A Randomized, Double-blind, Placebo-controlled Phase 1/2a Study for Safety and Immunogenicity Evaluations for Regimen Selection of Ad26.RSV.preF and/or RSV preF Protein Combinations Followed by Expanded Safety Evaluation in Adults Aged 60 Years and Older
Phase: PHASE1
Conditions: Healthy
Sponsor: Janssen Vaccines & Prevention B.V.

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Status: Approved, Date: 6 November 2020
Janssen Vaccines & Prevention B.V.*
Clinical Protocol
A Randomized, Double-blind, Placebo-controlled Phase 1/2a Study for Safety and 
Immunogenicity Evaluations for Regimen Selection of Ad26.RSV.preF and/or RSV preF 
Protein Combinations Followed by Expanded Safety Evaluation in Adults Aged 60 Years 
and Older
Protocol VAC18193RSV1004; Phase 1/2a
Amendment 6
VAC18193 (JNJ-64400141)
* Janssen Vaccines & Prevention B.V. is a Janssen pharmaceutical company of Johnson &
Johnson and is hereafter referred to as the sponsor of the study. The sponsor is identified on the
Contact Information page that accompanies the protocol
This study will be conducted under US Food & Drug Administration IND regulations (21 CFR 
Part 312).
Status:
Approved
Date:
6 November 2020
Prepared by:
Janssen Vaccines & Prevention B.V.
EDMS number:
EDMS-ERI-143743616, 16.0
GCP Compliance: This study will be conducted in compliance with Good Clinical Practice, and applicable regulatory 
requirements.
Confidentiality Statement
The information provided herein contains Company trade secrets, commercial or financial information that the Company 
customarily holds close and treats as confidential. The information is being provided under the assurance that the recipient 
will maintain the confidentiality of the information under applicable statutes, regulations, rules, protective orders or 
otherwise.
NCT03502707

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TABLE OF CONTENTS
TABLE OF CONTENTS ............................................................................................................................... 2
LIST OF ATTACHMENTS............................................................................................................................ 4
LIST OF IN-TEXT TABLES AND FIGURES................................................................................................ 4
PROTOCOL AMENDMENTS....................................................................................................................... 6
SYNOPSIS.................................................................................................................................................. 13
SCHEDULE OF ACTIVITIES – COHORT 1............................................................................................... 28
SCHEDULE OF ACTIVITIES – COHORT 2............................................................................................... 30
SCHEDULE OF ACTIVITIES – COHORT 2 (GROUPS 14-15) LONG-TERM FOLLOW-UP 
PHASE............................................................................................................................................... 32
SCHEDULE OF ACTIVITIES – COHORT 3 WITH ONE-DOSE REGIMEN AND MONTH 12 AND 
MONTH 24 BOOSTER ...................................................................................................................... 33
SCHEDULE OF ACTIVITIES – COHORT 3 WITH TWO-DOSE REGIMEN AND MONTH 12 
BOOSTER ......................................................................................................................................... 35
ABBREVIATIONS ...................................................................................................................................... 38
1.
INTRODUCTION................................................................................................................................ 39
1.1.
Background .................................................................................................................................... 40
1.2.
Overall Rationale for the Study...................................................................................................... 45
2.
OBJECTIVES, ENDPOINTS, AND HYPOTHESIS........................................................................... 46
2.1.
Objectives and Endpoints .............................................................................................................. 46
2.2.
Hypothesis ..................................................................................................................................... 49
3.
STUDY DESIGN AND RATIONALE ................................................................................................. 49
3.1.
Overview of Study.......................................................................................................................... 49
3.1.1.
Study Design .............................................................................................................................. 49
3.1.2.
Study Procedures ....................................................................................................................... 54
3.2.
Study Design Rationale.................................................................................................................. 60
4.
PARTICIPANT POPULATION .......................................................................................................... 62
4.1.
Inclusion Criteria ............................................................................................................................ 62
4.2.
Exclusion Criteria ........................................................................................................................... 64
4.3.
Prohibitions and Restrictions ......................................................................................................... 66
5.
TREATMENT ALLOCATION AND BLINDING................................................................................. 66
6.
DOSAGE AND ADMINISTRATION .................................................................................................. 68
7.
VACCINE COMPLIANCE.................................................................................................................. 69
8.
PRE-STUDY AND CONCOMITANT THERAPY ............................................................................... 69
9.
STUDY PROCEDURES AND EVALUATIONS................................................................................. 70
9.1.
Study Procedures........................................................................................................................... 70
9.1.1.
Overview..................................................................................................................................... 70
9.1.2.
Visit Windows ............................................................................................................................. 71

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9.1.3.
Screening Phase (Days -28 to 0 for Cohorts 1 and 2; Before Randomization on Day 1 for 
Cohort 3) ..................................................................................................................................... 75
9.1.4.
Randomization (Day 1)............................................................................................................... 76
9.1.5.
Vaccination ................................................................................................................................. 77
9.1.6.
Post-Vaccination Follow-up ........................................................................................................ 78
9.1.7.
Final Visit .................................................................................................................................... 79
9.1.8.
Early Withdrawal: Early Exit Visit................................................................................................ 79
9.1.9.
Long-term Follow-up (Groups 14 and 15 from Cohort 2) ........................................................... 79
9.2.
Study Evaluations .......................................................................................................................... 80
9.2.1.
Immunogenicity........................................................................................................................... 80
9.2.2.
RTI Procedures........................................................................................................................... 82
9.2.3.
Safety Evaluations...................................................................................................................... 83
9.2.3.1.
Adverse Events ....................................................................................................................... 83
9.2.3.2.
Clinical Laboratory Tests......................................................................................................... 85
9.2.3.3.
Electrocardiogram ................................................................................................................... 87
9.2.3.4.
Vital Signs................................................................................................................................ 87
9.2.3.5.
Physical Examination .............................................................................................................. 87
10.
PARTICIPANT COMPLETION/DISCONTINUATION OF STUDY VACCINE/ 
WITHDRAWAL FROM THE STUDY................................................................................................. 88
10.1.
Completion ..................................................................................................................................... 88
10.2.
Discontinuation of Study Vaccine/Withdrawal from the Study....................................................... 88
10.3.
Contraindications to Vaccination.................................................................................................... 89
11.
STATISTICAL METHODS................................................................................................................. 90
11.1.
Analysis Sets.................................................................................................................................. 90
11.2.
Sample Size Determination ........................................................................................................... 91
11.2.1.
Initial Safety Cohort (Cohort 1) ................................................................................................... 91
11.2.2.
Regimen Selection Cohort (Cohort 2) ........................................................................................ 91
11.2.3.
Expanded Safety Cohort (Cohort 3) ........................................................................................... 92
11.3.
Participant Information ................................................................................................................... 92
11.4.
Immunogenicity Analyses .............................................................................................................. 92
11.5.
Safety Analyses ............................................................................................................................. 93
11.6.
Planned Analyses .......................................................................................................................... 94
11.6.1.
Initial Safety Cohort (Cohort 1) ................................................................................................... 94
11.6.2.
Regimen Selection Cohort (Cohort 2) ........................................................................................ 95
11.6.3.
Expanded Safety Cohort (Cohort 3) ........................................................................................... 96
11.6.4.
Final Analysis.............................................................................................................................. 97
11.7.
Additional Interim Analyses............................................................................................................ 97
11.8.
Data Review Committee ................................................................................................................ 97
11.9.
Study Vaccination Pausing Rules .................................................................................................. 98
12.
ADVERSE EVENT REPORTING ...................................................................................................... 99
12.1.
Definitions .................................................................................................................................... 100
12.1.1.
Adverse Event Definitions and Classifications ......................................................................... 100
12.1.2.
Attribution Definitions................................................................................................................ 102
12.1.3.
Severity Criteria ........................................................................................................................ 102
12.2.
Special Reporting Situations........................................................................................................ 103
12.3.
Procedures................................................................................................................................... 103
12.3.1.
All Adverse Events.................................................................................................................... 103
12.3.2.
Serious Adverse Events ........................................................................................................... 105
12.3.3.
Pregnancy................................................................................................................................. 106
12.4.
Contacting Sponsor Regarding Safety......................................................................................... 106
13.
PRODUCT QUALITY COMPLAINT HANDLING............................................................................ 106
13.1.
Procedures................................................................................................................................... 106
13.2.
Contacting Sponsor Regarding Product Quality .......................................................................... 106

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14.
VACCINE INFORMATION .............................................................................................................. 107
14.1.
Physical Description of the Vaccines ........................................................................................... 107
14.2.
Packaging and Labelling.............................................................................................................. 107
14.3.
Storage and Handling .................................................................................................................. 108
14.4.
Vaccine Accountability ................................................................................................................. 108
15.
STUDY-SPECIFIC MATERIALS..................................................................................................... 108
16.
ETHICAL ASPECTS ....................................................................................................................... 109
16.1.
Study-Specific Design Considerations......................................................................................... 109
16.2.
Regulatory Ethics Compliance..................................................................................................... 111
16.2.1.
Investigator Responsibilities ..................................................................................................... 111
16.2.2.
Independent Ethics Committee or Institutional Review Board ................................................. 111
16.2.3.
Informed Consent ..................................................................................................................... 113
16.2.4.
Privacy of Personal Data .......................................................................................................... 114
16.2.5.
Long-Term Retention of Samples for Additional Future Research .......................................... 114
16.2.6.
Country Selection ..................................................................................................................... 114
17.
ADMINISTRATIVE REQUIREMENTS ............................................................................................ 115
17.1.
Protocol Amendments.................................................................................................................. 115
17.2.
Regulatory Documentation .......................................................................................................... 115
17.2.1.
Regulatory Approval/Notification .............................................................................................. 115
17.2.2.
Required Pre-study Documentation ......................................................................................... 115
17.3.
Participant Identification, Enrollment, and Screening Logs ......................................................... 116
17.4.
Source Documentation................................................................................................................. 116
17.5.
Case Report Form Completion .................................................................................................... 117
17.6.
Data Quality Assurance/Quality Control ...................................................................................... 118
17.7.
Record Retention ......................................................................................................................... 118
17.8.
Monitoring .................................................................................................................................... 118
17.9.
Study Completion/Termination..................................................................................................... 119
17.9.1.
Study Completion/End of Study................................................................................................ 119
17.9.2.
Study Termination..................................................................................................................... 119
17.10.
On-Site Audits .............................................................................................................................. 120
17.11.
Use of Information and Publication.............................................................................................. 120
18.
APPENDIX 1: GUIDANCE ON STUDY CONDUCT DURING THE COVID-19 PANDEMIC.......... 122
REFERENCES.......................................................................................................................................... 124
INVESTIGATOR AGREEMENT ............................................................................................................... 133
LIST OF ATTACHMENTS
Attachment 1:
Toxicity Tables ............................................................................................................. 127
LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1:
Study Design: Initial Safety Cohort (Cohort 1).......................................................................... 18
Table 2:
Study Design: Regimen Selection Cohort (Cohort 2) ............................................................... 19
Table 3:
Study Design: Expanded Safety Cohort (Cohort 3) with One-dose Regimen and
Month 12 and Month 24 Booster .............................................................................................. 20
Table 4:
Study Design: Expanded Safety Cohort (Cohort 3) with Two-dose Regimen and 
Month 12 Booster...................................................................................................................... 20
Table 5:
Summary of Immunogenicity Assays (Humoral) ...................................................................... 21

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Table 6:
Summary of Immunogenicity Assays (Cellular)........................................................................ 22
Table 7:
Other Ongoing Clinical Studies with Ad26.RSV.preF............................................................... 43
Table 8:
Study Design: Initial Safety Cohort (Cohort 1).......................................................................... 52
Table 9:
Study Design: Regimen Selection Cohort (Cohort 2) ............................................................... 53
Table 10:
Study Design: Expanded Safety Cohort (Cohort 3) with One-dose Regimen and 
Month 12 and Month 24 Booster .............................................................................................. 54
Table 11:
Study Design: Expanded Safety Cohort (Cohort 3) with Two-dose Regimen and 
Month 12 Booster...................................................................................................................... 54
Table 12:
Visit Windows: Initial Safety Cohort (Cohort 1)......................................................................... 72
Table 13:
Visit Windows: Regimen Selection Cohort (Cohort 2).............................................................. 73
Table 14:
Visit Windows: Expanded Safety Cohort (Cohort 3) - One-dose Regimen and 
Month 12 and Month 24 Booster .............................................................................................. 74
Table 15:
Visit Windows: Expanded Safety Cohort (Cohort 3) - Two-dose Regimen and 
Month 12 Booster...................................................................................................................... 75
Table 16:
Summary of Immunogenicity Assays (Humoral) ...................................................................... 81
Table 17:
Summary of Immunogenicity Assays (Cellular)........................................................................ 81
Table 18:
Probability of Observing at Least One Adverse Event in the Initial Safety Cohort 
(Cohort 1) at a Given True Adverse Event Rate....................................................................... 91
Table 19:
Probability of Observing at Least One Adverse Event in the Expanded Safety Cohort 
(Cohort 3) at a Given True Adverse Event Rate....................................................................... 92
FIGURES
Figure 1:
Schematic Overview of the Study for Cohort 1......................................................................... 57
Figure 2:
Schematic Overview of the Study for Cohort 2......................................................................... 58
Figure 3:
Schematic Overview of the Study for Cohort 3 One-dose Regimen and Month 12 and 
Month 24 Booster...................................................................................................................... 59
Figure 4:
Schematic Overview of the Study for Cohort 3 Two-dose Regimen and Month 12 
Booster...................................................................................................................................... 60

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PROTOCOL AMENDMENTS
Protocol Version 
Issue Date
Original Protocol
30 January 2018
Amendment 1
19 March 2018
Amendment 2
24 September 2018
Amendment 3
28 January 2019
Amendment 4
12 July 2019
Amendment 5
8 June 2020
Amendment 6
06 November 2020
Amendment 6 (Issued date: 06 November 2020)
The overall reason for the amendment: To further examine the immune response to revaccination at different 
time intervals, this amendment changes the Month 24 vaccination for Group 20, Cohort 3, from placebo to the 
selected regimen. A 14 day post-third vaccination visit is also added to further examine the kinetics of the 
immune responses.
The table below gives an overview of each change and all affected sections
Rationale: For Cohort 3, participants in Group 20 will receive the selected regimen at Month 24.
Synopsis: Objectives, Endpoints and Hypothesis 
Synopsis: Overview of Study Design – Expanded Safety Cohort (Cohort 3)
2.1 Objectives and Endpoints
3.1.1 Study Design – Expanded Safety Cohort (Cohort 3)
5 Treatment Allocation and Blinding
11.6.4 Final Analysis
Rationale: For Cohort 3, an additional visit 14 days after the Month 24 vaccination is added.
Schedule of Activities – Cohort 3 with One-dose Regimen and Month 12 and Month 24 Booster
3.1.1 Study Design (Figure 3)
9.1.1 Overview
9.1.2 Visit Windows
9.1.6 Post-vaccination Follow-up
Rationale: Corrections of errors in footnote numbering have been made.
Throughout the protocol
Amendment 5 (Issued date: 8 June 2020)
The overall reason for the amendment: This amendment is made to further extend the assessment of durability 
of the immune response in Groups 14 and 15 in Cohort 2 and to assess the safety and immunogenicity of the 
selected dose after 2 annual revaccinations in Cohort 3. For Cohort 2, participants in Groups 14 and 15 will 
continue into a long-term follow-up phase with a final visit 36 months after the first vaccination. For the one-dose 
regimen in Cohort 3, an additional revaccination at Month 24 (Day 730) with a 1-year post-vaccination follow-up 
period is added.

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The table below gives an overview of each change and all affected sections
Rationale: For Cohort 2, participants in 2 groups (Groups 14 and 15) will continue into a long-term follow-up 
phase to further extend the assessment of the long-term durability of the immune response in, and to understand 
the potential effect of a decreased dose level of Ad26.RSV.preF on long-term durability of the immune response.
During the long-term follow-up phase, only SAEs related to study vaccine, study procedures, or non-
investigational (concomitant) Janssen products, and all AEs leading to discontinuation will be collected.
Synopsis: Objectives and Endpoints
Synopsis: Overview of Study Design
Synopsis: Safety Evaluations
Synopsis: Statistical Methods
Schedule of Activities – Cohort 2 (new table for long-term follow-up created)
2.1 Objectives and Endpoints
3.1.1 Study Design
3.1.2 Study Procedures
3.2 Study Design Rationale
4.2 Exclusion Criteria
5 Treatment Allocation and Blinding
8 Pre-study and Concomitant Therapy
9.1.1 Overview
9.1.2 Visit Windows
9.1.7 Final Visit
9.1.9 Long-term Follow-up (Groups 14 and 15 from Cohort 2)
9.2.3.1 Adverse Events
10.1 Completion
11.6.2 Regimen Selection Cohort (Cohort 2)
12.1.1 Adverse Event Definitions and Classifications
12.3.1 All Adverse Events
12.3.2 Serious Adverse Events
16.2.3 Informed Consent
17.9.1 Study Completion/End of Study
Rationale: For the one-dose regimen in Cohort 3, to add an additional revaccination at Month 24 (Day 730) with 
a 1-year post-vaccination follow-up period to assess the long-term durability of the immune response of the 
selected dose, and to assess the safety and immunogenicity of the selected dose after two annual revaccinations 
(Month 12 and Month 24).
Synopsis: Objectives and Endpoints (Cohort 3)
Synopsis: Overview of Study Design
Synopsis: Statistical Methods
Schedule of Activities – Cohort 3
2.1 Objectives and Endpoints (Cohort 3)
3.1.1 Study Design
3.1.2 Study Procedures
3.2 Study design Rationale
9.1.1 Overview
9.1.2 Visit Windows
9.1.6 Post-Vaccination Follow-up
9.1.7 Final Visit
9.2.3.5 Physical Examination
10.1 Completion
11.4 Immunogenicity Analyses
11.6.3 Expanded Safety Cohort (Cohort 3)
16.2.3 Informed Consent
11.8 Data Review Committee
17.9.1 Study Completion/End of Study

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Rationale: To specify RTI follow-up will only be recorded during the first 2 RSV seasons of the study, relative
to the enrollment date of the first participant in Cohort 1.
Synopsis: Objectives and Endpoints
Synopsis: RTI Procedures
Schedule of Activities – Cohorts 1, 2 and 3
2.1 Objectives and Endpoints
3.1.2 Study Procedures
9.1.1 Overview
9.1.5 Vaccination
9.1.6 Post-vaccination Follow-up
9.2.2 RTI Procedures
Rationale: To specify that eligibility for revaccination is determined by assessment of signs and symptoms of 
potential underlying illnesses that should be medically stable in the weeks preceding revaccination.
4.1 Inclusion Criteria
Rationale: For health and safety reasons due to the Coronavirus Disease 2019 (COVID-19), participants may not 
be able to come to the study site for scheduled procedures. Appendix 1 has been added to provide guidance to the 
investigator for managing study-related procedures during the COVID-19 pandemic.
Appendix 1
Rationale: Minor textual changes, clarifications and corrections have been made.
Throughout the protocol
Amendment 4 (Issued date: 12 July 2019)
The overall reason for the amendment: This amendment is made to include changes to the dosing regimen to 
obtain more data on the long-term durability of the immune response. For Cohort 2, study vaccination at the 
Month 12 visit is removed, and the 7-day and 28-day visits after the Month 12 visit are deleted.
Month 12 re-vaccination of the selected regimen is already included in Cohort 3. The window for the Month 12 
re-vaccination for Cohort 3 is amended to –2 months to allow that dose to be administered as early as Month 10, 
with the intention that the immunogenicity data from the analysis of the 28-day post-dose blood sample would be 
available in parallel with data from the primary analysis of the proof-of-concept study VAC18193RSV2001 to 
aid decision making on Month 12 revaccination in that study.
The table below gives an overview of each change and all affected sections
Rationale: For Cohort 2, to remove study vaccination from the procedures at the Month 12 visit, and to delete the 
7-day and 28-day visits after the Month 12 visit. Also, to add an analysis at 1 year after the first vaccination for 
this cohort.
Synopsis: Objectives and Endpoints (Cohort 2)
Synopsis: Overview of Study Design
Synopsis: Statistical Methods
Synopsis: Schedule of Activities – Cohorts 1 and 2 (new table for Cohort 2 created)
2.1 Objectives and Endpoints (Cohort 2)
3.1.1 Study Design
3.1.2 Study Procedures (new figure for Cohort 2 created)
3.2 Study Design Rationale
9.1.1 Overview
9.1.2 Visit Windows

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9.1.6 Post-vaccination Follow-up
9.1.7 Final Visit: 12 Months Post-last Vaccination (Month 12 Booster)
9.2.3.5 Physical Examination
10.1 Completion
11.6.2 Regimen Selection Cohort (Cohort 2)
11.8 Data Review Committee
17.9.1 Study Completion/End of Study
Rationale: To amend the visit window for the Month 12 vaccination in Cohort 3 from ±2 months to –2 months; 
and to align the visit windows for Visits 10, 11 and 12 in Cohort 2 to ±1 month.
Synopsis: Schedule of Activities – Cohort 2
Synopsis: Schedule of Activities – Cohort 3
9.1.2 Visit Windows
Rationale: Clarification that participants discontinued from study vaccine should be monitored for 
immunogenicity, if this does not result in safety risks for the participant, as well as safety, and/or for other 
procedures (eg, RTI follow-up).
10.2 Discontinuation of Study Vaccine/Withdrawal from the Study 
Amendment 3 (Issued date: 28 January 2019)
The overall reason for the amendment: To investigate the durability of the immune response both with and 
without revaccination at Month 12, blood samples for humoral immunogenicity assessments will be collected 
from all 315 participants in Cohort 3, instead of just the 63 in the subset of Cohort 3 participants. No change is 
made for the collection of blood for cellular immunogenicity assessments.
The table below gives an overview of the rationale for each change and all affected sections
Rationale: To allow collection of blood samples for humoral immunogenicity assessments from all 315 
participants in Cohort 3, instead of just the 63 in the Cohort 3 subset.
Synopsis: Objectives and Endpoints (Cohort 3); Immunogenicity Evaluations
Schedule of Activities (Cohort 3)
2.1 Objectives and Endpoints (Cohort 3)
3.1.2 Study Procedures
5 Treatment Allocation and Blinding
9.1.1 Overview
9.2.1 Immunogenicity
Rationale: To clarify that a participant who misses a vaccination can receive subsequent vaccinations if the 
investigator determines that the participant is eligible according to the criteria in Section 10.3.
10.2 Discontinuation of Study Vaccine/Withdrawal from the Study
Rationale: Clarification of the data to be used in the primary analysis of Cohort 3.
11.6.3 Expanded Safety Cohort (Cohort 3)
Rationale: Other minor changes, clarifications and corrections made throughout the protocol.

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Amendment 2 (Issued date: 24 September 2018)
The overall reason for the amendment: To remove the concomitant seasonal influenza vaccination for Cohort 
3, and to increase the sample size in Cohort 3 to generate sufficient safety data to support late stage development.
Also, additional blood sample collection for cellular and humoral immunogenicity is included for a subset of 
63 participants from Cohort 3 to provide a more in-depth characterization of immune response. Furthermore, to 
ensure availability of immunogenicity data from Cohort 2 primary analysis in time to support late stage 
development decisions, assessments of RSV neutralizing antibody levels of the one-dose regimen with separate 
injections (Group 16) and the two-dose regimen (Group 17) have been moved from primary to secondary 
endpoints.
The table below gives an overview of the rationale for each change and all affected sections
Rationale: Removal of the seasonal influenza vaccination (or placebo) as timing of Cohort 3 vaccination will no
longer coincide with the influenza season.
Title
Synopsis: Objectives, Endpoints and Hypothesis; Overview of Study Design; Dosage and Administration;
Immunogenicity Evaluations; Statistical Methods
Schedule of Activities (Cohort 3)
1 Introduction
2.1 Objectives and Endpoints
2.2 Hypothesis
3.1.1 Study Design
3.1.2 Study Procedures
3.2 Study Design Rationale
4 Participant Population
4.2 Exclusion Criteria
5 Treatment Allocation and Blinding
6 Dosage and Administration
7 Vaccine Compliance
8 Pre-study and Concomitant Therapy
9.1.1 Overview
9.1.2 Visit Windows
9.1.3 Screening Phase
9.1.4 Randomization
9.1.5 Vaccination
9.1.6 Post-vaccination Follow-up
9.1.8 Early Withdrawal: Early Exit Visit
9.2.1 Immunogenicity
11.1 Analysis Sets
11.2.3 Sample Size Determination (Cohort 3)
11.4 Immunogenicity Analyses
11.9 Study Vaccination Pausing Rules
12.1.1 Adverse Event Definitions and Classifications
14.1 Physical Description of the Vaccines
15 Study-Specific Materials
16.1 Study-Specific Design Considerations
Rationale: Increase in the sample size for Cohort 3 to 315 participants to provide sufficient safety data on the 
selected regimen to support late stage development.

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Synopsis: Overview of Study Design; Immunogenicity Evaluations
1.2 Overall Rationale for the Study
3.1.1 Study Design
5 Treatment Allocation and Blinding
9.1.1 Overview
Rationale: Inclusion of additional blood sample collection (at additional timepoints) for cellular and humoral 
immunogenicity for a subset of 63 participants from Cohort 3 to provide sufficient timepoints with 
immunogenicity samples which will be used for immune response modelling in preparation of Phase 3 studies.
Synopsis: Immunogenicity Evaluations
Schedule of Activities (Cohort 3)
5 Treatment Allocation and Blinding
9.1.1 Overview
9.1.2 Visit Windows
9.1.6 Post-vaccination Follow-up
9.2.1 Immunogenicity
Rationale: Assessments of RSV neutralizing antibody levels of the one-dose regimen with separate injections 
(Group 16) and the two-dose regimen (Group 17) were moved from primary to secondary endpoints to ensure 
availability of immunogenicity data from Cohort 2 primary analysis in time to support late stage development 
decisions.
Synopsis: Objectives, Endpoints and Hypothesis; Overview of Study Design; Immunogenicity Evaluations; 
Statistical Methods
2.1 Objectives and Endpoints
3.1.1 Study Design
9.2.1 Immunogenicity
11.6.2 Regimen Selection Cohort (Cohort 2)
Rationale: Other minor changes, clarifications and corrections made throughout the protocol.
Amendment 1 (Issued date: 19 March 2018)
The overall reason for the amendment: The protocol amendment is made to change the timing of the seasonal 
influenza vaccination for Cohort 3. Changes in project timelines have resulted in the likelihood that some 
participants in this study would not receive seasonal influenza vaccination until very late in the influenza season. 
The amended vaccination regimen for Cohort 3 now provides the seasonal influenza vaccination earlier in the 
season, either at least 14 days prior to Day 1, or at the latest on Day 1 itself. Also, the sample size for Cohort 3 is 
reduced.
The table below gives an overview of the rationale for each change and all affected sections
Rationale: Retiming of the seasonal influenza vaccination (or placebo)
Synopsis: Objectives and Endpoints; Overview of Study Design; Immunogenicity Evaluations; Statistical 
Methods
Schedule of Activities (Cohort 3)
1.2 Overall Rationale for the Study
2.1 Objectives and Endpoints
3.1.1 Study Design
3.1.2 Study Procedures
3.2 Study Design Rationale
4 Participant Population
5 Treatment Allocation and Blinding

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9.1.1 Overview
9.1.2 Visit Windows
9.1.3 Screening Phase
9.1.4 Randomization
9.1.5 Vaccination
9.1.6 Post-vaccination Follow-up
9.1.8 Early Withdrawal: Early Exit Visit
9.2.1 Immunogenicity
11.1 Analysis Sets
11.2.3 Sample Size Determination (Cohort 3)
11.4.2 Immunogenicity Analyses (Cohort 3)
11.6.3 Planned Analyses (Cohort 3)
11.8 Data Review Committee
Rationale: Clarification that participants with a history of allergy to egg protein will be excluded from the study
4.2 Exclusion Criteria
Rationale: Clarification that, for pausing rules 1, 3 and 4, the term “related to study vaccine” excludes seasonal 
influenza vaccine/placebo for seasonal influenza vaccine
11.9 Study Vaccination Pausing Rules
Rationale: Other clarifications and minor corrections to remove inconsistencies
Synopsis: Dosage and Administration
Schedule of Activities
1.1 Background
5 Treatment Allocation and Blinding
6 Dosage and Administration
10.2 Discontinuation of Study Vaccine
12.1.1 Adverse Event Definitions and Classifications
12.3.3 Pregnancy

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SYNOPSIS
A Randomized, Double-blind, Placebo-controlled Phase 1/2a Study for Safety and Immunogenicity 
Evaluations for Regimen Selection of Ad26.RSV.preF and/or RSV preF Protein Combinations 
Followed by Expanded Safety Evaluation in Adults Aged 60 Years and Older
A human adenovirus-vectored vaccine candidate and a pre-fusion conformation-stabilized respiratory 
syncytial virus (RSV) F protein which have shown promise in preclinical animal models of RSV will be 
assessed in this study:

Ad26.RSV.preF (JNJ-64400141), a replication-incompetent adenovirus serotype 26 (Ad26)
containing a deoxyribonucleic acid (DNA) transgene that encodes the pre-fusion conformation-
stabilized F protein (pre-F) derived from the RSV A2 strain.

RSV preF protein (JNJ-64213175) is a pre-fusion conformation-stabilized F protein derived from the 
RSV A2 strain.
This will be the first-in-human (FIH) study for RSV preF protein, and for the Ad26.RSV.preF/RSV preF 
protein combination (administered as separate injections in opposite arms) and Ad26.RSV.preF/RSV preF 
protein mixture (administered as a single injection).
OBJECTIVES, ENDPOINTS, AND HYPOTHESIS
Objectives and Endpoints
The current study has an adaptive design to determine a regimen for further clinical development in adults 
aged ≥60 years based on safety and immunogenicity. The selected regimen should improve humoral 
immune response with no adverse effect on cellular response compared to Ad26.RSV.preF alone.
SAFETY COHORT OBJECTIVE (COHORT 1): To determine in small numbers of participants aged 60 years and older the 
safety of intramuscular homologous two-dose regimens comprising RSV preF protein or Ad26.RSV.preF/RSV preF protein 
mixture on Days 1 and 57, with a booster at Month 12, or separate administration of Ad26.RSV.preF and RSV preF protein in 
opposite arms on Day 1 with a booster at Month 12, before progression to regimen selection in a larger number of participants
Objectives
Endpoints
PRIMARY

To assess the safety and reactogenicity of the 
intramuscular one- and two-dose regimens, with 
a booster at Month 12

Serious adverse events (SAEs) from first dose 
administration until the end of the study

Solicited local and systemic adverse events (AEs) for 
7 days after each vaccine administration

Unsolicited AEs from the time of each vaccine 
administration through the following 28 days
SECONDARY

To assess the humoral and cellular immune responses 
elicited by Ad26.RSV.preF, RSV preF protein, and the 
Ad26.RSV.preF/RSV preF protein combination and 
mixture

RSV neutralization assay, F protein binding antibodies 
(enzyme-linked immunosorbent assay [ELISA]; pre-F 
and/or post-F), and interferon-gamma (IFN-γ) enzyme-
linked immunospot (ELISpot) assay
EXPLORATORY

Additional exploratory analyses may be performed to 
investigate vaccine-elicited immune responses further

Assays to be used include, but are not limited to, RSV 
strain cross-neutralization, anti-F protein antibody 
specificity and functionality characterization, adenovirus 
neutralization assays, molecular antibody 
characterization (avidity, Fc cell interaction, antibody 
isotyping, antibody sequencing for repertoire), and nasal 
antibodies to RSV, including but not limited to 
immunoglobulin (Ig)A and IgG; evaluation of the 
cellular immune response and the functional and 
memory immune response by intracellular cytokine 
staining (ICS) and transcriptome analysis

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Objectives
Endpoints

To evaluate symptoms of respiratory illness (including
respiratory illness due to RSV) via the Respiratory 
Tract Infection (RTI) Symptoms Form

During the RSV season: Signs and symptoms of RTI 
(including RTI due to RSV) from Day 1 until the end of 
the second RSV season of the studya

Characterization of viral or bacterial infections in the 
respiratory tract

Assessment, typing and level of infection by reverse 
transcriptase polymerase chain reaction (RT-PCR) or 
response to respiratory infection by serology
REGIMEN SELECTION COHORT OBJECTIVE (COHORT 2): To select a regimen for progression to evaluation in an 
expanded safety cohort (Cohort 3; see below) by assessment of the safety and immunogenicity in participants aged 60 years 
and older of intramuscular one-dose regimens of Ad26.RSV.preF, Ad26.RSV.preF/RSV preF protein mixture, or separate 
administration of Ad26.RSV.preF and RSV preF protein in opposite arms on Day 1, or a two-dose regimen of Ad26.RSV.preF/
RSV preF protein mixture on Days 1 and 57 
Objectives
Endpoints
PRIMARY

To assess the safety and reactogenicity of the 
intramuscular one- and two-dose regimens

SAEs from first dose administration until the end of 
the study

Solicited local and systemic AEs for 7 days after each 
vaccine administration

Unsolicited AEs from the time of each vaccine 
administration through the following 28 days

To assess RSV neutralizing antibody levels of the 
one-dose regimens (Groups 11 to 15) containing
RSV preF protein compared to the one-dose 
Ad26.RSV.preF regimen 

RSV A2 neutralizing antibody levels of the one-dose 
regimens (Groups 11 to 15) on Day 29b
SECONDARY

To assess RSV neutralizing antibody levels of the 
one-dose regimen with separate injections 
(Group 16) and the two-dose regimen (Group 17) 
containing RSV preF protein compared to the 
one-dose Ad26.RSV.preF regimen

RSV A2 neutralizing antibody levels of:

the one-dose regimen with separate injections
(Group 16) on Day 29

the two-dose regimen (Group 17) on Day 85b

To assess additional humoral immune responses 
elicited by Ad26.RSV.preF and the 
Ad26.RSV.preF/RSV preF protein combination 
and mixture

F protein binding antibodies (ELISA; pre-F and/or post-F)

To assess cellular immune responses by 
IFN-γ ELISpot of all regimens containing RSV 
preF protein compared to the one-dose 
Ad26.RSV.preF regimen 

RSV F protein by IFN-γ ELISpot assay
- the one-dose regimens on Day 29b (Groups 11 to 16)
- the two-dose regimen on Day 85b (Group 17)
EXPLORATORY

Additional exploratory analyses may be performed 
to investigate vaccine-elicited immune responses 
further

Assays to be used include, but are not limited to, RSV strain 
cross-neutralization, anti-F protein antibody specificity and 
functionality characterization, adenovirus neutralization 
assays, molecular antibody characterization (avidity, Fc cell 
interaction, antibody isotyping, antibody sequencing for 
repertoire), and nasal antibodies to RSV, including but not 
limited to IgA and IgG; evaluation of the cellular immune 
response and the functional and memory immune response 
by ICS and transcriptome analysis
                                                
a The second RSV season of the study is defined relative to the enrollment date of the first participant in Cohort 1.
b See “STATISTICAL METHODS - Immunogenicity Analyses” for details.

