level on Day 1095. Participants were then followed up for safety assessments till Day 1460.
Eligible participants who received IM injection of placebo on Day 1 in the main cohort entered the revaccination subcohort and received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 1095. Participants were then followed up for safety assessments till Day 1460.
Overall Number of Participants Analyzed 120 126 28 28 28 137 149 37 37 37 131 119
Measure Type: Count of Participants
Unit of Measure: Participants
2
   1.7%
6
   4.8%
0
   0.0%
3
  10.7%
1
   3.6%
4
   2.9%
6
   4.0%
2
   5.4%
0
   0.0%
0
   0.0%
2
   1.5%
2
   1.7%
17.Secondary Outcome
Title Main Cohorts: Geometric Mean Titers (GMTs) of Prefusion F-protein (Pre-F) A Antibodies as Assessed by Enzyme-linked Immunosorbent Assay (ELISA)
Hide Description GMTs of preF-A antibodies after the administration of Ad26.RSV.preF-based vaccine as assessed by ELISA were reported.
Time Frame Days 15, 85, 169, 365, 533
Hide Outcome Measure Data
Hide Analysis Population Description
PPI: all randomized and vaccinated participants who were part of immunogenicity subset and for whom immunogenicity data were available. Here, 'N' (Overall number of participants analyzed)=participants who were evaluable for this outcome measure, "n"=participants evaluable for specific timepoints.
Arm/Group Title Arm 1: Main Cohort: Group 1: Ad26.RSV.preF and RSV preF Protein (Protein Mixture) Arm 2: Main Cohort: Group 2: Placebo
Hide Arm/Group Description:
Adult participants aged greater than or equal to (>=) 65 years received a single intramuscular (IM) injection of adenovirus serotype 26 respiratory syncytial virus pre-fusion conformation stabilized F-protein (Ad26.RSV.preF) 1*10^11 viral particles (vp) and RSV preF protein 150 micrograms (mcg) (protein mixture) on Day 1. Participants were divided into revaccination subcohorts: 1A, 1B, and 1C. Participants further received revaccination with the Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) at 1 (Subcohort 1A), 2 (Subcohort 1B), and 3 (Subcohort 1C) years, respectively after the first vaccination on Day 1. Participants who were not re-vaccinated continued in the main cohort and were followed up for safety assessments until Day 1095.
Adult participants aged >=65 years received a single IM injection of placebo on Day 1. Participants were divided into revaccination subcohorts: 2A, 2B, and 2C. Participants further received revaccination with Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) at 1 (Subcohort 2A), 2 (Subcohort 2B), and 3 (Subcohort 2C) years, respectively after the first vaccination on Day 1. Participants in subcohorts 2A and 2B were additionally re-randomised in three groups at Year 3 and Year 4, respectively, to receive either Ad26.RSV.preF 1*10^11 vp alone, RSV preF protein 150 mcg alone or the Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture). Participants who were not re-vaccinated continued in the main cohort and were followed up for safety assessments until Day 1095.
Overall Number of Participants Analyzed 95 96
Geometric Mean (95% Confidence Interval)
Unit of Measure: Titers
Day 15 Number Analyzed 95 participants 91 participants
4001
(3354 to 4772)
305
(256 to 364)
Day 85 Number Analyzed 94 participants 96 participants
2475
(2129 to 2876)
359
(302 to 426)
Day 169 Number Analyzed 94 participants 93 participants
1604
(1381 to 1863)
335
(293 to 383)
Day 365 Number Analyzed 81 participants 72 participants
1044
(908 to 1201)
281
(237 to 334)
Day 533 Number Analyzed 70 participants 63 participants
991
(863 to 1137)
315
(267 to 371)
Time Frame All-cause mortality: Day 1 to Day 1095 (Arms 1, 2); Day 365 to Day 730 (Arms 3, 4); Day 730 to Day 1095 (Arms 5 to 9); Day 1095 to Day 1460 (Arms 10 to 14); Serious/other AEs: Day 1 to Day 1095 (Arms 1, 2), 6 months after revacc at Day 365 (Arms 3, 4): up to Day 547, 6 months after revacc at Day 730 (Arms 5 to 9): up to Day 912, 6 months after revacc at Day 1095 (Arms 10 to 14): up to Day 1277
Adverse Event Reporting Description All-cause mortality and SAEs analyzed based on FAS population which included all randomized participants with a documented vaccine administration, regardless of occurrence of protocol deviations. Other (not including serious) AEs as solicited and unsolicited AEs were collected and analyzed in safety subset (subset of FAS) for main cohorts and in FAS for revaccination subcohorts. The safety subset included all participants that consented to the collection of AEs (solicited and unsolicited AEs).
