A Randomized, Controlled, Observer-blind, Phase 1/2a Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of Ad26.RSV.preF in RSV-seronegative Toddlers 12 to 24 Months of Age
Phase: PHASE1
Conditions: Respiratory Syncytial Virus
Sponsor: Janssen Vaccines & Prevention B.V.

CONFIDENTIAL – FOIA Exemptions Apply in U.S.
1
Status: Approved, Date: 25 May 2020
Janssen Vaccines & Prevention B.V.
Clinical Protocol
A Randomized, Controlled, Observer-blind, Phase 1/2a Study to Evaluate the Safety, 
Reactogenicity, and Immunogenicity of Ad26.RSV.preF in RSV-seronegative Toddlers 12 
to 24 Months of Age
Protocol VAC18194RSV2002; Phase 1/2a
Amendment 6
VAC18194 (Ad26.RSV.preF)
EudraCT Number: 2017-003859-36
Status:
Approved
Date:
25 May 2020
Prepared by:
Janssen Vaccines & Prevention B.V.
EDMS number:
EDMS-ERI-148616815, 18.0
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.
NCT03606512

VAC18194 (Ad26.RSV.preF)
Clinical Protocol VAC18194RSV2002 Amendment 6
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Status: Approved, Date: 25 May 2020
TABLE OF CONTENTS
TABLE OF CONTENTS ............................................................................................................................... 2
LIST OF ATTACHMENTS............................................................................................................................ 4
LIST OF IN-TEXT TABLES AND FIGURES................................................................................................ 5
PROTOCOL AMENDMENTS....................................................................................................................... 6
SYNOPSIS.................................................................................................................................................. 14
TIME AND EVENTS SCHEDULE .............................................................................................................. 25
ABBREVIATIONS ...................................................................................................................................... 29
1.
INTRODUCTION................................................................................................................................ 30
1.1.
Background .................................................................................................................................... 31
1.2.
Nimenrix ......................................................................................................................................... 35
1.3.
Overall Rationale for the Study...................................................................................................... 36
2.
OBJECTIVES, ENDPOINTS, AND HYPOTHESIS........................................................................... 36
2.1.
Objectives and Endpoints .............................................................................................................. 36
2.1.1.
Objectives ................................................................................................................................... 36
2.1.2.
Endpoints.................................................................................................................................... 37
2.2.
Hypothesis ..................................................................................................................................... 39
3.
STUDY DESIGN AND RATIONALE ................................................................................................. 39
3.1.
Overview of Study Design.............................................................................................................. 39
3.2.
Study Design Rationale.................................................................................................................. 46
3.3.
Risk/Benefit Section....................................................................................................................... 47
3.3.1.
Known Benefits........................................................................................................................... 47
3.3.2.
Potential Benefits........................................................................................................................ 47
3.3.3.
Known Risks............................................................................................................................... 47
3.3.4.
Potential Risks............................................................................................................................ 48
3.3.5.
Overall Benefit/Risk Assessment ............................................................................................... 50
4.
SUBJECT POPULATION.................................................................................................................. 52
4.1.
Inclusion Criteria ............................................................................................................................ 52
4.2.
Exclusion Criteria ........................................................................................................................... 53
4.3.
Prohibitions and Restrictions ......................................................................................................... 55
5.
STUDY VACCINE ALLOCATION AND BLINDING.......................................................................... 55
6.
DOSAGE AND ADMINISTRATION .................................................................................................. 57
7.
STUDY VACCINE COMPLIANCE .................................................................................................... 58
8.
PRE-STUDY AND CONCOMITANT THERAPY ............................................................................... 58
9.
STUDY EVALUATIONS .................................................................................................................... 59
9.1.
Study Procedures........................................................................................................................... 59
9.1.1.
Overview..................................................................................................................................... 59
9.1.2.
Visit Windows ............................................................................................................................. 60
9.1.3.
Screening and Study Visits......................................................................................................... 60
9.1.3.1.
Screening Phase: Days -42 to 1.............................................................................................. 60
9.1.3.2.
Vaccination Phase: Day 1 to Day 239..................................................................................... 62
9.1.3.2.1.
Vaccination (Days 1, 29, and 57)......................................................................................... 62

VAC18194 (Ad26.RSV.preF)
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Status: Approved, Date: 25 May 2020
9.1.3.2.2.
Post-vaccination Follow-Up.................................................................................................. 63
9.1.3.2.2.1.
Post-first, Post-second and Post-third Vaccination Follow-Up ......................................... 63
9.1.3.2.2.2.
Post-last Vaccination Follow-Up ....................................................................................... 64
9.1.3.2.3.
End of RSV Season Visit ..................................................................................................... 64
9.1.3.2.4.
Early Withdrawal: Early Exit Visit ......................................................................................... 64
9.1.3.3.
Safety Follow-up...................................................................................................................... 65
9.2.
Study Evaluations .......................................................................................................................... 65
9.2.1.
Immunogenicity........................................................................................................................... 65
9.2.2.
RTI Procedures........................................................................................................................... 66
9.2.3.
Safety Evaluations...................................................................................................................... 70
9.2.3.1.
Vital Signs................................................................................................................................ 72
9.2.3.2.
Physical Examination .............................................................................................................. 72
9.2.4.
Other Evaluations ....................................................................................................................... 72
10.
SUBJECT COMPLETION/DISCONTINUATION OF STUDY VACCINE/ WITHDRAWAL
FROM THE STUDY ........................................................................................................................... 72
10.1.
Completion ..................................................................................................................................... 72
10.2.
Discontinuation of Study Vaccine/Withdrawal from the Study....................................................... 72
10.3.
Contraindications to Vaccination.................................................................................................... 74
11.
STATISTICAL METHODS................................................................................................................. 74
11.1.
Analysis Sets.................................................................................................................................. 74
11.2.
Sample Size Determination ........................................................................................................... 75
11.3.
Criteria for Endpoints of RSV Infection .......................................................................................... 76
11.3.1.
Definitions for Endpoints of RSV Infection.................................................................................. 76
11.3.1.1.
Definitions of Severe RSV-LRTI.............................................................................................. 76
11.3.1.2.
Presence of Severe RSV-LRTI as Assessed by the Clinical Endpoint Committee 
(CEC)....................................................................................................................................... 76
11.3.1.3.
Monitoring Rule for Severe RSV-LRTI .................................................................................... 77
11.3.2.
Definitions of RSV MA-RTI ......................................................................................................... 78
11.4.
Subject Information ........................................................................................................................ 78
11.5.
Immunogenicity Analyses .............................................................................................................. 78
11.6.
RSV Infection ................................................................................................................................. 79
11.7.
Safety Analyses ............................................................................................................................. 79
11.8.
Planned Analyses .......................................................................................................................... 80
11.9.
Data Review Committees............................................................................................................... 80
11.9.1.
Clinical Endpoint Committee (CEC) ........................................................................................... 80
11.9.2.
Independent Data Monitoring Committee (IDMC) ...................................................................... 81
11.10.
Study Vaccination Pausing Rules .................................................................................................. 81
12.
ADVERSE EVENT REPORTING ...................................................................................................... 83
12.1.
Definitions ...................................................................................................................................... 83
12.1.1.
Adverse Event Definitions and Classifications ........................................................................... 83
12.1.2.
Attribution Definitions.................................................................................................................. 85
12.1.3.
Severity Criteria .......................................................................................................................... 85
12.2.
Special Reporting Situations.......................................................................................................... 86
12.3.
Procedures..................................................................................................................................... 86
12.3.1.
All Adverse Events...................................................................................................................... 86
12.3.2.
Serious Adverse Events ............................................................................................................. 88
12.4.
Contacting Sponsor Regarding Safety........................................................................................... 89
13.
PRODUCT QUALITY COMPLAINT HANDLING.............................................................................. 89
13.1.
Procedures..................................................................................................................................... 89
13.2.
Contacting Sponsor Regarding Product Quality ............................................................................ 89
14.
STUDY VACCINE INFORMATION ................................................................................................... 89
14.1.
Physical Description of Study Vaccine........................................................................................... 89

VAC18194 (Ad26.RSV.preF)
Clinical Protocol VAC18194RSV2002 Amendment 6
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Status: Approved, Date: 25 May 2020
14.2.
Packaging and Labeling................................................................................................................. 90
14.3.
Storage and Handling .................................................................................................................... 90
14.4.
Vaccine Accountability ................................................................................................................... 91
15.
STUDY-SPECIFIC MATERIALS....................................................................................................... 91
16.
ETHICAL ASPECTS ......................................................................................................................... 92
16.1.
Study-Specific Design Considerations........................................................................................... 92
16.2.
Regulatory Ethics Compliance....................................................................................................... 93
16.2.1.
Investigator Responsibilities ....................................................................................................... 93
16.2.2.
Independent Ethics Committee or Institutional Review Board ................................................... 93
16.2.3.
Informed Consent ....................................................................................................................... 94
16.2.4.
Privacy of Personal Data ............................................................................................................ 95
16.2.5.
Long-Term Retention of Samples for Additional Future Research ............................................ 96
16.2.6.
Country Selection ....................................................................................................................... 96
17.
ADMINISTRATIVE REQUIREMENTS .............................................................................................. 96
17.1.
Protocol Amendments.................................................................................................................... 96
17.2.
Regulatory Documentation ............................................................................................................ 97
17.2.1.
Regulatory Approval/Notification ................................................................................................ 97
17.2.2.
Required Pre-study Documentation ........................................................................................... 97
17.3.
Subject Identification, Enrollment, and Screening Logs ................................................................ 98
17.4.
Source Documentation................................................................................................................... 98
17.5.
Case Report Form Completion ...................................................................................................... 99
17.6.
Data Quality Assurance/Quality Control ........................................................................................ 99
17.7.
Record Retention ........................................................................................................................... 99
17.8.
Monitoring .................................................................................................................................... 100
17.9.
Study Completion/Termination..................................................................................................... 100
17.9.1.
Study Completion/End of Study................................................................................................ 100
17.9.2.
Study Termination..................................................................................................................... 101
17.10.
On-Site Audits .............................................................................................................................. 101
17.11.
Use of Information and Publication.............................................................................................. 101
REFERENCES.......................................................................................................................................... 103
INVESTIGATOR AGREEMENT ............................................................................................................... 113
LIST OF ATTACHMENTS
Attachment 1:
Toxicity Tables ............................................................................................................. 106
Attachment 2:
Vaccination of Subjects From the Control Group With the Licensed Vaccine 
Nimenrix....................................................................................................................... 110
Attachment 3:
Guidance on Study Conduct during the COVID-19 Pandemic.................................... 111

VAC18194 (Ad26.RSV.preF)
Clinical Protocol VAC18194RSV2002 Amendment 6
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Status: Approved, Date: 25 May 2020
LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1:
Study Design VAC18194RSV2002........................................................................................... 17
Table 2:
Summary of Immunogenicity Assays (Humoral) ...................................................................... 20
Table 3:
Summary of Immunogenicity Assays (Cellular)........................................................................ 20
Table 4:
Study Design VAC18194RSV2002........................................................................................... 40
Table 5:
Summary of Immunogenicity Assays (Humoral) ...................................................................... 65
Table 6:
Summary of Immunogenicity Assays (Cellular)........................................................................ 66
Table 7:
Probability of Observing at Least One Adverse Event at a Given True Adverse Event 
Rate........................................................................................................................................... 76
FIGURES
Figure 1:
Schematic Overview of the Study............................................................................................. 45
Figure 2:
Procedures in the Event of a Respiratory Tract Infection or Otitis Media Case ....................... 69

VAC18194 (Ad26.RSV.preF)
Clinical Protocol VAC18194RSV2002 Amendment 6
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Status: Approved, Date: 25 May 2020
PROTOCOL AMENDMENTS
Protocol Version 
Issue Date
Original Protocol
21 December 2017
Amendment 1
06 April 2018
Amendment 2
13 July 2018
Amendment 3
07 November 2018
Amendment 4
08 April 2019
Amendment 5
05 July 2019
Amendment 6
25 May 2020
Amendment 6 (Issued date: 25 May 2020)
The overall reason for the amendment:
This protocol amendment is made primarily to reduce the overall number of RSV-seronegative toddlers in the study 
from 48 to 36. The reduction is made because of difficulties in recruiting seronegative toddlers due to a higher than 
expected seropositivity rate in the 12-24 month age group.
The table below gives an overview of the rationale for each change and all affected sections
Rationale: To reduce the overall number of RSV-seronegative toddlers in the study from 48 to 36.
Synopsis: Overview of Study Design
3.1 Overview of Study Design
11.2 Sample Size Determination
Rationale: Clarification that all concomitant medications utilized during an RTI or OM case will be collected, 
including outside of the 28-day post-vaccination period.
Synopsis: Safety Evaluations
Time and Events Schedule
3.1 Overview of Study Design
8 Pre-study and concomitant therapy
Rationale: Clarification that any RTI or OM case should be assessed and reported to the sponsor as an AE 
between the time of study vaccination through the following 28 days even if the event was not medically-
attended and happened outside of the RSV season.
9.2.2 RTI Procedures (Figure 2)
Rationale: To add guidance on study conduct during the COVID-19 pandemic
Time and Events Schedule
Attachment 3: Guidance on Study Conduct during the COVID-19 Pandemic