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Objectives
Endpoints

To assess the long-term durability of the immune 
response in selected groups

Assays to be used include, but are not limited to, RSV 
neutralizing antibody levels against A and B strain, RSV F 
protein binding antibodies (ELISA; pre-F and/or post-F), 
RSV F protein specific functional antibodies, and RSV F 
protein specific IFN-γ ELISpot in Groups 14 and 15 at Days 
912 and 1095

To evaluate symptoms of respiratory illness
(including respiratory illness due to RSV) via the 
RTI Symptoms Form

During the RSV season: Signs and symptoms of RTI 
(including RTI due to RSV) from Day 1 until the end of the 
second RSV season of the studya

Characterization of viral or bacterial infections in 
the respiratory tract

Assessment, typing and level of infection by RT-PCR or 
response to respiratory infection by serology
EXPANDED SAFETY COHORT OBJECTIVE (COHORT 3): To determine the safety and immunogenicity of the selected 
regimen in an expanded cohort of participants aged 60 years and older; and to determine the need for a booster dose at 
Month 12 and/or Month 24
Objectives
Endpoints
PRIMARY

To assess the safety and reactogenicity of the selected 
regimen and a booster at Month 12 and/or Month 24

SAEs from first administration until the end of the study

Solicited local and systemic AEs for 7 days after each 
vaccine administration

Unsolicited AEs from the time of each vaccine 
administration through the following 28 days
SECONDARY

To assess humoral immune responses to the selected 
regimen in all participants 

RSV neutralization A2 strain

To assess cellular immune responses to the selected 
regimen in a subset of participants

IFN-γ ELISpot assay 
EXPLORATORY

Additional exploratory analyses may be performed to 
further investigate vaccine-elicited immune responses 
Assays to be used include, but are not limited to:

F protein binding antibodies (ELISA; pre-F and/or 
post-F)

Flow cytometry 

RSV cross-neutralization of B and/or other A strain

F-protein antibody specificity characterization

Cytokines/chemokines in nasal samples (if feasible)

Adenovirus neutralization assays

Functional and molecular antibody characterization

Analysis of nasal antibodies to RSV including, but not 
limited to IgA and IgG

To assess the long-term durability of the immune 
response in groups receiving a booster at different time 
intervals 

Assays to be used include, but are not limited to, RSV 
neutralizing antibody levels against A and B strain, RSV 
F protein binding antibodies (ELISA; pre-F and/or post-
F), RSV F protein specific functional antibodies, and RSV 
F protein specific IFN-γ ELISpot at Days 758, 912 and 
1095

To evaluate symptoms of respiratory illness (including 
respiratory illness due to RSV) via the RTI Symptoms 
Form

During the RSV season: Signs and symptoms of RTI 
(including RTI due to RSV) from Day 1 until the end of 
the second RSV season of the studya

Characterization of viral or bacterial infections in the 
respiratory tract

Assessment, typing and level of infection by RT-PCR or 
response to respiratory infection by serology
                                                
a The second RSV season of the study is defined relative to the enrollment date of the first participant in Cohort 1.

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Hypothesis
No formal statistical testing of safety and immunogenicity data is planned. Data will be analyzed 
descriptively.
OVERVIEW OF STUDY DESIGN
This is a multi-center, randomized, double-blind, placebo-controlled Phase 1/2a study for safety and 
immunogenicity evaluations for regimen selection of Ad26.RSV.preF and RSV preF protein combinations 
followed by expanded safety evaluation of the selected regimen in male and female participants aged ≥60
years who are in stable health.
To further extend the assessment of the long-term durability of the immune response to the study vaccine, 
participants in Groups 14 and 15 (Cohort 2) will continue into a long-term follow-up phase.
The study design includes 3 sequential cohorts: an initial safety cohort (Cohort 1 in a total of 
64 participants), a regimen selection cohort (Cohort 2 in a total of 288 participants), and an expanded safety 
cohort (Cohort 3 in a total of 315 participants).
The overall total number of participants will be approximately 667.
Thestudyduration will be approximately 730 days (2 years) per participant in Cohorts 1 and 2 (Groups 11-
13 and Groups 16-18), and approximately 1095 days (3 years) per participant in Cohort 2 (Groups 14-15) 
and Cohort 3. The study comprises a maximum 28-day screening period for Cohorts 1 and 2 (screening for 
Cohort 3 will be performed pre-vaccination on Day 1), study vaccination (active or placebo) with a one-
dose (on Day 1) or two-dose (on Day 1 and Day 57) regimen and a booster dose (active or placebo) at 
Month 12 (Cohort 1) or at Month 12 and Month 24 (Cohort 3), a minimum 28-day follow-up period after 
each vaccination, and a follow-up period until 2 years after the first Ad26.RSV.preF or RSV preF protein 
vaccination (Cohorts 1 and 2 [Groups 11-13 and Groups 16-18]) or until 3 years after the first 
Ad26.RSV.preF or RSV preF protein vaccination (Cohort 2 [Groups 14-15] and Cohort 3). The end of the 
study is defined as the last participant’s last visit 24 months after the first vaccination (Cohorts 1 and 2 
[Groups 11-13 and Groups 16-18]) or the last participant’s last visit approximately 1095 days (3 years) after 
the first vaccination (Cohort 2 [Groups 14-15] and Cohort 3). 
An internal data review committee (DRC) will be established for this study to evaluate safety and 
reactogenicity data on a regular basis.
If any of the pre-specified study vaccination pausing rules is met, further study vaccination will be paused 
and a DRC meeting will be convened.
The DRC may also review unblinded immunogenicity data during the course of the study if this is deemed 
necessary for future vaccine development-related decisions.
Initial Safety Cohort (Cohort 1)
In the initial safety cohort, participants will be randomized progressively in 1 of 4 randomizations (R1a 
through R1d) with safety checks in place before extending enrollment and progressing from one 
randomization step to the next as follows (Table 1):

Cohort R1a. Initially 2 participants will be enrolled, 1 into Group 1 and 1 into Group 2, and will receive 
a single dose of placebo or 50 g of RSV preF protein, respectively. Enrollment will be paused to 
allow for 24-hour safety assessments in these 2 sentinel participants by the principal investigator(s) 
(PI[s]), the sponsor’s study responsible physician/scientist (SRP/S), and the sponsor’s medical leader 
(ML). In the absence of any clinical safety concerns over the 24-hour assessment, the remaining 
10 participants will be randomized and dosed. Seven days after the last participant has received his/her 

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first dose, available safety data will be reviewed by the PI(s), SRP/S, ML, and the sponsor’s therapeutic 
area safety head (TASH) before proceeding to Cohort R1b.

Cohort R1b. Initially 3 participants will be enrolled, 1 into each of Groups 3 through 5, and will receive 
a single dose of placebo, 5×1010 viral particles (vp) Ad26.RSV.preF/50g RSV preF protein, or 150 g
RSV preF protein, respectively. Enrollment will be paused to allow for 24-hour safety assessments in 
the 3 sentinel participants by the PI(s), SRP/S, and ML. In the absence of any clinical safety concerns 
over the 24-hour assessment, the remaining 17 participants will be randomized and dosed. Seven days 
after the last participant has received his/her first dose, available safety data will be reviewed by the 
PI(s), SRP/S, ML, and TASH before proceeding to Cohort R1c.

Cohort R1c. Initially 2 participants will be enrolled, 1 into Group 6 and 1 into Group 7, and will receive 
a single dose of placebo or 5×1010 vp Ad26.RSV.preF/150 g RSV preF protein, respectively. 
Enrollment will be paused to allow for 24-hour safety assessments in these 2 sentinel participants by 
the PI(s), SRP/S, and ML. In the absence of any clinical safety concerns over the 24-hour assessment, 
the remaining 10 participants will be randomized and dosed. Seven days after the last participant has 
received his/her first dose, available safety data will be reviewed by the PI(s), SRP/S, ML, and TASH
before proceeding to Cohort R1d.

Cohort R1d. Initially 3 participants will be enrolled, 1 into each of Groups 8 through 10, and will 
receive 2 doses of placebo (1 in each arm), or 1×1011 vp Ad26.RSV.preF/150 g RSV preF protein, 
with placebo in the opposite arm, or 1×1011 vp Ad26.RSV.preF in one arm and 150 g RSV preF 
protein in the opposite arm. Enrollment will be paused to allow 24-hour safety assessments in the 
3 sentinel participants by the PI(s), SRP/S, and ML. In the absence of any clinical safety concerns over 
the 24-hour assessment, the remaining 17 participants will be randomized and dosed.

Seven days after the final participant in Cohort 1 has received his/her first dose, all available safety 
data at that time for the whole cohort will be reviewed by the DRC before proceeding to Cohort 2.
Sentinel participants will be contacted by telephone 24 hours post-dose to collect safety information.
Progression to the regimen selection cohort will be based on acceptable safety in the initial safety cohort, 
as determined by DRC review of Day 8 safety data in all participants.

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Table 1:
Study Design: Initial Safety Cohort (Cohort 1)
Group
R
N
Day 1
Day 57
Month 12
1
R1a
4
Placebo
Placebo
Placebo 
2
R1a
8
RSV preF protein 50 g
RSV preF protein 50 g
RSV preF protein 50 g
3
R1b
4
Placebo
Placebo
Placebo 
4
R1b
8
Ad26.RSV.preF/
RSV preF protein mixture:
5×1010 vp/50 g
Ad26.RSV.preF/
RSV preF protein mixture:
5×1010 vp/50 g
Ad26.RSV.preF/
RSV preF protein mixture:
5×1010 vp/50 g
5
R1b
8
RSV preF protein 150 g
RSV preF protein 150 g
RSV preF protein 150 g
6
R1c
4
Placebo
Placebo
Placebo 
7
R1c
8
Ad26.RSV.preF/
RSV preF protein mixture:
5×1010 vp/150 g
Ad26.RSV.preF/
RSV preF protein mixture:
5×1010 vp/150 g
Ad26.RSV.preF/
RSV preF protein mixture:
5×1010 vp/150 g
8
R1d
4
Placebo
+ Placebo*
Placebo
Placebo
+ Placebo*
9
R1d
8
Ad26.RSV.preF/
RSV preF protein mixture:
1×1011 vp/150 g
+ Placebo*
Ad26.RSV.preF/
RSV preF protein mixture:
1×1011 vp/150 g
Ad26.RSV.preF/
RSV preF protein mixture:
1×1011 vp/150 g
+ Placebo*
10
R1d
8
Separate injections: 
Ad26.RSV.preF 1×1011 vp 
+ RSV preF protein 150 g*
Placebo
Separate injections: 
Ad26.RSV.preF 1×1011 vp 
+ RSV preF protein 150 g*
R1 TOTAL:
64
N: number of participants; R: randomization; vp: viral particles
* Each injection to be given in opposite arms
Regimen Selection Cohort (Cohort 2)
In the regimen selection cohort, approximately 288 participants will be randomized in parallel to 1 of 
8 groups (Groups 11 through 18; Table 2). No pauses in enrollment for safety assessments are planned.
Based on safety and immunogenicity results available at the time of primary analysis, a sponsor committee 
will decide which regimen will be used for the expanded safety cohort (Cohort 3). In case none of the 
groups that are part of the primary objective meet internal criteria, regimen selection may be delayed until 
additional analyses will be available. Additional factors such as data from other assays, manufacturability, 
and ease of administration will be taken into account to select the regimen for the expanded safety phase.

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Table 2:
Study Design: Regimen Selection Cohort (Cohort 2)
Group
R
N
Day 1
Day 57
11
R2
24
Ad26.RSV.preF 1×1011 vp
+ Placebo*
Placebo
12
R2
42
Ad26.RSV.preF/
RSV preF protein mixture:
5×1010 vp/50 g
+ Placebo*
Placebo
13
R2
42
Ad26.RSV.preF/
RSV preF protein mixture:
1×1011 vp/50 g
+ Placebo*
Placebo
14
R2
42
Ad26.RSV.preF/
RSV preF protein mixture:
1×1011 vp/150 g
+ Placebo*
Placebo
15
R2
42
Ad26.RSV.preF/
RSV preF protein mixture:
5×1010 vp/150 g
+ Placebo*
Placebo
16
R2
36
Separate injections*: 
Ad26.RSV.preF 1×1011 vp 
+ RSV preF protein 150 g
Placebo
17
R2
36
Ad26.RSV.preF/
RSV preF protein mixture:
1×1011 vp/150 g
+ Placebo*
Ad26.RSV.preF/
RSV preF protein mixture:
1×1011 vp/150 g
18
R2
24
Placebo
+ Placebo*
Placebo
R2 TOTAL:
288
N: number of participants (Note: Data from Groups 9 and 10 of Cohort 1 will be pooled with those from Groups 16 and 17 of 
Cohort 2) up to Month 12; R: randomization; vp: viral particles
* Each injection to be given in opposite arms
Expanded Safety Cohort (Cohort 3)
In the expanded safety cohort, approximately 315 participants will be randomized in parallel to 1 of 3
groups (Groups 19 through 21; Table 3 and Table 4). No pauses in enrollment for safety assessments are 
planned.
Participants will receive the selected one- or two-dose regimen from Cohort 2 or placebo.
If the one-dose regimen is selected (Groups 11 through 16 from Cohort 2), Groups 19 and 20 would receive 
the selected regimen on Day 1, and a booster at Month 12 (the selected regimen or placebo, respectively)
and Month 24 (the selected regimen). Group 21 will receive placebo at all timepoints (Table 3).
If the two-dose regimen is selected (Group 17 of Cohort 2), Groups 19 and 20 would receive the selected 
regimen on Day 1 and on Day 57, and a booster (the selected regimen or placebo, respectively) at Month 
12. Group 21 will receive placebo at all three timepoints (Table 4).

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Table 3:
Study Design: Expanded Safety Cohort (Cohort 3) with One-dose Regimen and Month 12 and Month 24 
Booster
Group
R
N
Day 1
Month 12
Month 24
19
R3
135
Selected Regimen
Selected Regimen
Selected Regimen
20
R3
135
Selected Regimen
Placebo for the Selected 
Regimen
Selected Regimen
21
R3
45
Placebo for the Selected 
Regimen
Placebo for the Selected 
Regimen
Placebo for the Selected 
Regimen
R3 TOTAL:
315
OVERALL 
TOTAL:
667
N: number of participants; R: randomization
Table 4:
Study Design: Expanded Safety Cohort (Cohort 3) with Two-dose Regimen and Month 12 Booster
Group
R
N
Day 1
Day 57
Month 12
19
R3
135
Selected Regimen
Selected Regimen
Selected Regimen
20
R3
135
Selected Regimen
Selected Regimen
Placebo for the Selected Regimen
21
R3
45
Placebo for the Selected Regimen Placebo for the Selected Regimen Placebo for the Selected Regimen
R3 TOTAL:
315
OVERALL 
TOTAL:
667
N: number of participants; R: randomization
PARTICIPANT POPULATION
Participants will be adult men and women, aged ≥60 years on the day of signing the informed consent form 
(ICF). Participants will be in good or stable health (on the basis of physical examination, medical history, 
laboratory safety dataa, 12-lead electrocardiogram,a and vital signs measurement performed at screening).
DOSAGE AND ADMINISTRATION
Ad26.RSV.preF and RSV preF protein will be administered as a combination (ie, as separate injections in 
opposite arms) or as a mixture (ie, as a single injection) into the deltoid muscle according to the schedules 
shown in Table 1, Table 2, Table 3, and Table 4:

Ad26.RSV.preF (JNJ-64400141) will be supplied at a concentration of 2×1011 vp/1 mL in single-use 
vials. Dose levels of 5×1010 vp and 1×1011 vp will be used.

RSV preF protein (JNJ-64213175) will be supplied at a concentration of 0.3 mg/1 mL in single use 
vials. Dose levels of 50 μg and 150 μg will be used.

Placebo for Ad26.RSV.preF and RSV preF protein.
All injections of Ad26.RSV.preF and RSV preF protein (or corresponding placebo) will be 1 mL in volume. 
An unblinded pharmacist or other qualified individual will prepare the appropriate vial and/or syringe and 
provide the syringe in a blinded manner to the vaccine administrator who will perform the injection. The 
unblinded pharmacist, or other qualified individual, may also perform vaccine administration, but will have 
no other study function following dosing. Diluent will be used as required.
                                                
a For participants in Cohorts 1 and 2 only.

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All vaccines should be administered in the deltoid muscle:

When participants receive 2 injections at any given visit, the injections will be given in opposite arms 
at the same time with no more than 45 minutes between the injections.

When participants receive a single injection per visit, eg, in Groups 1 through 7 in Cohort 1, alternating 
injection sites will be used for subsequent injections unless there is a medically justifiable reason in the 
judgment of the PI(s).
IMMUNOGENICITY EVALUATIONS
All sample collection and processing will be performed by the staff at the clinical sites according to current 
versions of approved standard operating procedures.
Humoral and cellular immunogenicity assays that may be used in this study (as available and applicable) 
are summarized in Table 5 and Table 6 below.
Blood for humoral and cellular immune responses will be drawn from all participants in Cohorts 1 and 2.
In Cohort 3, blood will be drawn for humoral immune responses from all participants and for cellular 
immune responses from a subset of 63 participants. Nasal samples will be used for immunogenicity 
assessments (eg, immunoglobulin or cellular immune component) and identification of the etiology of 
respiratory infections (if needed). Blood samples for transcriptome analysis will be collected in Cohorts 1 
and 2 only.
In addition to RT-PCR performed on nasal samples,a any immunogenicity blood sample collected from all 
participants may be assayed by serology (including but not limited to RSV virus neutralizing antibodies 
[VNAs] or ELISA specific to RSV protein G [glycoprotein] and/or N [nucleoprotein] as available and 
applicable) for RSV exposure.
Table 5:
Summary of Immunogenicity Assays (Humoral)
Assay 
Purpose
Primary endpoint (Regimen Selection Cohort [Cohort 2] – Groups 11 to 15 only)
RSV neutralization A 
Analysis of neutralizing antibodies to an A strain
Secondary endpoints
RSV neutralization A 
Analysis of neutralizing antibodies to an A strain
F protein antibodies
(ELISA; pre-F and/or post-F) 
Analysis of antibodies binding to RSV F protein in pre-fusion and/or post-fusion form
Exploratory endpoints
RSV strain cross-neutralization 
Analysis of cross-neutralizing antibodies to B and/or a different A strain(s) 
F protein antibody specificity 
characterization 
Pre- and post-F specificity by binding or functional assays as ELISA, and/or competition 
ELISA. Adsorption of serum or plasma with pre-F and post-F protein before any 
antibody assay, epitope mapping, functional VNAs
G and/or N protein antibodies 
(ELISA) 
Analysis of antibodies binding to RSV G and/or N protein 
Adenovirus neutralization assay
Analysis of neutralizing antibodies to adenovirus
Functional and molecular antibody 
characterization
Analysis of antibody characteristics including, but not limited to, ADCC, ADCP, avidity, 
other respiratory viral neutralizing or binding assays, Ig isotype, functional VNAs to 
other respiratory viruses, and antibody assessments for antibody repertoire
ADCC: antibody-dependent cell-mediated cytotoxicity; ADCP: antibody-dependent cellular phagocytosis; ELISA: enzyme-linked 
immunosorbent assay; F: fusion; G: glycoprotein; Ig: immunoglobulin; N: nucleoprotein; RSV: respiratory syncytial virus; VNA:
virus neutralizing antibody
Note: Antibody analyses might be performed in nasal samples, serum and plasma.
                                                
a All references to the collection of a “nasal sample” imply a “nasal turbinate sample or its alternative”.

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Table 6:
Summary of Immunogenicity Assays (Cellular)
Assay 
Purpose
Secondary endpoints
IFN-γ ELISpot
T-cell IFN-γ responses to RSV F protein peptides
Exploratory endpoints
ICS
Analysis of T-cell responses to RSV F protein peptide-stimulated PBMC (including, 
but not limited to, CD4+/CD8+, IL-2, IFN-γ, TNF-α, activation markers and memory)
Transcriptome analysis
Regulation of genes (clusters), expression patterns, that predict specific immune 
responses after vaccination
Chemokine/cytokine analysis
Levels of chemokines and cytokines in nasal samples
Sequencing of B-cells
Including but not limited to sequencing of BCR (B-cell receptor) or VH/VL 
(heavy/light chain characterization) for specificity
ELISpot: enzyme-linked immunospot; F: fusion; ICS: intracellular cytokine staining; IFN-γ: interferon gamma; IL-2:
interleukin-2; PBMC: peripheral blood mononuclear cells; RSV: respiratory syncytial virus; TNF-α: tumor necrosis factor 
alpha
RTI PROCEDURES
During the first 2 RSV seasons of the study (relative to the enrollment date of the first participant in 
Cohort 1), participants should record any signs and symptoms of RTI (such as runny nose, fever, severe 
cough, rapid breathing, or difficulty breathing), including measurement of body temperature, on a daily 
basis using a specific RTI Symptoms Form, starting on the first day they experience symptoms, including 
the day on which the symptoms resolve.
If respiratory symptoms develop during the first 2 RSV seasons of the study, the following should take 
place:

Participants should contact the site as soon as possible to notify the site of an RTI.

Participants should record signs and symptoms of the RTI (including measurement of body temperature) 
daily using the RTI Symptoms Form until the day of symptom resolution.

If feasible, participants should take a nasal sample at home, preferably between 2 and 3 days after the 
onset of the RTI symptoms. The sample should be stored refrigerated and brought to the site by the 
participant within 3 to 4 days.

Alternatively, participants may go to the site preferably within 2 to 3 days after the onset of the RTI to 
have a nasal sample taken by the study staff.
During the first 2 RSV seasons of the study, participants will be contacted by telephone every 30±7 days 
(unless a planned clinic visit has occurred or will occur within 30 days). These calls will remind participants 
to complete the RTI Symptoms Form in the event of any symptoms of RTI, to contact the site at the time 
of symptom onset, and to take a nasal sample (or go to the site to have a nasal sample taken by study staff). 
These calls will also check for any SAEs and concomitant medications associated with SAEs since the 
previous visit or telephone contact.
The presence of RSV or any other respiratory infection may be assessed by the sponsor by RT-PCR 
diagnostics on the nasal samples, which may include viral load and RSV subtyping.
Blood from participants with a suspected RTI may be assayed by a serological assay (eg, protein G and/or 
N ELISA) to confirm RSV infection. (No additional blood sampling is necessary – any serological assay 
conducted to confirm RSV infection will use blood from the existing samples.)
Every effort should be made to collect data on the clinical course of RTIs including information on 
oxygenation status, supplemental oxygen requirements and specific drug treatments, as well as other 
concurrent respiratory illness present at the time of the diagnosis of the event and up to symptom resolution.

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Any RTI that is not due to RSV infection will be reported as an AE if it occurs between the time of any 
vaccination through the next 28 days. Any RTI recorded as an AE in the eCRF will be excluded from any 
AE analysis if the central laboratory RT-PCR is subsequently found to be positive for RSV. RTIs arising 
from RSV infection will not be reported as (S)AEs in the Clinical Study Report as they are endpoints of the 
study and will be tabulated separately.
Any RTI fulfilling the criteria of an SAE will be reported as such during the entire study period if RT-PCR 
indicates it is not an RSV-RTI. If the RT-PCR is positive for RSV the event should not be reported as an 
SAE. If the RT-PCR information is not available within 24 hours of knowledge of the event, the event will 
be reported as an SAE, but will be subsequently downgraded from SAE status if it later turns out to be RT-
PCR positive for RSV.
SAFETY EVALUATIONS
On a daily basis, for 7 days after each vaccination, participants will be asked to record the following AEs 
via the participant diary:

Solicited local AEs: erythema (measured using the ruler supplied), swelling/induration (measured using 
the ruler supplied and graded using the functional scale), and pain/tenderness.

Solicited systemic AEs: fatigue, headache, myalgia, arthralgia, chills, nausea, and fever (ie, body 
temperature ≥38.0 °C).
Body temperature (oral route preferred) should be measured at approximately the same time each day, 
preferably in the evening, using the thermometer supplied. All diary assessments, including body 
temperature, 7 days after each vaccination may be collected earlier in the day to coincide with the clinic
visit.
Unsolicited AEs will be collected for 28 days after each vaccination (ie, from the time of each vaccination 
through the following 28 days).a SAEs will be collected from first dose administration to the end of the 
double-blind phase of the study. During the long-term follow-up phase (Groups 14 and 15 from Cohort 2), 
only SAEs related to study vaccine, study procedures, or non-investigational (concomitant) Janssen 
products, and all AEs leading to discontinuation will be collected. All AEs, including any that are ongoing 
at 28 days after each dose, will be followed until clinical resolution or stabilization. Concomitant 
medications will be collected from the time of each vaccination, through 28 days after each vaccination, 
and additionally outside these periods when associated with any SAE. During the long-term follow-up 
phase (Groups 14 and 15 from Cohort 2), only medications in conjunction with SAEs related to study 
vaccine, study procedures, or non-investigational (concomitant) Janssen products, or in conjunction with 
AEs leading to discontinuation should be recorded.
All SAEs and AEs leading to discontinuation from the study/vaccination (regardless of the causal 
relationship) are to be reported from the moment of first vaccination until completion of the participant’s 
last study-related procedure, which may include contact for safety follow-up.
                                                
a AEs that start more than 28 days after a vaccination, but that are still present at the time of the next vaccination will 
also be recorded.

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STATISTICAL METHODS
Sample Size Determination
For Cohort 1, no formal sample size calculations are done.
For Cohort 2, the objective is to compare the RSV A2 neutralizing antibody levels of all regimens 
containing RSV preF protein (Groups 12 through 17) to the one-dose Ad26.RSV.preF regimen (Group 11). 
This will be based on the GMT ratios and corresponding 95% confidence intervals (CIs) of the VNA A2 
levels of the regimens containing RSV preF protein on Day 29 for the one-dose regimens (Groups 12 
through 16) and on Day 85 for the two-dose regimen (Group 17) versus the VNA A2 levels on Day 29 of 
the one-dose Ad26.RSV.preF regimen (Group 11). The sample size was selected to provide a precision of 
~0.53 on the log2 scale.
Note: Immunogenicity data from Groups 9 and 10 of the initial safety cohort (Cohort 1) will be combined 
with those from Groups 16and 17 of the regimen selection cohort (Cohort 2).
The table below presents the resulting 95% CIs for several observed ratios, assuming a standard deviation 
for VNA of 1 on the log2 scale and accounting for 5% dropout.
Observed Ratio
Corresponding 95% CI
1
[0.69; 1.44]
1.2
[0.83; 1.73]
1.5
[1.04; 2.17]
In addition to the above, factors such as data from other assays, reactogenicity profiles, manufacturability 
and ease of administration will be considered when selecting the regimen for the expanded safety phase.
The expanded safety cohort (Cohort 3) should provide sufficient safety data on the selected regimen to 
support late stage development if the immunogenicity results of Cohort 2 are satisfactory.
Planned Analyses
Note: Depending on the timing, some of the planned analyses might be combined.
Initial Safety Cohort (Cohort 1) – Primary Analysis
Primary analysis: analysis of safety data 28 days post-dose 2. Data collected up to the time of the visit at 
28 days after the second dose of study vaccine for the last participant in Cohort 1 will be included in the 
analysis. This analysis will be performed on unblinded data. The blind will be maintained at the 
participant/site level.
As immunogenicity data from Groups9 and 10 of the initial safety cohort (Cohort 1) will be combined with 
those from Groups 16 and 17 of the regimen selection cohort (Cohort 2), immunogenicity data from the 
initial safety cohort will be analyzed at the time of the primary analysis of the regimen selection cohort.
Initial Safety Cohort (Cohort 1) – Analysis 28 Days Post-Month 12 Booster
This analysis will include safety and immunogenicity data, and will be performed on unblinded data. Data 
collected up to the time of the visit at 28 days after the Month 12 booster dose of study vaccine for the last 
participant in this cohort will be included in the analysis. The blind will be maintained at the participant/site 
level.
Regimen Selection Cohort (Cohort 2) – Primary Analysis
Primary analysis: analysis of safety data 28 days post-dose 2 and immunogenicity data up to at least 28 days 
post-dose 1. 

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
This analysis should contain all safety data collected up to the time of the visit at 28 days after the 
second dose for the last participant in this cohort.

Immunogenicity data from at least Groups 11 to 15 and part of Group 18 (placebo group), up to at 
least 28 days post-dose 1 will be included as well.a

This analysis will be performed on unblinded data. The blind will be maintained at the participant/site 
level.
In this analysis, all available immunogenicity data of the initial safety cohort (Cohort 1) will be analyzed 
as well.
Regimen Selection Cohort (Cohort 2) – Additional Analysis
Additional analysis: analysis of immunogenicity data 28 days post-dose 1 for all one-dose regimens 
(including the one-dose regimen with separate injections) and 28 days post-dose 2 for the two-dose regimen.
This analysis may include immunogenicity data available from additional timepoints.
This analysis should contain immunogenicity data up to at least day 28 post-dose 1 for one-dose regimens 
and 28 days post-dose 2 for the two-dose regimen. This analysis will be performed on unblinded data. The 
blind will be maintained at the participant/site level.
In this analysis, all available immunogenicity data of Groups 9 and 10 from the initial safety cohort (Cohort 
1) and immunogenicity data of Cohort 2 included in the primary analysis will be analyzed as well.
The primary analysis of Cohort 1 and Cohort 2 and the additional analysis may be combined into one 
analysis.
Regimen Selection Cohort (Cohort 2) – Analysis 1 Year Post-first Vaccination
This analysis will include immunogenicity data, and will be performed on unblinded data. Data collected 
up to the time of the visit at 12 months after the first dose of study vaccine for the last participant in this 
cohort will be included in the analysis. The blind will be maintained at the participant/site level.
Regimen Selection Cohort (Cohort 2-Groups 14 and 15) – Analysis 2 Years Post-first Vaccination
This analysis will include immunogenicity data, and will be performed on unblinded data. Data collected 
up to the time of the visit at 24 months after the first dose of study vaccine for the last participant in these
2 groups will be included in the analysis. 
Expanded Safety Cohort (Cohort 3) – Primary Analysis
Primary analysis: analysis of safety and immunogenicity data up to Day 29 if a one-dose regimen is selected 
or up to Day 85 if a two-dose regimen is selected. This analysis should at least contain safety data collected 
up to the time of the Day 29 visit for the last participant in this cohort in case a one-dose regimen is selected 
and up to the time of the Day 85 visit for the last participant in this cohort in case a two-dose regimen is 
selected.a If the corresponding immunogenicity data are not available at the time of database lock, they will 
be analyzed at a later timepoint. This analysis will be performed on unblinded data. The blind will be 
maintained at the participant/site level.
                                                
a An unblinded person who is not part of the study team (or another independent party) will dictate which Day 29 samples should 
be analyzed by the clinical immunology laboratory. Half of the Day 29 samples of Group 18 (placebo group) will be included to 
ensure the blind at the level of the clinical immunology laboratory.

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Expanded Safety Cohort – Analysis 28 Days Post-Month 12 Booster
This analysis will include safety and immunogenicity data, and will be performed on unblinded data. Data 
collected up to the time of the visit at 28 days after the Month 12 booster dose of study vaccine for the last 
participant in this cohort will be included in the analysis. The blind will be maintained at the participant/site 
level.
Expanded Safety Cohort – Analysis 28 Days Post-Month 24 Booster
This analysis will include safety and immunogenicity data, and will be performed on unblinded data. Data 
collected up to the time of the visit at 28 days after the Month 24 booster dose of study vaccine for the last 
participant in this cohort will be included in the analysis. The blind will be maintained at the participant/site 
level.
Final Analysis
The final analysis at the end of the study will include safety and immunogenicity data from all cohorts.a
Data collected up to the time of the last visit for the last participant will be included in the analysis. This 
analysis will be performed on unblinded data.
Additional Interim Analyses
Additional interim analyses (blinded or, if occurring after the primary analysis of the respective cohort,
unblinded) may be performed during the study for the purpose of informing future vaccine development-
related decisions in a timely manner, or upon health authority request. If they occur, these unplanned interim 
analyses may replace planned analyses, depending on the timing. The results will not influence the conduct 
of the study in terms of early termination or later safety or immunogenicity endpoint assessments, and will 
only be available to a selected group of sponsor personnel.
Immunogenicity Analyses
No formal hypothesis for immunogenicity will be tested. For the regimen selection cohort (Cohort 2), GMT 
ratios with corresponding 95% CI of the VNA A2 levels of the combination/mixture regimens on Day 29 
for the one-dose regimens (Groups 12 through 16) and Day 85 for the two-dose regimen (Group 17) versus 
the Day 29 VNA A2 levels of the one-dose Ad26.RSV.preF regimen (Group 11) will be calculated. 
Therefore, a regression model will be fitted with the respective VNA A2 levels as dependent variable and 
the respective regimens and baseline levels as covariates, using Satterthwaite’s method to calculate the 
degrees of freedom and allowing different variances for the vaccines. The estimate and CIs obtained as 
such will be back-transformed (by exponentiation) to a GMT ratio and the corresponding CI. Note that the 
effect of additional factors, such as age and the interaction with the regimen, might also be explored in this 
model.
Note: Immunogenicity data from Groups 9 and 10 of the initial safety cohort (Cohort 1) will be combined 
with those from Groups 16 and 17 of the regimen selection cohort (Cohort 2).
In the expanded safety cohort (Cohort 3), the effect of the Month 12 booster will be assessed. Therefore, 
the following ratios for VNA A2 will be calculated:

In the groups with an active vaccination at Month 12, the ratio of the Month 12 booster Day 29 level 
versus the prime Day 29 level with the corresponding 95% CI will be calculated.

The groups with an active vaccination at Month 12 will be compared to corresponding groups with 
placebo vaccination at Month 12 by calculating the ratio with the corresponding 95% CI.
Note that the above might also be repeated for other assays.
                                                
a Might be done per cohort, depending on the timing.

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In addition, for all cohorts, continuous variables will be summarized with descriptive statistics of the actual 
values and the changes from baseline where appropriate. Graphical representations of immunologic 
parameters will be made as applicable. For categorical variables, frequency tables will be presented.
Safety Analyses
No formal statistical testing of safety data is planned.