 
Arm/Group Title Arm 1: Main Cohort: Group 1: Ad26.RSV.preF and RSV preF Protein (Protein Mixture) Arm 2: Main Cohort: Group 2: Placebo Arm 3: Revaccination (ReVacc) Subcohort 1A: Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 4: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein Mixture Arm 5: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein + Ad26.RSV.PreF Alone Arm 6: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein + RSV preF Protein Alone Arm 7: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 8: ReVacc Subcohort 1B: Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 9: ReVacc Subcohort 2B:Placebo to Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 10: ReVacc Subcohort 2B: Placebo to Ad26.RSV.preF/RSV preF Protein + Ad26.RSV.preF Arm 11: ReVacc Subcohort 2B: Placebo to Ad26.RSV.preF/RSV preF Protein + RSV preF Protein Alone Arm 12: ReVacc Subcohort 2B: Placebo to Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 13: ReVacc Subcohort 1C: Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 14: ReVacc Subcohort 2C: Placebo to Ad26.RSV.preF/RSV preF Protein (Protein Mixture)
Hide Arm/Group Description Adult participants aged greater than or equal to (>=) 65 years received a single intramuscular (IM) injection of adenovirus serotype 26 respiratory syncytial virus pre-fusion conformation stabilized F-protein (Ad26.RSV.preF) 1*10^11 viral particles (vp) and RSV preF protein 150 micrograms (mcg) (protein mixture) on Day 1. Participants were divided into revaccination subcohorts: 1A, 1B, and 1C. Participants further received revaccination with the Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) at 1 (Subcohort 1A), 2 (Subcohort 1B), and 3 (Subcohort 1C) years, respectively after the first vaccination on Day 1. Participants who were not re-vaccinated continued in the main cohort and were followed up for safety assessments until Day 1095. Adult participants aged >=65 years received a single IM injection of placebo on Day 1. Participants were divided into revaccination subcohorts: 2A, 2B, and 2C. Participants further received revaccination with Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) at 1 (Subcohort 2A), 2 (Subcohort 2B), and 3 (Subcohort 2C) years, respectively after the first vaccination on Day 1. Participants in subcohorts 2A and 2B were additionally re-randomised in three groups at Year 3 and Year 4, respectively, to receive either Ad26.RSV.preF 1*10^11 vp alone, RSV preF protein 150 mcg alone or the Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture). Participants who were not re-vaccinated continued in the main cohort and were followed up for safety assessments until Day 1095. Eligible participants who received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 1 in the main cohort entered the revaccination subcohort 1A and received IM injection of the protein mixture at the same dose level on Day 365. Participants were then followed up for safety assessments till Day 730. Eligible participants who received IM injection of placebo on Day 1 in the main study cohort entered the revaccination subcohort and received Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 365. Participants were then followed up for safety assessments till Day 730. Eligible participants who received IM injection of placebo on Day 1 in the main cohort followed by Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 365 in the revaccination subcohort further received Ad26.RSV.preF 1*10^11 vp alone as IM injection on Day 730. Participants were then followed up for safety assessments till Day 1095. Eligible participants who received IM injection of placebo on Day 1 in the main cohort followed by Ad26.RSV.preF 1*10^11 vp and RSV preF protein (protein mixture) on Day 365 in the revaccination subcohort further received RSV preF protein 150 mcg alone as IM injection on Day 730. Participants were then followed up for safety assessments till Day 1095. Eligible participants who received IM injection of placebo on Day 1 in the main study cohort entered the revaccination subcohort and received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 365 and 730. Participants were then followed up for safety assessments till Day 1095. Eligible participants who received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 1 in the main cohort entered the revaccination subcohort and received the protein mixture at the same dose level on Day 730. Participants were then followed up for safety assessments till Day 1095. Eligible participants who received IM injection of placebo on Day 1 in the main cohort entered the revaccination subcohort and received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 730. Participants were then followed up for safety assessments till Day 1095. Eligible participants who received IM injection of placebo on Day 1 in the main cohort entered the revaccination subcohort and received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 730 followed by Ad26.RSV.preF 1*10^11 vp alone on Day 1095. Participants were then followed up for safety assessments till Day 1460. Eligible participants who received IM injection of placebo on Day 1 in the main cohort entered the revaccination subcohort and received IM injection Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 730 followed by RSV preF protein 150 mcg alone on Day 1095. Participants were then followed up for safety assessments