VAC18194 (Ad26.RSV.preF)
Clinical Protocol VAC18194RSV2002 Amendment 6
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Status: Approved, Date: 25 May 2020
Amendment 5 (Issued date: 05 July 2019)
The overall reason for the amendment:
This amendment is made to align the global protocol with changes made following requests from the German 
Health Authority:

Clarification is added that the consent of both parents/legal guardians will be required in countries where this 
is specified by local regulation;

Clarification is added on the reporting of any RTI or case of otitis media fulfilling the criterion of an SAE: all 
RTIs and cases of otitis media meeting seriousness criteria will be reported as SAEs; any RTI or case of otitis 
media reported as an (S)AE that is found to be positive for RSV will be excluded from the analyses of (S)AEs. 
However, the case will remain in the clinical database and will be tabulated separately in the clinical study 
report;

Update of the monitoring rule for severe RSV-LRTI to reduce the numbers of events required to start an 
analysis from 3 to 2.
The table below gives an overview of the rationale for each change and all affected sections
Rationale: To clarify that in countries where local regulation requires that both parents/legal guardians give 
consent, this will be applicable.
4.1 Inclusion Criteria
9.1.3.1 Screening Phase: Days -42 to 1
16.1 Study-Specific Design Considerations
16.2.3 Informed Consent
16.2.4 Privacy of Personal Data
Rationale: To clarify the reporting of any RTI or case of otitis media fulfilling the criterion of an SAE.
Synopsis: RTI Procedures
Time and Events Schedule
9.2.2 RTI Procedures
11.6 RSV Infection
11.7 Safety Analyses
12.1.1 Adverse Event Definitions and Classifications
Rationale: Update of the monitoring rule for severe RSV-LRTI to reduce the numbers of events required to start 
an analysis from 3 to 2.
Synopsis: Statistical Methods
11.3.1.3 Monitoring Rule for Severe RSV-LRTI
Rationale: In addition, other minor changes, clarifications, and corrections were made throughout the protocol.
Amendment 4 (Issued date: 08 April 2019)
The overall reason for the amendment: To introduce more active follow-up of ongoing RTIs/otitis media cases to 
capture the potential worsening of RTI/otitis media cases that are reported as not severe during the initial RTI visit 
and to clarify the responsibilities of the CEC in terms of evaluation of RTI cases and severity grading of RTIs.
Updates and clarifications are made as specified below.
The table below gives an overview of the rationale for each change and all affected sections
Rationale: To introduce active follow-up of ongoing RTIs/otitis media cases to capture the potential worsening of 
RTI/otitis media cases that are reported as not severe during the initial RTI visit.

VAC18194 (Ad26.RSV.preF)
Clinical Protocol VAC18194RSV2002 Amendment 6
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Status: Approved, Date: 25 May 2020
Synopsis: RTI Procedures
Time and Events Schedule
9.2.2 RTI Procedures
Rationale: To clarify the responsibilities of the CEC in terms of evaluation of RTI cases and severity grading of 
RTIs in line with their responsibilities in the ongoing pediatric RSV study VAC18194RSV2001. Following items 
will be removed from the responsibility of the CEC: (i) the assessment of RSV positivity if a test result for RSV is 
missing, as an RTI will not be considered RSV-related in that case, and (ii) severity evaluation of all RTI and otitis 
media cases, as the severity evaluation of all cases will be performed by the PI(s).The CEC will confirm RTIs 
considered severe by the PI(s) by reviewing all available clinical information related to the cases.
Synopsis: Objectives, Endpoints, and Hypothesis; Overview of Study Design
2.1.2 Endpoints
3.1 Overview of Study Design
11.3.1.2 Presence of Severe RSV-LRTI as Assessed by the Clinical Endpoint Committee (CEC)
11.3.2 Definitions of RSV MA-RTI
11.3.3 Definitions of RSV RTI and LRTI
11.9.1 Clinical Endpoint Committee (CEC)
Rationale: To clarify that EIA cut-off criterion for seronegativity is a titer <1 EIA unit and that a cut-off for 
seropositivity is not applicable in this study. Only subjects with a titer <1 that meet the in- and exclusion criteria will 
be enrolled in the study.
Synopsis: Overview of Study Design
3.1 Overview of Study Design
9.1.3.1 Screening Phase: Days -42 to 1
Rationale: Clarification that vaccination with Nimenrix on Day 57 (replacing the third placebo dose) for subjects in 
the control group is optional. For these subjects, placebo (0.9% saline) will be replaced with Nimenrix as the Day 57 
vaccination, only if permitted by the subject’s parent/legal guardian and following PI assessment on a case-by-case 
basis as vaccination with Nimenrix outside this study might be preferred (joint parent/legal guardian and PI 
decision).
Synopsis: Overview of Study Design; Dosage and Administration
3.1 Overview of Study Design
3.3.1 Known Benefits
6 Dosage and Administration
Attachment 2
Rationale: To introduce the Participant Experience Survey that parents/legal guardians or caregivers of each study 
subject will be invited to complete at the final study visit.
Synopsis: Other Evaluations
Time and Events Schedule
9.1.3.2.3End of RSV Season Visit
9.2.4 Qualitative Interviews
15 Study-specific Materials
Rationale: To introduce the rationale for incorporating vaccination with Nimenrix® as an alternative for the Day 57 
vaccination with placebo (0.9% saline) for subjects in the control group.
1.2 Nimenrix
3.2 Study Design Rationale 
Rationale: Clarification that eCRF entry is the primary pathway for reporting SAEs in this study.
12.3.2 Serious Adverse Events

VAC18194 (Ad26.RSV.preF)
Clinical Protocol VAC18194RSV2002 Amendment 6
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Status: Approved, Date: 25 May 2020
Rationale: Removal of the requirement for surveillance of primary care physicians, and/or hospitals’ urgent care 
facilities to monitor for subjects seeking medical attention for an RTI as adequate follow-up of RTI cases is ensured 
by introducing follow-up phone calls every 2 days and requesting subjects to notify sites in the event of worsening
symptoms. This will enable closer follow-up of cases and prospective capture of medical seeking behaviors.
3.3.5 Overall Benefit/Risk Assessment
9.2.2 RTI Procedures
Rationale: Specification that for severe RTI events, expedited handling (ie, shipment on day of collection) of nasal 
swabs and expedited data entry (ie, on the day of knowledge of the event) is required.
Synopsis: RTI Procedures
9.2.2 RTI Procedures
Rationale: Other minor changes, clarifications, and corrections made throughout the protocol.
Amendment 3 (Issued date: 07 November 2018)
The overall reason for the amendment: To incorporate vaccination with Nimenrix® as an alternative for the 
Day 57 vaccination with placebo (0.9% saline) for subjects in the control group (in accordance with the local label
and local regulations, and unless contra-indicated). The incorporation of a licensed vaccine as a control offers a 
more accepted approach to this pediatric vaccine study. Nimenrix has been selected for incorporation in the design 
of this study as it has an adverse events (AE) profile similar to the anticipated study vaccine AE profile, and the 
recommended one-dose vaccination in the targeted age group matches the existing study design, which is essential 
to preserve the blind in the current study.
Other updates and clarifications are made as specified below.
The table below gives an overview of the rationale for each change and all affected sections
Rationale: To incorporate Nimenrix as the Day 57 vaccination for subjects in the control group (in accordance with 
the local label and local regulations, and unless contra-indicated).
Synopsis: Overview of Study Design; Dosage and Administration
3.1 Overview of Study Design
3.3.2 Potential Benefits
3.3.3 Known Risks
3.3.5 Overall Benefit/Risk Assessment
6 Dosage and Administration
Attachment 2
Rationale: Clarification that the exclusion criterion for urticaria, eczema and atopic dermatitis relates to a moderate 
to severe history of these illnesses.
4.2 Exclusion Criteria
Rationale: Clarification that in the event of an ongoing AE or other situation precluding subject vaccination within 
10 days, subjects may be vaccinated beyond the 10-day window at the discretion of the sponsor.
Time and Events Schedule
3.3.5 Overall Benefit/Risk Assessment
9.1.3.2.1 Vaccination (Days 1, 29, and 57)
10.3 Contraindications to Vaccination
Rationale: Clarification that for cases of otitis media that occur during the study, the procedures are similar as for 
RTIs that occur during the study.

VAC18194 (Ad26.RSV.preF)
Clinical Protocol VAC18194RSV2002 Amendment 6
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Status: Approved, Date: 25 May 2020
Synopsis: Overview of Study Design; RTI Procedures
Time and Events Schedule
3.1 Overview of Study Design
9.2.2 RTI Procedures
Rationale: Specification that injections may also be administered in the deltoid muscle, only if required by local 
health authority guidance.
Synopsis: Dosage and Administration
6 Dosage and Administration
14.3 Storage and Handling
Rationale: Clarification that an interim analysis will be performed when all subjects have data of 1 RSV season 
post-Dose 1.
Synopsis: Statistical Methods
11.8 Planned Analyses
Rationale: Other minor changes, clarifications, and corrections made throughout the protocol.
Amendment 2 (Issued date: 13 July 2018)
The overall reason for the amendment: The protocol amendment is made to reduce the dose of Ad26.RSV.preF 
from 5×1010 vp to 2.5×1010 vp. In study VAC18194RSV2001 in RSV-seropositive toddlers, transient fevers were 
observed following initial dosing with 5×1010 vp of Ad26.RSV.preF in some subjects. Although the IDMC reviewed
the interim analysis when 12 toddlers had reached Day 8 post-dose 1, with the recommendation that 
VAC18194RSV2001 should continue unmodified, the sponsor decided to implement a dose reduction in the current 
study in RSV-seronegative toddlers. An expanded rationale is presented in Section 3.2. 
The table below gives an overview of the rationale for each change and all affected sections
Rationale: To reduce the dose of Ad26.RSV.preF from 5×1010 vp to 2.5×1010 vp.
Synopsis: Primary Objectives; Overview of Study Design; Dosage and Administration
1.2 Overall Rationale for the Study
2.1.1 Objectives
3.1 Overview of Study Design
3.2 Study Design Rationale
0 Potential Risks
6 Dosage and Administration
14.1 Physical Description of Study Vaccine
Rationale: Update of preclinical information.
1.1 Background
Rationale: Update of IDMC review criteria and data availability from VAC18194RSV2001 prior to dosing in the 
current study.
1.1 Background
Rationale: Correction of inconsistencies in the description of Formulation Buffer 2.
1.1 Background
Rationale: Update of study VAC18193RSV2003 status.
1.1 Background

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Status: Approved, Date: 25 May 2020
Rationale: Clarification that exclusion criterion for known allergies at screening refers to vaccines or vaccine 
components, but not to egg allergies.
4.2 Exclusion Criteria
Rationale: Clarification that telephone calls to subjects for RTI monitoring after the first dose will be made during 
both the vaccination and safety follow-up phases.
Synopsis: Overview of Study Design
Time and Events Schedule
3.1 Overview of Study Design
9.1.3.3 Safety Follow-up Phase
Rationale: Clarification that a mid-turbinate swab for RSV RT-PCR testing will also be collected from any subject 
with otitis media during the study, independent of other RTI symptoms.
Synopsis: Overview of Study Design; RTI Procedures
3.1 Overview of Study Design
9.2.2 RTI Procedures
Rationale: Clarification that the primary analysis at 28 days post-final dose and the interim analysis after 1 RSV 
season post-first dose will be in all subjects.
11.8 Planned Analyses
Amendment 1 (Issued date: 06 April 2018)
The overall reason for the amendment: The protocol amendment is made to remove seropositive subjects from 
the study so that seronegative toddlers can be evaluated independent of any findings that might occur in seropositive 
toddlers at the 1x1011 vp dose level. Also, the number of blood draws for immunogenicity is reduced from five to 
four for each subject. In addition, a 7-day safety review post-first dose by the principal investigator/study 
responsible physician/scientist in the first 8 subjects has been added.
In order to be able to administer two vaccine doses to subjects before the start of the RSV season, the subset of 
subjects in study VAC18194RSV2001 for whom safety data will be reviewed by the IDMC prior to dosing in the 
current study is reduced from 24 to 12. This reduction is supported by additional safety data that have been 
collected. Humoral immunogenicity data in RSV-experienced adults aged ≥60 years indicate Th1-skewed responses 
with no safety concerns. No differences in immunogenicity or safety are expected between RSV-seropositive 1-year 
old-toddlers and seropositive adults; no differences in safety (solicited/unsolicited AEs) are expected between 1-
year-old RSV-seropositive toddlers and RSV-seronegative toddlers. Additionally, preclinical data in RSV naïve 
animals indicate Th1-skewed responses, and show that Ad26.RSV.preF does not predispose to enhanced respiratory 
disease (ERD) after RSV challenge in cotton rats and mice.
The table below gives an overview of the rationale for each change and all affected sections
Rationale: Removal of the cohort of seropositive toddlers.