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SCHEDULE OF ACTIVITIES – COHORT 1
Clinic Visit #
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Visit Timing
Vac 1
Vac 1
+ 7 d
Vac 1
+ 14 d
Vac 1
+ 28 d
Vac 1
+ 56 d
Vac 2
+ 7 d
Vac 2
+ 28 d
Vac 1
+ 26 wk
Vac 1
+ 12 mo
Vac 3
+ 7 d
Vac 3
+ 28 d
Vac 3
+ 26 wk
Vac 3
+ 12 mo r
Early
Exit a
Visit Day(s)
-28 to 0
1
8 b c
15
29
57
64 d
85 d
183
365
372 d
393 d
547 d
730 d
Visit Window
±2 d
±2 d
±3 d
±3 d
±2 d
-3/+10 d
±14 d
±2 mo
±2 d
±3 d
±14 d
±1 mo
Visit Type
Screening
STUDY 
VACCINATION 
1
Safety
Safety and 
Immunogenicity
Safety and 
Immunogenicity
STUDY 
VACCINATION 
2
Safety
Safety and 
Immunogenicity
Safety and 
Immunogenicity
STUDY 
VACCINATION
3
Safety
Safety and 
Immunogenicity
Safety and 
Immunogenicity
Safety and 
Immunogenicity
Early exit
Written informed consent e

Inclusion/exclusion criteria

Demographics

Medical history/pre-study 
medications

Physical examination f















Vital signs g incl. body temperature















12-lead ECG h

Serology (HIV-1/2, hepatitis B/C)

Randomization

Verification of selected eligibility 
criteria i



Contraindications to vaccination j



Safety lab blood sample, mL
10
5
5
5
Cellular immunity sample, mL k
50
50
50
50
50
50
50
50
50
50
50
Humoral immunity sample, mL
10
10
10
10
10
10
10
10
10
10
10
Transcriptome sample, mL
2.5
2.5
2.5
Nasal turbinate sample (or its 
alternative)







Vaccination



30 minute post-vaccination 
observation l



Solicited AE recording
- - Continuous - -
- - Continuous - -
- - Continuous - -

Unsolicited AE recording m
- - - - - - - - - - Continuous - - - - - - - - - - - - - - - Continuous - - - - - -
- - - - - - Continuous - - - - - -

SAE recording m
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Continuous - -- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Concomitant medications n
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Continuous - -- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Respiratory tract infection (RTI) o,p
- - - - - - - - - - - - - - - - - - - - - - - - - During the first 2 RSV seasons of the study - -- - - - - - - - - - - - - - - - - - - - - - - - - - - - -

RTI Symptoms Form distribution
- - - - - - - - - - - - - - - - - - - - - To be distributed before the start of the first 2 RSV seasons of the study- - - - - - - - - - - - - - - - - - -
Nasal swab kit distribution
- - - - - - - - - - - - - - - - - - - - - To be distributed before the start of the first 2 RSV seasons of the study- - - - - - - - - - - - - - - - - - -
Participant diary distribution q



Participant diary review by site staff




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SCHEDULE OF ACTIVITIES – COHORT 2
Phase
Screening
Vac
Post-vac FU
Vac
Post-vac FU
Second Year FU s
Clinic Visit #
1
2
3
4
5
6
7
8
9
10
11
12
Visit Timing
Vac 1
Vac 1
+ 7 d
Vac 1
+ 14 d
Vac 1
+ 28 d
Vac 1
+ 56 d
Vac 2
+ 7 d
Vac 2
+ 28 d
Vac 1
+ 26 wk
Vac 1
+ 12 mo
Vac 1
+ 18 mo
Vac 1
+ 24 mo
Early
Exit a
Visit Day(s)
-28 to 0
1
8 c
15
29
57
64 d
85 d
183
365
547 
730 
Visit Window
±2 d
±2 d
±3 d
±3 d
±2 d
-3/+10 d
±14 d
±1 mo
±1 mo
±1 mo
Visit Type
Screening
STUDY 
VACCINATION 
1
Safety
Safety and 
Immunogenicity
Safety and 
Immunogenicity
STUDY 
VACCINATION 
2
Safety
Safety and 
Immunogenicity
Safety and 
Immunogenicity
Safety and 
Immunogenicity
Safety and 
Immunogenicity
Safety and 
Immunogenicity
Early exit
Written informed consent e


Inclusion/exclusion criteria

Demographics

Medical history/pre-study medications

Physical examination f













Vital signs g incl. body temperature













12-lead ECG h

Serology (HIV-1/2, hepatitis B/C)

Randomization

Verification of selected eligibility criteria 


Contraindications to vaccination j


Safety lab blood sample, mL
10
5
5
5
Cellular immunity sample, mL k
50
50
50
50
50
50
50
50
50
50
Humoral immunity sample, mL
10
10
10
10
10
10
10
10
10
10
Transcriptome sample, mL 
2.5
2.5
2.5
Nasal turbinate sample (or its alternative)






Vaccination


30 minute post-vaccination observation l


Solicited AE recording
- - Continuous - -
- - Continuous - -

Unsolicited AE recording m
- - - - - - - - - - Continuous - - - - - - - - -
- - - - - - Continuous - - - - - -

SAE recording m
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Continuous - -- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Concomitant medications n
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Continuous - -- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Respiratory tract infection (RTI) o,p
- - - - - - - - - - - - - - - - - - - - - - During the first 2 RSV seasons of the study - -- - - - - - - - - - - - - - - - - - - - - -

RTI Symptoms Form distribution
- - - - - - - - - - - - - - - - To be distributed before the start of the first 2 RSV seasons of the study- - - - - - - - - - - - - - - - - - - -
Nasal swab kit distribution
- - - - - - - - - - - - - - - - To be distributed before the start of the first 2 RSV seasons of the study- - - - - - - - - - - - - - - - - - - -
Participant diary distribution q


Participant diary review by site staff



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Table footnotes for all cohorts:
a.
For those participants who are unable to continue participation in the study, but for whom consent is not withdrawn, an exit visit will be conducted as soon as possible.
b.
In addition, sentinel participants will be contacted by telephone 24 hours post-dose to collect safety information.
c.
If any of the participants for 7-day post-first study vaccine dose safety review come in earlier than Day 8 for Visit 3 in Cohorts 1 and 2, and Visit 2 in Cohort 3 (allowed window is 
±2 days), a subsequent phone call will be made at the end of the diary period to collect diary card information recorded between the actual visit and the end of the diary period on 
Day 8.
d.
The timings of the post-vaccination visits will be determined relative to the actual day of that vaccination.
e.
Signing of the Informed Consent Form (ICF) should be done before any study-related activity. Additional written informed consent for participants in Groups 14 and 15 (Cohort 2) 
progressing into the long-term follow-up phase and participants in Cohort 3 who will receive an additional vaccination at Day 730 (Month 24 booster) will be required.
f.
A full physical examination, including height and body weight, will be carried out at screening and before the Month 12 booster (Cohorts 1 and 3) and before the Month 24 booster 
(Day 730) (Cohort 3 only). At other visits, an abbreviated, symptom-directed examination will be performed if determined necessary by the investigator.
g.
Body temperature (oral route preferred), supine systolic and diastolic blood pressure, heart rate and respiratory rate after at least 5 minutes rest. Vital signs are to be measured before 
blood draws and nasal samples.
h.
Supine electrocardiogram (ECG) after at least 5 minutes rest.
i.
To include inclusion criteria 4 and 5, and exclusion criteria 1, 4, 12, 13, and 14.
j.
Investigator must check for acute illness or body temperature ≥38.0 °C at the time of vaccination. In such cases, the participant may be vaccinated up to, and no later than 10 days 
after the scheduled vaccination, or be withdrawn from vaccination at the discretion of the investigator.
k.
Blood for cellular and humoral immune responses will be drawn from all participants in Cohorts 1 and 2. In Cohort 3, blood will be drawn for humoral immune responses from all 
participants and for cellular immune responses from a subset of 63 participants.
l.
Participants will be closely observed for a minimum of 30 minutes post-vaccination. Any unsolicited, solicited local and solicited systemic AEs, and vital signs (supine systolic and
diastolic blood pressure, heart rate, respiratory rate, and body temperature) will be documented by study-site personnel following this observation period.
m.
All adverse events (AEs) and special reporting situations related to study procedures or to non-investigational (concomitant) Janssen products will be reported from ICF signature 
onwards. All other AEs (unsolicited) and special reporting situations will be reported from each vaccination through the following 28 days. All serious adverse events (SAEs) related 
to study procedures or to non-investigational (concomitant) Janssen products will be reported from ICF signature onwards. All other SAEs will be reported from the first vaccination 
onwards.
n.
Concomitant medications will be collected from the time of each vaccination, through 28 days after each vaccination, and additionally outside of these periods when associated with 
any SAE. Pre-study therapies administered up to 30 days before first dose of study vaccine will be recorded during screening.
o.
Signs and symptoms of RTI will be recorded during the first 2 RSV seasons of the study (relative to the enrollment date of the first participant in Cohort 1) using the specific RTI 
Symptoms Form. Participants will be notified of the RSV season. During the first 2 RSV seasons, they will be contacted by telephone every 30±7 days (unless a prescheduled clinic 
visit has occurred or will occur within 30 days). Calls will remind participants to complete the RTI Symptoms Form in the event of any symptoms of RTI, to contact the site at the 
time of symptom onset, and to take a nasal sample at home preferably between 2 and 3 days after the onset of the RTI symptoms (or go to the site preferably within 2 to 3 days after 
the onset of the RTI to have a nasal sample taken by study staff). Calls will also check for any SAEs and associated concomitant medications since the previous visit or telephone 
contact. Details of the RTI procedures are provided in Section 9.2.2.
p.
During the first 2 RSV seasons of the study (relative to the enrollment date of the first participant in Cohort 1), every effort should be made to collect data on the clinical course of 
RTIs including information on oxygenation status, supplemental oxygen requirements and specific drug treatments, as well as other concurrent respiratory illness present at the time 
of the diagnosis of the event and up to symptom resolution.
q.
Rulers and thermometers will also be distributed at these visits.
r.
Vac 3+12 mo is the same as Vac 1+24 mo.
s.
Participants in Groups 14 and 15 will continue into the long-term follow-up phase (see Cohort 2 long-term follow-up phase Time and Events Schedule).
t.
During the long-term follow-up phase, only SAEs related to study vaccine, study procedures, or non-investigational (concomitant) Janssen products, and all AEs leading to 
discontinuation will be collected during the long-term follow-up phase
u.
During the long-term follow-up phase, only medications in conjunction with SAEs related to study vaccine, study procedures, or non-investigational (concomitant) Janssen products, 
or in conjunction with AEs leading to discontinuation should be recorded.
v.
Visit 13 (7 days post-third vaccination) is not required for any Cohort 3 participant who misses the third vaccination.

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ABBREVIATIONS
Ad26
adenovirus serotype 26
Ad35
adenovirus serotype 35
AE
adverse event
CDC
Clinical Development Committee
CI
confidence interval
CS
circumsporozoite
DNA
deoxyribonucleic acid
DRC
Data Review Committee
ECG
electrocardiogram
eCRF
electronic case report form 
eDC
electronic data capture
ELISA
enzyme-linked immunosorbent assay
ELISpot
enzyme-linked immunospot (assay)
ERD
enhanced respiratory disease
F protein
fusion protein
FA
full analysis (set)
FA2
fusion protein of the RSV A2 strain
FDA
United States Food and Drug Administration
FI
formalin-inactivated
FIH
first-in-human
G protein
glycoprotein
GCP
Good Clinical Practice
GMT
geometric mean titer
HIV
human immunodeficiency virus
ICF
informed consent form
ICH
International Council for Harmonisation
ICS
intracellular cytokine staining
IEC
Independent Ethics Committee
IFN-γ
interferon gamma
Ig
immunoglobulin
IL
interleukin
IRB
Institutional Review Board
IWRS
interactive web response system
ML
medical leader
N protein
nucleoprotein
NSAID
non-steroidal anti-inflammatory drug
PBMC
peripheral blood mononuclear cells
PI
principal investigator
PPI
per-protocol RSV immunogenicity (set)
pre-F
pre-fusion
post-F
post-fusion
PQC
Product Quality Complaint
RSV
respiratory syncytial virus
RTI
respiratory tract infection
RT-PCR
reverse transcriptase polymerase chain reaction
SAE
serious adverse event
SRP/S
study responsible physician/scientist
SUSAR
suspected unexpected serious adverse reaction
TASH
therapeutic area safety head
Th 
T-helper (cell)
TNF-α
tumor necrosis factor alpha
VNA
virus neutralizing antibody
vp
viral particles

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1.
INTRODUCTION
A human adenovirus-vectored vaccine candidate and a pre-fusion conformation-stabilized 
respiratory syncytial virus (RSV) F protein which have shown promise in preclinical animal 
models of RSV will be assessed in this study:

Ad26.RSV.preF (JNJ-64400141), a replication-incompetent adenovirus serotype 26 (Ad26) 
containing a deoxyribonucleic acid (DNA) transgene that encodes the pre-fusion 
conformation-stabilized F protein (pre-F) derived from the RSV A2 strain.

RSV preF protein (JNJ-64213175), a pre-fusion conformation-stabilized F protein derived 
from the RSV A2 strain.
Different naming conventions are being used for clinical studies. The first part of the study 
identifier is one of the following, depending on the vaccine and study population:

VAC18192 (used for studies to test the Ad26.RSV.FA2 vaccine in the adult population)

VAC18193 (used for studies to test the Ad26.RSV.preF vaccine in the adult and elderly 
populations)

VAC18194 (used for studies to test the Ad26.RSV.preF vaccine in the pediatric population)
Studies are given a suffix of a 4-digit number preceded by the letters RSV (for ‘Respiratory 
Syncytial Virus’).
The following sponsor RSV vaccine studies are referenced in this protocol:
Study Identifier
Clinical Phase
Vaccine
Study Population
VAC18192RSV1001 
1
Ad26.RSV.FA2 
Adults aged 18 to 50 years
VAC18192RSV1003
1
Ad26.RSV.FA2 
Adults aged 18 to 50 years
VAC18193RSV1003
1
Ad26.RSV.preF vaccine 
Adults aged 60 years and older
Current study:
VAC18193RSV1004
1/2a
Ad26.RSV.preF vaccine 
Adults aged 60 years and older
VAC18193RSV2002
2a
Ad26.RSV.preF vaccine
Adults aged 18 to 50 years
VAC18193RSV2003
2a
Ad26.RSV.preF vaccine
Adults aged 60 years and older
VAC18194RSV2001
1/2a
Ad26.RSV.preF vaccine
Adults aged 18 to 50 years and RSV-
seropositive toddlers aged 12 to 
24 months
This will be the first-in-human (FIH) study for RSV preF protein, and for the Ad26.RSV.preF/ 
RSV preF protein combination (administered as separate injections in opposite arms) and the
Ad26.RSV.preF/RSV preF protein mixture (administered as a single injection).
For the most comprehensive nonclinical information regarding Ad26.RSV.preF, refer to the latest 
version of the Investigator’s Brochure for Ad26.RSV.preF.17

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For the most comprehensive nonclinical information regarding RSV preF protein, refer to the latest 
version of the Investigator’s Brochure for RSV preF protein.18
The term “sponsor” used throughout this document refers to the entities listed in the Contact 
Information page(s), which will be provided as a separate document.
1.1.
Background
Background
RSV is an important cause of serious respiratory infections in the elderly, immunocompromised, 
and those with underlying chronic cardiopulmonary conditions.8 Although most adults mount a 
long-lasting fully protective immune response, waning immune responses in the elderly might
contribute to increased susceptibility to severe disease after RSV infection causing significant 
morbidity and mortality. In long-term care facilities, RSV is estimated to infect 5% to 10% of the 
residents per year with significant rates of pneumonia (10% to 20%) and death (2% to 5%).9 In an
epidemiology study of RSV burden, it was estimated that 11,000 elderly persons die annually of 
RSV in the United States.35 These data support the importance of developing an effective vaccine 
for certain adult populations, such as the elderly.
RSV is also considered to be the most important cause of serious acute respiratory illness in infants 
and children under 5 years of age: worldwide in 2005, RSV caused an estimated 33.8 million new 
episodes of acute lower respiratory tract infections in this age range, with 3.4 million cases 
requiring hospitalization due to severe illness.13,32,33
Despite the high RSV disease burden, no licensed vaccine is available for RSV. The first vaccine 
candidate for use in young children, which consisted of formalin-inactivated RSV (FI-RSV), was 
associated with enhanced respiratory disease (ERD) upon infection with RSV.21 Although the 
mechanisms for ERD are not fully understood, it is thought that FI-RSV failed to induce adequate 
neutralizing antibody titers and CD8+ priming, and induced a T-helper (Th)2 skewed response.28
As all adults have been exposed to RSV, and therefore previously primed by a live virus infection, 
ERD is not expected to be a concern in this study.6
Adenoviral-vectored Vaccines
It is thought that an efficacious RSV vaccine should induce high levels of neutralizing antibodies, 
antigen-specific CD8+ T-cell responses, and Th1-type CD4+ T-cells.2 The Ad26.RSV.preF 
candidate RSV vaccine being evaluated in this protocol is based on the AdVac® platform which 
has been shown to promote a strong antibody response as well as CD8+ T-cell and Th1-type CD4+
T-cell responses.
The immunogenicity profile of adenoviral vectors, with particular emphasis on Th1 responses, is 
illustrated by data obtained following the immunization of adults with an Ad26-vectored human 
immunodeficiency virus (HIV) vaccine (Ad26.ENVA.01), and immunization of adults and infants 
with an adenovirus serotype 35 (Ad35)-vectored tuberculosis (TB) vaccine (Ad35.TB-S). These 

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data demonstrate predominantly interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-
α) production in CD4+ and CD8+ T-cells.1,5,31
Ad26.RSV.FA2 Clinical Data
Ad26 encoding for a wild-type RSV F protein of the RSV A2 strain (FA2) has been evaluated in 
studies VAC18192RSV1001 and VAC18192RSV1003 (N=48 and N=32, respectively, of which 
35 and 24 participants, respectively, received Ad26.RSV.FA2) in healthy adults at doses of 5×1010
viral particles (vp). Both studies have been completed.
The results indicate that there have been no safety concerns following vaccination in either study. 
After vaccination with Ad26.RSV.FA2, local reactogenicity comprised almost exclusively mild to 
moderate pain of median duration 1 to 3 days. The most commonly experienced solicited systemic 
adverse events (AEs) (headache, fatigue, chills, and myalgia) were also mostly mild to moderate 
in severity, with a median duration of 1 to 3 days; most unsolicited AEs and most laboratory
toxicities were mild to moderate in severity. No serious adverse events (SAEs) were reported and 
no AEs led to withdrawal from study vaccine.19,20
Single vaccination with 5×1010 vp of Ad26.RSV.FA2 raised both humoral and cellular immunity. 
Anincrease in RSV neutralizing antibody titers was observed; RSV-specific T-cell responses were 
also increased.
FA2 and preF RSV Vaccines
The clinical studies VAC18192RSV1001 (FIH for Ad35.RSV.FA2) and VAC18192RSV1003 
(FIH for Ad26.RSV.FA2) have been completed with Ad26.RSV.FA2 and Ad35.RSV.FA2 (a 
similar recombinant, replication-incompetent vaccine using an Ad35 vector), in which Ad26 and 
Ad35, respectively, encode for a wild-type RSV F protein of the RSV A2 strain.
The adenoviral vectors Ad26 and Ad35 are derived from Group B and D serotype adenoviruses 
and have been similarly modified to be replication-incompetent; expression of the antigen is 
controlled by the same promotor. An Ad26-based RSV vaccine was chosen for further clinical 
development over the Ad35-based counterpart based on a better immunogenicity profile from 
nonclinical data, a similar safety and immunogenicity profile but at half the Ad35 dose from 
clinical data, and a better manufacturing profile.
The F protein of RSV undergoes a conformational transition from a metastable pre-fusion 
conformation to a stable post-fusion conformation. Neutralizing sensitive epitopes reside on both 
proteins, but recent evidence indicates that those epitopes specific to the pre-F protein seem to be 
more potent than those previously identified and present on the post-F protein.11,12 This evidence 
resulted in the design of the candidate RSV vaccine (Ad26.RSV.preF) in which the adenoviral 
vector encodes a full length RSV F protein stabilized in the pre-F protein conformation. The full 
length membrane-bound RSV F protein in a pre-F configuration encoded by this vector differs by 
only 5 amino acids from the wild-type used in the FA2 construct.24 This change in the transgene 
confers more stability to the pre-fusion form of the molecule before it undergoes its natural 
transition to the post-fusion form.24 This change also induces higher immune responses against 

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pre-fusion epitopes because the majority of neutralizing antibodies target the pre-fusion protein 
conformation.25,29 For these reasons, it is anticipated that the Ad26.RSV.preF vaccine candidate 
will generate more neutralizing antibodies relative to the Ad26.RSV.FA2 vaccine.16
Ad26.RSV.preF and RSV preF Protein Preclinical Data
Preclinical studies were performed in naïve and RSV pre-exposed animals. Ad26.RSV.preF is 
immunogenic in mice and cotton rats, with humoral responses that include the induction of RSV 
neutralizing antibodies. In addition, in mice it was shown that Ad26.RSV.preF elicits cellular 
responses, characterized by the induction of RSV F-specific CD8+ IFN-γ+ T-cells. The immune 
response following Ad26.RSV.preF immunization was Th1-biased.
RSV preF protein induced virus neutralizing antibody (VNA) titers in mice, cotton rats, and non-
human primates. Furthermore, prime-boost immunization with non-adjuvanted RSV preF protein
gave partial protection from RSV infection in the lung in cotton rats. In RSV pre-exposed mice, 
high neutralizing antibody titers were boosted by a single administration of RSV preF protein; 
RSV preF protein induced low RSV F-specific cellular responses in pre-exposed mice, in contrast 
to Ad26.RSV.preF which induced high cellular responses.
The mixture of Ad26.RSV.preF and RSV preF protein induced both high VNA titers and a cellular 
response in mice, maintaining the advantage of each vaccine component. RSV preF protein boost-
immunization, after Ad26.RSV.preF prime, induced high virus neutralizing titers, and the cellular 
responses induced by the adenoviral vector were also maintained. In RSV pre-exposed non-human 
primates, the mixture of Ad26.RSV.preF and RSV preF protein induced both cellular responses 
and high VNA titers by single administration.16
The RSV preF protein has been evaluated in a single dose pilot toxicology study in the rabbit up 
to 250 μg. No clinically significant toxicological changes were noted. In a follow-up good 
laboratory practice (GLP) toxicology study in the rabbit, RSV preF protein was evaluated at 250 μg 
per injection, either alone in a prime-boost regimen with Ad26.RSV.preF (1×1011 vp) or in a single 
injection mixture with Ad26.RSV.preF for 3 dosing days with 2-week intervals. Test article-related 
mortality was not observed, and no effects were noted on clinical observations, dermal scores, 
body weight, hematology, ophthalmology, and body temperature. All vaccine regimens were well 
tolerated and without adverse effects.
Ad26.RSV.preF and RSV preF Protein Clinical Data
Ad26.RSV.preF:
Ad26.RSV.preF is currently under evaluation in four other ongoing studies: one Phase 1 study 
(VAC18193RSV1003), two Phase 2a studies (VAC18193RSV2002 and VAC18193RSV2003) 
and one Phase 1/2a study (VAC18194RSV2001) (Table 7).

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Table 7:
Other Ongoing Clinical Studies with Ad26.RSV.preF
Study Identifier
Clinical 
Phase
Vaccine
N Planned
Study Population
VAC18193RSV1003
1
Ad26.RSV.preF 
72
Adult participants aged 60 years and older
VAC18193RSV2002
2a
Ad26.RSV.preF
44-70
Adult participants aged 18 to 50 years
VAC18193RSV2003
2a
Ad26.RSV.preF
180
Adult participants aged 60 years and older
VAC18194RSV2001
1/2a
Ad26.RSV.preF 
12 adults
48 toddlers
Adult participants aged 18 to 50 years and 
RSV-seropositive toddlers aged 12 to 
24 months
In one of these studies, interim safety and immunogenicity data are available, as follows:
VAC18193RSV1003: This is an ongoing single-center, randomized, placebo-controlled, double-
blind, FIH, Phase 1 study to evaluate the safety, tolerability and immunogenicity of 
2 Ad26.RSV.preF vaccinations, administered 1 year apart, in 72 male and female subjects aged 
60 years and older in stable health. Participants were randomized to 1of5 groups and have received
2 intramuscular injections as follows:

Group 1: 5×1010 vp Ad26.RSV.preF on Day 1 and 1 year* later

Group 2: 5×1010 vp Ad26.RSV.preF on Day 1 and placebo 1 year later

Group 3: 1×1011 vp Ad26.RSV.preF on Day 1 and 1 year later

Group 4: 1×1011 vp Ad26.RSV.preF on Day 1 and placebo 1 year later

Group 5: placebo on Day 1 and 1 year later.
* Window of -2 months to +1 month
Safety and immunogenicity data from the unblinded (at the study group level) analysis 28 days 
post-Dose 1 from all 72 participants who received Ad26.RSV.preF (5×1010 vp or 1×1011 vp) or 
placebo confirmed that the 1×1011 vp dose of Ad26.RSV.preF was more immunogenic compared 
with the 5×1010 vp dose. Data from this ongoing study, which is still blinded, show that the 
Ad26.RSV.preF vaccine is immunogenic and that there is a favorable Th1/Th2 profile. No safety 
concerns were revealed; the reactogenicity of both doses was comparable.
In study VAC18194RSV2001, first 12 male and female adults, and then 48 male and female RSV-
seropositive toddlers, are randomized to receive 2 intramuscular injections as follows:
Adults (aged ≥18 to ≤50 years):

Group 1: 1×1011 vp Ad26.RSV.preF on Day 1 and Day 29

Group 2: placebo on Day 1 and Day 29
RSV-seropositive toddlers (aged 12 to 24 months):

Group 3: 5×1010 vp Ad26.RSV.preF on Day 1 and Day 29

Group 4: placebo on Day 1 and Day 29

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All participants are planned to have been dosed prior to the start of the current study.
In study VAC18193RSV2002, more than 44 (and up to 70) healthy male and female participants 
aged 18 to 50 years who have been prescreened for susceptibility to RSV infection receive a single 
intramuscular injection with Ad26.RSV.preF 1×1011 vp or placebo, followed by intranasal 
challenge with the RSV-A Memphis 37b virus within 24 to 90 days following vaccination. All 
participants are planned to have been dosed prior to the start of the current study.
In study VAC18193RSV2003, 180 male and female participants aged ≥60 years in stable health 
are randomized to 1 of 2 groups. Participants in Group 1 receive Ad26.RSV.preF 1×1011 vp on 
Day 1 administered at the same time as a commercially available seasonal influenza vaccine
(Fluarix® Quadrivalent), and placebo on Day 29. Participants in Group 2 receive placebo on Day 1, 
administered at the same time as a commercially available seasonal influenza vaccine (Fluarix
Quadrivalent), and Ad26.RSV.preF 1×1011 vp on Day 29. All vaccines are given by intramuscular 
injection. The primary analysis for safety and immunogenicity at 28 days after the second dose is 
expected to have been completed prior to the start of the current study.
In study VAC18193RSV1003, Ad26.RSV.preF was provided in a different formulation buffer 
(Formulation Buffer 1a) from the one used in the current study and studies VAC18194RSV2001, 
VAC18193RSV2002 and VAC18193RSV2003 (Formulation Buffer 2b).
RSV preF Protein:
To date, RSV preF protein has not been tested in humans. This is the FIH study for RSV preF 
protein, and for the Ad26.RSV.preF/RSV preF protein combination (administered as separate 
injections in opposite arms) and Ad26.RSV.preF/RSV preF protein mixture (administered as a 
single injection).
Safety Data Supporting the Ad26.RSV.preF Dose Selection
The dose levels for Ad26.RSV.preF used in the current study are supported by experience in adults 
with other Ad26-based vaccines encoding for different antigens (including EnvA [in 
Ad26.ENVA.01 against HIV];4,5 circumsporozoite (CS) protein [in Ad26.CS.01 against malaria];34
and Ebola glycoprotein [in Ad26.ZEBOV against Ebola virus]27).
In completed clinical studies, the safety of Ad26.ENVA.01, Ad26.CS.01, and Ad26.RSV.FA2 has 
been evaluated in 584 adults, of whom 519 (88.9%) received Ad26 at a dose level of 5×1010 vp 
and 25 (4.3%) were vaccinated with Ad26 at the highest dose level tested (1×1011 vp).
                                                
CCI

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In addition, 17 clinical studies with Ad26 vaccines (Ad26.RSV.preF, Ad26.Mos[4].HIV, and 
Ad26.ZEBOV) are ongoing. At least 4,579 participants have been enrolled in these ongoing 
studies, of whom approximately 456 received at least one vaccination with an Ad26-based vaccine 
(mainly 5×1010 vp) up to 31 August 2017. For the remainder of participants, study vaccine 
assignment is not yet known. To date, all Ad26-based vaccines were found to be well-tolerated, 
no safety concerns have been identified. Note that, in general, at a given dose level, no significant 
differences in safety profiles of Ad26-based vaccines have been observed based upon the transgene 
used.14,15
Overall, these clinical data are supportive of dosing Ad26.RSV.preF at 5×1010 vp and 1×1011 vp 
in the current study.
1.2.
Overall Rationale for the Study
Despite the high RSV disease burden, no licensed vaccine is available for RSV.
The current study has an adaptive design to determine a regimen for further clinical development 
in adults aged ≥60 years based on safety and immunogenicity. The selected regimen should 
improve humoral immune responses with no adverse effect on cellular responses compared with
Ad26.RSV.preF alone.
The potential use of RSV preF protein as a component of an RSV vaccine will be assessed by 
evaluation of the safety and reactogenicity of intramuscular regimens of Ad26.RSV.preF, RSV 
preF protein, the combination or mixture of Ad26.RSV.preF and RSV preF protein, or placebo.
Approximately 667 male and female participants aged ≥60 years will be randomized in 3 cohorts 
as outlined in Table 8, Table 9, Table 10, and Table 11, respectively.
The current study will be the FIH study for the RSV preF protein, and for the Ad26.RSV.preF/
RSV preF protein combination and mixture.
The initial safety cohort (Cohort 1) is designed to assess the safety and immunogenicity of 2 dose
levels of RSV preF protein (50 μg and 150 μg). The safety of RSV preF protein at each dose will
be checked before administration of the combination or mixture of Ad26.RSV.preF and RSV preF 
protein.
The dose selection rationale is provided in Section 3.2.
An internal data review committee (DRC) will be established for this study to evaluate safety and 
reactogenicity data on a regular basis.

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2.
OBJECTIVES, ENDPOINTS, AND HYPOTHESIS
2.1.
Objectives and Endpoints
SAFETY COHORT OBJECTIVE (COHORT 1):
To determine in small numbers of participants aged 60 years and older the safety of intramuscular homologous 
two-dose regimens comprising RSV preF protein or Ad26.RSV.preF/RSV preF protein mixture on Days 1 and 57, 
with a booster at Month 12, or separate administration of Ad26.RSV.preF and RSV preF protein in opposite arms 
on Day 1 with a booster at Month 12, before progression to regimen selection in a larger number of participants
Objectives
Endpoints
PRIMARY

To assess the safety and reactogenicity of the 
intramuscular one- and two-dose regimens, 
with a booster at Month 12

SAEs from first dose administration until the end 
of the study

Solicited local and systemic AEs for 7 days after 
each vaccine administration

Unsolicited AEs from the time of each vaccine 
administration through the following 28 days
SECONDARY

To assess the humoral and cellular immune 
responses elicited by Ad26.RSV.preF, RSV 
preF protein, and the Ad26.RSV.preF/RSV 
preF protein combination and mixture

RSV neutralization assay, F protein binding 
antibodies (enzyme-linked immunosorbent assay 
[ELISA]; pre-F and/or post-F), and IFN-γ 
enzyme-linked immunospot (ELISpot) assay
EXPLORATORY

Additional exploratory analyses may be 
performed to investigate vaccine-elicited 
immune responses further

Assays to be used include, but are not limited to, 
RSV strain cross-neutralization, anti-F protein 
antibody specificity and functionality 
characterization, adenovirus neutralization assays, 
molecular antibody characterization (avidity, Fc 
cell interaction, antibody isotyping, antibody 
sequencing for repertoire), and nasal antibodies to 
RSV, including but not limited to immunoglobulin 
(Ig)A and IgG; evaluation of the cellular immune 
response and the functional and memory immune 
response by intracellular cytokine staining (ICS) 
and transcriptome analysis

To evaluate symptoms of respiratory illness
(including respiratory illness due to RSV) via the 
Respiratory Tract Infection (RTI) Symptoms 
Form

During the RSV season: Signs and symptoms of 
RTI (including RTI due to RSV) from Day 1 until 
the end of the second RSV season of the studya

Characterization of viral or bacterial infections 
in the respiratory tract

Assessment, typing and level of infection by 
reverse transcriptase polymerase chain reaction 
(RT-PCR) or response to respiratory infection by 
serology
                                                
a The second RSV season of the study is defined relative to the enrollment date of the first participant in Cohort 1.

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REGIMEN SELECTION COHORT OBJECTIVE (COHORT 2):
To select a regimen for progression to evaluation in an expanded safety cohort (Cohort 3; see below) by 
assessment of the safety and immunogenicity in participants aged 60 years and older of intramuscular one-dose 
regimens of Ad26.RSV.preF, Ad26.RSV.preF/RSV preF protein mixture, or separate administration of 
Ad26.RSV.preF and RSV preF protein in opposite arms on Day 1, or a two-dose regimen of Ad26.RSV.preF/RSV 
preF protein mixture on Days 1 and 57 
Objectives
Endpoints
PRIMARY

To assess the safety and reactogenicity of the 
intramuscular one- and two-dose regimens

SAEs from first dose administration until the end 
of the study

Solicited local and systemic AEs for 7 days after 
each vaccine administration

Unsolicited AEs from the time of each vaccine 
administration through the following 28 days

To assess RSV neutralizing antibody levels of
the one-dose regimens (Groups 11 to 15)
containing RSV preF protein compared to the 
one-dose Ad26.RSV.preF regimen 

RSV A2 neutralizing antibody levels of the 
one-dose regimens (Groups 11 to 15) on Day 29a
SECONDARY

To assess RSV neutralizing antibody levels of 
the one-dose regimen with separate injections
(Group 16) and the two-dose regimen
(Group 17) containing RSV preF protein 
compared to the one-dose Ad26.RSV.preF 
regimen

RSV A2 neutralizing antibody levels of:

the one-dose regimen with separate injections
(Group 16) on Day 29

the two-dose regimen (Group 17) on Day 85a

To assess additional humoral immune responses 
elicited by Ad26.RSV.preF and the 
Ad26.RSV.preF/RSV preF protein combination 
and mixture

F protein binding antibodies (ELISA; pre-F and/or 
post-F)

To assess cellular immune responses by 
IFN-γ ELISpot of all regimens containing
RSV preF protein compared to the one-dose 
Ad26.RSV.preF regimen 

RSV F protein by IFN-γ ELISpot assay
- the one-dose regimens on Day 29a
(Groups 11 to 16)
- the two-dose regimen on Day 85a (Group 17)
EXPLORATORY

Additional exploratory analyses may be 
performed to investigate vaccine-elicited 
immune responses further

Assays to be used include, but are not limited to, 
RSV strain cross-neutralization, anti-F protein 
antibody specificity and functionality 
characterization, adenovirus neutralization assays, 
molecular antibody characterization (avidity, Fc 
cell interaction, antibody isotyping, antibody 
sequencing for repertoire), and nasal antibodies to 
RSV, including but not limited to IgA and IgG; 
evaluation of the cellular immune response and the 
functional and memory immune response by ICS 
and transcriptome analysis
                                                
a See “STATISTICAL METHODS - Immunogenicity Analyses” for details.