till Day 1460. Eligible participants who received IM injection of placebo on Day 1 in the main cohort entered the revaccination subcohort and received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Days 730 and Day 1095. Participants were then followed up for safety assessments till Day 1460. Eligible participants who received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 1 in the main cohort entered the revaccination subcohort and received the protein mixture at the same dose level on Day 1095. Participants were then followed up for safety assessments till Day 1460. Eligible participants who received IM injection of placebo on Day 1 in the main cohort entered the revaccination subcohort and received IM injection of Ad26.RSV.preF 1*10^11 vp and RSV preF protein 150 mcg (protein mixture) on Day 1095. Participants were then followed up for safety assessments till Day 1460.
All-Cause Mortality
Arm 1: Main Cohort: Group 1: Ad26.RSV.preF and RSV preF Protein (Protein Mixture) Arm 2: Main Cohort: Group 2: Placebo Arm 3: Revaccination (ReVacc) Subcohort 1A: Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 4: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein Mixture Arm 5: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein + Ad26.RSV.PreF Alone Arm 6: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein + RSV preF Protein Alone Arm 7: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 8: ReVacc Subcohort 1B: Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 9: ReVacc Subcohort 2B:Placebo to Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 10: ReVacc Subcohort 2B: Placebo to Ad26.RSV.preF/RSV preF Protein + Ad26.RSV.preF Arm 11: ReVacc Subcohort 2B: Placebo to Ad26.RSV.preF/RSV preF Protein + RSV preF Protein Alone Arm 12: ReVacc Subcohort 2B: Placebo to Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 13: ReVacc Subcohort 1C: Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 14: ReVacc Subcohort 2C: Placebo to Ad26.RSV.preF/RSV preF Protein (Protein Mixture)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   39/2891 (1.35%)   38/2891 (1.31%)   1/120 (0.83%)   0/126 (0.00%)   0/28 (0.00%)   0/28 (0.00%)   0/28 (0.00%)   0/137 (0.00%)   2/149 (1.34%)   0/37 (0.00%)   0/37 (0.00%)   0/37 (0.00%)   0/131 (0.00%)   1/119 (0.84%) 
Hide Serious Adverse Events
Arm 1: Main Cohort: Group 1: Ad26.RSV.preF and RSV preF Protein (Protein Mixture) Arm 2: Main Cohort: Group 2: Placebo Arm 3: Revaccination (ReVacc) Subcohort 1A: Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 4: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein Mixture Arm 5: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein + Ad26.RSV.PreF Alone Arm 6: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein + RSV preF Protein Alone Arm 7: ReVacc Subcohort 2A: Placebo to Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 8: ReVacc Subcohort 1B: Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 9: ReVacc Subcohort 2B:Placebo to Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 10: ReVacc Subcohort 2B: Placebo to Ad26.RSV.preF/RSV preF Protein + Ad26.RSV.preF Arm 11: ReVacc Subcohort 2B: Placebo to Ad26.RSV.preF/RSV preF Protein + RSV preF Protein Alone Arm 12: ReVacc Subcohort 2B: Placebo to Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 13: ReVacc Subcohort 1C: Ad26.RSV.preF/RSV preF Protein (Protein Mixture) Arm 14: ReVacc Subcohort 2C: Placebo to Ad26.RSV.preF/RSV preF Protein (Protein Mixture)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   203/2891 (7.02%)   196/2891 (6.78%)   2/120 (1.67%)   6/126 (4.76%)   0/28 (0.00%)   3/28 (10.71%)   1/28 (3.57%)   4/137 (2.92%)   6/149 (4.03%)   2/37 (5.41%)   0/37 (0.00%)   0/37 (0.00%)   2/131 (1.53%)   2/119 (1.68%) 
Blood and lymphatic system disorders                             
Anaemia * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Blood Loss Anaemia * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Splenic Infarction * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Cardiac disorders                             
Acute Coronary Syndrome * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Acute Left Ventricular Failure * 1  0/2891 (0.00%)  2/2891 (0.07%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Acute Myocardial Infarction * 1  1/2891 (0.03%)  2/2891 (0.07%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Angina Unstable * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  1/28 (3.57%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Aortic Valve Disease * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Aortic Valve Stenosis * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Arrhythmia * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Arteriosclerosis Coronary Artery * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Atrial Fibrillation * 1  10/2891 (0.35%)  3/2891 (0.10%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  1/28 (3.57%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Atrial Flutter * 1  2/2891 (0.07%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  1/137 (0.73%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Bradycardia * 1  1/2891 (0.03%)  2/2891 (0.07%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Cardiac Arrest * 1  2/2891 (0.07%)  3/2891 (0.10%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Cardiac Failure * 1  1/2891 (0.03%)  2/2891 (0.07%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Cardiac Failure Congestive * 1  9/2891 (0.31%)  3/2891 (0.10%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  1/119 (0.84%) 