VAC18194 (Ad26.RSV.preF)
Clinical Protocol VAC18194RSV2002 Amendment 6
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Status: Approved, Date: 25 May 2020
Synopsis: Primary Objectives; Hypothesis; Overview of Study Design; Subject Population; Dosage and 
Administration; Statistical Methods
Time and Events Schedule
1 Introduction
1.2 Overall Rationale for the Study
2.1.1 Objectives
2.2 Hypothesis
3.1 Overview of Study Design
3.2 Study Design Rationale
3.3.5 Overall Benefit/Risk Assessment
4.1 Inclusion Criteria
5 Study Vaccine Allocation and Blinding
6 Dosage and Administration
9.1.3.2 Vaccination Phase: Day 1 to Day 239
9.1.3.3 Safety Follow-up Phase: After Day 239
10.1 Completion
11.1 Analysis Sets
11.2 Sample Size Determination
11.3.1.3 Monitoring Rule for Severe RSV-LRTI
11.10 Study Vaccination Pausing Rules
14.1 Physical Description of Study Vaccine
14.3 Storage and Handling
17.9.1 Study Completion/End of Study
Rationale: Removal of blood draws for immunogenicity at Days 29, 57 and 239; addition of study visit to include 
blood draw for immunogenicity at the end of the first RSV season after the first dose; addition of blood for cellular 
immunogenicity to the existing draw for humoral immunogenicity at Day 85. 
Synopsis: Overview of Study Design; Statistical Methods
Time and Events Schedule
3.1 Overview of Study Design
9.1.1 Overview
9.1.2 Visit Windows
9.1.3.2.3 End of RSV Season Visit
11.8 Planned Analyses
Rationale: In order to be able to dose subjects before the start of the RSV season, the subset of subjects in study 
VAC18194RSV2001 for whom safety data will be reviewed by the IDMC prior to dosing in the current study is 
reduced from 24 to 12.
1.1 Background
3.2 Study Design Rationale
Rationale: A 7-day safety review by the principal investigator/study responsible physician/scientist in the first 8 
subjects has been added to increase monitoring after the first dose. It is also clarified that the 7-day IDMC review in 
the first 12 subjects will be done without a pause in enrollment.
Synopsis
3.1 Overview of Study Design
3.3.5 Overall Benefit/Risk Assessment
Rationale: Added clarification that serostatus can be assessed via the RSV EIA if available from a different study. 
Synopsis
Time and Events Schedule
3.1 Overview of Study Design
4.1 Inclusion Criteria
9.1.3.1 Screening Phase

VAC18194 (Ad26.RSV.preF)
Clinical Protocol VAC18194RSV2002 Amendment 6
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
13
Status: Approved, Date: 25 May 2020
Rationale: Added requirement to assess oxygen saturation (SpO2) at each visit. 
Time and Events Schedule
9.1.3.1 Screening Phase
9.2.3.1 Vital Signs
Rationale: Added requirement to assess whether subjects are breastfeeding, with breastfeeding history, and whether 
family members smoke in the home environment, with smoking history. 
9.1.3.1 Screening Phase
Rationale: Clarification that subjects will not be automatically withdrawn from the study if consent is withdrawn 
only for blood draws; subjects may remain and continue to receive study vaccine and undergo safety follow-up. 
9.1.3.2.4 Early Withdrawal: Early Exit Visit
10.2 Discontinuation of Study Vaccine/Withdrawal from the Study
Rationale: Other minor corrections to remove inconsistencies. 
1.1 Background
4.2 Exclusion Criteria

VAC18194 (Ad26.RSV.preF)
Clinical Protocol VAC18194RSV2002 Amendment 6
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
14
Status: Approved, Date: 25 May 2020
SYNOPSIS
A Randomized, Controlled, Observer-blind, Phase
1/2a Study to Evaluate the Safety, 
Reactogenicity, and Immunogenicity of Ad26.RSV.preF in RSV-seronegative Toddlers 12 to 24 
Months of Age
The adenovirus-vectored vaccine candidate assessed in this study is:
Ad26.RSV.preF (JNJ-64400141), a replication-incompetent adenovirus serotype 26 (Ad26) containing a 
deoxyribonucleic acid (DNA) transgene that encodes for the pre-fusion conformation-stabilized F protein
(pre-F) derived from the respiratory syncytial virus (RSV) A2 strain.
OBJECTIVES, ENDPOINTS, AND HYPOTHESIS
Objectives
Primary Objective

To assess the safety and reactogenicity of an intramuscular regimen of 3 doses of 2.5×1010 viral 
particles (vp) of Ad26.RSV.preF in RSV-seronegative toddlers aged 12 to 24 months.
Secondary Objectives

To assess the humoral and cellular immune responses elicited by Ad26.RSV.preF as measured by 
virus neutralizing antibodies (VNAs), F protein binding antibodies (pre-F and/or post-F), and T-
helper (Th)1/Th2 subtyping.

To monitor for severe RSV-lower respiratory tract infection (LRTI) as a preliminary indication of 
enhanced respiratory disease (ERD).
Exploratory Objectives

To further assess the humoral and cellular immune responses elicited by Ad26.RSV.preF. The assays 
to be used can include, but may not be limited to, RSV strain cross-neutralization, RSV F protein 
antibody specificity characterization, RSV G and/or N protein binding antibodies, adenovirus 
neutralization assay, functional and molecular antibody characterization (eg, avidity and antibody
isotyping) and antibody sequencing if feasible, and evaluation of cellular immune response 
(interferon gamma [IFN-γ] enzyme-linked immunospot [ELISpot] assay, intracellular cytokine 
staining [ICS], cytokine analysis).

To assess RSV infection rates (symptomatic and asymptomic) in Ad26.RSV.preF and control
subjects.

To assess symptomatic RSV infection rates in Ad26.RSV.preF and control subjects.

To assess symptoms of respiratory illness via the Respiratory Tract Infection (RTI) Symptoms Form.
Primary Endpoints – Safety and Reactogenicity

Solicited local and systemic adverse events (AEs) for 7 days after each vaccination.

Unsolicited AEs for 28 days after each vaccination.

Serious adverse events (SAEs) from first dose administration to the end of the study.

VAC18194 (Ad26.RSV.preF)
Clinical Protocol VAC18194RSV2002 Amendment 6
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
15
Status: Approved, Date: 25 May 2020
Secondary Endpoints – Immune Responses
The analysis of the immunogenicity of the vaccine regimens will include the characterization of both 
humoral and cellular responses. The focus of the immunogenicity analysis will be on VNAs, F protein 
antibodies (pre-F and/or post-F), and Th1/Th2 cytokine profile response.
Humoral Immune Response

RSV neutralization A strain
Analysis of neutralizing antibodies to an A strain.

F protein antibodies (enzyme-linked immunosorbent assay [ELISA]; pre- and/or post-F)
Analysis of antibodies binding to RSV F protein in pre-fusion and/or post-fusion form.
Cell-mediated Immune Response

Flow cytometry (ICS)*
Analysis of T-cell responses to RSV F protein peptides for Th1/Th2 subtyping.
* Cytokine analysis for Th1/Th2 profiling will be done if no ICS can be generated due to an 
insufficient number of peripheral blood mononuclear cells (PBMCs) for ICS assay (see the 
Exploratory Endpoints below).
Secondary Endpoints – RSV Infection

Severe RSV-LRTI
Severe RSV-LRTI will be defined as the presence of severe LRTI as assessed by the Clinical 
Endpoint Committee (CEC), and confirmation of RSV infection from a nasal (mid-turbinate or 
nasopharyngeal) sample using independent reverse transcriptase polymerase chain reaction (RT-
PCR) by a central laboratory. If no central laboratory RT-PCR result is available, a positive test 
result for RSV from a local laboratory (if available) could be used to confirm RSV infection upon
evaluation by the CEC.
Exploratory Endpoints – Immune Responses
Exploratory analyses may be performed to evaluate the vaccine-elicited immune responses further. These 
can include, but may not be limited to, the following assays (as available and applicable):
Humoral Immune Response

RSV cross-neutralization of B and/or other A strain(s)
Assessment of the strain cross-neutralizing capacity of the vaccine-induced immune response.

F protein antibody specificity characterization
Assessment of pre-F and post-F specificity by binding or functional assays as ELISA, and/or 
competition ELISA, epitope mapping, and functional VNAs.

Nasal immunoglobulin antibodies to RSV F protein
Analysis of immunoglobulin IgA or IgG antibodies to RSV pre-F and/or post-F.

G and/or N protein antibodies (ELISA)
Assessment of antibodies binding to RSV G and/or N protein to estimate the RSV infection rate 
(symptomatic and asymptomatic) in the study.

Adenovirus neutralization assay
Assessment of neutralizing antibody responses against the adenoviral vector.

VAC18194 (Ad26.RSV.preF)
Clinical Protocol VAC18194RSV2002 Amendment 6
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
16
Status: Approved, Date: 25 May 2020

Functional and molecular antibody characterization
Functional characterization of antibodies may be performed: antibody-dependent cell-mediated 
cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). A molecular 
characterization of vaccine-elicited antibodies will include antibody avidity, other respiratory viral 
neutralizing or binding assays, immunoglobin isotype, functional VNAs to other respiratory viruses, 
and antibody assessments.
Cell-mediated Immune Response

ICS
Analysis of T-cell responses to RSV F protein peptide-stimulated PBMC (including, but not limited 
to, CD4+/CD8+, interleukin-2 [IL-2], IFN-γ, tumor necrosis factor alpha (TNF-α), activation 
markers and memory)

Cytokine analysis
Cytokine profiles of (in vitro) stimulated PBMC supernatant will be analyzed to assess the quantity 
and quality of elicited immune responses, including Th1/Th2 balance. The analysis can include, but 
may not be limited to, IFN-γ, IL-2, IL-4, IL-5, IL-13, and TNF-α.

IFN-γ ELISpot assay
An ELISpot assay is used to quantify the amount of PBMCs able to produce IFN-γ upon RSV F
protein peptide antigen stimulation.

Sequencing of the antibody repertoire will be done if feasible.
Exploratory Endpoints – RSV Infection

RSV-RTI and RSV-LRTI confirmed by RT-PCR.

Serology for, but not limited to, RSV protein G and/or N (and/or F) may be used to confirm exposure 
to RSV at the end of the season.
To detect RSV infections by serology, a fold increase will be applied to determine if a subject is a 
seroconverter based on G and/or N ELISA. Fold increases for RSV infection will be determined 
based on 2 consecutive blood samples as planned in the Time and Events Schedule.

RSV medically-attended respiratory tract infection (MA-RTI): includes all subjects with RSV-RTI 
that is medically-attended, ie, when the subject’s parent/legal guardian or caregiver seeks medical 
attention outside normal study procedures, including healthcare professional visits to the home, 
clinic visits, emergency room attendance, hospital admission.
Hypothesis
No formal statistical hypothesis is planned. The study will evaluate whether Ad26.RSV.preF is safe, well-
tolerated, and immunogenic in RSV-seronegative toddlers.
OVERVIEW OF STUDY DESIGN
This is a multi-center, randomized, observer-blind, Phase 1/2a study, to be conducted in 36 male and 
female RSV-seronegative toddlers aged ≥12 to ≤24 months.
Each subject’s RSV serostatus will be assessed by RSV enzyme immunoassay (EIA) at screeninga. Note: 
serostatus may be assessed via this assay if available from a different study of the sponsor
                                                
a
The cut-off for seronegativity is a titer <1 EIA unit.