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Objectives
Endpoints

To assess the long-term durability of the 
immune response in selected groups

Assays to be used include, but are not limited to, 
RSV neutralizing antibody levels against A and B 
strain, RSV F protein binding antibodies (ELISA; 
pre-F and/or post-F), RSV F protein specific 
functional antibodies, and RSV F protein specific 
IFN-γ ELISpot in Groups 14 and 15 at Days 912 
and 1095

To evaluate symptoms of respiratory illness 
(including respiratory illness due to RSV) via the 
RTI Symptoms Form

During the RSV season: Signs and symptoms of 
RTI (including RTI due to RSV) from Day 1 until 
the end of the second RSV season of the studya

Characterization of viral or bacterial infections 
in the respiratory tract

Assessment, typing and level of infection by 
RT-PCR or response to respiratory infection by 
serology
EXPANDED SAFETY COHORT OBJECTIVE (COHORT 3):
To determine the safety and immunogenicity of the selected regimen in an expanded cohort of participants aged 
60 years and older; and to determine the need for a booster dose at Month 12 and/or Month 24
Objectives
Endpoints
PRIMARY

To assess the safety and reactogenicity of the 
selected regimen and a booster at Month 12
and/or Month 24

SAEs from first administration until the end of 
the study

Solicited local and systemic AEs for 7 days after 
each vaccine administration

Unsolicited AEs from the time of each vaccine 
administration through the following 28 days
SECONDARY

To assess humoral immune responses to the 
selected regimen in all participants 

RSV neutralization A2 strain

To assess cellular immune responses to the 
selected regimen in a subset of participants

IFN-γ ELISpot assay 
EXPLORATORY

Additional exploratory analyses may be 
performed to further investigate vaccine-elicited 
immune responses 
Assays to be used include, but are not limited to:

F protein binding antibodies (ELISA; pre-F 
and/or post-F)

Flow cytometry

RSV cross-neutralization of B and/or other A 
strain

F-protein antibody specificity characterization

Cytokines/chemokines in nasal samples (if 
feasible)

Adenovirus neutralization assays
                                                
a The second RSV season of the study is defined relative to the enrollment date of the first participant in Cohort 1.

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Objectives
Endpoints

Functional and molecular antibody 
characterization

Analysis of nasal antibodies to RSV including, 
but not limited to IgA and IgG

To assess the long-term durability of the immune 
response in groups receiving a booster at different 
time intervals 

Assays to be used include, but are not limited to, 
RSV neutralizing antibody levels against A and B 
strain, RSV F protein binding antibodies (ELISA; 
pre-F and/or post-F), RSV F protein specific 
functional antibodies, and RSV F protein specific 
IFN-γ ELISpot at Days 758, 912 and 1095

To evaluate symptoms of respiratory illness 
(including respiratory illness due to RSV) via the 
RTI Symptoms Form

During the RSV season: Signs and symptoms of 
RTI (including RTI due to RSV) from Day 1 until 
the end of the second RSV season of the studya

Characterization of viral or bacterial infections in 
the respiratory tract

Assessment, typing and level of infection by 
RT-PCR or response to respiratory infection by 
serology
See Section 9.2 for evaluations related to endpoints.
2.2.
Hypothesis
No formal statistical testing of safety and immunogenicity data is planned.
Data will be analyzed descriptively.
3.
STUDY DESIGN AND RATIONALE
3.1.
Overview of Study
3.1.1.
Study Design
This is a multi-center, randomized, double-blind, placebo-controlled Phase 1/2a study for safety 
and immunogenicity evaluations for regimen selection of Ad26.RSV.preF and RSV preF protein 
combinations followed by expanded safety evaluation of the selected regimen in male and female 
participants aged ≥60 years who are in stable health.
To further extend the assessment of the long-term durability of the immune response to the study 
vaccine, participants in Groups 14 and 15 in Cohort 2 will continue into a long-term follow-up 
phase.
The study design includes 3 sequential cohorts: an initial safety cohort (Cohort 1 in a total of 
64 participants), a regimen selection cohort (Cohort 2 in a total of 288 participants), and an
expanded safety cohort (Cohort 3 in a total of 315 participants).
                                                
a The second RSV season of the study is defined relative to the enrollment date of the first participant in Cohort 1.

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The overall total number of participants will be approximately 667.
This study will be the FIH study for RSV preF protein, and for the Ad26.RSV.preF/RSV preF 
protein combination (administered as separate injections in opposite arms) and Ad26.RSV.preF/
RSV preF protein mixture (administered as a single injection).
The study duration will be approximately 730 days (2 years) per participant in Cohorts 1 and 2
(Groups 11-13 and Groups 16-18), and approximately 1095 days (3 years) per participant in 
Cohort 2 (Groups 14-15) and Cohort 3. The study comprises a maximum 28-day screening period
for Cohorts 1 and 2 (screening for Cohort 3 will be done pre-vaccination on Day 1), study
vaccination (active or placebo) with a one-dose (on Day 1) or two-dose (on Day 1 and Day 57) 
regimen and a booster dose (active or placebo) at Month 12 (Cohort 1) or at Month 12 and Month 
24 (Cohort 3), a minimum 28-day follow-up period after each vaccination, and a follow-up period 
until 2 years after the first Ad26.RSV.preF or RSV preF protein vaccination (Cohorts 1 and 2 
[Groups 11-13 and Groups 16-18]) or until 3 years after the first Ad26.RSV.preF or RSV preF 
protein vaccination (Cohort 2 [Groups 14-15] and Cohort 3). The end of the study is defined as the 
last participant’s last visit 24 months after the first vaccination (Cohorts 1 and 2 [Groups 11-13 
and Groups 16-18]) or the last participant’s last visit approximately 1095 days (3 years) after the 
first vaccination (Cohort 2 [Groups 14-15] and Cohort 3).
If any of the pre-specified studyvaccination pausing rules is met, further study vaccination will be 
paused and a DRC meeting will be convened. For details on the pausing rules, see Section 11.9.
Initial Safety Cohort (Cohort 1)
In the initial safety cohort, participants will be randomized progressively in 1 of 4 randomizations 
(R1a through R1d) with safety checks in place before extending enrollment and progressing from 
one randomization step to the next as follows (see also Table 8):

Cohort R1a. Initially 2 participants will be enrolled, 1 into Group 1 and 1 into Group 2, and 
will receive a single dose of placebo or 50 g of RSV preF protein, respectively. Enrollment 
will be paused to allow for 24-hour safety assessments in these 2 sentinel participants by the 
principal investigator(s) (PI[s]), the sponsor’s study responsible physician/scientist (SRP/S), 
and the sponsor’s medical leader (ML). In the absence of any clinical safety concerns over the 
24-hour assessment, the remaining 10 participants will be randomized and dosed. Seven days 
after the last participant has received his/her first dose, available safety data will be reviewed 
by the PI(s), SRP/S, ML, and the sponsor’s therapeutic area safety head (TASH) before 
proceeding to Cohort R1b.

Cohort R1b. Initially 3 participants will be enrolled, 1 into each of Groups 3 through 5, and 
will receive a single dose of placebo, 5×1010 vp Ad26.RSV.preF/50 g RSV preF protein, or 
150 g RSV preF protein, respectively. Enrollment will be paused to allow for 24-hour safety 
assessments in the 3 sentinel participants by the PI(s), SRP/S, and ML. In the absence of any 
clinical safety concerns over the 24-hour assessment, the remaining 17 participants will be 
randomized and dosed. Seven days after the last participant has received his/her first dose, 

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available safety data will be reviewed by the PI(s), SRP/S, ML, and TASH before proceeding 
to Cohort R1c.

Cohort R1c. Initially 2 participants will be enrolled, 1 into Group 6 and 1 into Group 7, and 
will receive a single dose of placebo or 5×1010 vp Ad26.RSV.preF/150 g RSV preF protein, 
respectively. Enrollment will be paused to allow for 24-hour safety assessments in these 
2 sentinel participants by the PI(s), SRP/S, and ML. In the absence of any clinical safety 
concerns over the 24-hour assessment, the remaining 10 participants will be randomized and 
dosed. Seven days after the last participant has received his/her first dose, available safety data 
will be reviewed by the PI(s), SRP/S, ML, and TASH before proceeding to Cohort R1d.

Cohort R1d. Initially 3 participants will be enrolled, 1 into each of Groups 8 through 10, and 
will receive 2 doses of placebo (1 in each arm), or 1×1011 vp Ad26.RSV.preF/150 g RSV 
preF protein, with placebo in the opposite arm, or 1×1011 vp Ad26.RSV.preF in one arm and 
150 g RSV preF protein in the opposite arm. Enrollment will be paused to allow 24-hour 
safety assessments in the 3 sentinel participants by the PI(s), SRP/S, and ML. In the absence 
of any clinical safety concerns over the 24-hour assessment, the remaining 17 participants will 
be randomized and dosed.

Seven days after the final participant in Cohort 1 has received his/her first dose, all available 
safety data at that time for the whole cohort will be reviewed by the DRC before proceeding 
to Cohort 2.
Sentinel participants will be contacted by telephone 24 hours post-vaccination to collect safety 
information.
Progression to the regimen selection cohort will be based on acceptable safety in the initial safety 
cohort, as determined by DRC review of Day 8 safety data in all participants.

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Table 8:
Study Design: Initial Safety Cohort (Cohort 1)
Group
R
N
Day 1
Day 57
Month 12
1
R1a
4
Placebo
Placebo
Placebo 
2
R1a
8
RSV preF protein 50 g
RSV preF protein 50 g
RSV preF protein 50 g
3
R1b
4
Placebo
Placebo
Placebo 
4
R1b
8
Ad26.RSV.preF/
RSV preF protein mixture:
5×1010 vp/50 g
Ad26.RSV.preF/
RSV preF protein mixture:
5×1010 vp/50 g
Ad26.RSV.preF/
RSV preF protein mixture:
5×1010 vp/50 g
5
R1b
8
RSV preF protein 150 g
RSV preF protein 150 g
RSV preF protein 150 g
6
R1c
4
Placebo
Placebo
Placebo 
7
R1c
8
Ad26.RSV.preF/
RSV preF protein mixture:
5×1010 vp/150 g
Ad26.RSV.preF/
RSV preF protein mixture:
5×1010 vp/150 g
Ad26.RSV.preF/
RSV preF protein mixture:
5×1010 vp/150 g
8
R1d
4
Placebo
+ Placebo*
Placebo
Placebo
+ Placebo*
9
R1d
8
Ad26.RSV.preF/
RSV preF protein mixture:
1×1011 vp/150 g
+ Placebo*
Ad26.RSV.preF/
RSV preF protein mixture:
1×1011 vp/150 g
Ad26.RSV.preF/
RSV preF protein mixture:
1×1011 vp/150 g
+ Placebo*
10
R1d
8
Separate injections: 
Ad26.RSV.preF 1×1011 vp 
+ RSV preF protein 150 g*
Placebo
Separate injections: 
Ad26.RSV.preF 1×1011 vp 
+ RSV preF protein 150 g*
R1 TOTAL:
64
N: number of participants; R: randomization; vp: viral particles
* Each injection to be given in opposite arms
Regimen Selection Cohort (Cohort 2)
In the regimen selection cohort, approximately 288 participants will be randomized in parallel to 
1 of 8 groups (Groups 11 through 18; Table 9). No pauses in enrollment for safety assessments are 
planned.
Based on safety and immunogenicity results available at the time of primary analysis, a sponsor 
committee will decide which regimen will be used for the expanded safety cohort (Cohort 3). In 
case none of the groups that are part of the primary objective meet internal criteria, regimen 
selection may be delayed until additional analyses will be available. 
The sponsor committee will consist of the Clinical Development Committee (CDC), Head of 
Clinical Development, Senior Advisors on Clinical Development, Head of Regulatory Affairs,
Senior Statistician, Head of Biomarkers, Representative of Chemistry, Manufacturing Control, 
Head of Early Development and Translational Medicine, Head of Late Development, and other 
Senior Functions from the CDC. Additional factors such as data from other assays, 
manufacturability, and ease of administration will be taken into account to select the regimen for 
the expanded safety phase. More details will be described in the Statistical Analysis Plan.

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Table 9:
Study Design: Regimen Selection Cohort (Cohort 2)
Group
R
N
Day 1
Day 57
11
R2
24
Ad26.RSV.preF 1×1011 vp
+ Placebo*
Placebo
12
R2
42
Ad26.RSV.preF/
RSV preF protein mixture:
5×1010 vp/50 g
+ Placebo*
Placebo
13
R2
42
Ad26.RSV.preF/
RSV preF protein mixture:
1×1011 vp/50 g
+ Placebo*
Placebo
14
R2
42
Ad26.RSV.preF/
RSV preF protein mixture:
1×1011 vp/150 g
+ Placebo*
Placebo
15
R2
42
Ad26.RSV.preF/
RSV preF protein mixture:
5×1010 vp/150 g
+ Placebo*
Placebo
16
R2
36
Separate injections*: 
Ad26.RSV.preF 1×1011 vp 
+ RSV preF protein 150 g
Placebo
17
R2
36
Ad26.RSV.preF/
RSV preF protein mixture:
1×1011 vp/150 g
+ Placebo*
Ad26.RSV.preF/
RSV preF protein mixture:
1×1011 vp/150 g
18
R2
24
Placebo
+ Placebo*
Placebo
R2 TOTAL:
288
N: number of participants (Note: Data from Groups 9 and 10 of Cohort 1 will be pooled with those from Groups 16 and 17 of 
Cohort 2 up to Month 12); R: randomization; vp: viral particles
* Each injection to be given in opposite arms
Expanded Safety Cohort (Cohort 3)
In the expanded safety cohort, approximately 315 participants will be randomized in parallel to
1 of 3 groups (Groups 19 through 21; Table 10 and Table 11). No pauses in enrollment for safety 
assessments are planned.
Participants will receive the selected one- or two-dose regimen from Cohort 2 or placebo.
If the one-dose regimen is selected (Groups 11 through 16 from Cohort 2), Groups 19 and 20
would receive the selected regimen on Day 1, and a booster at Month 12 (the selected regimen or 
placebo, respectively) and Month 24 (the selected regimen). Group 21 will receive placebo at all
timepoints (Table 10).

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If the two-dose regimen is selected (Group 17 of Cohort 2), Groups 19 and 20 would receive the 
selected regimen on Day 1 and Day 57, and a booster (the selected regimen or placebo, 
respectively) at Month 12. Group 21 will receive placebo at all three timepoints (Table 11).
Table 10:
Study Design: Expanded Safety Cohort (Cohort 3) with One-dose Regimen and Month 12 and 
Month 24 Booster
Group
R
N
Day 1
Month 12
Month 24
19
R3
135
Selected Regimen
Selected Regimen
Selected Regimen
20
R3
135
Selected Regimen
Placebo for the Selected 
Regimen 
Selected Regimen
21
R3
45
Placebo for the Selected 
Regimen
Placebo for the Selected 
Regimen
Placebo for the Selected 
Regimen
R3 TOTAL:
315
OVERALL 
TOTAL:
667
N: number of participants; R: randomization
Table 11:
Study Design: Expanded Safety Cohort (Cohort 3) with Two-dose Regimen and Month 12 
Booster
Grou
p
R
N
Day 1
Day 57
Month 12
19
R3
135
Selected Regimen
Selected Regimen
Selected Regimen
20
R3
135
Selected Regimen
Selected Regimen
Placebo for the Selected 
Regimen
21
R3
45
Placebo for the Selected 
Regimen
Placebo for the Selected 
Regimen
Placebo for the Selected 
Regimen
R3 TOTAL:
315
OVERALL 
TOTAL:
667
N: number of participants; R: randomization
3.1.2.
Study Procedures
After each vaccination, participants will be closely observed for a minimum of 30 minutes post-
vaccination to monitor for the development of any acute reactions, or longer if deemed necessary 
by the investigator. Any unsolicited, solicited local or solicited systemic AEs will be documented 
by study personnel following this observation period. Participants will be given a thermometer, 
ruler and daily assessment (participant) diary with instructions for the proper recording of events. 
Each participant will record solicited local (at injection site) and solicited systemic AEs and body 
temperatures, beginning on the evening of each vaccine dosing day and on a daily basis for the 
following 7 days. Body temperatures (oral route preferred) should be taken at approximately the 
same time each day.a Study-site personnel will collect and review participant diary information 
and confirm the entries at subsequent site visits.
                                                
a Temperature 7 days after each vaccination may be collected earlier in the day to coincide with the clinic visit.

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Unsolicited AEs will be collected from the time of each vaccine administration through the 
following 28 days.a SAEs will be collected from first dose administration until the end of the
double-blind phase of the study. During the long-term follow-up phase (Groups 14 and 15 from 
Cohort 2), only SAEs related to study vaccine, study procedures, or non-investigational 
(concomitant) Janssen products, and all AEs leading to discontinuation will be collected. All AEs, 
including any that are ongoing at 28 days after each dose, will be followed until clinical resolution 
or stabilization. Concomitant therapies will be collected and recorded in the electronic case report 
form (eCRF) from time of each vaccine administration through 28 days after each vaccination, and 
additionally outside of these periods when associated with an SAE. During the long-term follow-
up phase (Groups 14 and 15 from Cohort 2), only medications in conjunction with SAEs related 
to study vaccine, study procedures, or non-investigational (concomitant) Janssen products, or in 
conjunction with AEs leading to discontinuation should be recorded.
All SAEs and AEs leading to discontinuation from the study/vaccination (regardless of the causal 
relationship) are to be reported from the moment of first vaccination until completion of the 
participant’s last study-related procedure, which may include contact for safety follow-up.
For participants in Cohorts 1 and 2, blood will be collected for serology and for laboratory safety 
assessments at the screening visit. Additionally, for participants in Cohorts 1 and 2, blood will be 
collected for laboratory safety assessments on Day 1 (pre-vaccination) and Day 8 (or at the exit 
visit if early exit is within 8 days of the first vaccination and the participant terminates without 
withdrawing consent).
Blood for humoral and cellular immune responses will be drawn from all participants in Cohorts 
1 and 2. In Cohort 3, blood will be drawn for humoral immune responses from all participants and 
for cellular immune responses from a subset of 63 participants, as specified in the Schedule of 
Activities.
Transcriptome analysis will be performed on samples collected on Day 1 (prior to vaccination), 
Day 8, and Day 15 in Cohorts 1 and 2 only.
Nasal samples will be collected for immunogenicity assessments as specified in the Schedule of 
Activities.
Note: All references throughout the protocol to the collection of a “nasal sample” imply a “nasal 
turbinate sample or its alternative”.
During the first 2 RSV seasons of the study (relative to the enrollment date of the first participant 
in Cohort 1), participants should record any signs and symptoms of RTI (eg, runny nose, fever, 
severe cough, rapid breathing, or difficulty breathing) on a daily basis using a study-specific RTI 
                                                
a AEs that start more than 28 days after a vaccination, but that are still present at the time of the next vaccination will 
also be recorded.

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Symptoms Form, starting on the first day they experience symptoms, including the day on which 
the symptoms resolve. For details of RTI procedures, including nasal sampling, see Section 9.2.2.
During the first 2 RSV seasons of the study, participants will be contacted by telephone every 30±7 
days (unless a planned clinic visit has occurred or will occur within 30 days). Calls will remind 
the participants to complete the RTI Symptoms Form in the event of any symptoms of RTI, to 
contact the site at the time of symptom onset, and to take a nasal sample at home preferably 
between 2 and 3 days after the onset of the RTI symptoms (or go to the site preferably within 2 to 
3 days after the onset of the RTI to have a nasal sample taken by study staff). Calls will also check 
for any SAEs and associated concomitant medications since the previous visit or telephone contact.
Unscheduled visits may be performed based on investigator’s clinical judgment and may include 
further evaluations, as needed.
A diagram of the study design is provided in Figure 1, Figure 2, Figure 3, and Figure 4.

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Figure 1:
Schematic Overview of the Study for Cohort 1
* In addition, sentinel participants in Cohort 1 will be contacted by telephone 24 hours post-dose to collect safety 
information.
Safety – 7 days post-first study vaccination*
Screening: 
Days -28 to 0
Study Vaccination 1: Day 1
Study Vaccination 3: Month 12
2
3
5
6
7
1
VISIT
Safety – 7 days post-third study vaccination
Safety and Immunogenicity – 28 days post-third study vaccination
8
9
Safety and Immunogenicity – 28 days post-first study vaccination
10
11
4
Safety and Immunogenicity – 26 weeks post-third study vaccination
Safety and Immunogenicity – 12 months post-third study vaccination
12
13
14
Safety and Immunogenicity – 14 days post-first study vaccination
Safety – 7 days post-second study vaccination
Study Vaccination 2: Day 57
Safety and Immunogenicity – 28 days post-second study vaccination
Safety and Immunogenicity – 26 weeks post-first study vaccination

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Figure 2:
Schematic Overview of the Study for Cohort 2
* Participants in Groups 14 and 15 will continue into the long-term follow-up phase.

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Figure 3:
Schematic Overview of the Study for Cohort 3 One-dose Regimen and Month 12 and Month 24
Booster
* Visit 13 (7 days post-third vaccination) is not required for any Cohort 3 participant who misses the third vaccination.
Safety: 7 days post-first study vaccination
Screening + Study Vaccination 1: 
Day 1
Study Vaccination 3: Month 24
1
2
4
5
6
Safety*: 7 days post-third study vaccination
Safety and Immunogenicity: 28 days post-third study vaccination
7
8
Safety and Immunogenicity: 28 days post-first study vaccination
9
10
3
Safety and Immunogenicity: 26 weeks post-third study vaccination
Safety and Immunogenicity: 36 months post-first study vaccination
11
12
13
Safety and Immunogenicity: 14 days post-first study vaccination
Safety: 7 days post-second study vaccination
Study Vaccination 2: Month 12 
Safety and Immunogenicity: 28 days post-second study vaccination
Safety and Immunogenicity: 26 weeks post-second study vaccination
Safety and Immunogenicity: 12 weeks post-first study vaccination
Safety and Immunogenicity: 56 days post-first study vaccination
Safety and Immunogenicity: 26 weeks post-first study vaccination
Safety and Immunogenicity: 14 days post-third study vaccination
14
15
16
17

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Figure 4:
Schematic Overview of the Study for Cohort 3 Two-dose Regimen and Month 12 Booster
3.2.
Study Design Rationale
Vector Selection
The rationale behind the selection of the Ad26 vector is described in Section 1.1.
Dose Selection
The 5×1010 vp dose is the most commonly used dose in previous RSV vaccine studies and other 
programs, and has
good safety and immunogenicity profiles. Moreover, in study 
VAC18193RSV1003, the 1×1011 vp dose of Ad26.RSV.preF was well-tolerated in adults aged 
≥60 years and was found to induce higher humoral immune responses than the 5×1010 vp dose

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whilst maintaining good cellular responses. As the current study is FIH for the Ad26.RSV.preF/
RSV preF protein combination (separate injections in opposite arms) and Ad26.RSV.preF/RSV 
preF protein mixture (single injection), both the 5×1010 vp and 1×1011 vp Ad26.RSV.preF doses 
will be assessed.
The dose levels of 50 μg and 150 μg of RSV preF protein to be used were chosen based on the 
supposition that half log intervals in dose response are biologically meaningful for vaccines. Dose 
levels of 15 μg, 50 μg, 150 μg, and 500 μg would correspond to such a series. It was decided that 
the 15 μg dose would be too low, while the 500 μg dose did not appear to be feasible at this time. 
Therefore, the 50 μg and 150 μg were chosen for initial exploration. These doses are comparable
to doses utilized by other investigators studying RSV protein vaccines in humans.3,7,30
Regimen Selection
In the initial safety cohort (Cohort 1), RSV preF protein dosing is increased from 50 μg to 150 μg 
for initial safety assessment. Safety of protein at each dose is assessed before dosing of the
Ad26.RSV.preF/RSV preF protein combination or mixture. The dose of the mixture will also be
increased from a protein/adeno dose of 50 μg/5×1010 vp to a protein/adeno dose of 150 μg/1×1011
vp for initial safety assessment.
In Group 10 of Cohort 1 (Ad26.RSV.preF/RSV preF protein 1×1011 vp/150 μg combination given 
as separate injections in opposite arms on Day1 and at Month 12), no active boost vaccination will 
be administered on Day 57 as the combination will not be investigated further for immunogenicity 
in the regimen selection (Cohort 2).
In the regimen selection cohort (Cohort 2), regimens under consideration include dose ranging 
with all dose combinations of the mixture, including high dose Ad26.RSV.preF with high dose 
RSV preF protein; a 2-month prime-boost regimen with a mixture of high dose Ad26.RSV.preF 
with high dose RSV preF protein; and separate administration (in opposite arms) of high dose 
Ad26.RSV.preF and high dose RSV preF protein.
In Cohort 2, only Group 17 (Ad26.RSV.preF/RSV preF protein mixture 1×1011 vp/150 μg given 
as a single injection on Day 1 and Day 57) will include an active boost vaccination on Day 57, 
becauseit is anticipated that if a Day 57 boost is required it would be the highest dose combination 
of Ad26.RSV.preF and RSV preF protein.
All Cohort 1 and 3 regimens include a Month 12 booster dose to assess the need for a yearly 
revaccination. Additionally, the Cohort 3 one-dose regimen includes a Month 24 booster dose to 
assess the long-term durability of the immune response to the selected dose.
Screening Period
The study includes a maximum 28-day screening period for Cohorts 1 and 2, including but not 
limited to safety laboratory testing and a 12-lead ECG. As the screening period of participants for 
Cohorts 1 and 2 will generate sufficient safety data before the start of Cohort 3, screening of 

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participants for Cohort 3 will be performed on Day 1 without safety laboratory testing and a 
12-lead ECG.
Blinding, Control, Study Phase/Periods, Vaccine Groups
Placebo controls will be used to establish the frequency and magnitude of changes in endpoints 
that may occur in the absence of active vaccine. Randomization will be used to minimize bias in 
the assignment of participants to vaccine groups, to increase the likelihood that known and 
unknown participant attributes (eg, demographics, baseline characteristics) are evenly balanced 
across vaccine groups, and to enhance the validity of statistical comparisons across vaccine groups. 
Blinded treatment will be used to reduce potential bias during data collection and evaluation of 
endpoints.
4.
PARTICIPANT POPULATION
Screening for eligible participants in Cohorts 1 and 2 will be performed within 28 days before 
administration of the first dose of study vaccine. Screening for eligible participants in Cohort 3
will be performed on Day 1.
The inclusion and exclusion criteria for enrolling participants in this study are described in the 
following 2 subsections. If there is a question about the inclusion or exclusion criteria below, the 
investigator must consult with the appropriate sponsor representative and resolve any issues before 
enrolling a participant in the study. Waivers are not allowed.
Note: Investigators should ensure that all study enrollment criteria have been met at screening. If 
a participant’s clinical status changes (including any available laboratory results or receipt of 
additional medical records) after screening but before the first dose of study vaccine is given such 
that he or she no longer meets all eligibility criteria, then the participant should be excluded from 
participation in the study. Section 17.4, Source Documentation, describes the required 
documentation to support meeting the enrollment criteria.
4.1.
Inclusion Criteria
Each potential participant must satisfy all of the following criteria to be enrolled in the study:
1.
Each participant must sign an informed consent form (ICF) indicating that he or she 
understands the purpose of and procedures required for the study, is willing to participate in 
the study and attend all scheduled visits, and is willing and able to comply with all study 
procedures and adhere to the prohibitions and restrictions specified in this protocol.
2.
Participant must be a man or woman, ≥60 years old on the day of signing the ICF and available 
for the duration of the study.
3.
Criterion amended per Amendment 2
3.1.
Before randomization, a woman must be:

postmenopausal (postmenopausal state is defined as no menses for 12 months without 
an alternative medical cause); and

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
not intending to conceive by any methods.
Note: Hysterectomized women are also eligible for the study.
4.
Criterion amended per Amendment 5
4.1
In the investigator’s clinical judgment, participant must be either in good or stable 
health. Participants may have underlying illnesses such as hypertension, type 2 
diabetes mellitus, hyperlipoproteinemia, or hypothyroidism, as long as their symptoms
and signs are medically controlled. If they are on medication for a condition, the 
medication dose must have been stable for at least 12 weeks preceding vaccination and 
expected to remain stable for the duration of the study. Participants will be included 
on the basis of physical examination, medical history, vital signsa, and 12-lead 
electrocardiogram (ECG)b performed at screening.
Note: To determine eligibility for revaccination, signs and symptoms of potential 
underlying illnesses should be medically stable in the weeks preceding revaccination.
Participants with changes in medication 12 weeks preceding revaccination may be 
revaccinated if the change is considered minor and judged by the investigator not to 
impact signs or symptoms of the underlying illness.
5.
For participants in Cohorts 1 and 2 only: Participant must be healthy on the basis of clinical 
laboratory tests performed at screening. If the results of the laboratory screening tests are 
outside the central laboratory normal reference ranges and additionally within the limits of 
toxicity Grade 2 according to the US Food and Drug Administration (FDA) toxicity tables (ie, 
for tests in the FDA tablec), the participant may be included only if the investigator judges the 
abnormalities or deviations from normal to be not clinically significant and appropriate and 
reasonable for the population under study. This determination must be recorded in the 
participant’s source documents and initialed by the investigator.
Note: If laboratory screening tests are out of central laboratory normal ranges and deemed 
clinically significant, repeat of screening tests is permitted once, using an unscheduled visit 
during the screening period to assess eligibility. Screening laboratory tests are to be done 
within 28 days of randomization.
6.
From the time of each vaccination through 3 months after each vaccination, participant agrees 
not to donate blood.
7.
Participant must be willing to provide verifiable identification, have means to be contacted 
and to contact the investigator during the study.
                                                
a Participants can be enrolled with Grade 1 or Grade 2 values for vital signs measurements.
b For participants in Cohorts 1 and 2 only.
c For the FDA toxicity grading tables, see Attachment 1: FDA Guidance document “Toxicity Grading Scale for 
Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials” (September 2007).

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4.2.
Exclusion Criteria
Any potential participant who meets any of the following criteria will be excluded from 
participating in the study:
1.
Participant has acute illness (this does not include minor illnesses such as diarrhea) or body 
temperature ≥38.0 ºC within 24 hours prior to the first dose of study vaccine. In such a 
situation, the participant may be vaccinated up to, and no later than 10 days after the scheduled 
vaccination.
Note: For participants in Cohorts 1 and 2, safety laboratory tests should be repeated if 
vaccination is postponed and the time between the safety laboratory tests and vaccination 
exceeds 28 days.
2.
Participant has a serious chronic disorder, including severe chronic obstructive pulmonary 
disease or clinically significant congestive heart failure, requirement for supplemental oxygen, 
end-stage renal disease with or without dialysis, clinically unstable cardiac disease, 
Alzheimer’s disease, or has any condition for which, in the opinion of the investigator, 
participation would not be in the best interest of the participant (eg, compromise well-being) 
or that could prevent, limit, or confound the protocol-specified assessments.
3.
Participant has history of malignancy within 5 years before screening (exceptions are 
squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or 
malignancy, which is considered cured with minimal risk of recurrence).
4.
Participant has had major surgery (per the investigator’s judgment), within 4 weeks before 
dosing, or will not have fully recovered from surgery, or has surgery planned during the time 
the participant is expected to participate in the study or within 6 months after the last dose of 
study vaccine.
Note: Participants with planned surgical procedures to be conducted under local or 
locoregional anesthesia and not judged as major by the investigator may participate.
5.
Per serology testing in Cohorts 1 and 2 and per medical history in Cohort 3: Participant has 
chronic active hepatitis B or hepatitis C infection, documented by hepatitis B surface antigen 
and hepatitis C antibody, respectively.
6.
Per serology testing in Cohorts 1 and 2 and per medical history in Cohort 3: Participant has 
HIV type 1 or type 2 infection.
7.
Participant has had major psychiatric illness and/or drug or alcohol abuse which in the 
investigator’s opinion would compromise the participant’s safety and/or compliance with the 
study procedures.
8.
Participant has a known allergy, or history of anaphylaxis or other serious adverse reactions 
to vaccines or vaccine components (including any of the constituents of the study vaccine).
9.
Participant has a history of chronic urticaria (recurrent hives), eczema and/or atopic dermatitis.
10. Participant has a history of acute polyneuropathy (eg, Guillain-Barré syndrome).

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11. Criterion amended per Amendment 2:
11.1
Participant has abnormal function of the immune system resulting from:

Clinical conditions (eg, autoimmune disease or immunodeficiency)

Chronic (longer than 10 days) or recurrent use of systemic corticosteroids during the 
study and within 6 months before first administration of study vaccine (Note: Ocular, 
topical or inhaled steroids are allowed; intra-articular steroid injections are not 
allowed.)