Cardiomyopathy * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Coronary Artery Disease * 1  2/2891 (0.07%)  5/2891 (0.17%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  1/131 (0.76%)  0/119 (0.00%) 
Ischaemic Cardiomyopathy * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Left Ventricular Failure * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Myocardial Infarction * 1  8/2891 (0.28%)  9/2891 (0.31%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  1/131 (0.76%)  0/119 (0.00%) 
Myocardial Ischaemia * 1  2/2891 (0.07%)  2/2891 (0.07%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Stress Cardiomyopathy * 1  0/2891 (0.00%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  1/37 (2.70%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Ventricular Tachycardia * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Ear and labyrinth disorders                             
Vertigo * 1  0/2891 (0.00%)  2/2891 (0.07%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Endocrine disorders                             
Hypothyroidism * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Inappropriate Antidiuretic Hormone Secretion * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Gastrointestinal disorders                             
Abdominal Pain * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Ascites * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Colitis * 1  1/2891 (0.03%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Diarrhoea * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Duodenal Ulcer Haemorrhage * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Food Poisoning * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Gastric Perforation * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Gastrointestinal Haemorrhage * 1  2/2891 (0.07%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Hiatus Hernia * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Inguinal Hernia * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Intestinal Obstruction * 1  3/2891 (0.10%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Intestinal Perforation * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Large Intestinal Obstruction * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Nausea * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Obstructive Pancreatitis * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Oesophageal Obstruction * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Oesophageal Perforation * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Oesophagitis * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Pancreatic Cyst * 1  0/2891 (0.00%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  1/137 (0.73%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Pancreatic Mass * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Pancreatitis * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Pancreatitis Acute * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Rectal Prolapse * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Small Intestinal Obstruction * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Upper Gastrointestinal Haemorrhage * 1  1/2891 (0.03%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Vomiting * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
General disorders                             
Adverse Drug Reaction * 1  0/2891 (0.00%)  0/2891 (0.00%)  0/120 (0.00%)  1/126 (0.79%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Asthenia * 1  1/2891 (0.03%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Chest Discomfort * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Chest Pain * 1  1/2891 (0.03%)  3/2891 (0.10%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Death * 1  7/2891 (0.24%)  4/2891 (0.14%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  1/149 (0.67%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Drowning * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Generalised Oedema * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Multiple Organ Dysfunction Syndrome * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Non-Cardiac Chest Pain * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Hepatobiliary disorders                             
Cholecystitis * 1  1/2891 (0.03%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Cholelithiasis * 1  2/2891 (0.07%)  1/2891 (0.03%)  0/120 (0.00%)  1/126 (0.79%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Cirrhosis Alcoholic * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Infections and infestations                             