VAC18194 (Ad26.RSV.preF)
Clinical Protocol VAC18194RSV2002 Amendment 6
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
17
Status: Approved, Date: 25 May 2020
(VAC18194RSV2001). If done within 42 days of first dose, this assessment would not have to be 
repeated in the absence of a history of respiratory infection during that period. Additionally, the 
seronegative status will be confirmed by the absence of an anamnestic humoral immune response (which 
is usually observed 7-10 days post antigen re-exposure in RSV seropositive subjects) from blood samples 
taken 7 days after the first dose.
Subjects will be randomized 1:1 to receive either Ad26/Ad26/Ad26 (at 2.5×1010
vp) or 
placebo/placebo/Nimenrix®b,c (or placebo/placebo/placebo) (Table 1).
Table 1:
Study Design VAC18194RSV2002
Group
Na
Day 1 
Day 29/Week 4 
Day 57/Week 8 
RSV-seronegative toddlers 12 to 24 months
Group 1
18
Ad26.RSV.preF (2.5×1010 vp)
Ad26.RSV.preF (2.5×1010 vp)
Ad26.RSV.preF (2.5×1010 vp)
Group 2
18
Placebo (saline)
Placebo (saline)
Nimenrix b or Placebo (saline)
N = number of subjects; vp = viral particles
a:
At the time of Amendment 6, 37 subjects have been enrolled.
b:
In countries where the commercial vaccine Nimenrix is licensed, placebo (0.9% saline) can be replaced with
Nimenrix as the Day 57 vaccination for the study subjects in the control group, in accordance with the local label
and local regulations, and unless contra-indicated. Nimenrix will be administered, only if permitted by the 
subject’s parent/legal guardian and following PI assessment on a case-by-case basis as vaccination with 
Nimenrix outside this study might be preferred (joint parent/legal guardian and PI decision). In the US, Nimenrix 
will not be used unless it has been licensed for use or an Investigational New Drug (IND) has been submitted.
An Independent Data Monitoring Committee (IDMC) will evaluate safety and reactogenicity data on a 
regular basis.
An independent, blinded CEC has been established for ongoing study VAC18194RSV2001 in RSV-
seropositive toddlers and all subsequent studies with Ad26.RSV.preF in children (including the current 
study), to assess suspected cases of severe LRTI and the occurrence of RSV infection.
The study will have 3 phases: a screening phase, a vaccination phase, and a safety follow-up phase
through 2 RSV seasons after the first dose. The durations of the respective phases are as follows:
                                                
b
In countries where the commercial vaccine Nimenrix is licensed, placebo (0.9% saline) can be replaced with Nimenrix as the 
Day 57 vaccination for the study subjects in the control group, in accordance with the local label and local regulations, and 
unless contra-indicated. Nimenrix will be administered, only if permitted by the subject’s parent/legal guardian and following 
PI assessment on a case-by-case basis as vaccination with Nimenrix outside this study might be preferred (joint parent/legal 
guardian and PI decision). In the US, Nimenrix will not be used unless it has been licensed for use or an IND has been 
submitted. It should be recorded in the eCRF by the unblinded pharmacist whether the subject was vaccinated with either 
Nimenrix or placebo on Day 57.
c
Nimenrix is a vaccine used to protect adults, adolescents, and children from the age of 6 weeks against invasive 
meningococcal disease caused by 4 groups of the bacterium Neisseria meningitidis (group A, C, W-135, and Y).12

VAC18194 (Ad26.RSV.preF)
Clinical Protocol VAC18194RSV2002 Amendment 6
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
18
Status: Approved, Date: 25 May 2020
Phase
Screening:
up to 6 weeks before the first dose
Vaccination:
34 weeks

dosing on Days 1, 29 and 57

safety follow-up through 6 months post-final 
dose

immunogenicity at:
pre-Dose 1 (Day 1)
7 days post-Dose 1 (Day 8)
28 days post-Dose 3 (Day 85)
end of the first RSV season after the first 
dose
Safety follow-up:
through 2 RSV seasons after the first dose
The end of the vaccination phase will be when the last subject completes the visit at 6 months after the 
final dose. The end of the study will be the last subject’s last visit (by telephone) at the end of the safety 
follow-up phase.
First-dose Safety
No sentinel approach is taken for the 2.5×1010 vp dose, as this dose is lower than the 5×1010 vp dose 
currently being evaluated in several other studies, including study VAC18193RSV1003 in adults aged 
≥60 years in stable health and study VAC18194RSV2001 in RSV-seropositive toddlers aged 12 to 24 
months.

The first 8 subjects will be enrolled and receive the first dose (Ad26.RSV.preF 2.5×1010 vp or 
placebo).

7-day safety in these first 8 subjects will be monitored by the principal investigator (PI[s]) or 
designee and the sponsor’s study responsible physician/scientist (SRP/S). In the event of a 
significant safety finding, the IDMC will be consulted.

4 more subjects will be enrolled and receive the first dose (Ad26.RSV.preF 2.5×1010 vp or placebo).

The IDMC will assess post-first dose reactogenicity by review of 7-day safety data for these first 12
subjects (6 subjects receiving Ad26.RSV.preF 2.5×1010 vp and 6 subjects receiving placebo).
Any safety finding will be closely monitored, although enrollment will not be paused for either the PI(s)/
SRP/S review of the first 8 subjects or the IDMC review of the first 12 subjects. 
If the IDMC review does not take place before the first subject receives the scheduled second or third
dose (due to potential slow recruitment), the PI(s) or designee and SRP/S will review the available data 
prior to the second or third dose being given as scheduled, respectively. In the event of a significant safety 
finding, the IDMC will be consulted.
In all post-first dose 7-day safety reviews, safety data for review will include solicited and unsolicited 
AEs and SAEs. 
Second-dose Safety
Safety assessments will also be made 7 days after the second dose in the first 12 toddlers before 
administering the second dose to the remaining toddlers. Post-second dose 7-day safety will be monitored 
by the PI(s) or designee and SRP/S. Safety data for review will include solicited and unsolicited AEs and 
SAEs. Any safety finding will be closely monitored, although dosing will not be paused for this PI(s) or 
designee and SRP/S review.

VAC18194 (Ad26.RSV.preF)
Clinical Protocol VAC18194RSV2002 Amendment 6
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
19
Status: Approved, Date: 25 May 2020
Third-dose Safety
Safety assessments will also be made 7 days after the third dose in the first 12 toddlers before 
administering the third dose to the remaining toddlers. Post-third dose 7-day safety will be monitored by 
the PI(s) or designee and SRP/S. Safety data for review will include solicited and unsolicited AEs and 
SAEs. Any safety finding will be closely monitored, although dosing will not be paused for this PI(s) or 
designee and SRP/S review.
Safety Follow-up
During the entire study after the first dose, including during the vaccination phase and safety follow-up 
phase, the subject’s parent/legal guardian or caregiver will be contacted periodically by telephone (or 
other communication, or by clinic visit) through 2 RSV seasons after the first dose (every 14 days ±3 days 
within the RSV season and every 30 days ±7 days outside of the season, unless the timing coincides with 
a visit). During the RSV season, these calls will remind the subject’s parent/legal guardian or caregiver to 
record signs and symptoms of RTI and otitis media on a specific RTI Symptoms Form (see below under 
‘RTI PROCEDURES’), and to contact the site at the time of symptom onset d. During and outside the 
RSV season, these calls will check for SAEs and associated concomitant medications, MA-RTIs, 
medically-attended otitis media cases, and any subsequent medical care that may have been sought, since 
the previous visit or telephone contact (this includes contacts with subjects who received at least one dose 
of study vaccine but withdrew from further dosing). The sponsor will provide the site with a checklist for
these follow-up phone calls.
SUBJECT POPULATION
Healthy (on the basis of physical examination, medical history and vital signs measurement performed at 
screening) male or female subjects, aged ≥12 to ≤24 months on the day of informed consent form (ICF)
signature, who are seronegative for RSV within 42 days prior to dosing.
DOSAGE AND ADMINISTRATION
Every effort will be made to administer the first 2 doses before the start of the RSV season. The start and 
end of the RSV season will be determined based on the information from the national surveillance system 
(if available) or the local surveillance at the site (standard of care assessments, if available). The site will 
communicate to the sponsor when RSV starts to circulate in their region; the decision to stop screening of 
subjects at affected sites will be taken together with the sponsor.
Ad26.RSV.preF (JNJ-64400141) will be supplied in single-use vials. The 2.5×1010 vp dose will be 
administered in a volume of 0.25 mL by intramuscular injection.
Placebo will be supplied as sterile 0.9% saline for intramuscular injection.
Nimenrix e will be supplied as Nimenrix powder and solvent for solution for injection in pre-filled syringe 
or ampoule and administered as 0.5 mL solution for intramuscular injection.
The study vaccine will be prepared and may also be administered by the unblinded pharmacist, or other 
qualified individual, who will have no other study function following dosing.
                                                
d
Note: The RTI procedures also apply to all otitis media cases.
e
In countries where the commercial vaccine Nimenrix is licensed, placebo (0.9% saline) can be replaced with Nimenrix as the 
Day 57 vaccination for the study subjects in the control group, in accordance with the local label and local regulations, and 
unless contra-indicated. Nimenrix will be administered, only if permitted by the subject’s parent/legal guardian and following 
PI assessment on a case-by-case basis as vaccination with Nimenrix outside this study might be preferred (joint parent/legal 
guardian and PI decision). In the US, Nimenrix will not be used unless it has been licensed for use or an IND has been 
submitted. It should be recorded in the eCRF by the unblinded pharmacist whether the subject was vaccinated with either 
Nimenrix or placebo on Day 57.

VAC18194 (Ad26.RSV.preF)
Clinical Protocol VAC18194RSV2002 Amendment 6
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
20
Status: Approved, Date: 25 May 2020
To ensure that the site staff or qualified professional staff who will do the observation as well as the 
subjects (and their parents/legal guardians) will be blinded, the necessary precautions will be taken as
documented by the clinical sites and agreed upon by the sponsor.
Injections should be administered in the anterolateral aspect of the thigh. Only if required by local health 
authority guidance, injections may be administered in the deltoid muscle. Alternating injection sites will 
be used for all study vaccinations unless there is a medically justifiable reason in the judgment of the PI(s).
IMMUNOGENICITY EVALUATIONS
The humoral and cellular immunogenicity assays that may be used in this study (as available and 
applicable) are summarized in Table 2 and Table 3 below. Sample collection and processing will be 
performed by the staff at clinical sites according to current and approved Standard Operating Procedures.
In addition to RT-PCR performed on RTI nasal samples, any immunogenicity blood sample collected 
from all subjects may also be assayed by serology (eg, ELISA specific to RSV protein G and/or N as 
available and applicable) to confirm exposure to RSV at the end of the season if the sample volumes
allow.
Table 2:
Summary of Immunogenicity Assays (Humoral)
Assay 
Purpose
Secondary endpoints
RSV neutralization A strain
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-F and post-F specificity by binding or functional assays as ELISA, and/or 
competition ELISA, epitope mapping, and functional VNAs 
Nasal Ig antibodies to RSV F protein
Analysis includes, but not limited to, IgA or IgG antibodies to RSV pre-F and/or 
post-F
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
ADCC = antibody-dependent cell-mediated cytotoxicity; ADCP = antibody-dependent cellular phagocytosis; 
ELISA = enzyme-linked immunosorbent assay; F = fusion; Ig = immunoglobulin; RSV = respiratory syncytial 
virus; VNA = virus neutralizing antibody
Table 3:
Summary of Immunogenicity Assays (Cellular)
Assay 
Purpose
Secondary endpoints
Flow cytometry (ICS)
Analysis of T-cell responses to RSV F protein peptides for Th1/Th2 subtyping
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)
Cytokine analysis
Analysis of secreted cytokines (eg, IFN-γ, IL-2, IL-4, IL-5, IL-13, and TNF-α) in RSV F 
peptide-stimulated PBMC supernatant, including, but not limited to, measurement of Th1/Th2 
cytokine balance
IFN-γ ELISpot
T-cell IFN-γ responses to RSV F protein peptides
ELISpot = enzyme-linked immunospot; F = fusion; ICS = intracellular cytokine staining; IFN-γ = interferon gamma; IL =
interleukin; PBMC = peripheral blood mononuclear cell; Th = T-helper (cell); RSV = respiratory syncytial virus; TNF-α = 
tumor necrosis factor alpha
Note: Cytokine analysis for Th1/Th2 profiling will be done if no ICS data can be generated due to insufficient PBMCs for ICS 
assay.