Administration of antineoplastic and immunomodulating agents or radiotherapy 
during the study and within 6 months before the first administration of study vaccine.
12. Participant has received treatment with immunoglobulins in the 2 months, immunoglobulins 
specific to RSV, human metapneumovirus or parainfluenza viruses in the last 12 months, or 
blood products in the 4 months before the planned administration of the first dose of study 
vaccine or has any plans to receive such treatment during the study.
13. Criterion amended per Amendment 2:
13.1
Participant is in receipt of, or planning to receive, licensed live attenuated vaccine 
within 28 days of each study vaccination (ie, before and after); other licensed vaccines (ie, not 
live: eg, influenza, tetanus, hepatitis A or B, rabies) should be given at least 14 days before or 
14 days after each study vaccination.
14. Criterion amended per Amendment 5:
14.1
Participant has received an investigational drug or used an invasive investigational 
medical device within 30 days or received an investigational vaccine within 6 months 
before the planned administration of the first dose of study vaccine or is currently enrolled 
or plans to participate in another investigational study during the course of the double-
blind phase of this study.
Note: Participation in an observational clinical study (ie, with no intervention) is allowed 
upon approval of the sponsor.
Note: During the long-term follow-up period (Groups 14 and 15 from Cohort 2 only), 
participation in another investigational study is allowed only upon approval of the sponsor.
15. Participant has a contraindication to intramuscular injections and blood draws, eg, bleeding 
disorders.
16. Criterion deleted per Amendment 2.
17. Participant has received RSV vaccine in a previous RSV vaccine study at any time prior to 
randomization.
18. Participant who, in the opinion of the investigator, is unlikely to adhere to the requirements of 
the study, or is unlikely to complete the full course of vaccination and observation.
19. Participant cannot communicate reliably with the investigator.

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20. Participant is an employee of the investigator or study site, with direct involvement in the 
proposed study or other studies under the direction of that investigator or study site, as well 
as family members of the employees or the investigator, or an employee of the sponsor.
21. Criterion deleted per Amendment 2.
4.3.
Prohibitions and Restrictions
Potential participants must be willing and able to adhere to the following prohibitions and 
restrictions during the course of the study to be eligible for participation:
1.
See Section 8 regarding prohibited and restricted therapies and vaccines during the study.
2.
Agree to follow all requirements that must be met during the study as noted in the inclusion 
and exclusion criteria (Section 4.1 and Section 4.2, respectively).
5.
TREATMENT ALLOCATION AND BLINDING
Study Vaccine Allocation
Central randomization will be implemented in this study. Participants will be randomly assigned 
to a vaccination group based on a computer-generated randomization schedule prepared before the 
study by or under the supervision of the sponsor. The randomization will be balanced by using 
randomly permuted blocks.
In the initial safety cohort (Cohort 1), the randomization ratio in Cohorts R1a and R1c is 1:2, in 
Cohorts R1b and R1d the ratio is 1:2:2. In each of those cohorts, 1 sentinel participant from each 
group (each active group and the placebo group to maintain the blind) will initially be enrolled to 
monitor for any unexpected severe adverse reaction. Therefore, the randomization will be phased 
to accommodate this and to end up with the overall randomization ratios specified above. No 
stratification will be applied.
In the regimen selection cohort (Cohort 2), the randomization ratio is 4:7:7:7:7:6:6:4. No 
stratification will be applied.
In the expanded safety cohort (Cohort 3), stratification will be applied: participants will be 
assigned to 1 of 2 strata prior to randomization, depending on the blood mononuclear cell (PBMC)
sampling capability and capacity of the site. One stratum will contain a maximum of 
63 participants from whom blood samples to assess humoral and cellular (PBMC samples) 
immunogenicity will be collected. The other stratum will contain the remaining participants, from 
whom blood samples will be collected only for humoral immunogenicity assessments, to reach the 
target of a total of 315 participants in Cohort 3. Within each stratum, participants will be 
randomized 3:3:1 ratio to one of the respective groups.
The interactive web response system (IWRS) will assign a unique code, which will dictate the 
group assignment for the participant. The requestor must use his or her own user identification and 

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personal identification number when contacting the IWRS, and will then give the relevant 
participant details to uniquely identify the participant.
If randomized participants are withdrawn from vaccination before the first dose of study vaccine
is administered, additional participants may be recruited to replace these participants at the 
discretion of the sponsor. Any replacement participant will be assigned to the same group as the 
original (discontinued) participant. The replacement participant’s randomization number will 
equal the randomization number of the discontinued participant +1000 (eg, participant 0001 would 
be replaced by participant 1001). These additional participants should also be randomized through 
IWRS.
In the initial safety cohort (Cohort 1), any randomized participant who is withdrawn from the study 
for reasons other than due to an AE after the first dose but before the second dose might be replaced 
at the discretion of the sponsor. Any replacement participant will be randomized through IWRS. 
The replacement participant’s randomization number will equal the randomization number of the 
discontinued participant +2000.
In the regimen selection cohort (Cohort 2), no replacements or additional randomizations will be 
done for withdrawals after the first dose.
Blinding
The investigator will not be provided with randomization codes. The codes will be maintained 
within the IWRS, which has the functionality to allow the investigator to break the blind for an 
individual participant.
At the sponsor level, unblinding (at the participant level) will occur at the time of the primary 
analysis for each cohort. After the primary analysis, group level results may be shared as needed;
however, efforts will be made to preserve the blinding to the individual participant allocation until 
the timepoints specified below.
While the responsibility to break the study vaccine allocation code in emergency situations resides 
solely with the investigator, it is recommended that the investigator contact the sponsor or sponsor 
designee to discuss the particular situation, before breaking the blind. Telephone contact with the 
sponsor or the sponsor designee will be available 24 hours per day, 7 days per week. In such cases, 
the investigator may in an emergency determine the identity of the study vaccine by contacting the 
IWRS. If the blind is broken, the sponsor must be informed as soon as possible. Date, time and 
reason for the unblinding must be documented by the IWRS, in the appropriate section of the 
eCRF, and in the source document. Documentation received from the IWRS indicating the code 
break must be retained with the participant’s source documents in a secure manner.
For Cohorts 1 and 3, the participants, study-site personnel and investigator will be blinded to study 
vaccine allocation throughout the main study until after the database lock of the final analysis at 
Day 730 for Cohort 1 and at Day 1095 for Cohort 3, except for the pharmacist or qualified staff 
member with primary responsibility for study vaccine preparation and dispensing.

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For Cohort 2, the participants, study-site personnel and investigator will be blinded to study 
vaccine allocation throughout the double-blind phase of the main study until after the database 
lock of the analysis at Day 730, except for the pharmacist or qualified staff member with primary 
responsibility for study vaccine preparation and dispensing. By participating in the long-term 
follow-up phase of the study, clinical staff, the investigator and eligible participants from Groups 
14 and 15 (Cohort 2), will be partially unblinded to their treatment received (ie, will be informed 
that they were randomized to either Group 14 or 15) prior to full unblinding after the database lock 
of the final analysis at the end of the long-term follow-up phase (Day 1095). The pharmacy and 
the preparation of study vaccines will be monitored by an independent vaccine monitor (see also 
Section 17.8).
Note: The unblinded pharmacist, or other qualified individual, may also perform administration of 
the vaccine, but will have no other study function following dosing.
If the randomization code is broken by the investigator or the study-site personnel, the participant
must discontinue further study vaccine administration and must be followed as appropriate (see 
Section 10.2 for details). If the randomization code is broken by the sponsor for safety reporting 
purposes, the participant should not discontinue further vaccine administration and may remain in 
the study (if the randomization code is still blinded to the study-site personnel and the participant).
6.
DOSAGE AND ADMINISTRATION
Ad26.RSV.preF and RSV preF protein will be administered either as a combination (as separate 
injections in opposite arms) or as a mixture (a single injection) into the deltoid muscle according 
to the schedules shown in Table 8, Table 9, Table 10 and Table 11:

Ad26.RSV.preF (JNJ-64400141): will be supplied at a concentration of 2×1011 vp/1 mL in 
single-use vials. Dose levels of 5×1010 vp and 1×1011 vp will be used.

RSV preF protein (JNJ-64213175): will be supplied at a concentration of 0.3 mg/1 mL in 
single use vials. Dose levels of 50 μg and 150 μg will be used.

Placebo for Ad26.RSV.preF and RSV preF protein.
All injections of Ad26.RSV.preF and RSV preF protein (or corresponding placebo) will be 1 mL 
in volume. 
An unblinded pharmacist, or other qualified individual, will prepare the appropriate vial and/or
syringe and provide the syringe in a blinded manner to the vaccine administrator who will perform 
the injection. The unblinded pharmacist, or other qualified individual, may also perform vaccine 
administration, but will have no other study function following dosing. Diluent will be used as 
required. 
Full details of vaccine preparation, including mixing of Ad26.RSV.preF and RSV preF protein,
are provided in the Investigational Product Preparation Instructions.
All vaccines should be administered in the deltoid muscle:

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
When participants receive 2 injections at any given visit, these injections will be given in 
opposite arms at the same time with no more than 45 minutes between the injections.

When participants receive a single injection per visit, eg, in Groups 1 through 7 in Cohort 1, 
alternating injection sites will be used for subsequent injections unless there is a medically 
justifiable reason in the judgment of the PI(s).
No local or topical anesthetic should be used prior to the injection.
For each injection, a record should be made in the eCRF of which arm was injected.
7.
VACCINE COMPLIANCE
Study vaccine (active or placebo) will be administered intramuscularly by a blinded vaccine 
administrator (a trained and qualified study nurse, medical doctor, or otherwise qualified 
healthcare professional). The unblinded pharmacist, or other qualified individual, may also 
perform vaccine administration, but will have no other study function following dosing. The date 
and time of each study vaccine administration will be recorded in the eCRF.
8.
PRE-STUDY AND CONCOMITANT THERAPY
Pre-study therapies such as analgesic/antipyretic medications and non-steroidal anti-inflammatory 
drugs (NSAIDs) used up to 30 days before the first dose of study vaccine must be recorded in the 
eCRF during screening.
Concomitant therapies will be collected and recorded in the eCRF from the time of each vaccine 
administration through 28 days after each vaccination, and additionally outside of these periods 
when associated with any SAE that meets the criteria outlined in Section 12.3.2. During the long-
term follow-up phase (Groups 14 and 15 from Cohort 2), only concomitant therapies in 
conjunction with SAEs related to study vaccine, study procedures, or non-investigational 
(concomitant) Janssen products, or in conjunction with AEs leading to discontinuation should be 
recorded.
Information on concomitant use of herbal supplements or vitamins will not be collected.
Use of experimental medications (including experimental vaccines other than the study vaccine) 
during the study is not allowed. Note: During the long-term follow-up period (Groups 14 and 15 
from Cohort 2 only), use of experimental medications during participation in another 
investigational study is allowed only upon approval of the sponsor.
Analgesic/antipyretic medications and NSAIDs may be used post-vaccination only in case of 
medical need (eg, fever or pain) and their use must be documented. Use of these medications as 
routine prophylaxis prior to study vaccine administration is discouraged.
Chronic (longer than 10 days) or recurrent use of systemic corticosteroids is prohibited during the 
study and within 6 months before first administration of study vaccine (ocular, topical or inhaled 
steroids are allowed; intra-articular steroid injections are not allowed). Antineoplastic and 

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immunomodulating agents or radiotherapy are prohibited in the 6 months before the first 
administration of study vaccine and during the study.
If chronic use of prohibited therapies becomes medically indicated during the study for any 
participant, the sponsor should be contacted.
Vaccination with live attenuated vaccines within 28 days of a vaccination in this study (ie, before 
and after) is prohibited. Other licensed vaccines (ie, not live: eg, influenza, tetanus, hepatitis A, 
hepatitis B, rabies) should be given at least 14 days before or 14 days after each study vaccination 
to avoid potential confusion of adverse reactions and potential immune interference. If a vaccine 
is indicated in a post-exposure setting (eg, rabies or tetanus), it must take priority over the vaccines 
in this study.
The sponsor must be notified in advance (or as soon as possible thereafter) of any instances in 
which prohibited therapies are administered.
9.
STUDY PROCEDURES AND EVALUATIONS
9.1.
Study Procedures
9.1.1.
Overview
Evaluation of the safety and reactogenicity will include laboratory assessments (Cohorts 1 and 2 
only), measurements of vital signs, physical examination by study-site personnel, and participant
reports on signs and symptoms post-vaccination. Additional study visits may be required if, in the 
investigator’s opinion, further clinical or laboratory evaluation is needed.
All participants will be provided with a thermometer, a ruler and a participant diary to measure and 
record body temperature, solicited local AEs (at the injection site), and solicited systemic AEs.
The diary includes instructions on how to capture data and grading scales to assess the severity of 
the symptoms. Study staff are responsible for providing appropriate training to the participant to 
avoid any missing or incorrect data. The diary card will be reviewed by the study-site personnel at 
visits indicated in the Schedule of Activities. If the diary card review is missed, the diary card will
be reviewed at the next visit. If a participant misses a vaccination, the diary card covering the 
period after the missed vaccination does not have to be completed.
During the first 2 RSV seasons of the study (relative to the enrollment date of the first participant 
in Cohort 1), participants will be contacted by telephone every 30±7 days (unless a planned visit 
has occurred or will occur within 30 days). These calls will remind participants to complete the 
RTI Symptoms Form in the event of any symptoms of RTI, to contact the site at the time of 
symptom onset, and to take a nasal sample at home preferably between 2 and 3 days after the onset
of the RTI symptoms (or go to the site preferably within 2 to 3 days after the onset of the RTI to 
have a nasal sample taken by study staff). These calls will also check for any SAEs and associated 
concomitant medications since the previous visit or telephone contact.

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The Schedule of Activities summarizes the frequency and timing of safety and immunogenicity 
assessments applicable to this study. The total blood volume to be collected over the entire study 
from each participant will be:

In Cohort 1: approximately 627.5 mL. The maximum volume of blood to be drawn at any 
given visit will be 67.5 mL.

In Cohort 2 (Groups 11-13 and Groups 16-18): approximately 567.5 mL. The maximum 
volume of blood to be drawn at any given visit will be 67.5 mL.

In Cohort 2 participants in Groups 14 and 15 who continue into the long-term follow-up phase: 
approximately 687.5 mL. The maximum volume of blood to be drawn at any given visit will 
be 67.5 mL.

In the randomly selected subset of 63 participants in Cohort 3 with blood draws for humoral 
as well as cellular responses: approximately 840 mL. The maximum volume of blood to be 
drawn at any given visit will be 60 mL.

In the remaining 252 participants in Cohort 3, blood samples will be taken for humoral 
responses only, with a total blood draw of approximately 140 mL. The maximum volume of 
blood to be drawn at any given visit will be 10 mL.
9.1.2.
Visit Windows
Visit windows will be allowed as indicated in Table 12, Table 13, Table 14, and Table 15.
The timings of the post-vaccination visits will be determined relative to the actual day of the 
corresponding vaccination. If a participant misses a vaccination, the post-vaccination visits will be 
calculated from the imputative vaccination date according to protocol.

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Table 12:
Visit Windows: Initial Safety Cohort (Cohort 1) 
VISIT
Visit Day
Window
Primary Purpose
Visit 2
Day 1
--
FIRST STUDY VACCINATION
Visit 3
Day 8
±2 days
7-day post-first study vaccination safety only visit
Visit 4
Day 15
±2 days
14-day post-first study vaccination safety and
immunogenicity visit
Visit 5
Day 29
±3 days
28-day post-first study vaccination safety and 
immunogenicity visit
Visit 6
Day 57
±3 days
SECOND STUDY VACCINATION
Visit 7
Day 64
(Vac 2
+7 days)
±2 days
7-day post-second study vaccination safety only visit
Visit 8
Day 85
(Vac 2
+28 days)
3 days/10 
days
28-day post-second study vaccination safety and 
immunogenicity visit
Visit 9
Day 183
(Vac 1
+26 weeks)
±14 days
26-week post-first study vaccination safety and 
immunogenicity visit
Visit 10
Day 365
±2 months
THIRD STUDY VACCINATION
(MONTH 12 BOOSTER)
Visit 11
Day 372
(Vac 3
+7 days)
±2 days
7-day post-third study vaccination safety only visit
Visit 12
Day 393
(Vac 3
+28 days)
±3 days
28-day post-third study vaccination safety and
immunogenicity visit
Visit 13
Day 547
(Vac 3
+26 weeks)
±14 days
26-week post-third study vaccination safety and 
immunogenicity visit
Visit 14
Day 730
(Vac 3
+12 months)
±1 month
FINAL VISIT: 12-month post-third study vaccination 
safety and immunogenicity visit

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Table 13:
Visit Windows: Regimen Selection Cohort (Cohort 2)
VISIT
Visit Day
Window
Primary Purpose
Visit 2
Day 1
--
FIRST STUDY VACCINATION
Visit 3
Day 8
±2 days
7-day post-first study vaccination safety only visit
Visit 4
Day 15
±2 days
14-day post-first study vaccination safety and 
immunogenicity visit
Visit 5
Day 29
±3 days
28-day post-first study vaccination safety and 
immunogenicity visit
Visit 6
Day 57
±3 days
SECOND STUDY VACCINATION
Visit 7
Day 64
(Vac 2 
+7 days)
±2 days
7-day post-second study vaccination safety only visit
Visit 8
Day 85
(Vac 2
+28 days)
3 days/10 
days
28-day post-second study vaccination safety and 
immunogenicity visit
Visit 9
Day 183
(Vac 1
+26 weeks)
±14 days
26-week post-first study vaccination safety and 
immunogenicity visit
Visit 10
Day 365
(Vac 1
+12 months)
±1 month
12-month post-first study vaccination safety and 
immunogenicity visit
Visit 11
Day 547
(Vac 1
+18 months)
±1 month
18-month post-first study vaccination safety and 
immunogenicity visit
Visit 12
Day 730
(Vac 1
+24 months)
±1 month
FINAL VISIT for Groups 11-13 and Groups 16-18: 
24-month post-first study vaccination safety and 
immunogenicity visit
Visit 13*
Day 912
(Vac 1
+ 911 days)
±30 days
30-month post-first study vaccination immunogenicity 
visit
Visit 14*
Day 1095
(Vac 1
+1094 days)
±30 days
FINAL VISIT: 36-month post-first study vaccination 
immunogenicity visit
*Visits during long-term follow-up phase for participants in Groups 14 and 15 only.

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Table 14:
Visit Windows: Expanded Safety Cohort (Cohort 3) - One-dose Regimen and Month 12 and 
Month 24 Booster
VISIT
Visit Day
Window
Primary Purpose
Visit 1
Day 1
–
FIRST STUDY VACCINATION 
Visit 2
Day 8
±2 days
7-day post-first study vaccination safety only visit
Visit 3
Day 15
±2 days
14-day post-first study vaccination safety and 
immunogenicity visit
Visit 4
Day 29
±3 days
28-day post-first study vaccination safety and 
immunogenicity visit
Visit 5
Day 57
±3 days
56-day post-first study vaccination safety and 
immunogenicity visit
Visit 6
Day 85 
(Vac 1
+12 weeks)
-3/+10 days
12-week post-first study vaccination safety and 
immunogenicity visit
Visit 7
Day 183
(Vac 1
+26 weeks)
±14 days
26-week post-first study vaccination safety and 
immunogenicity visit
Visit 8
Day 365
–2 months
SECOND STUDY VACCINATION
(MONTH 12 BOOSTER)
Visit 9
Day 372
(Vac 2
+7 days)
±2 days
7-day post-second study vaccination safety only visit
Visit 10
Day 393
(Vac 2
+28 days)
±3 days
28-day post-second study vaccination safety and 
immunogenicity visit
Visit 11
Day 547
(Vac 2
+26 weeks)
±14 days
26-week post-second study vaccination safety and 
immunogenicity visit
Visit 12
Day 730
(Vac 1
+729 days)
±30 days
THIRD STUDY VACCINATION
(MONTH 24 BOOSTER)
Visit 13
Day 737
(Vac 3
+7 days)
±2 days
7-day post-third study vaccination safety only visit
Visit 14
Day 744
(Vac 3
+14 days)
±2 days
14-day post-third study vaccination safety and 
immunogenicity visit
Visit 15
Day 758
(Vac 3
+28 days)
±3 days
28-day post-third study vaccination safety and 
immunogenicity visit
Visit 16
Day 912
(Vac 3
+182 days)
±14 days
26-week post-third study vaccination safety and 
immunogenicity visit
Visit 17
Day 1095
(Vac 1
+1094 days)
±30 days
FINAL VISIT: 12-month post-third study vaccination 
safety and immunogenicity visit

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Table 15:
Visit Windows: Expanded Safety Cohort (Cohort 3) - Two-dose Regimen and Month 12 Booster
VISIT
Visit Day
Window
Primary Purpose
Visit 1
Day 1
–
FIRST STUDY VACCINATION
Visit 2
Day 8
±2 days
7-day post-first study vaccination safety only visit
Visit 3
Day 15
±2 days
14-day post-first study vaccination safety and 
immunogenicity visit
Visit 4
Day 29
±3 days
28-day post-first study vaccination safety and 
immunogenicity visit
Visit 5
Day 57
±3 days
SECOND STUDY VACCINATION 
Visit 6
Day 64
(Vac 2
+7 days)
±2 days
7-day post-second study vaccination safety only visit
Visit 7
Day 85 (Vac 2
+28 days)
-3/+10 days
28-day post-second study vaccination safety and 
immunogenicity visit
Visit 8
Day 183
(Vac 1
+26 weeks)
±14 days
26-week post-first study vaccination safety and 
immunogenicity visit
Visit 9
Day 365
–2 months
THIRD STUDY VACCINATION
(MONTH 12 BOOSTER)
Visit 10
Day 372
(Vac 3
+7 days)
±2 days
7-day post-third study vaccination safety only visit
Visit 11
Day 393
(Vac 3
+28 days)
±3 days
28-day post-third study vaccination safety and 
immunogenicity visit
Visit 12
Day 547
(Vac 3
+26 weeks)
±14 days
26-week post-third study vaccination safety and 
immunogenicity visit
Visit 13
Day 730
(Vac 3
+12 months)
±1 month
FINAL VISIT: 12-month post-third study vaccination 
safety and immunogenicity visit
9.1.3.
Screening Phase (Days -28 to 0 for Cohorts 1 and 2; Before 
Randomization on Day 1 for Cohort 3)
Only participants in good or stable health without acute illness or fever and complying with the 
inclusion and exclusion criteria as specified in Sections 4.1 and 4.2 will be included in the study. 
The investigator will provide detailed information on the study to the participants and will obtain 
written informed consent prior to each participant’s participation in the study. All the procedures 
described in the Schedule of Activities will only take place after the written informed consent has 
been obtained.
The following evaluations will be performed to determine eligibility requirements as specified in 
the inclusion and exclusion criteria:

Demographic information

Medical history

Review of pre-study medications

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
Review of inclusion/exclusion criteria

Full physical examination including vital signs measurement (respiratory rate, heart rate, 
supine systolic and diastolic blood pressure, and body temperature) and height and weight
The following evaluations will additionally be performed for participants in Cohorts 1 and 2:

12-lead ECG

Serology testing (HIV type 1 or type 2, hepatitis B, hepatitis C)

Blood sampling for laboratory safety testing (hematology and biochemistry)
Study participants who qualify for inclusion in Cohorts 1 and 2 will be contacted and scheduled 
for enrollment and first vaccination (Visit 2) within 28 days. If necessary, the screening visit may 
be split into several visits.
Participants in Cohorts 1 and 2 with laboratory values or vital signs (eg, elevated blood pressure) 
not meeting eligibility criteria at the screening visit may have 1 repeat testing at the discretion of 
the investigator if the abnormality is not clinically significant and may be a testing aberrancy. 
Enrollment of a participant with laboratory values representing toxicity Grade 2 is allowed if the 
investigator considers the values not to be clinically significant and reasonable for the population 
under study. Details on toxicity grade assessment are provided in Section 12.1.3.
After all data have been reviewed for completeness and adherence to the inclusion and exclusion 
criteria, the participant can be deemed eligible for the study.
SAEs (and any concomitant medications associated with SAEs) will be collected from first dose 
administration until the end of the study. Unsolicited AEs will be recorded on the Adverse Event 
page of the eCRF from the time of each vaccination through the following 28 days, together with 
information on any concomitant medications.a Additionally, (S)AEs that are related to the study 
procedures or to non-investigational (concomitant) Janssen products will be collected from ICF 
signature onwards.
9.1.4.
Randomization (Day 1)
Cohorts 1 and 2: After verification of selected inclusion and exclusion criteria,b abbreviated 
physical examination (at the discretion of the investigator),andmeasurement ofvital signs, eligible 
participants will be randomized as described in Section 5. If the medical status and/or physical
examination suggest that significant changes have occurred since screening, the safety laboratory 
                                                
a AEs that start more than 28 days after a vaccination, but that are still present at the time of the next vaccination will 
also be recorded.
b Inclusion criteria 4 and 5, and exclusion criteria 1, 4, 12, 13, and 14.

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tests will be repeated and the randomization visit re-scheduled, or the participant excluded from 
the study if he or she fails to meet the inclusion and exclusion criteria.
Cohort 3: After verification of all inclusion and exclusion criteria, physical examination, and
measurement of vital signs, eligible participants will be randomized as described in Section 5.
All eligible participants will receive their first vaccination following the procedures as described 
in Section 9.1.5.
9.1.5.
Vaccination
On each vaccination day according to the schedules presented in Table 8, Table 9, Table 10 and 
Table 11, the following procedures will apply pre- and post-vaccination:

Pre-vaccination, verification of selected inclusion/exclusion criteria, a physical examination,b
and measurement of vital signs will be performed for all participants.

Pre-vaccination, blood and nasal samples will be collected for immunogenicity assessments.
In Cohorts 1 and 2, pre-dose blood samples will be taken on Day 1 for transcriptome analysis
and safety laboratory tests (hematology and biochemistry).

Pre-vaccination, the investigator must check for any symptoms of acute illness or fever (body 
temperature ≥38.0 °C). In such a situation, the participant may be vaccinated up to, and no 
later than 10 days after the scheduled vaccination, or withdrawn from further vaccination at 
the discretion of the investigator.

Post-vaccination, participants will be closely observed for at least 30 minutes to monitor for 
development of any acute reactions, or longer if deemed necessary by the investigator. Vital 
signs measurement will be performed. Any unsolicited or solicited AEs and vital signs will 
be documented in the eCRF by study-site personnel following this observation period.

All participants will be provided with a participant diary, thermometer, and ruler to measure 
and record body temperature, and solicited local and solicited systemic AEs for 7 days post-
vaccination.

Nasal swab kits and RTI Symptoms Forms will be distributed to all participants before the 
start of the first 2 RSV seasons of the study (relative to the enrollment date of the first 
participant in Cohort 1); during these RSV seasons, participants should record signs and 
symptoms of RTI using the RTI Symptoms Form.
                                                
a To include receipt of any routine immunizations.
b A full physical examination, including height and body weight, will be carried out at screening, and before final 
vaccination. At other vaccination visits, an abbreviated, symptom-directed examination will be performed if 
determined necessary by the investigator.

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9.1.6.
Post-Vaccination Follow-up
At 24 hours after vaccination on Day 1, a telephone call will be made to each sentinel participant
in Cohort 1 to collect safety information (solicited and unsolicited AEs, SAEs, and concomitant 
medications).
The 7-day post-vaccination visits include an abbreviated physical examination (at the discretion 
of the investigator), measurement of vital signs, and recording of any AEs/SAEs, concomitant 
medications and RTIs.a,b The participant diary will be reviewed and collected. If the visit occurs 
before the end of the diary period after the vaccination, review of the diary will still take place, but 
the diary will be returned by the participant at the next study visit. In Cohorts 1 and 2, blood 
samples for transcriptome analysis and for safety laboratory tests (hematology and biochemistry) 
will be collected (after the first dose only, not applicable to subsequent doses).
The 14-day post-vaccination visit (post-dose 1 and post-dose 3) includes an abbreviated physical
examination (at the discretion of the investigator), measurement of vital signs, and recording of
unsolicited AEs/SAEs, concomitant medications and RTIs.a Blood and nasal samples for 
immunogenicity assessments will be collected. Blood samples for transcriptome analysis will also 
be taken (in Cohorts 1 and 2 only).
The 28-day post-vaccination visits include an abbreviated physical examination (at the discretion 
of the investigator), measurement of vital signs, and recording of unsolicited AEs/SAEs, 
concomitant medications, and RTIs.a Blood and nasal samples for immunogenicity assessments 
will be collected.
The 56-day post-vaccination visit (post-dose 1 in Cohort 3 with one-dose regimen only) includes
an abbreviated physical examination and vital signs measurement (both at the discretion of the
investigator), and recording of any SAEs and concomitant medications,andRTIs.a Bloodandnasal
samples for immunogenicity assessments will be collected.
The12-weekpost-vaccination visit (post-dose 1 in Cohort 3 with one-dose regimen only) includes
an abbreviated physical examination and vital signs measurement (both at the discretion of the
investigator), and recording of any SAEs and concomitant medications,andRTIs.a Bloodandnasal
samples for immunogenicity assessments will be collected.
The 26-week post-vaccination visits include an abbreviated physical examination and vital signs 
measurement (both at the discretion of the investigator) and recording of any SAEs and associated
concomitant medications, and RTIs.a Blood samples for immunogenicity assessments will be 
collected.
                                                
a RTIs will only be recorded during the first 2 RSV seasons of the study (relative to the enrollment date of the first participant in 
Cohort 1).
b Visit 13 (7 days post-third vaccination) is not required for any Cohort 3 participant who misses the third vaccination.

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The12-month post-first vaccination visit includes an abbreviated physical examination and vital 
signs measurement (both at the discretion of the investigator) and recording of any SAEs and 
associated concomitant medications, and RTIs.a Blood and nasal samples for immunogenicity 
assessments will be collected.
The 18-month post-first vaccination visit (Cohort 2 only) includes an abbreviated physical 
examination and vital signs measurement (both at the discretion of the investigator) and recording 
of any SAEs and associated concomitant medications, and RTIs.a Blood samples for 
immunogenicity assessments will be collected.
9.1.7.
Final Visit
For Cohorts 1 and 2 (Groups 11-13 and Groups 16-18), the visit at 24 months after the first
vaccination will be the final visit and include an abbreviated physical examination and vital signs 
measurement (both at the discretion of the investigator), and recording of any SAEs and associated 
concomitant medications, and RTIs.a Blood samples for immunogenicity assessments will be 
collected. Participants in Groups 14 and 15 (Cohort 2) will continue into a long-term follow-up 
phase. Their final visit will be the visit at 36 months after the first vaccination.
For Cohort 3, the visit at 36 months after the first vaccination will be the final visit and include an 
abbreviated physical examination and vital signs measurement (both at the discretion of the 
investigator), and recording of any SAEs and associated concomitant medications. Blood samples 
for immunogenicity assessments will be collected.
9.1.8.
Early Withdrawal: Early Exit Visit
For participants who are unable to continue participation in the study, but who do not withdraw 
consent, an early exit visit will be conducted as soon as possible. In the event of early withdrawal 
from the study, all procedures as required at the final visit (see Section 9.1.7) will be performed. 
Blood samples for safety laboratory assessments (hematology and biochemistry; Cohorts 1 and 2 
only) will be collected if the early exit is within 8 days of the first vaccination. Blood samples for 
immunogenicity assessments will only be collected if the early exit is at least 14 days after the 
previous immunogenicity blood draw.
If the early exit visit takes place within 7 days of the previous vaccination, solicited AEs will be 
recorded; if the early exit visit takes place within 28 days of the previous vaccination, unsolicited 
AEs will be recorded.
9.1.9.
Long-term Follow-up (Groups 14 and 15 from Cohort 2)
Participants in Groups 14 and 15 will continue into the long-term follow-up phase.
                                                
a RTIs will only be recorded during the first 2 RSV seasons of the study (relative to the enrollment date of the first participant 
in Cohort 1).

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Participants will make follow-up visits at the clinic every 6 months (26 weeks) until the final visit 
at Day 1095. Each visit includes recording of any SAEs related to study vaccine, study procedures, 
or non-investigational (concomitant) Janssen products, recording of any AEs leading to 
discontinuation; recording of concomitant medications in conjunction with SAEs related to study 
vaccine, study procedures, or non-investigational (concomitant) Janssen products, or in 
conjunction with AEs leading to discontinuation; and collection of samples for cellular and 
humoral immunogenicity assays.
9.2.
Study Evaluations
9.2.1.
Immunogenicity
Venous blood samples of approximately 10 mL and 50 mL will be collected for determination of 
humoral and cellular immune responses, respectively, at the timepoints shown in the Schedule of 
Activities, or at the early exit visit if the participant prematurely terminates without withdrawing 
consent (if the early exit is at least 14 days after the previous immunogenicity blood draw).
Venous blood samples (2.5 mL) for transcriptome analysis will be collected on Day 1 (pre-dose), 
Day 8, and Day 15 in Cohorts 1 and 2.
All sample collection and processing will be performed by the staff at the clinical sites according 
to current approved standard operating procedures.
It is assumed that all participants will have a pre-existing immune response due to previous RSV 
exposure.
The humoral and cellular immunogenicity assays that may be used in this study (as available and 
applicable) are summarized in Table 16 and Table 17 below.
Blood for humoral and cellular immune responses will be drawn from all participants in Cohorts 1 
and 2. In Cohort 3, blood will be drawn for humoral immune responses from all participants and 
for cellular immune responses from a subset of 63 participants.
Immunogenicity samples will be prioritized as outlined in the Laboratory Manual.

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Table 16:
Summary of Immunogenicity Assays (Humoral)
Assay 
Purpose
Primary endpoint (Regimen Selection Cohort [Cohort 2] – Groups 11 to 15 only)
RSV neutralization A 
Analysis of neutralizing antibodies to an A strain
Secondary endpoints
RSV neutralization A 
Analysis of neutralizing antibodies to an A strain
F protein antibodies
(ELISA; pre-F and/or post-F) 
Analysis of antibodies binding to RSV F protein in pre-fusion and/or 
post-fusion form
Exploratory endpoints
RSV strain cross-neutralization 
Analysis of cross-neutralizing antibodies to B and/or a different A 
strain(s)
F protein antibody specificity 
characterization 
Pre- and post-F specificity by binding or functional assays as ELISA, 
and/or competition ELISA. Adsorption of serum or plasma with pre-F 
and post-F protein before any antibody assay, epitope mapping, 
functional VNAs
G and/or N protein antibodies
(ELISA) 
Analysis of antibodies binding to RSV G and/or N protein 
Adenovirus neutralization assay
Analysis of neutralizing antibodies to adenovirus
Functional and molecular antibody 
characterization
Analysis of antibody characteristics including, but not limited to, ADCC, 
ADCP, avidity, other respiratory viral neutralizing or binding assays, 
Ig isotype, functional VNAs to other respiratory viruses, and antibody 
assessments for antibody repertoire
ADCC: antibody-dependent cell-mediated cytotoxicity; ADCP: antibody-dependent cellular phagocytosis; ELISA: enzyme-
linked immunosorbent assay; F: fusion; G: glycoprotein; Ig: immunoglobulin; N: nucleoprotein; RSV: respiratory syncytial virus; 
VNA: virus neutralizing antibody
Note: Antibody analyses might be performed in nasal samples, serum and plasma.
Table 17:
Summary of Immunogenicity Assays (Cellular)
Assay 
Purpose
Secondary endpoints
IFN-γ ELISpot
T-cell IFN-γ responses to RSV F protein peptides
Exploratory endpoints
ICS
Analysis of T-cell responses to RSV F protein peptide-stimulated PBMC 
(including, but not limited to, CD4+/CD8+, IL-2, IFN-γ, TNF-α, 
activation markers and memory)
Transcriptome analysis
Regulation of genes (clusters), expression patterns, that predict specific 
immune responses after vaccination
Chemokine/cytokine analysis
Levels of chemokines and cytokines in nasal samples
Sequencing of B-cells
Including but not limited to sequencing of BCR (B-cell receptor) or 
VH/VL (heavy/light chain characterization) for specificity
ELISpot: enzyme-linked immunospot; F: fusion; ICS: intracellular cytokine staining; IFN-γ: interferon gamma; IL-2:
interleukin-2; PBMC: peripheral blood mononuclear cells; RSV: respiratory syncytial virus; TNF-α: tumor necrosis factor 
alpha
Nasal samples, collected at the timepoints indicated in the Schedule of Activities, will be used for 
immunogenicity assessments (for example, immunoglobulin or cellular immune component) and 
identification of the etiology of respiratory infections (if needed).
In addition to RT-PCR performed on nasal samples, any immunogenicity blood sample collected 
from all participants may also be assayed by serology (including but not limited to RSV VNA or 
ELISA specific to RSV protein G [glycoprotein] and/or N [nucleoprotein] as available and 
applicable) for RSV exposure.