Abscess Neck * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Alpha Haemolytic Streptococcal Infection * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Appendicitis * 1  2/2891 (0.07%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Bronchitis * 1  2/2891 (0.07%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Cellulitis * 1  0/2891 (0.00%)  0/2891 (0.00%)  0/120 (0.00%)  1/126 (0.79%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Clostridium Difficile Colitis * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Covid-19 * 1  13/2891 (0.45%)  13/2891 (0.45%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  1/37 (2.70%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Covid-19 Pneumonia * 1  13/2891 (0.45%)  16/2891 (0.55%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Cystitis * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Device Related Infection * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Diabetic Foot Infection * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Diverticulitis * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Gangrene * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Influenza * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Kidney Infection * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Meningitis Aseptic * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Osteomyelitis * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Periorbital Cellulitis * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Pneumonia * 1  16/2891 (0.55%)  10/2891 (0.35%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  1/28 (3.57%)  0/28 (0.00%)  0/137 (0.00%)  1/149 (0.67%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Pneumonia Aspiration * 1  1/2891 (0.03%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Pneumonia Bacterial * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Pneumonia Chlamydial * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Pneumonia Mycoplasmal * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Pneumonia Parainfluenzae Viral * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Pyelonephritis * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Sepsis * 1  3/2891 (0.10%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  1/149 (0.67%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Septic Shock * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Streptococcal Sepsis * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Tonsillitis * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Urinary Tract Infection * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Injury, poisoning and procedural complications                             
Ankle Fracture * 1  2/2891 (0.07%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Carbon Monoxide Poisoning * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Cervical Vertebral Fracture * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Craniocerebral Injury * 1  1/2891 (0.03%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Environmental Exposure * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Extradural Haematoma * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Facial Bones Fracture * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Femoral Neck Fracture * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Femur Fracture * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Fracture Displacement * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Head Injury * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Hip Fracture * 1  3/2891 (0.10%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Humerus Fracture * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  1/137 (0.73%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Hypobarism * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Lumbar Vertebral Fracture * 1  3/2891 (0.10%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Post Procedural Complication * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Road Traffic Accident * 1  0/2891 (0.00%)  2/2891 (0.07%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Scapula Fracture * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Skin Abrasion * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Spinal Compression Fracture * 1  1/2891 (0.03%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Spinal Fracture * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Subdural Haematoma * 1  3/2891 (0.10%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Tibia Fracture * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Traumatic Fracture * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Upper Limb Fracture * 1  2/2891 (0.07%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Wound Dehiscence * 1  0/2891 (0.00%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  1/137 (0.73%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Wrist Fracture * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Metabolism and nutrition disorders                             
Adult Failure to Thrive * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Dehydration * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Diabetes Mellitus * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Diabetic Ketoacidosis * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Hyperglycaemia * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Hyperkalaemia * 1  1/2891 (0.03%)  2/2891 (0.07%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Hypoglycaemia * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Hyponatraemia * 1  1/2891 (0.03%)  2/2891 (0.07%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Hypovolaemia * 1  1/2891 (0.03%)  0/2891 (0.00%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119 (0.00%) 
Type 2 Diabetes Mellitus * 1  0/2891 (0.00%)  1/2891 (0.03%)  0/120 (0.00%)  0/126 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/28 (0.00%)  0/137 (0.00%)  0/149 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/37 (0.00%)  0/131 (0.00%)  0/119&n