VAC18194 (Ad26.RSV.preF)
Clinical Protocol VAC18194RSV2002 Amendment 6
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
21
Status: Approved, Date: 25 May 2020
RTI PROCEDURES
All RTIs and otitis media cases will be collected during the RSV season f. Outside the RSV season, only 
MA-RTIs, including severe LRTIs, and medically-attended otitis media cases will be collected.
During the RSV season, the subject’s parent/legal guardian or caregiver should record any signs and 
symptoms of RTI (eg, runny nose, fever, severe cough, wheezing, rapid breathing, difficulty breathing) or 
otitis media on a daily basis using a specific RTI Symptoms Form, starting on the first day their child 
experiences symptoms, including the day on which the symptoms resolve. Outside the RSV season,
parents/guardians or caregivers should likewise record signs and symptoms of RTI or otitis media on a 
daily basis using the RTI Symptoms Form as soon as possible for any MA-RTI or medically-attended 
otitis media case until resolution of symptoms.
In the event of an RTI, MA-RTI, or (medically-attended) otitis media, parents/legal guardians or 
caregivers should contact the site. Parents/legal guardians or caregivers will themselves be contacted 
periodically during the study. During the RSV season, these calls are to remind them to complete the RTI 
Symptoms Form in the event of any signs or symptoms of RTI or otitis media, and to contact the site at 
the time of symptom onset; during and outside the RSV season, these calls will check for SAEs and 
associated concomitant medications, MA-RTIs, medically-attended otitis media cases, and any 
subsequent medical care that may have been sought, since the previous visit or telephone contact.
During the season, and where possible outside the season (for MA-RTIs, including severe LRTIs or for 
medically-attended otitis media cases), site staff will conduct a physical examination (with vital signs, 
including oxygen saturation), and collect nasal samples, preferably within 72 hours after onset of 
symptoms. For suspected severe RTI cases, nasal swabs should be shipped on the day of collection to 
enable timely assessment of samples for the presence of RSV infection by central laboratory RT-PCR.
(Nasal samples will not be collected if less than 7 days after the previous sample collection.) Note: A 
nasal swab for RSV RT-PCR testing will also be collected from any subject with otitis media (as recorded 
on the RTI Symptoms Form) during the study, independent of other RTI symptoms.
In all RTI or otitis media cases where results from the physical examination during the RTI site visit 
conclude that the RTI is not severe, and the RTI episode is still ongoing, a follow-up phone call (or other 
communication) to the parents/legal guardians or caregivers will be made once every 2 working days 
(±1 day) until symptom resolution. In the event of a worsening RTI, a follow-up RTI visit will be 
scheduled. (Note: In the event of a worsening RTI, a repeat nasal sample may be collected if less than 7 
days after the previous sample collection at the discretion of the investigator.) Further follow-up visits to
assess additional reported worsening of an RTI episode may be scheduled at the discretion of the 
investigator.
Note: RTI procedures (completion of the RTI symptoms form at home, and an RTI visit to the site with 
associated procedures, including nasal sampling) are not applicable for a non-medically-attended RTI that 
occurs outside the season, including those that started before the RSV season and continue into the season 
without worsening of symptoms.
Any RTI or otitis media case that is not due to RSV infection will be reported as an AE if it occurs 
between the time of any study vaccination through the following 28 days. During the study, any RTI or 
case of otitis media fulfilling the criterion of an SAE will be reported to the sponsor (and, when 
appropriate, extended to Regulatory Agencies). Any RTI or case of otitis media reported as an (S)AE that 
                                                
f
Note: The RTI procedures also apply to all otitis media cases.

VAC18194 (Ad26.RSV.preF)
Clinical Protocol VAC18194RSV2002 Amendment 6
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
22
Status: Approved, Date: 25 May 2020
is found to be positive for RSV will be excluded from the analyses of (S)AEs. However, the case will 
remain in the clinical database and will be tabulated separately in the clinical study report.
Any MA-RTI (including any severe LRTI) or (medically-attended) otitis media case which occurs 
between screening and Day 1 will be recorded on the Medical History page of the eCRF (RTI visit and 
RTI Symptoms Form completion is not required for these events prior to the first vaccination).
SAFETY EVALUATIONS
After each dose, subjects will be closely observed for a minimum of 30 minutes (or 60 minutes, 
depending on local or study-site requirements) post-vaccination, to monitor for development of any acute 
reactions, or longer if deemed necessary by the investigator. Any unsolicited, solicited local or systemic 
AEs and vital signs will be documented by study-site personnel after this observation period. The 
subject’s parent/legal guardian or caregiver will be given a thermometer, ruler and daily assessment 
(subject) diary with instructions for the proper recording of events. Each subject’s parent/legal guardian 
or caregiver will record solicited local (at injection site) and systemic AEs and body temperatures, 
beginning on the evening of each study vaccine dosing day and on a daily basis for the next 7 days. 
Temperatures should be taken at approximately the same time each day, preferably in the evening and 
additionally whenever the child feels warm. All diary assessments, including body temperature 7 days
post-vaccination, may be collected earlier in the day to coincide with the Day 8 clinic visit. Study-site 
personnel will collect and review subject diary information and confirm the entries at subsequent site 
visits.
All AEs, SAEs and special reporting situations related to study procedures or to non-investigational 
(concomitant) Janssen products will be reported from ICF signature onwards. Unsolicited AEs will be 
collected for 28 days after each vaccination (ie, from the time of each vaccination through the following 
28 days). SAEs will be collected from first dose administration to the end of the study. 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, RTI or OM case.
OTHER EVALUATIONS
At Visit 12 (6 months post-Dose 3), parents/legal guardians or caregivers (where allowed by local 
regulations) will be invited to complete an Institutional Review Board/Independent Ethics Committee 
(IRB/IEC) approved Participant Experience Survey.
STATISTICAL METHODS
Sample Size Determination
The number of subjects for this study will provide a preliminary safety and immunogenicity assessment. 
Control recipients are included for blinding and safety purposes and will provide additional control 
specimens for immunogenicity assays. While mild to moderate vaccine reactions (local site and systemic 
responses) are expected, AEs that preclude further dose administration or more serious ones that would 
limit product development are not anticipated.
Monitoring Rule for Severe RSV-LRTI
A monitoring rule with respect to severe RSV-LRTI will be installed for this study. If 1 event (regardless 
of the group) of severe RSV-LRTI is observed, no analysis will be done. If 2 or more events (regardless 
of the group) of severe RSV-LRTI have been observed, confidence limits for the difference in proportions 
(using Wilson score method) between the Ad26.RSV.preF group and control group (pooling 
placebo/placebo/Nimenrix and placebo/placebo/placebo) will be constructed by the external statistician 
who is supporting the IDMC:

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
If the upper (one-sided) 95% confidence limit for the difference is <10%: continue the study; if study 
enrollment is still ongoing, continue enrollment.

If the upper (one-sided) 95% confidence limit is ≥10% and the lower (one-sided) 80% confidence 
limit is >0: more frequent active monitoring of subjects, including weekly calls within the RSV 
season and more frequent medical review will be initiated.

If the upper (one-sided) 95% confidence limit is ≥10% and the lower (one-sided) 95% confidence 
limit is >0: halt enrollment in this study or the next study; more frequent active monitoring of 
subjects, including weekly calls within the RSV season and more frequent medical review for all
enrolled subjects should be initiated.
For example: assuming complete enrollment, if 2 or 3 severe RSV-LRTI events are observed and all 
occurred in the Ad26.RSV.preF group, the lower (one-sided) 80% (but not the 95%) confidence limit will 
be >0 and monitoring will be increased. If 4 severe RSV-LRTI events are observed and all occurred in the 
Ad26.RSV.preF group, the lower (one-sided) 95% confidence limit will be >0 and enrollment in all 
pediatric studies with Ad26.RSV.preF will be halted and monitoring of all enrolled subjects will be 
increased.
The IDMC will review unblinded data and give a recommendation to the sponsor. More details on this 
monitoring rule are specified in the IDMC charter.
Planned Analyses
The following analyses will be performed:

Primary analysis 28 days post-final dose includes safety and immunogenicity; unblinded

Interim analysis performed when all subjects have data of 1 RSV season post-Dose 1, includes safety 
and immunogenicity; unblinded

Final analysis at the end of the study; unblinded
The primary analysis and interim analysis may be combined into one analysis. These analyses will also be 
shared with the IDMC.
Additional interim analyses (blinded or unblinded) may be performed during the study for the purpose of 
informing future vaccine-related decisions in a timely manner, or upon health authority request. 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, excluding sponsor personnel involved in data collection or data management and clinical 
immunology laboratory personnel.
Immunogenicity Analyses
No formal hypothesis on immunogenicity will be tested. Descriptive statistics (geometric mean and 95% 
confidence interval for ELISA and virus neutralization assays; median and quartiles for ELISpot and ICS) 
will be calculated for continuous immunologic parameters at all timepoints. Graphical representations of 
immunologic parameters will be made as applicable.
Frequency tabulations will be calculated for discrete (qualitative) immunologic parameters as applicable.
RSV Infection
The incidence of any RSV infection, as described above under ‘RTI PROCEDURES’, in Ad26.RSV.preF 
and control subjects will be summarized by descriptive statistics.

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Safety Analyses
No formal statistical testing of safety data is planned. All safety data will be analyzed descriptively by 
regimen.

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pre-dose; abbreviated physical examination only at the discretion of the investigator (based on health status of the subject); pre- and post-dose; baseline immunogenicity blood 
draw and collection of a baseline nasal sample can take place either at screening or prior to vaccination on Day 1, at the discretion of the investigator, however both samples should be 
collected on the same day; if within 7 days of the previous vaccination; if within 28 days of the last vaccination; check of diary during the telephone call; at the discretion of the 
investigator (based on health status of the subject); if before Day 85 collect 4 mL cellular + 1 mL humoral; if after, collect 2 mL humoral only; MA-RTIs (including severe LRTIs)
that occur between screening and Day 1 will be recorded on the Medical History page of the eCRF.
Note: All blood samples (venous blood and fingerstick) collected during the study, including samples from subjects who have been screened but not enrolled into the study, will be stored 
and used for future research if the subject’s parent(s)/legal guardian(s) consent.
Note: Guidance on study conduct during the COVID-19 pandemic is available in Attachment 3. 
a.
Safety follow-up during both the vaccination and safety follow-up phases through 2 RSV seasons after the first dose: telephone call (or other communication, or clinic visit) to the 
parent/legal guardian or caregiver of subjects every 30 days ±7 days outside the RSV season, but every 14 days ±3 days in season (unless the timing coincides with a visit). If criteria
specified in the monitoring rule are met, calls during the RSV season will be made on a weekly basis.
b.
End of first RSV season after the first dose. Note: Subjects’ parents/legal guardians 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 (if available) or the local surveillance at the site (standard of care assessments, if available).
c.
For those subjects who are unable to continue participation in the study up to the visit at the end of the RSV season, but for whom consent is not withdrawn, an exit visit will be 
conducted as soon as possible.
d.
If any subject comes in earlier than Day 8 for Visit 4 or Day 36 for Visit 7 (allowed windows are -1/+3 and ±2 days, respectively), 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 (or Day 36).
e.
The timings of visits after the second/third vaccinations will be determined relative to the actual day of that vaccination.
f.
If any subject comes in earlier than Day 64 for Visit 10 (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 64.
g.
Signing of the ICF should be done before any study-related activity.
h.
Respiratory rate, heart rate, body temperature, oxygen saturation (SpO2). Note that body temperatures are recommended to be measured axillary (actual routes to be recorded in the 
eCRF).
i.
0.5 mL of blood for serostatus assessment can be collected at screening by venous blood sample or fingerstick, at the discretion of the investigator. If 0.5 mL is collected at screening, 
baseline blood draw for immunogenicity should be on Day 1.
j.
Note: serostatus may be assessed via the RSV EIA if available from a different study of the sponsor (VAC18194RSV2001). If done within 42 days of first dose, this assessment 
would not have to be repeated in the absence of a history of respiratory infection during that period.
k.
To include exclusion criteria 1, 2, 3, 4, 6, 7, 9, 10, 11, 13, 14, 15, 16, 17, and 18.
l.
Blood for cellular immunity will also provide plasma for humoral assessments.
m.
Investigator must check for acute illness or body temperature ≥38.0 °C at the time of vaccination. If before the first vaccination, the subject may be enrolled at a later date if within 
the screening window (otherwise, rescreening is required), or be withdrawn at the discretion of the investigator and after consultation with the sponsor. If before the second or third 
vaccination, the subject may be vaccinated up to, and no later than 10 days after the scheduled vaccination, or be withdrawn at the discretion of the investigator and after consultation 
with the sponsor. In the event of an ongoing AE or other situation precluding subject vaccination within 10 days, subjects may be vaccinated beyond the 10-day window at the 
discretion of the sponsor.
n.
PBMC samples to assess cellular immune responses will be collected at sites that have the capability to process the cells within the time frame specified in the laboratory manual.
o.
Subjects will be closely observed for a minimum of 30 minutes (or 60 minutes, depending on local or study-site requirements) post-vaccination. Any unsolicited, solicited local and 
systemic AEs, and vital signs will be documented by study-site personnel following this observation period.
p.
All 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.
q.
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, RTI or OM case. Pre-study therapies administered up to 30 days before first dose of study vaccine will be recorded during screening.
r.
Collection of any concomitant medication given in response to an RTI or OM case. 