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Instructions for the collection, handling, storage, and shipment of blood and nasal samples for the
immunogenicity assays can be found in the Laboratory Manual that will be provided. Collection, 
handling, storage, and shipment of samples to the central laboratory must be under the specified, 
and where applicable, controlled temperature conditions as indicated in the Laboratory Manual.
9.2.2.
RTI Procedures
Participants will be informed of the timing of the start and end of the RSV season in accordance 
with the country/region-specific RSV local surveillance system.
During the first 2 RSV seasons of the study (relative to the enrollment date of the first participant 
in Cohort 1), participants should record any signs and symptoms of RTI (such as runny nose, fever, 
severe cough, rapid breathing, difficulty breathing), including measurement of body temperature,
on a daily basis until symptoms have resolved using a specific RTI Symptoms Form. Signs and 
symptoms of RTI recorded on the RTI Symptoms Form will be transferred onto the RTI Symptoms 
page in the eCRF. RTI Symptoms Forms will be the primary source for RTI monitoring. 
Participants should complete a new form on each day they experience symptoms,includingthe day 
on which the symptoms resolve. Completed RTI forms can either be mailed to the site or brought 
to the site at the next visit.
If respiratory symptoms develop during the first 2 RSV seasons of the study, the following should 
take place:

Participants should contact the site as soon as possible to notify the site of an RTI.

Participants should record signs and symptoms of the RTI (including measurement of body 
temperature) daily using the RTI Symptoms Form until the day of symptom resolution.

If feasible, participants should take a nasal sample at home, preferably between 2 and 3 days 
after the onset of the RTI symptoms. The sample should be stored refrigerated and brought to 
the site by the participant within 3 to 4 days.

Alternatively, participants may go to the site preferably within 2 to 3 days after the onset of 
the RTI to have a nasal sample taken by the study staff.
The RTI Symptoms Forms and nasal swab kits for use at home will be distributed before the start 
of the RSV seasons.
During the first 2 RSV seasons of the study, participants will be contacted by telephone every 30±7 
days (unless a planned visit has occurred or will occur within 30 days). These calls will remind 
participants to complete the RTI Symptoms Form in the event of any symptoms of RTI, to contact 
the site at the time of symptom onset, and to take a nasal sample (or go to the site to have a nasal 
sample taken by study staff). These calls will also check for any SAEs and associated concomitant 
medications since the previous visit or telephone contact.
The presence of RSV or any other respiratory infection may be assessed by the sponsor by RT-PCR 
diagnostics on the nasal samples, which may include viral load and RSV subtyping.

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Blood from participants with a suspected RTI may be assayed by a serological assay (eg, protein 
G and/or N ELISA) to confirm RSV infection. (No additional blood sampling is necessary – any 
serological assay conducted to confirm RSV infection will use blood from the existing samples.)
Every effort should be made to collect data on the clinical course of RTIs including information 
on oxygenation status, supplemental oxygen requirements and specific drug treatments, as well as 
other concurrent respiratory illness present at the time of the diagnosis of the event and up to 
symptom resolution.
Any RTI that is not due to RSV infection will be reported as an AE if it occurs between the time 
of any vaccination through the following 28 days. Any RTI recorded as an AE in the eCRF will 
be excluded from any AE analysis if the central laboratory RT-PCR is subsequently found to be 
positive for RSV. RTIs arising from RSV infection will not be reported as (S)AEs in the Clinical 
Study Report as they are endpoints of the study and will be tabulated separately.
Any RTI fulfilling the criteria of an SAE will be reported as such during the entire study period if 
RT-PCR indicates it is not an RSV-RTI. If the RT-PCR is positive for RSV the event should not 
be reported as an SAE. If RT-PCR information is not available within 24 hours of knowledge of 
the event, the event will be reported as an SAE, but will be subsequently downgraded from SAE 
status if it later turns out to be RT-PCR positive for RSV.
9.2.3.
Safety Evaluations
Any clinically relevant changes must be recorded in the eCRF.
Any clinically significant abnormalities, including abnormalities persisting at the end of the study
or at early withdrawal, will be followed by the investigator until resolution or a clinically stable 
endpoint is reached.
The study includes the following evaluations of safety and reactogenicity on timepoints provided 
in the Schedule of Activities.
9.2.3.1.
Adverse Events
All AEs will be reported as specified in Section 12, Adverse Event Reporting. All SAEs will be 
collected until the end of the double-blind phase; only SAEs related to study vaccine, study 
procedures, or non-investigational (concomitant) Janssen products, and all AEs leading to 
discontinuation will be collected during the long-term follow-up phase (Groups 14-15 in 
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Unsolicited AEs
Unsolicited AEs will be reported by the participant from the time of each vaccination through the 
following 28 days, or early discontinuation.a Relatedness of the AEs should be determined by the 
investigator. Additionally, AEs that are related to the study procedures or to non-investigational 
(concomitant) Janssen products will be reported from ICF signature onwards.
Solicited AEs
Information related to solicited AEs defined below, will be recorded by participants in a diary for 
7 days after each vaccination. Each participant will be provided with a diary and instructions on 
how to complete the diary (Section 9.1.1). There will be a minimum 30-minute post-vaccination 
assessment of solicited events at the site. Diary information will be transcribed by the study-site
personnel in the appropriate diary pages of the eCRF. Once a solicited symptom from a diary is 
considered to be of severity Grade 1 or above, it will be referred to as a solicited AE.
Injection Site (Local) Adverse Events
Participants will be asked to note in the diary occurrences of pain/tenderness, induration/swelling 
and erythema at the vaccine injection site daily for 7 days post-vaccination. The extent (ie, largest 
diameter) of any erythema and induration/swelling should be measured (using the ruler supplied),
graded (using the functional scale) and recorded daily.

Injection Site Pain/Tenderness
Injection site pain (eg, stinging, burning) is an unpleasant sensory and emotional experience 
associated with actual or potential tissue damage and occurring at the immunization site (with 
or without involvement of surrounding tissue). Injection site tenderness is a painful sensation 
localized at the injection site upon palpation or movement of the limb. Due to the subjective 
nature of the reaction, the severity assessment of pain/tenderness is self-reported (if a 
participant is unable to provide self-report, other reporters include a healthcare provider or 
caregiver).10

Injection Site Erythema
Injection site erythema is a redness of the skin caused by dilatation and congestion of the 
capillaries localized at the injection site. It can best be described by looking and measuring.

Injection Site Swelling/Induration
Injection site swelling is a visible enlargement of an injected limb. It may be soft (typically) 
or firm (less typical). Injection site induration is a palpable thickening, firmness, or hardening 
of soft tissue, usually has well-demarcated palpable borders, can be visible (raised or sunken 
compared to surrounding skin), is often ‘woody’ to touch, and has a flat shape. As
differentiation between swelling and induration may be difficult without a healthcare
                                                
a AEs that start more than 28 days after a vaccination, but that are still present at the time of the next vaccination will 
also be recorded.

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professional’s assessment, both symptoms have been combined to allow self-assessment by 
the participants. Swelling and induration can best be described by looking and measuring.
Note: Any other injection site events not meeting the above case definitions should be reported 
separately as unsolicited AEs.22,23
Systemic Adverse Events
Participants will be instructed on how to record daily body temperature using the thermometer 
provided for home use. Participants should record the temperature in the diary in the evening of 
each day of vaccination, and then daily for the next 7 days approximately at the same time each 
day.a If more than 1 measurement is made on any given day, the highest temperature of that day 
will be used in the eCRF.
Fever is defined as an endogenous elevation of body temperature ≥38.0 °C, as recorded in at least 
one measurement.26
In addition to fever, participants will be instructed on how to record daily in the diary for 7 days 
after each vaccination symptoms of the following events: fatigue, headache, myalgia, arthralgia, 
chills, and nausea. Severity of these event will be graded by the investigator according to the 
criteria presented in Section 12.1.3.
If a solicited local or solicited systemic AE is not resolved by 7 days after the vaccination, the 
follow-up will be captured on the diary. The participant will be instructed to record the date of last 
symptoms and maximum severity in the diary after resolution.
9.2.3.2.
Clinical Laboratory Tests
In Cohorts 1 and 2, blood samples for biochemistry and hematology will be collected at screening, 
on Day 1, and at 7 days after the first vaccination (or at the exit visit if early exit is within 8 days 
of the vaccination and the participant terminates from the study without withdrawing consent).
The following tests will be performed by a central laboratory (*parameters will only be measured 
at screening):

Hematology Panel
hemoglobin
white blood cell (WBC) count with differential
platelet count
prothrombin time*
activated partial thromboplastin time*
                                                
a All diary assessments, including body temperature, 7 days after each vaccination may be collected earlier in the day 
to coincide with the clinic visit.

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
Biochemistry Panel
sodium
potassium
creatinine
blood urea nitrogen 
aspartate aminotransferase (AST)
alanine aminotransferase (ALT)
Review and Grading of Laboratory Data
The investigator must review each laboratory result, document this review, and systematically 
assess any clinical significance. The laboratory reports must be filed with the source documents.
Laboratory values will be initially evaluated by the investigator according to central laboratory
criteria. Abnormal values outside the central laboratory range of normal will be graded according 
to the FDA Guidance document “Toxicity Grading Scale from Healthy Adult and Adolescent 
Volunteers Enrolled in Preventive Vaccine Clinical Trials” (Attachment 1). Laboratory values 
within central laboratory normal limits will not be FDA graded and will be considered as normal.
Reporting Laboratory Abnormalities as Adverse Events
Any clinically significant abnormal laboratory value within 28 days post-vaccination that falls 
outside of the central laboratory normal range and that requires follow-up will be captured as an 
AE. Laboratory values outside normal ranges that are not clinically significant in the judgment of 
the investigator, should not be recorded as an AE. Any laboratory value falling within the central 
laboratory normal range will not be severity graded or recorded as an AE, regardless of whether 
the value falls within FDA ranges for Grade 1 or higher.
Values for parameters falling within the central laboratory normal range should not be reported as 
an AE.
Repeat of Clinically Significant Laboratory Tests
For any clinically significant abnormal laboratory value that has increased in grade over baseline, 
the test must be repeated at the next scheduled visit or sooner based on investigator’s judgment, 
however Grade 3 and above abnormalities should be retested within 48 hours. Any clinically 
significant abnormalities (including those persisting at the end of the study or early withdrawal)
will be followed by the investigator until resolution or a clinically stable endpoint is reached.
Screening Procedures (Cohorts 1 and 2 Only)
For entry into the study, each participant must be healthy on the basis of clinical laboratory tests
performed at screening. Enrollment of a participant with clinical laboratory values outside of the 
central laboratory normal range representing FDA toxicity Grade 2 is allowed if the investigator 
considers the values reasonable for the population under study and not clinically significant.

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Additional clinical laboratory assessments to be performed at screening include serology testing 
(HIV type 1 or type 2, hepatitis B, hepatitis C).
9.2.3.3.
Electrocardiogram
In Cohorts 1 and 2, supine 12-lead ECGs will be performed at screening and interpreted locally; 
ECGs will onlybe performed thereafter during the study if clinically indicated based on signs and 
symptoms.
For 30 minutes prior to the ECG, participants should refrain from meals, hot or cold beverages and 
strenuous exercise, and should remain in a room with a comfortable temperature. Each ECG should 
be obtained after the participant has been at rest for at least 5 minutes.
Enrollment of a participant is allowed even with abnormal ECG results as long as the investigator 
feels that these are not clinically significant and appropriate for the population.
9.2.3.4.
Vital Signs
Blood pressure and pulse/heart rate measurements should be preceded by at least 5 minutes of rest 
in a quiet setting without distractions (eg, television, cell phones).
Vital signs are to be measured before blood draws and nasal samples.
The following measurements will be performed:

Heart rate (beats per minutes), respiratory rate (breaths per minute), supine systolic blood 
pressure (mmHg) and supine diastolic blood pressure (mmHg)

Body temperature (oral route preferred, or in accordance with the local standard of care)
Confirmatory vital signs measurement can be done if inconsistent with a prior measurement. If 
any clinically significant changes in vital signs are observed, they will be reported as an AE and 
followed to resolution, or until reaching a clinically stable endpoint.
9.2.3.5.
Physical Examination
A full physical examination, including height and body weight, will be carried out at screening
and before the Month 12 booster (Cohorts 1 and 3) and before the Month 24 booster (Cohort 3
only). At all other visits, an abbreviated, symptom-directed examination will be performed by the 
investigator based on clinically relevant issues, clinically relevant symptoms and medical history. 
Symptom-directed physical examination may be repeated if deemed necessary by the investigator.
Physical examinations will be performed by the investigator or an appropriately trained delegate. 
Any clinically relevant abnormalities or changes in severity observed during the review of body 
systems should be documented in the eCRF as an AE.

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10.
PARTICIPANT COMPLETION/DISCONTINUATION OF STUDY VACCINE/ 
WITHDRAWAL FROM THE STUDY
10.1.
Completion
A participant will be considered to have completed study vaccination if he or she has received all
vaccinations. A participant will be considered to have completed the study if he or she completed 
assessments at the final visit 24 months (Cohort 1 and Cohort 2 [Groups 11-13 and Groups 16-18]) 
or 36 months (Cohort 2 [Groups 14 and 15] and Cohort 3) after the first vaccination.
10.2.
Discontinuation of Study Vaccine/Withdrawal from the Study
Discontinuation of Any Study Vaccine
A participant will not be automatically withdrawn from the study if he or she has to discontinue 
from study vaccination before the end of the study vaccine regimen.
Participants will be discontinued from vaccination for the reasons listed below. These participants 
must not receive any additional dose of any study vaccine but should continue to be monitored for 
safety and, if this does not result in safety risks for the participant, for immunogenicity (if the 
reason for discontinuation is not because of impaired functioning of the immune system) and/or 
other study procedures (eg, RTI follow-up). Additional unscheduled visits may be performed for 
safety/reactogenicity reasons, if needed.
In the event of questions, the investigator is encouraged to contact the sponsor:

Anaphylactic reaction post vaccination, not attributable to causes other than vaccination

An SAE or other potentially life-threatening (Grade 4) event that is determined to be related 
to study vaccine

Any related AE, worsening of health status or intercurrent illness that, in the opinion of the 
investigator, requires study vaccine discontinuation

Chronic or recurrent use of immunosuppressants (after discussion with the sponsor)

Unblinding on the participant level that, in the opinion of the sponsor, would compromise the 
integrity of the data
Participants who miss a vaccination, not due to the reasons above, can receive subsequent 
vaccinations if, at the time of administration, the investigator determines that they are eligible to 
receive the vaccination according to the criteria in Section 10.3. In the event of questions, the 
investigator is encouraged to contact the sponsor.
Withdrawal from the Study
Each participant has the right to withdraw from the study at any time for any reason without 
affecting the right to treatment by the investigator. The investigator should make an attempt to 
contact participants who did not return for scheduled visits or follow-up. Although participants are

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not obliged to give a reason for withdrawing prematurely, the investigator should make a 
reasonable effort to ascertain the reason(s) while fully respecting the participant’s rights.
A participant will be withdrawn from the study for any of the following reasons:

Lost to follow-up

Withdrawal of consent

Death

Repeated failure to comply with protocol requirements

Decision by sponsor, investigator, or local regulatory authorities and Institutional Review 
Board/Independent Ethics Committee (IRB/IEC)
If a participant is lost to follow-up, every reasonable effort must be made by the study-site 
personnel to contact the participant and determine the reason for discontinuation/withdrawal. The 
measures taken to follow-up must be documented.
When a participant withdraws before completing the study, the reason for withdrawal is to be 
documented in the eCRF and in the source document. Study vaccine assigned to the withdrawn 
participant may not be assigned to another participant. In general, participants who withdraw will 
not be replaced, unless the participant was randomized but did not receive any study vaccine.
In Cohort 1, any randomized participant withdrawn from the study for reasons other than (an)
AE(s) after the first dose but before the second dose might be replaced at the discretion of the 
sponsor. In Cohort 2, no replacements or additional randomizations will be done for withdrawals 
after the first dose. In Cohort 3, if randomized participants are withdrawn from vaccination before 
the first dose of the selected regimen is administered, additional participants may be recruited to 
replace these participants at the discretion of the sponsor.
If a participant withdraws prematurely from the study, assessments for early withdrawal should be 
obtained (see also Section 9.1.8). Participants who wish to withdraw consent from participation in 
the study will be offered a single exit visit for safety follow-up (prior to formal withdrawal of 
consent). They have the right to refuse.
Withdrawal from the Use of Samples in Future Research
The participant may withdraw consent for use of samples for future research (see Section 16.2.5). 
In such a case, samples will be destroyed after they are no longer needed for the clinical study. 
Details of the sample retention for research are presented in the main ICF.
10.3.
Contraindications to Vaccination
The following events constitute a contraindication to vaccination at that point in time. If any of
these events occur at the scheduled time for vaccination, the participant may be vaccinated up to 

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10 days beyond the scheduled vaccination, or be withdrawn from vaccination at the discretion of
the investigator and after consultation with the sponsor:

Severe acute illness at the time of vaccination. This does not include minor illnesses such as 
diarrhea.

Fever (body temperature ≥38.0 °C) at the planned time of vaccination.

Medically-indicated vaccines should be given at least 14 days before or 14 days after study 
vaccine administration (see Section 8).
11.
STATISTICAL METHODS
Statistical analysis will be done by the sponsor or under the authority of the sponsor. A general 
description of the statistical methods to be used to analyze the immunogenicity and safety data is 
outlined below. Specific details will be provided in the Statistical Analysis Plan.
Planned analyses are described in Section 11.6.
11.1.
Analysis Sets
Vaccine assignment will follow the as-treated principle.
The Full Analysis (FA) Set will include all participants who were randomized and received at least 
one dose of vaccine (active or placebo), regardless of the occurrence of protocol deviations or the 
type of vaccine (ie, Ad26.RSV.preF, RSV preF protein, Ad26.RSV.preF/RSV preF protein
combination or mixture). All safety and participant information analyses will be based on the FA 
set.
The Per-protocol RSV Immunogenicity (PPI) Set will include all participants who were
randomized and received the complete first dose, and for whom immunogenicity data are available, 
excluding participants with major protocol deviations expecting to impact the immunogenicity 
outcomes.
In addition, the following samples will not be included in the PPI set:

For participants who experience a natural RSV infection (based on RT-PCR, or other sources), 
samples collected after the natural infection will not be taken into account in the assessment 
of the immunogenicity of the selected regimen.

If a participant misses one or more active dose(s) of the selected regimen but continues the 
planned visit schedule, samples after the missed active dose(s) will not be taken into account.
The analysis of all secondary and exploratory immunogenicity endpoints related to RSV will be 
based on the PPI set. Depending on the number of samples excluded, a post-hoc exploratory 
analysis might be performed, including the excluded samples. To visualize excluded samples, 
participant profiles from several assays might be repeated, indicating the excluded samples.

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11.2.
Sample Size Determination
11.2.1.
Initial Safety Cohort (Cohort 1)
The number of participants chosen for the initial safety cohort will provide a preliminary safety 
assessment. Placebo recipients are included for blinding and safety purposes and will provide
additional control specimens for immunogenicity assays.
While mild to moderate vaccine reactions (local injection site, systemic responses) are expected, 
AEs that preclude further vaccine administration or more serious ones that would limit product 
development are not anticipated.
Table 18 shows the probabilities of observing at least one AE in the initial safety cohort at given 
true AE rates. In the analysis of the initial safety cohort (Cohort 1), placebo recipients will be 
shown pooled.
Table 18:
Probability of Observing at Least One Adverse Event in the Initial Safety Cohort (Cohort 1) at 
a Given True Adverse Event Rate
True Adverse 
Probability of Observing at Least One Adverse Event in N Participants
Event Rate
N=4
N=8
N=16
0.5%
2%
4%
8%
1%
4%
8%
15%
2.5%
10%
18%
33%
5%
19%
34%
56%
10%
34%
57%
81%
25%
68%
90%
99%
50%
94%
100%
100%
11.2.2.
Regimen Selection Cohort (Cohort 2)
The objective is to compare the RSV A2 neutralizing antibody levels of all regimens containing 
RSV preF protein (Groups 12 through 17) to the one-dose Ad26.RSV.preF regimen (Group 11). 
This will be based on the estimation of GMT ratios and corresponding 95% confidence intervals 
(CIs) of the VNA A2 levels of the regimens containing RSV preF protein on Day 29 for the one-
dose regimens (Groups 12 through 16) and on Day 85 for the two-dose regimen (Group 17) versus 
the VNA A2 levels on Day 29 of the one-dose Ad26.RSV.preF regimen (Group 11). The sample 
size was selected to provide a precision of ~0.53 on the log2 scale.
Note: Immunogenicity data from Groups 9 and 10 of the initial safety cohort (Cohort 1) will be 
combined with those from Groups 16 and 17 of the regimen selection cohort (Cohort 2).
The table below presents the resulting 95% CIs for several observed ratios, assuming a standard 
deviation for VNA of 1 on the log2 scale and accounting for 5% dropout.
Observed Ratio
Corresponding 95% CI
1
[0.69; 1.44]
1.2
[0.83; 1.73]
1.5
[1.04; 2.17]

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In addition to the above, factors such as data from other assays, reactogenicity profiles,
manufacturability and ease of administration will be considered when selecting the regimen for 
the expanded safety phase. A more detailed rule will be described in the Statistical Analysis Plan.
11.2.3.
Expanded Safety Cohort (Cohort 3)
The expanded safety cohort (Cohort 3) should provide sufficient safety data on the selected 
regimen to support late stage development if the immunogenicity results of Cohort 2 are 
satisfactory.
Table 19 shows the probabilities of observing at least one AE in the expanded safety cohort at 
given true AE rates. This table shows that the current numbers give a reasonable probability to 
also observe less frequent events in the active groups in this cohort.
Table 19:
Probability of Observing at Least One Adverse Event in the Expanded Safety Cohort (Cohort 3)
at a Given True Adverse Event Rate
True Adverse 
Probability of Observing at Least One Adverse Event in N Participants
Event Rate
N=45
N=135
N=270
0.5%
20%
49%
74%
1%
36%
74%
93%
2.5%
68%
97%
100%
5%
90%
100%
100%
10%
99%
100%
100%
25%
100%
100%
100%
11.3.
Participant Information
For all participants, demographic characteristics (eg, age, height, weight, body mass index, race, 
and gender), and other baseline characteristics (eg, physical examination, medical history, and 
concomitant diseases) will be tabulated and summarized with descriptive statistics. This will be 
done per cohort.
11.4.
Immunogenicity Analyses
No formal hypothesis on immunogenicity will be tested. Descriptive statistics (geometric mean 
and 95% CI for ELISA and RSV neutralization assay; median and quartiles for IFN-γ ELISpot and 
ICS) will be calculated for continuous immunologic parameters at all timepoints. For the humoral 
assays, geometric mean fold rises from baseline and corresponding 95% CIs might additionally be 
calculated. Baseline is considered as the last available assessment before the first vaccination. 
Graphical representations of immunologic parameters will be made as applicable.
For categorical variables, frequency tables will be presented.
In addition, for the regimen selection cohort (Cohort 2), GMT ratios with corresponding 95% CI 
of the VNA A2 levels of the combination/mixture regimens on Day 29 for the one-dose regimens 
(Groups 12 through 16) and Day85 for the two-dose regimen (Group 17) versus the Day 29 VNA 
A2 levels of the one-dose Ad26.RSV.preF regimen (Group 11) will be calculated. Therefore, a 
regression model will be fitted with the respective VNA A2 levels as dependent variable and the 
respective regimens and baseline levels as covariates, using Satterthwaite’s method to calculate 

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the degrees of freedom and allowing different variances for the vaccines. The estimate and CIs
obtained as such will be back-transformed (by exponentiation) to a GMT ratio and the 
corresponding CI. Note that the effect of additional factors, such as age and the interaction with 
the regimen, might also be explored in this model.
Note: Immunogenicity data from Groups 9 and 10 of the initial safety cohort (Cohort 1) will be 
combined with those from Groups 16 and 17 of the regimen selection cohort (Cohort 2).
The same model might be repeated for other assays.
In the expanded safety cohort (Cohort 3), the effect of the Month 12 and Month 24 booster will be 
assessed. Therefore, the following ratios for VNA A2 will be calculated:

In the groups with an active vaccination at Month 12/Month 24, the ratio of the 
Month 12/Month 24 booster Day 29 level versus the prime Day 29 level with the 
corresponding 95% CI will be calculated.

The groups with an active vaccination at Month 12/Month 24 will be compared to 
corresponding groups with placebo vaccination at Month 12/Month 24 by calculating the ratio 
with the corresponding 95% CI.
Note that the above might also be repeated for other assays.
The primary analysis set for the above is the PPI set. As a sensitivity analysis, key tables may also 
be based on the FA set. Depending on their occurrence, the effect of natural infections might be 
further explored.
11.5.
Safety Analyses
No formal statistical testing of safety data is planned. Per cohort, all safety data will be analyzed 
descriptively by regimen.
Adverse Events
The verbatim terms used in the eCRF by investigators to identify AEs will be coded using the 
Medical Dictionary for Regulatory Activities (MedDRA). All reported AEs with onset during the 
active phase (ie, AEs occurring after vaccination up to 28 days post-vaccination), and all SAEs 
will be included in the analysis. For each AE, the number and percentage of participants who 
experience at least one occurrence of the given event will be summarized by group.
Summaries, listings, datasets, or participant narratives may be provided, as appropriate, for those 
participants who die, who discontinue study vaccine due to an AE, or who experience a severe AE 
or an SAE.
Summaries and/or listings may be provided separately for AEs with onset outside the above 
defined timeframe (ie, beyond 28 days post-vaccination) and that were reported pre-dose at the 
time of subsequent vaccinations for studies using multiple doses.

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Solicited local (at injection sites) and solicited systemic AEs will be summarized descriptively. 
The overall frequencies per vaccine group as well as frequencies according to severity and duration 
will be calculated for solicited AEs. In addition, the number and percentages of participants with 
at least one solicited local (at the injection site) or solicited systemic AE will be presented. 
Frequencies of unsolicited AEs, separately for all and vaccine-related only, will be presented by 
System Organ Class and Preferred Term.
Any RTI recorded as an AE in the eCRF that is subsequently determined to be RSV-positive by 
central laboratory RT-PCR will be excluded from the safety analysis and tabulated separately.
Clinical Laboratory Tests
For participants in Cohorts 1 and 2, laboratory abnormalities will be determined according to the 
FDA toxicity grading tables (see Attachment 1), or in accordance with the normal ranges for the 
clinical laboratory parameter if no grades are available. Any laboratory value shown as a “graded” 
value in the FDA table that is within central laboratory normal ranges will not be graded for 
severity.
Vital Signs
A tabulation of the distribution of body temperatures per half degree intervals will be provided. 
For systolic and diastolic blood pressures, pulse rate and respiratory rate, the percentage of 
participants with values beyond clinically relevant limits will be summarized.
Electrocardiogram (ECG)
For Cohorts 1 and 2, any abnormalities in ECG parameters (at screening) will be listed.
Physical Examination
Physical examination abnormalities will be reported as AEs, according to the investigator.
11.6.
Planned Analyses
Note: Depending on the timing, some of the planned analyses might be combined.
11.6.1.
Initial Safety Cohort (Cohort 1)
Primary Analysis
Primary analysis: analysis of safety data 28 days post-dose 2. Data collected up to the time of the 
visit at 28 days after the second dose of study vaccine for the last participant in Cohort 1 will be 
included in the analysis. This analysis will be performed on unblinded data. The blind will be 
maintained at the participant/site level.
As immunogenicity data from Groups 9 and 10 of the initial safety cohort (Cohort 1) will be 
combined with those from Groups 16 and 17 of the regimen selection cohort (Cohort 2), 
immunogenicity data from the initial safety cohort will be analyzed at the time of the primary 
analysis of the regimen selection cohort.

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Analysis 28 Days Post-Month 12 Booster
This analysis will include safety and immunogenicity data, and will be performed on unblinded 
data. Data collected up to the time of the visit at 28 days after the Month 12 booster dose of study 
vaccine for the last participant in this cohort will be included in the analysis. The blind will be 
maintained at the participant/site level.
11.6.2.
Regimen Selection Cohort (Cohort 2)
Primary Analysis
Primary analysis: analysis of safety data 28 days post-dose 2 and immunogenicity data up to at 
least 28 days post-dose 1. 

This analysis should contain all safety data collected up to the time of the visit at 28 days after 
the second dose for the last participant in this cohort.

Immunogenicity data from at least Groups 11 to 15 and part of Group 18 (placebo group), up 
to at least 28 days post-dose 1 will be included as well.a

This analysis will be performed on unblinded data. The blind will be maintained at the 
participant/site level.
In this analysis, all available immunogenicity data of the initial safety cohort (Cohort 1) will be 
analyzed as well.
Additional Analysis
Additional analysis: analysis of immunogenicity data 28 days post-dose 1 for all one-dose 
regimens (including the one-dose regimen with separate injections) and 28 days post-dose 2 for
the two-dose regimen. This analysis may include immunogenicity data available from additional 
timepoints.
This analysis should contain immunogenicity data up to at least day 28 post-dose 1 for one-dose 
regimens and 28 days post-dose 2 for the two-dose regimen. This analysis will be performed on 
unblinded data. The blind will be maintained at the participant/site level.
In this analysis, all available immunogenicity data of Groups 9 and 10 from the initial safety cohort 
(Cohort 1) and immunogenicity data of Cohort 2 included in the primary analysis will be analyzed 
as well.
The primary analysis of Cohort 1 and Cohort 2 and the additional analysis may be combined into 
one analysis.
                                                
a An unblinded person who is not part of the study team (or another independent party) will dictate which Day 29 
samples should be analyzed by the clinical immunology laboratory. Half of the Day 29 samples of Group 18 (placebo 
group) will be included to ensure the blind at the level of the clinical immunology laboratory.

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Based on safety and immunogenicity results available at the time of primary analysis, a sponsor 
committee will decide if the expanded safety cohort can be opened and which regimen will be 
used. In case none of the groups that are part of the primary objective meet internal criteria, 
regimen selection may be delayed until additional analyses will be available. The sponsor 
committee will consist of the CDC, Head of Clinical Development, Senior Advisors on Clinical 
Development, Head of RegulatoryAffairs, Senior Statistician, Head of Biomarkers, Representative 
of Chemistry, Manufacturing Control, Head of Early Development and Translational Medicine, 
Head of Late Development, and other Senior Functions from the CDC. Additional factors such as 
data from other assays, manufacturability, and ease of administration will be taken into account to 
select the regimen for the expanded safety phase. More details will be described in the Statistical 
Analysis Plan.
Analysis 1 Year Post-first Vaccination
This analysis will include immunogenicity data, and will be performed on unblinded data. Data 
collected up to the time of the visit at 12 months after the first dose of study vaccine for the last 
participant in this cohort will be included in the analysis. The blind will be maintained at the 
participant/site level.
Analysis 2 Years Post-first Vaccination (Groups 14 and 15)
This analysis will include immunogenicity data, and will be performed on unblinded data. Data 
collected up to the time of the visit at 24 months after the first dose of study vaccine for the last 
participant in these 2 groups will be included in the analysis.
11.6.3.
Expanded Safety Cohort (Cohort 3)
Primary Analysis
Primary analysis: analysis of safety and immunogenicity data up to Day 29 if a one-dose regimen 
is selected or up to Day 85 if a two-dose regimen is selected. This analysis should at least contain 
safety data collected up to the time of the Day 29 visit for the last participant in this cohort in case 
a one-dose regimen is selected and up to the time of the Day 85 visit for the last participant in this 
cohort in case a two-dose regimen is selected.a If the corresponding immunogenicity data are not 
available at the time of database lock, they will be analyzed at a later timepoint. This analysis will 
be performed on unblinded data. The blind will be maintained at the participant/site level.
Analysis 28 Days Post-Month 12 Booster
This analysis will include safety and immunogenicity data, and will be performed on unblinded 
data. Data collected up to the time of the visit at 28 days after the Month 12 booster dose of study 
                                                
a An unblinded person who is not part of the study team (or another independent party) will dictate which Day 85 
samples should be analyzed. All Day 85 samples of the two-dose regimen will be included and some Day 85 samples 
of each of the other groups to ensure the blind at the level of the clinical immunology laboratory.

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vaccine for the last participant in this cohort will be included in the analysis. The blind will be 
maintained at the participant/site level.
Analysis 28 Days Post-Month 24 Booster
This analysis will include safety and immunogenicity data, and will be performed on unblinded 
data. Data collected up to the time of the visit at 28 days after the Month 24 booster dose of study 
vaccine for the last participant in this cohort will be included in the analysis. The blind will be 
maintained at the participant/site level. 
11.6.4.
Final Analysis
The final analysis at the end of the study, to be conducted on a per-cohort basis, will include safety 
and immunogenicity data. Data collected up to the time of the last visit for the last participant will 
be included in the analysis. This analysis will be performed on unblinded data.
11.7.
Additional Interim Analyses
Additional interim analyses (blinded or, if occurring after the primary analysis of the respective 
cohort, unblinded) may be performed during the study for the purpose of informing future vaccine
development-related decisions in a timely manner, or upon health authority request. If they occur, 
these unplanned interim analyses may replace planned analyses, depending on the timing. The 
results will not influence the conduct of the study in terms of early termination or later safety or 
immunogenicity endpoint assessments, and will only be available to a selected group of sponsor
personnel.
11.8.
Data Review Committee
Data Review Committee
An internal DRC will be commissioned for this study. The DRC will consist of sponsor personnel 
not directly involved in the conduct of the study and who have expertise in clinical study conduct 
and vaccines, at least one medical expert in the relevant therapeutic area, at least one statistician,
and a safety expert. The DRC will convene, according to their charter, to discuss any safety issues 
and any situation meeting a specific study pausing rule (Section 11.9). The PI(s) and SRP/S will 
inform the DRC of any AE of concern.
In addition, the DRC will review all safety data collected up to the time the final participant in the 
initial safety cohort (Cohort 1) had his/her Day 8 visit.
It will also be possible for the DRC to review unblinded immunogenicity data during the course 
of the study if this is deemed necessary for future vaccine development-related decisions. If this is 
the case, a biomarker representative (not involved in the conduct of the study) will be part of the 
DRC. 
After these reviews, the DRC will make recommendations regarding the continuation of the study. 
Conclusions of the DRC will be communicated to the investigators, the IRB/IEC and the national 
regulatory authorities as appropriate. Details will be provided in a separate DRC charter.

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If deemed necessary for safety review, the DRC may request randomization codes and review 
unblinded data, if applicable.
Safety data from the primary analyses and from the analyses at 28 days after the Month 12 booster 
dose (in Cohorts 1 and 3) and the Month 24 booster dose (Cohort 3 only) will be shared with the 
DRC.
11.9.
Study Vaccination Pausing Rules
The PI(s) and the SRP/S will monitor the study vaccination pausing rules. If study vaccination is 
considered to raise significant safety concerns, further study vaccination of participants will be 
suspended until DRC review is carried out and subsequent communication between the sponsor 
and the investigator takes place.
The occurrence of any of the following events will lead to pause in further study vaccination and 
trigger a meeting of the DRC to discuss study suspension, adaptation or discontinuation of further 
vaccination. The list is only applicable for concerned AEs that occur up to 4 weeks after each 
vaccination and to concerned SAEs:
1.
One or more participants per cohort experience an SAE or other potentially life-threatening 
(Grade 4) event that is determined to be related to study vaccine; OR
2.
One or more participants per cohort experience anaphylaxis clearly not attributable to other 
causes than vaccination with any study vaccine; OR
3.
Two or more participants per cohort experience a Grade 3 or 4 unsolicited AE of the same 
type, determined to be related to study vaccine, that persists for 72 hours or longer; OR
4.
Two or more participants per cohort experience a Grade 3 or 4 solicited systemic AE of the 
same type, determined to be related to study vaccine, that persists for 72 hours or longer; OR
5.
Two or more participants per cohort (in Cohorts 1 and 2 only) experience a persistent (upon 
repeat testing) Grade 3 or 4 laboratory abnormality related to the same laboratory parameter 
and considered related to study vaccine, that persists for 72 hours or longer; OR
6.
Death of any participant, considered related to any study vaccine or if the causal relationship 
to study vaccine cannot be excluded.
Note: All cases of death will be sent to the DRC. Upon their review, the DRC will decide 
whether a study pause is required.
After the first DRC meeting triggered by the occurrence of a given pausing rule, the DRC will 
convene thereafter for each additional participant meeting that pausing rule.
The DRC will review blinded data first, but is entitled to and has the right to require submission 
of unblinded data if deemed necessary.

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To enable prompt response to a situation that would trigger pausing rule 3, 4 or 5, the investigator 
should update the eCRF with information on any Grade 3 or 4 AE on the same day that the AE is 
reported.
Also, the investigator should notify the sponsor’s medical monitor (and fax/email the SAE Form 
to Global Medical Safety Operations, if applicable), immediately and no later than 24 hours after 
becoming aware of any related AE of Grade 3 or above (and update the eCRF with relevant 
information on the same day the AE information is collected). A thorough analysis of all Grade 3 
cases will be carried out by the sponsor’s medical monitor, irrespective of whether the criteria for 
pausing the study are met. Based on the pausing criteria, the sponsor’s medical monitor will then 
decide whether a study pause is warranted. All sites will be notified immediately in the event of a 
study pause. The sponsor’s medical monitor is responsible for the immediate notification of the 
DRC and coordination of a DRC meeting in the event of a study pause.
Vaccinations for an individual participant may be suspended for safety concerns other than those 
described in the pausing criteria, at the discretion of the investigator if he/she feels the participant’s 
safety may be threatened. The sponsor’s medical monitor or the PI(s) (upon consultation with the 
sponsor’s medical monitor) may initiate a DRC review for any single event or combination of 
events which, in their professional opinion, could jeopardize the safety of the participants or the 
reliability of the data.
Vaccinations for the study may be suspended for safety concerns other than those described above, 
or before pausing rules are met, if, in the judgment of the DRC, participant safety may be 
threatened.
Resumption of vaccinations will start only upon receipt by the site of written recommendations by 
the DRC. The clinical site(s) will be allowed to resume activities upon receipt of a written 
notification from the sponsor. These communications from the DRC will be forwarded by the 
investigator to the IRB/IEC and by the sponsor to the relevant health authorities according to local 
standards and regulations.
12.
ADVERSE EVENT REPORTING
Timely, accurate, and complete reporting and analysis of safety information from clinical studies 
are crucial for the protection of participants, investigators, and the sponsor, and are mandated by 
regulatory agencies worldwide. The sponsor has established Standard Operating Procedures in 
conformity with regulatory requirements worldwide to ensure appropriate reporting of safety 
information; all clinical studies conducted by the sponsor or its affiliates will be conducted in 
accordance with those procedures.
Method of Detecting Adverse Events and Serious Adverse Events
Care will be taken not to introduce bias when detecting AEs or SAEs. Open-ended and non-leading 
verbal questioning of the participant is the preferred method to inquire about AE occurrence.

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Solicited Adverse Events
Solicited AEs are pre-defined local (at the injection site) and systemic events for which participants
are specifically questioned and which are noted by participants in their diary (see Section 9.1.1).
Unsolicited Adverse Events
Unsolicited AEs are all AEs for which participants are specifically not questioned in the participant
diary.
12.1.
Definitions
12.1.1.
Adverse Event Definitions and Classifications
Adverse Event
An AE is 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 vaccines used in this study. An AE can therefore be any unfavorable and 
unintended sign (including an abnormal finding), symptom, or disease temporally associated with 
the use of a medicinal (investigational or non-investigational) product, whether or not related to 
that medicinal (investigational or non-investigational) product (Definition per International 
Council for Harmonisation [ICH]).
This includes any occurrence that is new in onset or aggravated in severity or frequency from the 
baseline condition, or abnormal results of diagnostic procedures, including laboratory test 
abnormalities.
Note: The sponsor collects AEs, whether serious or non-serious, related to the study procedures or 
non-investigational (concomitant) Janssen products from ICF signature onwards. All other non-
serious AEs and special reporting situations will be reported from each vaccination through the 
following 28 days on the Adverse Event eCRF pagea (see Section 12.3.1, All Adverse Events, for 
time of last AE recording). All other serious AEs will be reported from the first vaccination 
onwards. Clinically relevant medical events, occurring between ICF signature and time of first 
vaccination, are collected on the medical history eCRF page as pre-existing conditions. During the 
long-term follow-up phase for participants from Groups 14 and 15 in Cohort 2, only SAEs related 
to study vaccine, study procedures (ie, blood draws), or non-investigational (concomitant) Janssen 
products, and all AEs leading to discontinuation will be collected.
Note: For all cohorts, AE reporting starts from Day 1 onwards. Clinically relevant medical events 
before the vaccination on Day 1 should be reported as medical history. 
                                                
a AEs that start more than 28 days after a vaccination, but that are still present at the time of the next vaccination will 
also be recorded.

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Any RTI that is not due to RSV infection will be reported as an AE if it occurs between the time 
of any vaccination through the following 28 days. Any RTI recorded as an AE in the eCRF will 
be excluded from any AE analysis if the central laboratory RT-PCR is subsequently found to be 
positive for RSV. RTIs arising from RSV infection will not be reported as (S)AEs in the Clinical 
Study Report as they are endpoints of the study but will be tabulated separately.
Serious Adverse Event
An SAE based on ICH and European Union Guidelines on Pharmacovigilance for Medicinal 
Products for Human Use is any untoward medical occurrence that at any dose:

Results in death

Is life-threatening
(The participant was at risk of death at the time of the event. It does not refer to an event that 
hypothetically might have caused death if it were more severe.)

Requires inpatient hospitalization or prolongation of existing hospitalization

Results in persistent or significant disability/incapacity

Is a congenital anomaly/birth defect

Is a suspected transmission of any infectious agent via a medicinal product

Is Medically Important*
* Medical and scientific judgment should be exercised in deciding whether expedited reporting is 
also appropriate in other situations, such as important medical events that may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the participant or may 
require intervention to prevent one of the other outcomes listed in the definition above. These 
should usually be considered serious.
If a serious and unexpected AE occurs for which there is evidence suggesting a causal relationship 
between the vaccine and the event (eg, death from anaphylaxis), the event must be reported as a 
suspected unexpected serious adverse reaction (SUSAR) by the sponsor to health authorities and 
by the investigator to the IRB/IEC according to regulatory and local requirements.
Any RTI fulfilling the criteria of an SAE will be reported as such during the entire study period if 
RT-PCR indicates it is not an RSV-RTI. If the RT-PCR is positive for RSV the event should not 
be reported as an SAE. If RT-PCR information is not available within 24 hours of knowledge of 
the event, the event will be reported as an SAE, but will be subsequently downgraded from SAE 
status if it later turns out to be RT-PCR positive for RSV.
Unlisted (Unexpected) Adverse Event/Reference Safety Information
An AE is considered unlisted if the nature or severity is not consistent with the applicable product 
reference safety information. For Ad26.RSV.preF and RSV preF protein, expectedness of an AE
will be determined by whether or not it is listed in the respective Investigator’s Brochure.17,18

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Adverse Event Associated With the Use of Vaccine
An AE is considered associated with the use of the vaccines if the attribution is related by the 
definitions listed in Section 12.1.2.
12.1.2.
Attribution Definitions
Every effort should be made by the investigator to explain any AE and assess its potential causal 
relationship, ie, to administration of the vaccine or to alternative causes (eg, natural history of the 
underlying diseases, concomitant therapy). This applies to all AEs (serious or non-serious).
Causality of AEs should be assessed by the investigator based on the following:
Related: there is suspicion that there is a relationship between the vaccine and the AE (without 
determining the extent of probability); there is a reasonable possibility that the vaccine contributed 
to the AE.
Unrelated: there is no suspicion that there is a relationship between the vaccine and the AE; there 
are other more likely causes and administration of the vaccine is not suspected to have contributed 
to the AE.
By definition, all solicited AEs at the injection site (local) will be considered related to vaccine
administration.
12.1.3.
Severity Criteria
All AEs and laboratory data reported as AEs will be coded for severity using the toxicity grading 
table in Attachment 1. Note: Laboratory values within central laboratory normal ranges (even if 
within a toxicity grade range), or laboratory values outside normal ranges that are not clinically 
significant in the judgment of the investigator, should not be recorded as AEs.
For AEs not identified in the toxicity grading table, the following guidelines will be applied:
Mild (Grade 1): 
Awareness of symptoms that are easily tolerated, causing 
minimal discomfort and not interfering with everyday activities.
Moderate (Grade 2): 
Sufficient discomfort is present to cause interference with 
normal activity.
Severe (Grade 3): 
Extreme distress, causing significant impairment of functioning 
or incapacitation. Prevents normal everyday activities.
Potentially life-threatening
(Grade 4): 
Symptoms causinginabilityto perform basic self-care functions, 
OR
Medicaloroperativeintervention indicated to prevent permanent 
impairment, persistent disability.
The investigator should use clinical judgment in assessing the severity of events not directly 
experienced by the participant (eg, laboratory abnormalities).

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The toxicity grading scale used for laboratory assessments is based on the FDA toxicity grading 
table (see Attachment 1), consistent with the assessment grading used throughout the protocol. If 
a laboratory value falls within the grading as specified in the FDA table, but also within the 
laboratory normal limits, the value is considered as normal. For hemoglobin, both the actual value 
and the change from reference will be graded.
The severity of solicited AEs will be graded in the diary by the participant based on the severity 
assessment provided in the diary and then verified by the investigator using the FDA toxicity 
grading table (see Attachment 1).
12.2.
Special Reporting Situations
Safety events of interest on a sponsor study vaccine that may require expedited reporting or safety 
evaluation include, but are not limited to:

Suspected abuse/misuse of a sponsor study vaccine

Accidental or occupational exposure to a sponsor study vaccine

Medication error involving a sponsor product (with or without participant/patient exposure to 
the sponsor study vaccine, eg, name confusion)

Exposure to a sponsor study vaccine from breast-feeding
Special reporting situations should be recorded in the eCRF. Any special reporting situation that 
meets the criteria of an SAE should be recorded on the SAE page of the eCRF.
12.3.
Procedures
12.3.1.
All Adverse Events
All AEs and special reporting situations, whether serious or non-serious, that are related to 
study-related procedures or that are related to non-investigational (concomitant) Janssen products 
will be reported from the time a signed and dated ICF is obtained onwards.
All other AEs and special reporting situations will be reported until 28 days (including relevant 
visit window, if applicable) after first dose of vaccine and thereafter, pre-dose on the vaccination 
day, and for 28 days (including relevant visit window, if applicable) following each subsequent 
vaccination. Unsolicited AEs with the onset date outside the time frame defined above (>28 days 
after previous vaccination), which are ongoing on the day of the subsequent vaccination, should 
be recorded on the eCRF AE page.
All SAEs and AEs leading to discontinuation from the study/vaccination (regardless of the causal 
relationship) are to be reported from the moment of first vaccination until completion of the 
participant’s last study-related procedure, which may include contact for safety follow-up.
Clinically relevant medical events occurring between ICF signature and date of first vaccination 
will be collected on the Medical History eCRF page as pre-existing conditions.

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Solicited AEs will be recorded by each participant in the participant diary for 7 days after each 
vaccination. The investigator will review each participant’s diary at the subsequent in-clinic visit
and discuss the information from the diary with the participant. The diary information will be 
transcribed by the study-site personnel in the diary forms in the eCRF.
The sponsor will evaluate any safety information that is spontaneously reported by an investigator 
beyond the time frame specified in the protocol.
The investigator will monitor and check the study data, including all AE and clinical laboratory
data, as they become available and will make determinations regarding the severity of the adverse 
experiences and their relation to vaccine. All AEs will be deemed related to vaccine or not related 
to vaccine, according to Section 12.1.2.
The investigator must review both post-injection reactogenicity and other AEs to insure the prompt 
and complete identification of all events that require expedited reporting as SAEs, invoke pausing 
rules or are other serious and unexpected events.
All AEs, regardless of seriousness, severity, or presumed relationship to the vaccine, must be 
recorded using medical terminology in the source document and the eCRF. Whenever possible,
diagnoses should be given when signs and symptoms are due to a common etiology (eg, cough, 
runny nose, sneezing, sore throat, and head congestion should be reported as “upper respiratory 
infection”). Investigators must record in the eCRF their opinion concerning the relationship of the 
AE to the vaccine. All measures required for AE management must be recorded in the source 
document and reported according to sponsor instructions.
The sponsor assumes responsibility for appropriate reporting of AEs to the regulatory authorities. 
The sponsor will also report to the investigator (and the head of the investigational institute where 
required) all SUSARs. The investigator (or sponsor where required) must report SUSARs to the 
appropriate IEC/IRB that approved the protocol unless otherwise required and documented by the 
IEC/IRB. A SUSAR will be reported to regulatory authorities unblinded. Participating 
investigators and IEC/IRB will receive a blinded SUSAR summary, unless otherwise specified.
Each participant will be provided with a “wallet (study) card” and instructed to carry this card for 
the duration of the study indicating the following:

Study number

Statement, in the local language(s), that the participant is participating in a clinical study

Investigator’s name and 24-hour contact telephone number

Local sponsor’s name and 24-hour contact telephone number (for medical staff only)

Site number

Participant number

Any other information that is required to do an emergency breaking of the blind

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12.3.2.
Serious Adverse Events
SAEs related to the study procedures or non-investigational (concomitant) Janssen products will 
be reported from ICF signature throughout the rest of the study. All other SAEs will be reported 
from first vaccination throughout the rest of the study.
SAEs must be reported to the appropriate sponsor contact person by study-site personnel within 
24 hours of their knowledge of the event. During the long-term follow-up phase for participants 
from Groups 14 and 15 in Cohort 2, only SAEs related to study vaccine, study procedures (ie, 
blood draws), or non-investigational (concomitant) Janssen products, and all AEs leading to 
discontinuation will be collected.
Information regarding SAEs will be transmitted to the sponsor using the SAE Form, which must 
be completed and signed by a physician from the study site, and transmitted to the sponsor within 
24 hours. The initial and follow-up reports of an SAE should be made by facsimile (fax).
All SAEs that have not resolved by the end of the study, or that have not resolved upon 
discontinuation of the participant’s participation in the study, must be followed until any of the 
following occurs:

The event resolves

The event stabilizes

The event returns to baseline, if a baseline value/status is available

The event can be attributed to agents other than the vaccine or to factors unrelated to study 
conduct

It becomes unlikely that any additional information can be obtained (participant or healthcare 
practitioner refusal to provide additional information, lost to follow-up after demonstration of 
due diligence with follow-up efforts)
Suspected transmission of an infectious agent by a medicinal product will be reported as an SAE. 
Any event requiring hospitalization (or prolongation of hospitalization) that occurs during a 
participant’s participation in a study must be reported as an SAE, except hospitalizations for the 
following:

Hospitalizations not intended to treat an acute illness or an AE (eg, social reasons such as 
pending placement in long-term care facility)

Surgery or procedure planned before entry into the study (must be documented in the eCRF). 
Note: Hospitalizations that were planned before the signing of the ICF, and where the 
underlying condition for which the hospitalization was planned has not worsened, will not be 
considered as SAEs. Any AE that results in a prolongation of the originally planned 
hospitalization is to be reported as a new SAE.

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The cause of death of a participant in a study during the entire study period, whether or not the 
event is expected or associated with the vaccine, is considered an SAE and must be reported.
12.3.3.
Pregnancy
All initial reports of pregnancy in female participants and in partners of male participants must be 
reported to the sponsor by the study-site personnel within 24 hours of their knowledge of the event 
using the appropriate pregnancy notification form. Abnormal pregnancy outcomes (eg, 
spontaneous abortion, fetal death, stillbirth, congenital anomalies, and ectopic pregnancy) are 
considered SAEs and must be reported using the Serious Adverse Event Form.
Pregnancies in partners of male participants included in the study will be reported as noted above.
Follow-up information regarding the outcome of the pregnancy and any postnatal sequelae in the 
infant will be required.
12.4.
Contacting Sponsor Regarding Safety
The names (and corresponding telephone numbers) of the individuals who should be contacted 
regarding safety issues or questions regarding the study are listed in the Contact Information 
page(s), which will be provided as a separate document.
13.
PRODUCT QUALITY COMPLAINT HANDLING
A product quality complaint (PQC) is defined as any suspicion of a product defect related to 
manufacturing, labeling, or packaging, ie, any dissatisfaction relative to the identity, quality, 
durability, or reliability of a product, including its labeling or package integrity. A PQC may have 
an impact on the safety and immunogenicity of the product. Timely, accurate, and complete 
reporting and analysis of PQC information from studies are crucial for the protection of 
participants, investigators, and the sponsor, and are mandated by regulatory agencies worldwide. 
The sponsor has established procedures in conformity with regulatory requirements worldwide to 
ensure appropriate reporting of PQC information; all studies conducted by the sponsor or its 
affiliates will be conducted in accordance with those procedures.
13.1.
Procedures
All initial PQCs must be reported to the sponsor by the study-site personnel within 24 hours after 
being made aware of the event.
If the defect is combined with an SAE, the study-site personnel must report the PQC to the sponsor 
according to the SAE reporting timelines (see Section 12.3.2). A sample of the suspected product 
should be maintained for further investigation if requested by the sponsor.
13.2.
Contacting Sponsor Regarding Product Quality
The names (and corresponding telephone numbers) of the individuals who should be contacted 
regarding product quality issues are listed in the Contact Information page(s), which will be 
provided as a separate document.

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14.
VACCINE INFORMATION
14.1.
Physical Description of the Vaccines
A human replication-incompetent adenovirus-vectored vaccine candidate and RSV preF protein, 
manufactured and provided under the responsibility of the sponsor, will be assessed in this study:
Ad26.RSV.preF (JNJ-64400141)
Ad26.RSV.preF is a replication-incompetent Ad26 containing a DNA transgene that encodes the 
pre-fusion conformation-stabilized F protein derived from the RSV A2 strain.
For this study, Ad26.RSV.preF will be formulated as a solution for intramuscular injection and will 
be supplied as a frozen liquid to be thawed prior to use. Ad26.RSV.preF will be supplied in single-
use vials (2×1011 vp/mL). Refer to the Investigational Product Preparation Instructions for details 
on dosing preparation.
Refer to the Investigator’s Brochure for details of the components of Ad26.RSV.preF and a list of 
excipients.18
RSV preF protein (JNJ-64213175)
RSV preF protein is a pre-fusion conformation-stabilized F protein derived from the RSV A2 
strain.
For this study, RSV preF protein will be formulated as a solution for intramuscular injection. RSV 
preF protein will be supplied in a single-use vial. Refer to the Investigational Product Preparation 
Instructions for details on dosing preparation.
Refer to the Investigator’s Brochure for details of the components of RSV preF protein and a list 
of excipients.17
Note: RSV preF protein clinical trial material will be labelled as “RSV-F Vaccine”.
Placebo
Placebo for Ad26.RSV.preF and RSV preF protein will be supplied as sterile saline for 
intramuscular injection in vials.
14.2.
Packaging and Labelling
Vaccines will be manufactured and packaged in accordance with Current Good Manufacturing 
Practice. Vaccines will be packaged and labeled under the responsibility of the sponsor. Vaccine 
labels will contain information to meet the applicable regulatory requirements.
No vaccine can be repacked or relabeled without prior approval from the sponsor.
Further details for vaccine packaging and labeling can be found in the Investigational Product 
Preparation Instructions.

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14.3.
Storage and Handling
Vaccines must be stored in a secured location under controlled temperature with no access for 
unauthorized personnel. The study refrigerator/freezer must be equipped with a continuous 
temperature monitor and alarm, and with back-up power systems. If a vaccine is exposed to 
temperatures outside the specified temperature range, all relevant data will be sent to the sponsor
to determine if the affected vaccine can be used or will be replaced. The affected vaccine must be 
quarantined and not used until further instruction from the sponsor is received.
The vaccines will be prepared by the unblinded site pharmacist, or other qualified individual and 
administered by a vaccine administrator.
Note: The unblinded pharmacist, or other qualified individual, may also perform administration of 
the vaccines, but will have no other study function following dosing.
Further details for vaccine storage, preparation, handling and stability can be found in the 
Investigational Product Preparation Instructions.
14.4.
Vaccine Accountability
The investigator is responsible for ensuring that all vaccines received at the site is inventoried and 
accounted for throughout the study. All vaccines administered to the participant must be 
documented on the vaccine accountability form. All vaccines will be stored and disposed of 
according to the sponsor’s instructions.
Vaccines must be handled in strict accordance with the protocol and the container label, and must 
be stored at the study site in a limited-access area or in a locked cabinet under appropriate 
environmental conditions. Unused vaccines must be available for verification by the sponsor’s 
study-site monitor during on-site monitoring visits. The return to the sponsor of unused vaccines
will be documented on a vaccine return form. When the study site is an authorized destruction unit 
and vaccine supplies are destroyed on-site, this must also be documented on a vaccine return form.
Potentially hazardous materials such as used ampules, needles, syringes and vials containing 
hazardous liquids, should be disposed of immediately in a safe manner and therefore will not be 
retained for vaccine accountability purposes.
Vaccines should be dispensed under the supervision of the investigator or a qualified member of 
the study-site personnel, or by a hospital/clinic pharmacist. Vaccines will be supplied only to 
participants participating in the study. Vaccines may not be relabeled or reassigned for use by other 
participants. The investigator agrees neither to dispense vaccines from, nor store them at, any sites
other than the study site agreed upon with the sponsor.
15.
STUDY-SPECIFIC MATERIALS
The investigator will be provided with the following supplies:

Investigator’s Brochure for Ad26.RSV.preF18

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
Investigator’s Brochure for RSV preF protein17

Investigational Product Preparation Instructions/Investigational Product Procedures Manual

Laboratory Manual (including procedures for collection of nasal samples)

Trial Center File

IWRS Manual

Electronic Data Capture (eDC) Manual/eCRF completion guidelines and randomization 
instructions

Sample ICF

Participant diaries

Rulers

Thermometers

Nasal swab kits

RTI Symptoms Forms

Contact information page(s)
16.
ETHICAL ASPECTS
16.1.
Study-Specific Design Considerations
Potential participants will be fully informed of the risks and requirements of the study and, during 
the study, participants will be given any new information that may affect their decision to continue 
participation. They will be told that their consent to participate in the study is voluntary and may be 
withdrawn at any time with no reason given and without penalty or loss of benefits to which they 
would otherwise be entitled. Only participants who are fully able to understand the risks, benefits, 
and potential AEs of the study, and provide their consent voluntarily will be enrolled.
The total blood volume drawn from each participant will not exceed the US Department of Health 
and Human Services Office for Human Research Protections, and FDA guidelines of 550 mL in 
any 8-week period.36,37
Risks Related to Vaccination
Participants may exhibit local signs/symptoms associated with vaccination, including erythema, 
swelling/induration, and pain/tenderness. These local reactions will be monitored, but generally 
are short-term and do not require treatment.
Participants may exhibit general signs/symptoms associated with vaccination, including fatigue, 
headache, myalgia, arthralgia, chills, nausea, and fever. These side effects will be monitored, but 
are generally short-term and do not require treatment.

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Syncope can occur in association with administration of injectable vaccines. Syncope can be 
accompanied by falls. Procedures should be in place to avoid falling injury. If syncope develops, 
participants should be observed until the symptoms resolve.
Participants may have an allergic reaction to the vaccination. An allergic reaction may cause a 
rash, hives or even difficulty breathing. Severe reactions, including anaphylaxis, are rare but can 
occur with any vaccine. Participants with a known allergy, or a history of anaphylaxis or other 
serious adverse reactions to vaccines or vaccine components (including any of the constituents of 
the vaccines) will be excluded from the study. Sites should have medical treatment available in 
case of severe allergic reactions following vaccine administration.
Risks Related to Adenoviral-vectored Vaccines
Safety data available from completed clinical studies in adults with other Ad26-vectored vaccine 
candidates, in which Ad26 with different inserts has been evaluated at dose levels ranging from 
1×109 vp to 1×1011 vp, indicate that no safety concerns would be anticipated from vaccination with 
Ad26.RSV.preF at doses of 5×1010 vp and 1×1011 vp.14,15
Local AEs (moderate injection site pain/tenderness, moderate to severe redness at the injection 
site) and systemic AEs (headache, chills, joint pain, muscle pain, tiredness/generally not feeling 
well/fatigue, fever) have been reported after vaccination with Ad26-vectored vaccines. In a few 
participants, transient laboratory abnormalities have been observed, including changes in
neutrophils. Laboratory changes including decreased hemoglobin, decreased platelets, and 
moderate elevations in liver transaminases were observed that were not associated with any clinical 
findings and appear to be transient based on no reported persistent abnormalities in any of the 
participants.
For further details on the safety profiles of other Ad26-vectored vaccine candidates, see the 
Ad26.RSV.preF Investigator’s Brochure.18
Risks Related to RSV preF Protein
This study will be the FIH study for RSV preF protein. No clinical data are available to date.
For the most comprehensive nonclinical information regarding RSV preF protein, refer to the latest 
version of the Investigator’s Brochure for RSV preF protein.17
Risks from Blood Draws
Blood drawing may cause pain/tenderness, bruising, bleeding, lightheadedness, dizziness, 
vasovagal response, and, rarely, infection at the site where the blood is taken.
Risks from Collection of Nasal Samples
Collection of nasal samples may cause a nosebleed.

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Participants with Immuno-suppression/Reduced Immune Response
Limited evidence indicates that inactivated vaccines (or non-replicating viral vaccines) generally 
have the same safety profile in immunocompromised patients and immunocompetent individuals. 
However, the magnitude, breadth, and persistence of the immune response to vaccination may be 
reduced or absent in immunocompromised persons. Participants with abnormal function of the 
immune system will be excluded from the study.
Concomitant Vaccination
Concomitant vaccination might have an influence on both the safety profile and immunogenicity 
of Ad26.RSV.preF and/or RSV preF protein. Likewise, Ad26.RSV.preF and/or RSV preF protein
might have an influence on both the safety profile and immunogenicity of any concomitant 
vaccination. As a result, vaccination with live attenuated vaccines within 28 days of a vaccination 
in this study (ie, before and after) is prohibited. Other licensed vaccines (ie, not live: eg, influenza, 
tetanus, hepatitis A or B, or rabies) should be given at least 14 days before or 14 days after each 
study vaccination to avoid potential confusion of adverse reactions and potential immune 
interference. If a vaccine is indicated in a post-exposure setting (eg, rabies or tetanus), it must take 
priority over the vaccines in this study.
Potential Benefits
Ad26.RSV.preF and RSV preF protein are under development for prophylaxis of RSV, however,
vaccine efficacy has not yet been evaluated. There is no direct medical benefit to the participant
for participation in this study. Although study participants may benefit from clinical testing and 
physical examination, they may receive no direct benefit from participation. Others may benefit 
from knowledge gained in this study that may aid in the development of an RSV vaccine.
16.2.
Regulatory Ethics Compliance
16.2.1.
Investigator Responsibilities
The investigator is responsible for ensuring that the study is performed in accordance with the 
protocol, current ICH guidelines on Good Clinical Practice (GCP), and applicable regulatory and 
country-specific requirements.
GCP is an international ethical and scientific quality standard for designing, conducting, recording, 
and reporting studies that involve the participation of human participants. Compliance with this 
standard provides public assurance that the rights, safety, and well-being of study participants are 
protected, consistent with the principles that originated in the Declaration of Helsinki, and that the 
study data are credible.
16.2.2.
Independent Ethics Committee or Institutional Review Board
Before the start of the study, the investigator (or sponsor where required) will provide the IEC/IRB 
with current and complete copies of the following documents (as required by local regulations):

Final protocol and, if applicable, amendments

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
Sponsor-approved ICF (and any other written materials to be provided to the participants)

Investigator’s Brochures (or equivalent information) and amendments/addenda

Sponsor-approved participant recruiting materials

Information on compensation for study-related injuries or payment to participants for 
participation in the study, if applicable

Investigator’s curriculum vitae or equivalent information (unless not required, as documented 
by the IEC/IRB)

Information regarding funding, name of the sponsor, institutional affiliations, other potential 
conflicts of interest, and incentives for participants

Any other documents that the IEC/IRB requests to fulfill its obligation
This study will be undertaken only after the IEC/IRB has given full approval of the final protocol, 
amendments (if any, excluding the ones that are purely administrative, with no consequences for 
participants, data or study conduct, unless required locally), the ICF, applicable recruiting 
materials, and participant compensation programs, and the sponsor has received a copy of this 
approval. This approval letter must be dated and must clearly identify the IEC/IRB and the 
documents being approved.
During the study, the investigator (or sponsor where required) will send the following documents 
and updates to the IEC/IRB for their review and approval, where appropriate:

Protocol amendments (excluding the ones that are purely administrative, with no 
consequences for participants, data or study conduct)

Revision(s) to ICF and any other written materials to be provided to participants

If applicable, new or revised participant recruiting materials approved by the sponsor

Revisions to compensation for study-related injuries or payment to participants for 
participation in the study, if applicable

New edition(s) of the Investigator’s Brochure(s) and amendments/addenda

Summaries of the status of the study at intervals stipulated in guidelines of the IEC/IRB (at 
least annually)

Reports of AEs that are serious, unlisted/unexpected, and associated with the vaccine

New information that may adversely affect the safety of the participants or the conduct of the 
study

Deviations from or changes to the protocol to eliminate immediate hazards to the participants

Report of deaths of participants under the investigator’s care

Notification if a new investigator is responsible for the study at the site

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
Development Safety Update Report and Line Listings, where applicable

Any other requirements of the IEC/IRB
For all protocol amendments (excluding the ones that are purely administrative, with no 
consequences for participants, data or study conduct), the amendment and applicable ICF revisions 
must be submitted promptly to the IEC/IRB for review and approval before implementation of the 
change(s).
At least once a year, the IEC/IRB will be asked to review and reapprove this study, where required.
At the end of the study, the investigator (or sponsor where required) will notify the IEC/IRB about 
the study completion.
16.2.3.
Informed Consent
Each participant must give written consent according to local requirements after the nature of the 
study has been fully explained. The ICF(s) must be signed before performance of any study-related 
activity. The ICF(s) that is/are used must be approved by both the sponsor and by the reviewing 
IEC/IRB and be in a language that the participant can read and understand. The informed consent 
should be in accordance with principles that originated in the Declaration of Helsinki, current ICH 
and GCP guidelines, applicable regulatory requirements, and sponsor policy.
Before enrollment in the study, the investigator or an authorized member of the study-site 
personnel must explain to potential participants the aims, methods, reasonably anticipated benefits, 
and potential hazards of the study, and any discomfort participation in the study may entail. 
Participants will be informed that their participation is voluntary and that they may withdraw 
consent to participate at any time. They will be informed that choosing not to participate will not 
affect the care the participant will receive. Finally, they will be told that the investigator will 
maintain a participant identification register for the purposes of long-term follow-up if needed and 
that their records may be accessed by health authorities and authorized sponsor personnel without 
violating the confidentiality of the participant, to the extent permitted by the applicable law(s) or 
regulations. By signing the ICF the participant is authorizing such access. It also denotes that the 
participant agrees to allow his or her study physician to recontact the participant for the purpose 
of obtaining consent for additional safety evaluations, if needed.
The participant will be given sufficient time to read the ICF and the opportunity to ask questions. 
After this explanation and before entry into the study, consent should be appropriately recorded by 
means of the participant’s personally dated signature. After having obtained the consent, a copy of 
the ICF must be given to the participant.
Additional informed consent for participants progressing to the long-term follow-up phase 
(participants in Groups 14 and 15 in Cohort 2) will be required. Information relevant to 
participating in the follow-up phase of the study will be provided to the participant in a timely 
manner, and written informed consent for participation in this phase will be obtained. Additional 

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informed consent will also be required for participants in Cohort 3 who will receive the Month 24 
booster.
16.2.4.
Privacy of Personal Data
The collection and processing of personal data from participants enrolled in this study will be 
limited to those data that are necessary to fulfill the objectives of the study.
These data must be collected and processed with adequate precautions to ensure confidentiality 
and compliance with applicable data privacy protection laws and regulations. Appropriate 
technical and organizational measures to protect the personal data against unauthorized disclosures 
or access, accidental or unlawful destruction, or accidental loss or alteration must be put in place. 
Sponsor personnel whose responsibilities require access to personal data agree to keep the identity 
of participants confidential.
The informed consent obtained from the participant includes explicit consent for the processing of 
personal data and for the investigator/institution to allow direct access to his or her original medical 
records (source data/documents) for study-related monitoring, audit, IEC/IRB review, and 
regulatory inspection. This consent also addresses the transfer of the data to other entities and to 
other countries.
The participant has the right to request through the investigator access to his or her personal data 
and the right to request rectification of any data that are not correct or complete. Reasonable steps 
will be taken to respond to such a request, taking into consideration the nature of the request, the 
conditions of the study, and the applicable laws and regulations.
16.2.5.
Long-Term Retention of Samples for Additional Future Research
Samples collected in this study may be stored for up to 15 years (or according to local regulations) 
for additional research. Samples will only be used to understand Ad26.RSV.preF and RSV preF 
protein, to understand RSV, and to develop tests/assays related to Ad26.RSV.preF and RSV preF 
protein and RSV. The research may begin at any time during the study or the post-study storage 
period. Included are samples from participants who were screened but not randomized which may 
also be used to develop tests/assays related to Ad26.RSV.preF, RSV preF protein, and RSV.
Stored samples will be coded throughout the sample storage and analysis process and will not be 
labeled with personal identifiers. Participants may withdraw their consent for their samples to be 
stored for research (see Section 10.2).
16.2.6.
Country Selection
This study will only be conducted in those countries where the intent is to launch or otherwise help 
ensure access to the developed product.