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s.
All 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.
t.
Any RTI or otitis media case fulfilling the criteria of an SAE will be reported as such during the entire study period.
u.
The subject’s parent/legal guardian or caregiver should record any signs and symptoms of RTI (eg, runny nose, fever, severe cough, wheezing, rapid breathing, or difficulty breathing) 
on a daily basis, starting on the first day their child experiences symptoms, including the day on which symptoms resolve. They will be contacted periodically during the study (every 
14 days ±3 days within the RSV season and every 30 days ±7 days outside of the RSV season, unless the timing coincides with a visit): during the RSV season, these calls are to 
remind them to complete the RTI Symptoms Form in the event of symptoms and to contact the site at the time of symptom onset, preferably within 72 hours after onset of symptoms. 
During and outside the RSV season, these calls will be to check for any SAEs and associated concomitant medications and any MA-RTIs. Details of the RTI procedures are provided 
in Section 9.2.2.
v.
Severe LRTIs are a subset of MA-RTIs. The CEC will assess suspected cases of severe LRTI, and whether these have arisen from RSV infection.
w.
Nasal samples (mid-turbinate or nasopharyngeal samples) will not be collected if less than 7 days after the previous sample collection.
x.
Rulers and thermometers will be distributed to the subject’s parent/legal guardian or caregiver on each dosing day.
y.
At any time from screening throughout the study.
z.
In all RTI or otitis media cases where results from the physical examination during the RTI site visit conclude that the RTI is not severe, and the RTI episode is still ongoing, a 
follow-up phone call (or other communication) to the parents/legal guardians or caregivers will be made once every 2 working days (±1 day) until symptom resolution. In the event of 
a worsening RTI, a follow-up RTI visit will be scheduled.
AE = adverse event; CEC = Clinical Endpoint Committee; d = day; eCRF = electronic case report form; EoS = End of Season; FU = follow-up; ICF = informed consent form; LRTI = 
lower respiratory tract infection; mo = month; MA-RTI = medically-attended respiratory tract infection; PBMC = peripheral blood mononuclear cell; RT-PCR = reverse transcriptase 
polymerase chain reaction; RSV = respiratory syncytial virus; RTI = respiratory tract infection; SAE = serious adverse event; vac = vaccination

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ABBREVIATIONS
Ad26
adenovirus serotype 26
Ad35
adenovirus serotype 35
ADCC
antibody-dependent cell-mediated cytotoxicity
ADCP
antibody-dependent cellular phagocytosis
AE
adverse event
CEC
Clinical Endpoint Committee
CS
circumsporozoite
DNA
deoxyribonucleic acid
eCRF
electronic case report form 
eDC
electronic data capture
EIA
enzyme immunoassay
ELISA
enzyme-linked immunosorbent assay
ELISpot
enzyme-linked immunospot
ERD
enhanced respiratory disease
F
fusion
FA
Full Analysis (set)
FI
formalin-inactivated
FIH
first-in-human
GCP
Good Clinical Practice
HIV
human immunodeficiency virus
ICF
informed consent form
ICH
International Council for Harmonisation
ICS
intracellular cytokine staining
IDMC
Independent Data Monitoring Committee
IEC
Independent Ethics Committee
IFN-γ
interferon gamma
IgA/IgG
immunoglobulin A/immunoglobulin G
IL
interleukin
IND
Investigational New Drug
IRB
Institutional Review Board
IWRS
interactive web response system
LRTI
lower respiratory tract infection
MA-RTI
medically-attended respiratory tract infection
mITT
modified Intent-to-treat
PBMC
peripheral blood mononuclear cell
PI
principal investigator
post-F
post-fusion
PPI
Per-protocol Immunogenicity (set)
PQC
Product Quality Complaint
pre-F
pre-fusion
RSV
respiratory syncytial virus
RTI
respiratory tract infection
RT-PCR
reverse transcriptase polymerase chain reaction
SAE
serious adverse event
SpO2
peripheral capillary oxygen saturation
SRP/S
study responsible physician/scientist
SUSAR
suspected unexpected serious adverse reaction
TB
tuberculosis
Th 
T-helper (cell)
TNF-α
tumor necrosis factor alpha
URTI
upper respiratory tract infection
VNA
virus neutralizing antibody
vp
viral particles
WHO
World Health Organization

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1.
INTRODUCTION
A human adenovirus-vectored vaccine candidate which has shown promise in preclinical animal 
models of respiratory syncytial virus (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 for the pre-fusion 
conformation-stabilized F protein (pre-F) derived from the RSV A2 strain.
Study Naming Conventions
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 
Adult subjects aged 18 to 50 years
VAC18192RSV1003
1
Ad26.RSV.FA2 
Adult subjects aged 18 to 50 years
VAC18193RSV1003
1
Ad26.RSV.preF vaccine 
Adults aged 60 years and older
VAC18193RSV2002
2a
Ad26.RSV.preF vaccine
Adult subjects aged 18 to 50 years
VAC18193RSV2003
2a
Ad26.RSV.preF vaccine
Adults aged 60 years and older
VAC18194RSV2001
1/2a
Ad26.RSV.preF vaccine
Adult subjects aged 18 to 50 years
RSV-seropositive toddlers aged 12 to 24 months
Current study:
VAC18194RSV2002
1/2a
Ad26.RSV.preF vaccine
RSV-seronegative toddlers aged 12 to 24 months
VAC18194RSV2003
1/2
Ad26.RSV.preF vaccine
RSV-seronegative infants aged 6 to 12 months 
For the most comprehensive nonclinical and clinical information regarding Ad26.RSV.preF, 
refer to the latest version of the Investigator’s Brochure for Ad26.RSV.preF.1
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.

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1.1.
Background
Background
RSV is considered to be the most important cause of serious acute respiratory illness in infants 
and children under 5 years of age.18,43,47 Globally, in 2005, RSV was responsible for an estimated 
3.4 million hospitalizations worldwide in children under 5 years of age. Furthermore, 66,000 to 
199,000 children younger than 5 years died from RSV-associated acute lower respiratory tract 
infection (LRTI) in 2005, and 99% of the deaths occurred in developing countries.36
Nevertheless, the RSV disease burden in developed countries is substantial, with RSV infection 
during childhood linked to the development of wheezing, airway hyperreactivity, and 
asthma.40,42,44,45,46 In the United States, the infection rate was 68.8% in children younger than 12
months of age and 82.6% during the second year of life. Virtually all children had been infected 
at least once by 24 months of age, and about one half had experienced 2 infections.16 In the 
United States, RSV infection in children under 5 years of age is the cause of approximately 
57,000 to 175,000 hospitalizations, 500,000 emergency room visits, and 500 deaths each 
year.39,43,47 In children under 1 year of age, RSV is the most important cause of bronchiolitis, and 
RSV hospitalization is the highest among children under 6 months of age.6,18
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.26 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.35
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.3 The 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 data demonstrate predominantly interferon gamma (IFN-γ) and tumor necrosis factor alpha 
(TNF-α) production in CD4+ and CD8+ T-cells.2,5,38 Furthermore, in mice, Ad26- and Ad35-
vectored vaccines with circumsporozoite (CS) transgene inserts (Ad26.CS.01 and Ad35.CS.01), 
when given as single immunizations or in combination as a heterologous prime-boost regimen at 
dose levels ranging from 1×108 viral particles (vp) to 1×1010 vp, induce predominantly CD8+ T-
cell responses, as well as mainly immunoglobulin IgG2a antibody responses, indicative of a Th1-
biased response.41

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Thus, in contrast with the Th2-skewed profile of FI-RSV vaccine, which has been associated 
with ERD upon infection with RSV, the likely Th1 profile of an adenoviral-vectored RSV 
vaccine reduces the likelihood of disease enhancement in RSV-seronegative infants.
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 subjects, respectively, received Ad26.RSV.FA2) in healthy adults at doses of 
5×1010 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, 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.24,25
Single vaccination with Ad26.RSV.FA2 5×1010 vp raised both humoral and cellular immunity. 
An increase in RSV neutralizing antibody titers was observed, and RSV-specific T-cell 
responses were also increased.
FA2 and preF RSV Vaccines
The candidate vaccine assessed in the current study is Ad26.RSV.preF, a replication-incompetent 
Ad26 containing a DNA transgene that encodes for the pre-fusion (pre-F) conformation-
stabilized F protein derived from the RSV A2 strain.
The first-in-human (FIH) 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.15,17 This evidence 

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resulted in the design of the candidate RSV vaccine (Ad26.RSV.preF) in which the adenoviral 
vector encodes for 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.30 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.30 This change also induces higher immune responses 
against pre-fusion epitopes because the majority of neutralizing antibodies target the pre-fusion 
protein conformation.31,37 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.23
Ad26.RSV.preF Preclinical Data
In preclinical studies in mice and cotton rats, Ad26.RSV.preF is immunogenic, 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+ IFNγ+ T cells. The immune response following Ad26.RSV.preF immunization 
was T-helper 1 (Th1)-biased, based on the ratio of the Th1 cytokine IFNγ to Th2 cytokines, and 
on the ratio of RSV F-specific IgG2a/IgG1 antibodies. Also in neonatal mice, Ad26.RSV.preF 
was immunogenic and induced both humoral and cellular responses, with similar Th1 bias. In 
rodent models, single immunization with Ad26.RSV.preF induced dose-dependent protection in 
the upper and lower respiratory tract from RSV challenge with RSV A2 (in cotton rats and mice)
and RSV B strains (in cotton rats only). Histopathologic features of ERD were not observed in 
the lung after RSV challenge of mice and cotton rats vaccinated with Ad26.RSV.preF over a 
large dose range, including vaccine doses that were fully protective, as well as non-protective 
vaccine doses at which RSV replication in the lung was observed.23
Ad26.RSV.preF Clinical Data
Ad26.RSV.preF is currently under evaluation in 4 randomized, controlled, double-blind studies: 
the FIH Phase 1 study VAC18193RSV1003 in subjects aged ≥60 years in stable health; the 
Phase 1/2a study VAC18194RSV2001 in adults aged ≥18 to ≤50 years and RSV-seropositive 
toddlers aged 12 to 24 months; the exploratory Phase 2a study VAC18193RSV2002 in adults 
aged ≥18 to ≤50 years to evaluate Ad26.RSV.preF in a virus challenge model; and the Phase 2a 
study VAC18193RSV2003 in subjects aged ≥60 years in stable health to evaluate seasonal 
influenza vaccine and Ad26.RSV.preF, with and without co-administration.
In the VAC18193RSV1003 study, 72 male and female subjects were randomized to 1 of 5
groups and have received the first (Day 1) of 2 intramuscular injections as follows:

Group 1: 5×1010 vp Ad26.RSV.preF on Day 1 and 1 year (±1 month) later

Group 2: 5×1010 vp Ad26.RSV.preF on Day 1 and placebo 1 year (±1 month) later

Group 3: 1×1011 vp Ad26.RSV.preF on Day 1 and 1 year (±1 month) later

Group 4: 1×1011 vp Ad26.RSV.preF on Day 1 and placebo 1 year (±1 month) later

Group 5: placebo on Day 1 and 1 year (±1 month) later

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Safety and immunogenicity data from the unblinded interim analysis 28 days post-Dose 1 from 
all 72 subjects who received Ad26.RSV.preF (5×1010 vp or 1×1011 vp) or placebo confirmed the 
immunogenicity of the vaccine; the 1×1011 vp dose of Ad26.RSV.preF was more immunogenic 
than the 5×1010 vp dose. No safety concerns were revealed; the reactogenicity of both doses was 
comparable.
In the VAC18194RSV2001 study, first 12 male and female adult subjects and then at least 36
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
At the start of June 2018, the Independent Data Monitoring Committee (IDMC) evaluated Day 8 
safety data from the first 12 toddlers and Day 29 safety data from 8 toddlers. Prior to initiating 
dosing in the current study (VAC18194RSV2002), the IDMC will convene to review additional 
safety data (unblinded at the study group level) from VAC18194RSV2001 collected up to this 
point (ie, from at least the first 12 toddlers), including solicited AEs, unsolicited AEs and SAEs 
through 28 days after the first dose of 5×1010 vp of Ad26.RSV.preF; immune response data 
(RSV F protein binding antibodies [pre-F and/or post-F], RSV virus neutralization assay, 
Th1/Th2 subtyping) through 28 days after the first dose are also expected to be available for 
additional toddlers.
The formulation buffer that is used in study VAC18194RSV2001 and in all other ongoing 
studies (Formulation Buffer2)g will be used in the current study. In study VAC18193RSV1003, 
Ad26.RSV.preF is provided in a different formulation buffer (Formulation Buffer)1h.
In the VAC18193RSV2002 study, more than 44 (and up to 70) healthy male and female subjects 
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 after vaccination. All 
subjects are planned to have been dosed prior to the start of the current study.
                                                
g
Formulation Buffer 2: 15 mM citrate, 5% (w/w) hydroxypropyl--cyclodextrin, 0.4% (v/v) ethanol, 0.03% (w/w) 
polysorbate-80, 75 mM sodium chloride, pH 6.2.
h
Formulation Buffer 1: 20 mM histidine, 5% (w/v) sucrose, 0.1 mM ethylenediaminetetraacetic acid, 0.5% (v/v) ethanol, 
0.02% (w/w) polysorbate-80, 75 mM sodium chloride, pH 6.5.

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Status: Approved, Date: 25 May 2020
In the VAC18193RSV2003 study, 180 male and female subjects aged ≥60 years in stable health 
are randomized to 1 of 2 groups. Subjects 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. Subjects in Group 2 receive placebo on Day 1, 
administered at the same time as a commercially available seasonal influenza vaccine, 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 post-second dose has been completed.
Safety Data Supporting the Dose Selection
The dose level for Ad26.RSV.preF used in the current study is supported by experience in adults 
with other Ad26-based vaccines encoding for different antigens (including EnvA [in 
Ad26.ENVA.01 against HIV];4,5 CS protein [in Ad26.CS.01 against malaria];48 and Ebola 
glycoprotein [in Ad26.ZEBOV against Ebola virus]33).
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).
In addition, 17 clinical studies with Ad26 vaccines (Ad26.RSV.preF, Ad26.Mos[4].HIV, and 
Ad26.ZEBOV) are ongoing. At least 4,579 subjects (including approximately 96 subjects 4-11 
years of age in VAC52150EBL3001) have been enrolled in these ongoing studies, of whom 
approximately 456 received at least 1 vaccination with an Ad26-based vaccine (mainly 
5×1010 vp) up to 31 August 2017. For the remainder of subjects, 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.21,22
Apart from the ongoing VAC18193RSV1003, VAC18193RSV2003 and VAC18194RSV2001 
studies outlined in the previous section and VAC52150EBL3001, Ad26-vectored vaccines have 
only been tested in adults (ie, subjects 18 to 50 years of age). Ad35-vectored vaccines have been 
tested in 904 subjects, including 555 adults and 349 infants. Data from Bacillus Calmette-
Guérin-primed infants immunized with Ad35 encoding for TB antigens (AERAS-402) indicated 
that the highest immune responses were obtained following administration of 1×1011 vp. The 
safety of this Ad35-based TB vaccine was acceptable when tested in infants aged 14 weeks and 
older at doses from 1×108 vp to 1×1011 vp.
1.2.
Nimenrix
Nimenrix® is a vaccine indicated to protect adults, adolescents, and children from the age of 
6 weeks against invasive meningococcal disease caused by 4 groups of the bacterium Neisseria 
meningitidis (group A, C, W-135, and Y). Nimenrix is administered intramuscularly by injection 
into the thigh or deltoid muscle.
The rationale for the selection of Nimenrix is provided in Section 3.2.

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Status: Approved, Date: 25 May 2020
1.3.
Overall Rationale for the Study
Despite the high RSV disease burden, no licensed vaccine is available for RSV.
This current study will
evaluate the safety, reactogenicity,
and immunogenicity of 
Ad26.RSV.preF at a dose of 2.5×1010 vp in RSV-seronegative toddlers aged 12 to 24 months.
The dose selection rationale is provided in Section 3.2.
2.
OBJECTIVES, ENDPOINTS, AND HYPOTHESIS
2.1.
Objectives and Endpoints
2.1.1.
Objectives
Primary Objective
The primary objective is:

To assess the safety and reactogenicity of an intramuscular regimen of 3 doses of 2.5×1010
vp of Ad26.RSV.preF in RSV-seronegative toddlers aged 12 to 24 months.
Secondary Objectives
The secondary objectives are:

To assess the humoral and cellular immune responses elicited by Ad26.RSV.preF as 
measured by virus neutralizing antibodies (VNAs), F protein binding antibodies (pre-F 
and/or post-F), and Th1/Th2 subtyping.

To monitor for severe RSV-LRTI as a preliminary indication of ERD.
Exploratory Objectives
The exploratory objectives are:

To further assess the humoral and cellular immune responses elicited by Ad26.RSV.preF. 
The assays to be used can include, but may not be limited to, RSV strain cross-
neutralization, RSV F protein antibody specificity characterization, RSV G and/or N protein 
binding antibodies, adenovirus neutralization assay, functional and molecular antibody 
characterization (eg, avidity and antibody isotyping) and antibody sequencing if feasible, 
and evaluation of cellular immune response (IFN-γ enzyme-linked immunospot [ELISpot] 
assay, intracellular cytokine staining [ICS], cytokine analysis).

To assess RSV infection rates (symptomatic and asymptomic) in Ad26.RSV.preF and 
control subjects.

To assess symptomatic RSV infection rates in Ad26.RSV.preF and control subjects.

To assess symptoms of respiratory illness via the Respiratory Tract Infection (RTI) 
Symptoms Form.

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2.1.2.
Endpoints
Primary Endpoints – Safety and Reactogenicity

Solicited local and systemic AEs for 7 days after each vaccination.

Unsolicited AEs for 28 days after each vaccination.

SAEs from first dose administration to the end of the study.
Secondary Endpoints – Immune Responses
The analysis of the immunogenicity of the vaccine regimens will include the characterization of
both humoral and cellular responses. The focus of the immunogenicity analysis will be on 
VNAs, F protein antibodies (pre-F and/or post-F), and Th1/Th2 cytokine profile response.
Humoral Immune Response

RSV neutralization A strain
Analysis of neutralizing antibodies to an A strain.

F protein antibodies (enzyme-linked immunosorbent assay [ELISA]; pre- and/or post-F)
Analysis of antibodies binding to RSV F protein in pre-fusion and/or post-fusion form.
Cell-mediated Immune Response

Flow cytometry (ICS)*
Analysis of T-cell responses to RSV F protein peptides for Th1/Th2 subtyping.
* Cytokine analysis for Th1/Th2 profiling will be done if no ICS can be generated due to an 
insufficient number of peripheral blood mononuclear cells (PBMCs) for ICS assay (see the 
Exploratory Endpoints below).
Secondary Endpoints – RSV Infection

Severe RSV-LRTI
Severe RSV-LRTI will be defined as the presence of severe LRTI as assessed by the
Clinical Endpoint Committee (CEC; See Section 11.3.1.2), and confirmation of RSV 
infection from a nasal (mid-turbinate or nasopharyngeal) sample using independent reverse
transcriptase polymerase chain reaction (RT-PCR) by a central laboratory. If no central 
laboratory RT-PCR result is available, a positive test result for RSV from a local laboratory 
(if available) could be used to confirm RSV infection upon evaluation by the CEC.
Exploratory Endpoints – Immune Responses
Exploratory analyses may be performed to evaluate the vaccine-elicited immune responses 
further. These can include, but may not be limited to, the following assays (as available and 
applicable):

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Status: Approved, Date: 25 May 2020
Humoral Immune Response

RSV cross-neutralization of B and/or other A strain(s)
Assessment of the strain cross-neutralizing capacity of the vaccine-induced immune 
response.

F protein antibody specificity characterization
Assessment of pre-F and post-F specificity by binding or functional assays as ELISA, and/or 
competition ELISA, epitope mapping, and functional VNAs.

Nasal immunoglobulin antibodies to RSV F protein
Analysis of IgA or IgG antibodies to RSV pre-F and/or post-F

G and/or N protein antibodies (ELISA)
Assessment of antibodies binding to RSV G and/or N protein to estimate the RSV infection 
rate (symptomatic and asymptomatic) in the study.

Adenovirus neutralization assay
Assessment of neutralizing antibody responses against the adenoviral vector.

Functional and molecular antibody characterization
Functional characterization of antibodies may be performed: antibody-dependent cell-
mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).9 A 
molecular characterization of vaccine-elicited antibodies will include antibody avidity, other 
respiratory viral neutralizing or binding assays, immunoglobulin isotype, functional VNAs 
to other respiratory viruses, and antibody assessments.
Cell-mediated Immune Response

ICS
Analysis of T-cell responses to RSV F protein peptide-stimulated PBMC (including, but not 
limited to, CD4+/CD8+, interleukin [IL]-2, IFN-γ, TNF-α, activation markers and memory)

Cytokine analysis
Cytokine profiles of (in vitro) stimulated PBMC supernatant will be analyzed to assess the 
quantity and quality of elicited immune responses, including Th1/Th2 balance. The analysis 
can include, but may not be limited to, IFN-γ, IL-2, IL-4, IL-5, IL-13, and TNF-α.

IFN-ELISpot assay
An ELISpot assay is used to quantify the amount of PBMCs able to produce IFN-γ upon 
RSV F protein peptide antigen stimulation.

Sequencing of the antibody repertoire will be done if feasible.

VAC18194 (Ad26.RSV.preF)
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Status: Approved, Date: 25 May 2020
Exploratory Endpoints – RSV Infection

RSV-RTI and RSV-LRTI confirmed by RT-PCR.

Serology for, but not limited to, RSV protein G and/or N (and/or F) may be used to confirm 
exposure to RSV at the end of the season.
To detect RSV infections by serology, a fold increase will be applied to determine if a 
subject is a seroconverter based on G and/or N ELISA. Fold increases for RSV infection will 
be determined based on 2 consecutive blood samples as planned in the Time and Events
Schedule.

RSV medically-attended respiratory tract infection (MA-RTI): includes all subjects with 
RSV-RTI that is medically-attended, ie, when the subject’s parent/legal guardian or 
caregiver seeks medical attention outside normal study procedures, including healthcare 
professional visits to the home, clinic visits, emergency room attendance, hospital 
admission.
See Section 9.2, Study Evaluations, for evaluations related to endpoints.
2.2.
Hypothesis
No formal statistical hypothesis is planned. The study will evaluate whether Ad26.RSV.preF is 
safe, well-tolerated, and immunogenic in RSV-seronegative toddlers.
3.
STUDY DESIGN AND RATIONALE
3.1.
Overview of Study Design
This is a multi-center, randomized, observer-blindi, Phase 1/2a study, to be conducted in 36 male 
and female RSV-seronegative toddlers aged ≥12 to ≤24 months.
Each subject’s RSV serostatus will be assessed by RSV enzyme immunoassay (EIA) at 
screeningj (see Section 9.1.3.1). Note: serostatus may be assessed via this assay if available from
a different study of the sponsor (VAC18194RSV2001). If done within 42 days of first dose, this 
assessment would not have to be repeated in the absence of a history of respiratory infection 
during that period. Additionally, the seronegative status will be confirmed by the absence of an 
anamnestic humoral immune response (which is usually observed 7-10 days post antigen re-
exposure in RSV seropositive subjects) from blood samples taken 7 days after the first dose.
                                                
i
Note: The vaccine administrator will be unblinded but will have no other study function following dosing. The site staff or 
qualified professional staff who will do the observation and the subjects will be blinded.
j
The cut-off for seronegativity is a titer <1 EIA unit.