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17.
ADMINISTRATIVE REQUIREMENTS
17.1.
Protocol Amendments
Neither the investigator nor the sponsor will modify this protocol without a formal amendment by 
the sponsor. All protocol amendments must be issued by the sponsor, and signed and dated by the 
investigator. Protocol amendments must not be implemented without prior IEC/IRB approval, or 
when the relevant competent authority has raised any grounds for non-acceptance, except when 
necessary to eliminate immediate hazards to the participants, in which case the amendment must 
be promptly submitted to the IEC/IRB and relevant competent authority. Documentation of 
amendment approval by the investigator and IEC/IRB must be provided to the sponsor. When the 
change(s) involves only logistic or administrative aspects of the study, the IEC/IRB (where 
required) only needs to be notified.
During the course of the study, in situations where a departure from the protocol is unavoidable, 
the investigator or other physician in attendance will contact the appropriate sponsor representative 
listed in the Contact Information page(s), which will be provided as a separate document. Except 
in emergency situations, this contact should be made before implementing any departure from the 
protocol. In all cases, contact with the sponsor must be made as soon as possible to discuss the 
situation and agree on an appropriate course of action. The data recorded in the eCRF and source 
documents will reflect any departure from the protocol, and the source documents will describe 
this departure and the circumstances requiring it.
17.2.
Regulatory Documentation
17.2.1.
Regulatory Approval/Notification
This protocol and any amendment(s) must be submitted to the appropriate regulatory authorities 
in each respective country, if applicable. A study may not be initiated until all local regulatory 
requirements are met.
17.2.2.
Required Pre-study Documentation
The following documents must be provided to the sponsor before shipment of vaccines to the study
site:

Protocol and amendment(s), if any, signed and dated by the PI(s).

A copy of the dated and signed (or sealed, where appropriate per local regulations), written 
IEC/IRB approval of the protocol, amendments, ICF, any recruiting materials, and if 
applicable, participant compensation programs. This approval must clearly identify the 
specific protocol by title and number and must be signed (or sealed, where appropriate per 
local regulations) by the chairman or authorized designee.

Name and address of the IEC/IRB, including a current list of the IEC/IRB members and their 
function, with a statement that it is organized and operates according to GCP and the 
applicable laws and regulations. If accompanied by a letter of explanation, or equivalent, from 
the IEC/IRB, a general statement may be substituted for this list. If an investigator or a 

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member of the study-site personnel is a member of the IEC/IRB, documentation must be 
obtained to state that this person did not participate in the deliberations or in the vote/opinion 
of the study.

Regulatory authority approval or notification, if applicable.

Signed and dated statement of investigator (eg, Form FDA 1572), if applicable.

Documentation of investigator qualifications (eg, curriculum vitae).

Completed investigator financial disclosure form from the PI(s), where required.

Signed and dated Clinical Trial Agreement, which includes the financial agreement.

Any other documentation required by local regulations.
The following documents must be provided to the sponsor before enrollment of the first 
participant:

Completed investigator financial disclosure forms from all sub-investigators.

Documentation of sub-investigator qualifications (eg, curriculum vitae).

Name and address of any local laboratory conducting tests for the study, and a dated copy of 
current laboratory normal ranges for these tests, if applicable.

Local laboratory documentation demonstrating competence and test reliability (eg,
accreditation/license), if applicable.
17.3.
Participant Identification, Enrollment, and Screening Logs
The investigator agrees to complete a participant identification and enrollment log to permit easy 
identification of each participant during and after the study. This document will be reviewed by 
the sponsor study-site contact for completeness.
The participant identification and enrollment log will be treated as confidential and will be filed 
by the investigator in the study file. To ensure participant confidentiality, no copy will be made. 
All reports and communications relating to the study will identify participants by participant
identification and date of birth. In cases where the participant is not randomized into the study, the 
date seen and date of birth will be used.
The investigator must also complete a participant screening log, which reports on all participants 
who were seen to determine eligibility for inclusion in the study.
17.4.
Source Documentation
At a minimum, source documents consistent in the type and level of detail with that commonly 
recorded at the study site as a basis for standard medical care must be available for the following: 
participant identification, eligibility, and study identification; study discussion and date of signed 
informed consent; dates of visits; results of safety and immunogenicity parameters as required by 
the protocol; record of all AEs and follow-up of AEs; concomitant medication; vaccine

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receipt/dispensing/return records; vaccine administration information; and date of study 
completion and reason for early discontinuation of vaccine or withdrawal from the study, if 
applicable.
The author of an entry in the source documents should be identifiable.
Specific details required as source data for the study and source data collection methods will be 
reviewed with the investigator before the study and will be described in the monitoring guidelines 
(or other equivalent document).
The participant diary used to collect information regarding solicited events after vaccination will 
be considered source data. At the visits at 7 days after each vaccination, information from the 
participant diary will be reviewed by the investigator; diary information will be transcribed by 
study-site personnel into the eCRF as described in the eCRF Completion Guidelines.
An electronic source (eSource) system may be utilized, which contains data traditionally 
maintained in a hospital or clinic record to document medical care (eg, electronic source 
documents) as well as the clinical study-specific data fields as determined by the protocol. This 
data is electronically extracted for use by the sponsor. If eSource is utilized, references made to 
the eCRF in the protocol include the eSource system but information collected through eSource 
may not be limited to that found in the eCRF.
17.5.
Case Report Form Completion
CRFs are prepared and provided by the sponsor for each participant in electronic format. All eCRF
entries, corrections, and alterations must be made by the investigator or authorized study-site 
personnel. The investigator must verify that all data entries in the eCRF are accurate and correct.
The study data will be transcribed by study-site personnel from the source documents onto an 
eCRF, if applicable. Study-specific data will be transmitted in a secure manner to the sponsor.
Worksheets may be used for the capture of some data to facilitate completion of the eCRF. Any 
such worksheets will become part of the participant’s source documents. Data must be entered into 
the eCRF in English. The eCRF must be completed as soon as possible after a participant visit and 
the forms should be available for review at the next scheduled monitoring visit.
If necessary, queries will be generated in the eDC tool. If corrections to an eCRF are needed after 
the initial entry into the eCRF, this can be done in either of the following ways:

Investigator and study-site personnel can make corrections in the eDC tool at their own 
initiative or as a response to an auto query (generated by the eDC tool).

Sponsor or sponsor delegate can generate a query for resolution by the investigator and study-
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17.6.
Data Quality Assurance/Quality Control
Steps to be taken to ensure the accuracy and reliability of data include the selection of qualified 
investigators and appropriate study sites, review of protocol procedures with the investigator and 
study-site personnel before the study, and periodic monitoring visits by the sponsor. Written 
instructions will be provided for collection, handling, storage, and shipment of samples.
Guidelines for eCRF completion will be provided and reviewed with study-site personnel before 
the start of the study.
The sponsor will review eCRF for accuracy and completeness during on-site monitoring visits and 
after transmission to the sponsor; any discrepancies will be resolved with the investigator or 
designee, as appropriate. After upload of the data into the study database they will be verified for 
accuracy and consistency with the data sources.
17.7.
Record Retention
In compliance with the ICH/GCP guidelines, the investigator/institution will maintain all eCRF 
and all source documents that support the data collected from each participant, as well as all study 
documents as specified in ICH/GCP Section 8, Essential Documents for the Conduct of a Clinical 
Trial, and all study documents as specified by the applicable regulatory requirement(s). The 
investigator/institution will take measures to prevent accidental or premature destruction of these 
documents.
Essential documents must be retained until at least 2 years after the last approval of a marketing 
application in an ICH region and until there are no pending or contemplated marketing applications 
in an ICH region or until at least 2 years have elapsed since the formal discontinuation of clinical 
development of the investigational product. These documents will be retained for a longer period 
if required by the applicable regulatory requirements or by an agreement with the sponsor. It is the 
responsibility of the sponsor to inform the investigator/institution as to when these documents no 
longer need to be retained.
If the responsible investigator retires, relocates, or for other reasons withdraws from the 
responsibility of keeping the study records, custody must be transferred to a person who will accept 
the responsibility. The sponsor must be notified in writing of the name and address of the new 
custodian. Under no circumstance shall the investigator relocate or dispose of any study documents 
before having obtained written approval from the sponsor.
If it becomes necessary for the sponsor or the appropriate regulatory authority to review any 
documentation relating to this study, the investigator/institution must permit access to such reports.
17.8.
Monitoring
The sponsor will perform on-site monitoring visits as frequently as necessary. The monitor will 
record dates of the visits in a study-site visit log that will be kept at the study site. The first post-
initiation visit will be made as soon as possible after enrollment has begun. At these visits, the 
monitor will compare the data entered into the eCRF with the source documents (eg,

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hospital/clinic/physician’s office medical records). The nature and location of all source 
documents will be identified to ensure that all sources of original data required to complete the 
eCRF are known to the sponsor and study-site personnel and are accessible for verification by the 
sponsor study-site contact. If electronic records are maintained at the study site, the method of 
verification must be discussed with the study-site personnel.
Direct access to source documents (medical records) must be allowed for the purpose of verifying 
that the recorded data are consistent with the original source data. Findings from this review will 
be discussed with the study-site personnel. The sponsor expects that, during monitoring visits, the 
relevant study-site personnel will be available, the source documents will be accessible, and a 
suitable environment will be provided for review of study-related documents. The monitor will 
meet with the investigator on a regular basis during the study to provide feedback on the study
conduct.
17.9.
Study Completion/Termination
17.9.1.
Study Completion/End of Study
The end of the study will be the last participant’s last visit 24 months after the first vaccination
(Cohort 1 and Cohort 2 [Groups 11-13 and Groups 16-18]) or the last participant’s last visit 
36 months after the first vaccination (Cohort 2 [Groups 14-15] and Cohort 3). The study is 
considered completed with the last visit for the last participant participating in the study. The final 
data from the study site will be sent to the sponsor (or designee) after completion of the final 
participant visit at that study site, in the time frame specified in the Clinical Trial Agreement.
17.9.2.
Study Termination
The sponsor reserves the right to close the study site or terminate the study at any time for any 
reason at the sole discretion of the sponsor. Study sites will be closed upon study completion. A
study site is considered closed when all required documents and study supplies have been collected 
and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time, provided there is reasonable cause and 
sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a study site by the sponsor or investigator may include but are not 
limited to:

Failure of the investigator to comply with the protocol, the requirements of the IEC/IRB or 
local health authorities, the sponsor’s procedures, or GCP guidelines

Inadequate recruitment of participants by the investigator

Discontinuation of further study vaccine development

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17.10. On-Site Audits
Representatives of the sponsor’s clinical quality assurance department may visit the study site at 
any time during or after completion of the study to conduct an audit of the study in compliance 
with regulatory guidelines and company policy. These audits will require access to all study 
records, including source documents, for inspection. Participant privacy must, however, be 
respected. The investigator and study-site personnel are responsible for being present and available 
for consultation during routinely scheduled study-site audit visits conducted by the sponsor or its 
designees.
Similar auditing procedures may also be conducted by agents of any regulatory body, either as part 
of a national GCP compliance program or to review the results of this study in support of a 
regulatory submission. The investigator should immediately notify the sponsor if he or she has
been contacted by a regulatory agency concerning an upcoming inspection.
17.11. Use of Information and Publication
All information, including but not limited to information regarding Ad26.RSV.preF and RSV preF 
protein or the sponsor’s operations (eg, patent application, formulas, manufacturing processes, 
basic scientific data, prior clinical data, formulation information) supplied by the sponsor to the 
investigator and not previously published, and any data generated as a result of this study, are
considered confidential and remain the sole property of the sponsor. The investigator agrees to 
maintain this information in confidence and use this information only to accomplish this study, 
and will not use it for other purposes without the sponsor’s prior written consent.
The investigator understands that the information developed in the study will be used by the 
sponsor in connection with the continued development of Ad26.RSV.preF and RSV preF protein, 
and thus may be disclosed as required to other clinical investigators or regulatory agencies. To 
permit the information derived from the clinical studies to be used, the investigator is obligated to 
provide the sponsor with all data obtained in the study.
The results of the study will be reported in a Clinical Study Report generated by the sponsor and 
will contain data from all study sites that participated in the study as per-protocol. Recruitment 
performance or specific expertise related to the nature and the key assessment parameters of the 
study will be used to determine a coordinating investigator. Results of analyses performed after 
the Clinical Study Report has been issued will be reported in a separate report and will not require 
a revision of the Clinical Study Report. Study participant identifiers will not be used in publication 
of results. Any work created in connection with performance of the study and contained in the data 
that can benefit from copyright protection (except any publication by the investigator as provided 
for below) shall be the property of the sponsor as author and owner of copyright in such work.
Consistent with Good Publication Practices and International Committee of Medical Journal 
Editors guidelines, the sponsor shall have the right to publish such primary (multi-center) data and 
information without approval from the investigator. The investigator has the right to publish study 
site-specific data after the primary data are published. If an investigator wishes to publish 

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information from the study, a copy of the manuscript must be provided to the sponsor for review 
at least 60 days before submission for publication or presentation. Expedited reviews will be 
arranged for abstracts, poster presentations, or other materials. If requested by the sponsor in 
writing, the investigator will withhold such publication for up to an additional 60 days to allow for 
filing of a patent application. In the event that issues arise regarding scientific integrity or 
regulatory compliance, the sponsor will review these issues with the investigator. The sponsor will 
not mandate modifications to scientific content and does not have the right to suppress information.
For multi-center study designs and substudy approaches, secondary results generally should not 
be published before the primary endpoints of a study have been published. Similarly, investigators 
will recognize the integrity of a multi-center study by not submitting for publication data derived 
from the individual study site until the combined results from the completed study have been 
submitted for publication, within 12 months of the availability of the final data (tables, listings, 
graphs), or the sponsor confirms there will be no multi-center study publication. Authorship of 
publications resulting from this study will be based on the guidelines on authorship, such as those 
described in the Uniform Requirements for Manuscripts Submitted to Biomedical Journals, which 
state that the named authors must have made a significant contribution to the design of the study 
or analysis and interpretation of the data, provided critical review of the paper, and given final 
approval of the final version.
Registration of Clinical Studies and Disclosure of Results
The sponsor will register and disclose the existence of and the results of clinical studies as required 
by law.

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18.
APPENDIX 1: GUIDANCE ON STUDY CONDUCT DURING THE COVID-19 
PANDEMIC
It is recognized that the Coronavirus Disease 2019 (COVID-19) pandemic may have an impact on 
the conduct of this clinical study due to, for example, self-isolation/quarantine by participants and 
study-site personnel; travel restrictions/limited access to public places, including hospitals; study 
site personnel being reassigned to critical tasks. 
In alignment with recent health authority guidance, the sponsor is providing options for study 
related participant management in the event of disruption to the conduct of the study. This guidance 
does not supersede any local or government requirements or the clinical judgement of the 
investigator to protect the health and well-being of participants and site staff. If, at any time, a 
participant’s safety is considered to be at risk, study intervention will be discontinued, and study 
follow-up will be conducted.
Scheduled visits that cannot be conducted in person at the study site will be performed to the extent 
possible remotely/virtually or delayed until such time that on-site visits can be resumed. At each 
contact, participants will be interviewed to collect safety data. Key efficacy endpoint assessments 
should be performed if required and as feasible. Participants will also be questioned regarding 
general health status to fulfill any physical examination requirement. 
Every effort should be made to adhere to protocol-specified assessments for participants on study 
intervention, including follow up. Modifications to protocol-required assessments may be 
permitted via COVID-19 Appendix after consultation with the participant, investigator, and the 
sponsor. Missed assessments/visits will be captured in the clinical trial management system for 
protocol deviations. Discontinuations of study interventions and withdrawal from the study should 
be documented with the prefix “COVID-19-related” in the case report form (CRF). 
The sponsor will continue to monitor the conduct and progress of the clinical study, and any 
changes will be communicated to the sites and to the health authorities according to local guidance.
If a participant has tested positive for COVID 19, the investigator should contact the sponsor’s 
responsible medical officer to discuss plans for study intervention and follow-up. Modifications 
made to the study conduct as a result of the COVID-19 pandemic should be summarized in the 
clinical study report.
GUIDANCE SPECIFIC TO THIS PROTOCOL: 

When site visits are not possible due to local/national guidelines, sites should collect the 
assessments via telephone visits or home-based visits, if the participant allows. The actual 
visit date and the type of visit (ie, telephone or home-based visit) should be captured in the 
eCRF. Procedures that cannot be performed during a home-based visit (eg, clinical 
assessments, blood samples, nasal samples and physical examination), should be excluded. 
The missed procedures should be recorded as “missed due to COVID-19”.

When planning for vaccination visits, local/national or institutional guidelines will be 
followed. The study vaccine should be administered by an (unblinded) pharmacist or other 

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qualified individual at the study site. If this is not possible, a solution may be considered in 
consultation with the sponsor and taking into consideration participant safety. Of note, if a 
scheduled study vaccination is not possible at the scheduled visit time, the vaccination should 
occur within 3 weeks after the scheduled visit.

A revised ICF arising from this amendment needs to be signed by the participants during a 
site visit or home-based visit, if the participant allows. When a site or home-based visit is not 
possible due to local/national guidelines, the participant can sign the paper ICF and mail the 
signed document to the site. 

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Hall C, Weinberg G, Iwane M, et al. The burden of respiratory syncytial virus infection in young children. N 
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Janssen Vaccines & Prevention B.V. Adenoviral Vaccine Safety Database - Report December 2017. 
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Janssen Vaccines & Prevention B.V. Adenoviral Vaccine Safety Database v2.0. Addendum. September 
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Janssen Vaccines & Prevention B.V. Data on file. 
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Janssen Vaccines & Prevention B.V. Investigator’s Brochure: PreF Protein. Edition 4. 
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Janssen Vaccines & Prevention B.V. Investigator’s Brochure: Prophylactic RSV Vaccine. Edition 10. 
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Janssen Vaccines & Prevention B.V. Study VAC18192RSV1001: A Phase 1, First-in-Human Study to 
Evaluate the Safety, Tolerability and Immunogenicity of Ad35.RSV.FA2 Regimens Boosted With 
Ad26.RSV.FA2 in Healthy Adult Volunteers. Final Clinical Study Report. 

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Janssen Vaccines & Prevention B.V. Study VAC18192RSV1003: A Phase 1, First-in-Human Study to 
Evaluate the Safety, Tolerability and Immunogenicity of Ad26.RSV.FA2 Followed by Ad35.RSV.FA2 in 
Healthy Adult Volunteers. Final Clinical Study Report. 
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Krarup A, Truan D, Furmanova-Hollenstein P, et al. A highly stable prefusion RSV F vaccine derived from 
structural analysis of the fusion mechanism. Nat Commun. 2015:6;8143.
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syncytial virus fusion protein offer unique possibilities for clinical intervention. Proc Natl Acad Sci U S A. 
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Marcy S, Kohl K, Dagan R, et al. Fever as an adverse event following immunization: case definition and
guidelines of data collection, analysis, and presentation. Vaccine. 2004:22;551-556.
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Milligan I, Gibani M, Sewell R, et al. Safety and immunogenicity of novel adenovirus type 26- and modified 
vaccinia ankara-vectored ebola vaccines: a randomized clinical trial. JAMA. 2016:315;1610-1623.
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Moghaddam A, Olszewska W, Wang B, et al. A potential molecular mechanism for hypersensitivity caused 
by formalin-inactivated vaccines. Nat Med. 2006:12;905-907.
29.
Ngwuta J, Chen M, Modjarrad K, et al. Prefusion F-specific antibodies determine the magnitude of RSV 
neutralizing activity in human sera. Sci Transl Med. 2015:7;309ra162.
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[No authors listed] Dose, Safety, Tolerability and Immunogenicity of a Stabilized Prefusion RSV F Subunit 
Protein Vaccine, VRC-RSVRGP084-00-VP (DS-Cav1), Alone or With Alum Adjuvant, in Healthy Adults. 
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Accessed on 18 January 2018.
31.
Ouedraogo A, Tiono A, Kargougou D, et al. A phase 1b randomized, controlled, double-blinded dosage-
escalation trial to evaluate the safety, reactogenicity and immunogenicity of an adenovirus type 35 based 
circumsporozoite malaria vaccine in Burkinabe healthy adults 18 to 45 years of age. PLoS One. 
2013:8;e78679.
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Shay D, Holman R, Newman R, et al. Bronchiolitis-associated hospitalizations among US children, 1980-
1996. JAMA. 1999:282;1440-1446.
33.
Stockman L, Curns A, Anderson L, Fischer-Langley G. Respiratory syncytial virus-associated 
hospitalizations among infants and young children in the United States, 1997-2006. Pediatr Infect Dis J. 
2012:31;5-9.
34.
Talley A, Healy S, Salas C, et al. Safety and preliminary efficacy of CS-based recombinant adenoviral 
serotype 35 and serotype 26 malaria vaccine candidates in prime-boost vaccination of healthy adults 
undergoing subsequent experimental P. falciparum sporozoite challenge. Abstract presented at: 61st ASTMH 
Meeting, November 11-15, 2012; Atlanta, GA, USA. 
35.
Thompson W, Shay D, Weintraub E, et al. Mortality associated with influenza and respiratory syncytial virus 
in the United States. JAMA. 2003:289;179-186.

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36.
US Department of Health and Human Services. Office for Human Research Protections - OHRP Expedited 
Review Categories (1998). Available at: http://www.hhs.gov/ohrp/regulations-and-
policy/guidance/categories-of-research-expedited-review-procedure-1998/index html. Accessed on 18
January 2018.
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US Food and Drug Administration. Conditions for IRB Use of Expedited Review. Available at: 
https://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/GuidancesInformationSheetsan
dNotices/ucm118099 htm. Accessed on 18 January 2018.

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Attachment 1: Toxicity Tables
Adapted from the FDA Guidance document “Toxicity Grading Scale for Healthy Adult and 
Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials” (September 2007).

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A: Tables for Clinical Abnormalities
Local Reaction to
Injectable Product
Mild
(Grade 1)
Moderate
(Grade 2)
Severe
(Grade 3)
Potentially Life-threatening
(Grade 4)
Pain
Does not interfere
with activity
Repeated use of 
non-narcotic
pain reliever
> 24 hours or
interferes with
activity
Any use of
narcotic pain
reliever or
prevents daily
activity
Emergency room
(ER) visit or
hospitalization
Tenderness
Mild discomfort 
to
Touch
Discomfort with
Movement
Significant
discomfort at rest
ER visit or
Hospitalization
Erythema/redness*
2.5 – 5 cm
5.1 – 10 cm
> 10 cm
Necrosis or
exfoliative
dermatitis
Induration/swelling**
2.5 – 5 cm and
does not interfere
with activity
5.1 – 10 cm or
interferes with
activity
> 10 cm or
prevents daily
activity
Necrosis
* In addition to grading the measured local reaction at the greatest single diameter, the measurement should be recorded as a
continuous variable.
** Induration/Swelling should be evaluated and graded using the functional scale as well as the actual measurement.
Vital Signs *
Mild
(Grade 1)
Moderate
(Grade 2)
Severe
(Grade 3)
Potentially Life-threatening
(Grade 4)
Fever** (°C)
Fever** (°F)
38.0 – 38.4
100.4 – 101.1
38.5 – 38.9
101.2 – 102.0
39.0 – 40
102.1 – 104
> 40
> 104
Tachycardia - beats per 
minute
101 – 115
116 – 130
> 130
ER visit or hospitalization for 
arrhythmia
Bradycardia - beats per 
minute***
50 – 54
45 – 49
< 45
ER visit or hospitalization for 
arrhythmia
Hypertension (systolic) 
- mm Hg****
141 – 150
151 – 160
> 160
ER visit or hospitalization for 
malignant hypertension
Hypertension 
(diastolic) - mm Hg
91 – 95
96 – 100
> 100
ER visit or hospitalization for 
malignant hypertension
Hypotension (systolic) 
- mm Hg
85 – 89
80 – 84
< 80
ER visit or hospitalization for 
hypotensive shock
Respiratory rate -
breaths per minute
17 – 20
21 – 25
> 25
Intubation
* 
Participant should be at rest for all vital sign measurements.
** 
Oral body temperature; no recent hot or cold beverages or smoking.
***
When resting heart rate is between 60 and 100 beats per minute. Use clinical judgment when characterizing bradycardia 
among some healthy participant populations, for example, conditioned athletes.
**** Revised by the sponsor.

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Systemic
(General)
Mild
(Grade 1)
Moderate
(Grade 2)
Severe
(Grade 3)
Potentially Life-threatening 
(Grade 4)
Nausea/vomiting
No interference 
with activity or
1 - 2 episodes/24 
hours
Some interference 
with activity or 
> 2 episodes/24 
hours
Prevents daily 
activity, requires 
outpatient IV 
hydration
ER visit or hospitalization for 
hypotensive shock
Diarrhea
2 - 3 loose stools 
or < 400 gms/24 
hours
4 - 5 stools or
400 - 800 gms/24 
hours
6 or more watery 
stools or 
> 800 gms/24 
hours or requires 
outpatient IV 
hydration
ER visit or hospitalization
Headache
No interference 
with activity
Repeated use of 
non-narcotic pain 
reliever > 24 hours 
or some 
interference with 
activity
Significant; any 
use of narcotic 
pain reliever or 
prevents daily 
activity
ER visit or hospitalization
Fatigue
No interference 
with activity
Some interference 
with activity
Significant; 
prevents daily 
activity
ER visit or hospitalization
Myalgia
No interference 
with activity
Some interference 
with activity
Significant; 
prevents daily 
activity
ER visit or hospitalization
Systemic Illness
Mild
(Grade 1)
Moderate
(Grade 2)
Severe
(Grade 3)
Potentially Life-threatening 
(Grade 4)
Illness or clinical 
adverse event (as 
defined according to 
applicable regulations)
Awareness of 
symptoms that 
are easily 
tolerated, causing 
minimal 
discomfort and 
not interfering 
with everyday 
activities
Sufficient 
discomfort is 
present to cause 
interference with 
normal activity
Extreme distress, 
causing 
significant 
impairment of 
functioning or 
incapacitation. 
Prevents normal 
everyday 
activities
Symptoms causing inability to 
perform basic self-care 
functions OR medical or 
operative intervention 
indicated to prevent permanent 
impairment, persistent 
disability

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B: Tables for Laboratory Abnormalities
The grading scale used for laboratory assessments is based on the FDA Guidance document “Toxicity 
Grading Scale from Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical 
Trials”. Any laboratory value shown as a “graded” value in the table that is within the central laboratory
normal ranges will not be graded for severity or recorded as an AE. For hemoglobin, both the actual value 
and the change from reference will be graded. For the change from reference, the corresponding actual 
value should also be at least Grade 1.
Serum *
Mild
(Grade 1)
Moderate
(Grade 2)
Severe
(Grade 3)
Potentially Life-
threatening
(Grade 4) **
Sodium -
hyponatremia - mEq/L
132 – 134
130 – 131
125 – 129
< 125
Sodium -
hypernatremia -
mEq/L
144 – 145
146 – 147
148 – 150
> 150
Potassium -
hyperkalemia - mEq/L
5.1 – 5.2
5.3 – 5.4
5.5 – 5.6
> 5.6
Potassium -
hypokalemia - mEq/L
3.5 – 3.6
3.3 – 3.4
3.1 – 3.2
< 3.1
Glucose -
hypoglycemia - mg/dL
65 – 69
55 – 64
45 – 54
< 45
Glucose -
hyperglycemia fasting 
- mg/dL
100 – 110
111 – 125
> 125
Insulin requirements 
or hyperosmolar 
coma
Random glucose -
mg/dL
110 – 125
126 – 200
> 200
Blood urea nitrogen 
BUN - mg/dL
23 – 26
27 – 31
> 31
Requires dialysis
Creatinine - mg/dL
1.5 – 1.7
1.8 – 2.0
2.1 – 2.5
> 2.5 or requires 
dialysis
Calcium -
hypocalcemia - mg/dL
8.0 – 8.4
7.5 – 7.9
7.0 – 7.4
< 7.0
Calcium -
hypercalcemia - mg/dL
10.5 – 11.0
11.1 – 11.5
11.6 – 12.0
> 12.0
Magnesium -
hypomagnesemia -
mg/dL
1.3 – 1.5
1.1 – 1.2
0.9 – 1.0
< 0.9
Phosphorous -
hypophosphatemia -
mg/dL
2.3 – 2.5
2.0 – 2.2
1.6 – 1.9
< 1.6
CPK - mg/dL
1.25 – 1.5 x ULN*** 1.6 – 3.0 x ULN
3.1 –10 x ULN
> 10 x ULN
Albumin -
Hypoalbuminemia -
g/dL
2.8 – 3.1
2.5 – 2.7
< 2.5
--

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Serum *
Mild
(Grade 1)
Moderate
(Grade 2)
Severe
(Grade 3)
Potentially Life-
threatening
(Grade 4) **
Total protein -
hypoproteinemia -
g/dL
5.5 – 6.0
5.0 – 5.4
< 5.0
--
Alkaline phosphate -
increase by factor
1.1 – 2.0 x ULN
2.1 – 3.0 x ULN
3.1 – 10 x ULN
> 10 x ULN
Liver function tests -
ALT, AST increase by 
factor
1.1 – 2.5 x ULN
2.6 – 5.0 x ULN
5.1 – 10 x ULN
> 10 x ULN
Bilirubin - when 
accompanied by any 
increase in liver 
function test increase 
by factor
1.1 – 1.25 x ULN
1.26 – 1.5 x ULN
1.51 – 1.75 x ULN
> 1.75 x ULN
Bilirubin – when liver 
function test is normal; 
increase by factor
1.1 – 1.5 x ULN
1.6 – 2.0 x ULN
2.0 – 3.0 x ULN
> 3.0 x ULN
Cholesterol
201 – 210
211 – 225
> 226
--
Pancreatic enzymes -
amylase, lipase
1.1 – 1.5 x ULN
1.6 – 2.0 x ULN
2.1 – 5.0 x ULN
> 5.0 x ULN
* The laboratory values provided in the tables serve as guidelines and are dependent upon central laboratory normal parameters. 
Central laboratory normal reference ranges should be provided to demonstrate that they are appropriate.
** The clinical signs or symptoms associated with laboratory abnormalities might result in characterization of the laboratory
abnormalities as potentially life-threatening (Grade 4). For example, a low sodium value that falls within a Grade 3 parameter (125-
129 mE/L) should be recorded as a Grade 4 hyponatremia event if the participant had a new seizure associated with the low sodium 
value.
*** ULN is the upper limit of the normal range.

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Hematology *
Mild
(Grade 1)
Moderate
(Grade 2)
Severe
(Grade 3)
Potentially Life-
threatening
(Grade 4) **
Hemoglobin (female) -
gm/dL
11.0 – 12.0
9.5 – 10.9
8.0 – 9.4
< 8.0
Hemoglobin (female) 
change from baseline 
value - gm/dL
Any decrease – 1.5
1.6 – 2.0
2.1 – 5.0
> 5.0
Hemoglobin (male) -
gm/dL
12.5 – 13.5
10.5 – 12.4
8.5 – 10.4
< 8.5
Hemoglobin (male) 
change from baseline 
value - gm/dL
Any decrease – 1.5
1.6 – 2.0
2.1 – 5.0
> 5.0
WBC increase -
cell/mm3
10,800 – 15,000
15,001 – 20,000
20,001 – 25,000
> 25,000
WBC decrease -
cell/mm3
2,500 – 3,500
1,500 – 2,499
1,000 – 1,499
< 1,000
Lymphocytes decrease 
- cell/mm3
750 – 1,000
500 – 749
250 – 499
< 250
Neutrophils decrease -
cell/mm3
1,500 – 2,000
1,000 – 1,499
500 – 999
< 500
Eosinophils - cell/mm3
650 – 1,500
1,501 – 5,000
> 5,000 
Hypereosinophilic
Platelets decreased -
cell/mm3
125,000 – 140,000
100,000 – 124,000
25,000 – 99,000
< 25,000
PT - increase by factor 
(prothrombin time)
1.0 – 1.10 x ULN** 
1.11 – 1.20 x ULN
1.21 – 1.25 x ULN
> 1.25 ULN
PTT - increase by 
factor (partial 
thromboplastin time)
1.0 – 1.2 x ULN
1.21 – 1.4 x ULN
1.41 – 1.5 x ULN
> 1.5 x ULN
Fibrinogen increase -
mg/dL
400 – 500
501 – 600
> 600
--
Fibrinogen decrease -
mg/dL
150 – 200
125 – 149
100 – 124
< 100 or associated 
with gross bleeding 
or disseminated 
intravascular 
coagulation (DIC)
* The laboratory values provided in the tables serve as guidelines and are dependent upon central laboratory normal parameters. 
Central laboratory normal reference ranges should be provided to demonstrate that they are appropriate.
** ULN is the upper limit of the normal range.