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Status: Approved, Date: 25 May 2020
Subjects will be randomized 1:1 to receive either Ad26/Ad26/Ad26 (at 2.5×1010 vp) or 
placebo/placebo/Nimenrix k,l (or placebo/placebo/placebo) (Table 4).
Table 4:
Study Design VAC18194RSV2002
Group
Na
Day 1 
Day 29/Week 4 
Day 57/Week 8 
RSV-seronegative toddlers 12 to 24 months
Group 1
18
Ad26.RSV.preF (2.5×1010 vp)
Ad26.RSV.preF (2.5×1010 vp)
Ad26.RSV.preF (2.5×1010 vp)
Group 2
18
Placebo (saline)
Placebo (saline)
Nimenrix b or Placebo (saline)
N = number of subjects; vp = viral particles
a:
At the time of Amendment 6, 37 subjects have been enrolled.
b:
In countries where the commercial vaccine Nimenrix is licensed, placebo (0.9% saline) can be replaced with 
Nimenrix as the Day 57 vaccination for the study subjects in the control group, in accordance with the local label 
and local regulations, and unless contra-indicated. Nimenrix will be administered, only if permitted by the 
subject’s parent/legal guardian and following PI assessment on a case-by-case basis as vaccination with 
Nimenrix outside this study might be preferred (joint parent/legal guardian and PI decision). In the US, 
Nimenrix will not be used unless it has been licensed for use or an Investigational New Drug (IND) has been 
submitted.
An IDMC has been established for the ongoing study VAC18194RSV2001 in RSV-seropositive
toddlers and all subsequent studies with Ad26.RSV.preF in children (including the current study), 
to evaluate safety and reactogenicity data on a regular basis. See Section 11.9.2 for details.
An independent, blinded CEC has been established for ongoing study VAC18194RSV2001 in 
RSV-seropositive toddlers and all subsequent studies with Ad26.RSV.preF in children (including 
the current study), to assess suspected cases of severe LRTI and the occurrence of RSV 
infection. See Section 11.9.1 for details.
The study will have 3 phases: a screening phase, a vaccination phase, and a safety follow-up 
phase through 2 RSV seasons after the first dose. The durations of the respective phases are as 
follows:
                                                
k
In countries where the commercial vaccine Nimenrix is licensed, placebo (0.9% saline) can be replaced with Nimenrix as the 
Day 57 vaccination for the study subjects in the control group, in accordance with the local label and local regulations, and 
unless contra-indicated. Nimenrix will be administered, only if permitted by the subject’s parent/legal guardian and following 
PI assessment on a case-by-case basis as vaccination with Nimenrix outside this study might be preferred (joint parent/legal 
guardian and PI decision). In the US, Nimenrix will not be used unless it has been licensed for use or an IND has been 
submitted. It should be recorded in the eCRF by the unblinded pharmacist whether the subject was vaccinated with either 
Nimenrix or placebo on Day 57.
l
Nimenrix is a vaccine used to protect adults, adolescents, and children from the age of 6 weeks against invasive 
meningococcal disease caused by 4 groups of the bacterium Neisseria meningitidis (group A, C, W-135, and Y).12

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Status: Approved, Date: 25 May 2020
Phase
Screening:
up to 6 weeks before the first dose
Vaccination:
34 weeks

dosing on Days 1, 29 and 57

safety follow-up through 6 months post-final dose

immunogenicity at:
pre-Dose 1 (Day 1)
7 days post-Dose 1 (Day 8)
28 days post-Dose 3 (Day 85)
end of the first RSV season post-first dose
Safety follow-up:
through 2 RSV seasons after the first dose
The start and end of the RSV season will be determined based on the information from the 
national surveillance system (if available) or the local surveillance at the site (standard of care
assessments, if available). The site will communicate to the sponsor when RSV starts to circulate 
in their region; the decision to stop screening of subjects at affected sites will be taken together 
with the sponsor.
The end of the vaccination phase will be when the last subject completes the visit at 6 months 
after the final dose. The end of the study will be the last subject’s last visit (by telephone) at the 
end of the safety follow-up phase.
First-dose Safety
No sentinel approach is taken for the 2.5×1010 vp dose, as this dose is lower than the 5×1010 vp 
dose currently being evaluated in several other studies, including study VAC18193RSV1003 in 
adults aged ≥60 years in stable health and study VAC18194RSV2001 in RSV-seropositive 
toddlers aged 12 to 24 months (see Section 1.1).

The first 8 subjects will be enrolled and receive the first dose (Ad26.RSV.preF 2.5×1010 vp
or placebo).

7-day safety in these first 8 subjects will be monitored by the principal investigator (PI[s]) or 
designee and the sponsor’s study responsible physician/scientist (SRP/S). In the event of a 
significant safety finding, the IDMC will be consulted.

4 more subjects will be enrolled and receive the first dose (Ad26.RSV.preF 2.5×1010 vp or 
placebo).

The IDMC will assess post-first dose reactogenicity by review of 7-day safety data for these
first 12 subjects (6 subjects receiving Ad26.RSV.preF 2.5×1010 vp and 6 subjects receiving 
placebo).
Any safety finding will be closely monitored, although enrollment will not be paused for either 
the PI(s) or designee and SRP/S review of the first 8 subjects or the IDMC review of the first 12 
subjects.

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Status: Approved, Date: 25 May 2020
If the IDMC review does not take place before the first subject receives the scheduled second or 
third dose (due to potential slow recruitment), the PI(s) or designee and SRP/S will review the 
available data prior to the second or third dose being given as scheduled, respectively. In the 
event of a significant safety finding, the IDMC will be consulted.
In all post-first dose 7-day safety reviews, safety data for review will include solicited and 
unsolicited AEs and SAEs. 
Second-dose Safety
Safety assessments will also be made 7 days after the second dose in the first 12 toddlers before 
administering the second dose to the remaining toddlers. Post-second dose 7-day safety will be 
monitored by the PI(s) or designee and SRP/S. Safety data for review will include solicited and 
unsolicited AEs and SAEs. Any safety finding will be closely monitored, although dosing will 
not be paused for this PI(s) or designee and SRP/S review.
Third-dose Safety
Safety assessments will also be made 7 days after the third dose in the first 12 toddlers before 
administering the third dose to the remaining toddlers. Post-third dose 7-day safety will be 
monitored by the PI(s) or designee and SRP/S. Safety data for review will include solicited and 
unsolicited AEs and SAEs. Any safety finding will be closely monitored, although dosing will 
not be paused for this PI(s) or designee and SRP/S review.
The sponsor will monitor post-vaccination safety on an ongoing basis by reviewing blinded 
safety data.
After each dose, subjects will be closely observed for a minimum of 30 minutes (or 60 minutes, 
depending on local or study-site requirements) post-vaccination, to monitor for the development 
of any acute reactions, or longer if deemed necessary by the investigator. Any unsolicited, 
solicited local or systemic AEs and vital signs will be documented by study-site personnel after
this observation period. The subject’s parent/legal guardian or caregiver will be given a 
thermometer, ruler and daily assessment (subject) diary with instructions for the proper recording 
of events. Each subject’s parent/legal guardian or caregiver will record solicited local (at 
injection site) and systemic AEs and body temperatures, beginning on the evening of each study 
vaccine dosing day and on a daily basis for the next 7 days. Temperaturesm should be taken at 
approximately the same time each day, preferably in the eveningn and additionally whenever the 
child feels warm. Study-site personnel will collect and review subject diary information and 
confirm the entries at subsequent site visits.
                                                
m
Recommended to be measured axillary (actual routes to be recorded in the eCRF).
n
All Day 8 post-vaccination diary assessments, including temperature measurements, may be collected earlier to coincide with 
the corresponding clinic visit.

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Unsolicited AEs will be collected for 28 days after each vaccination (ie, from the time of each 
vaccination through the following 28 days). SAEs will be collected from first dose 
administration to the end of the study. 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, RTI or OM case.
Blood will be collected for immunogenicity assessments as follows:

pre-vaccination and 7 days after the first dose, at 28 days after the third dose and at the end 
of the RSV season.
A blood sample will be taken for RSV serology testing at the screening visito; the baseline blood 
sample for immunogenicity may either be drawn at the same screening visit or pre-dose on Day
1, at the discretion of the investigator.
All blood samples (venous blood and fingerstick) collected during the study, including samples 
from subjects who have been screened but not enrolled into the study, will be stored and used for 
future research if the subject’s parent(s)/legal guardian(s) consent (see also Section 16.2.5).
RTIs and otitis media cases will be collected during the RSV season p. Outside the RSV season, 
only MA-RTIs, including severe LRTIs, and medically-attended otitis media cases will be 
collected. During the RSV season, the subject’s parent/legal guardian or caregiver should record 
any signs and symptoms of RTI (eg, runny nose, fever, severe cough, wheezing, rapid breathing, 
or difficulty breathing) or otitis media on a daily basis using a study-specific RTI Symptoms 
Form, starting on the first day their child experiences symptoms, including the day on which the 
symptoms resolve. Outside the RSV season, parents/guardians or caregivers should likewise 
record signs and symptoms of RTI on a daily basis using the RTI Symptoms Form as soon as 
possible for any MA-RTI until resolution of symptoms. For details of RTI procedures, see 
Section 9.2.2.
During the entire study after the first dose, including during the vaccination phase and safety 
follow-up phase, the subject’s parent/legal guardian or caregiver will be contacted periodically 
by telephone (or other communication, or by clinic visit) through 2 RSV seasons after the first 
dose (every 14 days ±3 days within the RSV season, every 30 days ±7 days outside of the 
season, unless the timing coincides with a visit). During the RSV season, these calls will remind 
the subject’s parent/legal guardian or caregiver to record signs and symptoms of RTI, and to 
contact the site at the time of symptom onset. During and outside the RSV season, these calls will 
check for SAEs and associated concomitant medications, MA-RTIs, and any subsequent medical 
care that may have been sought, since the previous visit or telephone contact (this includes 
                                                
o
By venous blood sample or fingerstick, at the discretion of the investigator. If fingerstick is done at screening, baseline blood 
draw for immunogenicity should be on Day 1.
p
Note: The RTI procedures (see Section 9.2.2) also apply to all otitis media cases.

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Status: Approved, Date: 25 May 2020
contacts with subjects who received at least one dose of study vaccine but withdrew from further 
dosing). The sponsor will provide the site with a checklist for these follow-up phone calls.
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.

VAC18194 (Ad26.RSV.preF)
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3.2.
Study Design Rationale
Vector Selection
The rationale behind the selection of the Ad26 vector is described in Section 1.1.
Dose Selection
In study VAC18194RSV2001, ongoing in UK and Finland, the IDMC reviewed the interim 
analysis when 12 toddlers had reached Day 8 post-first dose (5×1010 vp of Ad26.RSV.preF or 
placebo). Their recommendation was that the study should continue unmodified. Transient fevers 
were observed in some subjects, comparable in intensity to those seen following measles, mumps 
and rubella (MMR) immunization in this age group. A recent study from Africa in 1- to 3-year-
old infants revealed only 5 cases of fever in over 380 subjects in which 2/3 infants had received 
5×1010 vp of an Ad26-vectored Ebola vaccine. Thus, the transient fevers observed in study 
VAC18194RSV2001 may be based on a regional effect. In addition, available immunogenicity 
data from study VAC18194RSV2001 in 8 toddlers after the first dose (5 after 5×1010 vp of 
Ad26.RSV.preF and 3 after placebo) showed that the vaccine was immunogenic, inducing a 
consistent increase in neutralizing antibody titers without affecting qualitative Th1/Th2 balances. 
Prior to dosing toddlers in the current study (VAC18194RSV2002), the IDMC will convene to 
review additional safety data (unblinded at the study group level) from VAC18194RSV2001 
collected up to this point (from at least the first 12 toddlers), including solicited AEs, unsolicited 
AEs and SAEs through 28 days after the first dose of 5×1010 vp of Ad26.RSV.preF; immune 
response data (RSV F protein binding antibodies [pre-F and/or post-F], RSV virus neutralization 
assay, and Th1/Th2 subtyping) through 28 days after the first dose are also expected to be 
available for additional toddlers dosed in VAC18194RSV2001. The continued general safety and 
tolerability of the vaccine in VAC18194RSV2001 will further support the expectation that safety 
will be acceptable at the dose of 2.5x1010 vp in the current study.
The 2.5×1010 vp dose will be used in the current study because this dose has been highly 
immunogenic for the individual Ad26 vector components in the sponsor’s HIV vaccine program 
where induction of Th1 responses in antigen-naïve individuals, similar to antigen-naïve 
RSV-seronegative toddlers, has been observed. It is hypothesised that an adenovirus-vectored 
vaccine with a Th1 profile against RSV will reduce the likelihood of disease enhancement in 
RSV-seronegative recipients. The 2.5×1010 vp dose is therefore thought to be an appropriate dose 
to start with for preliminary ERD assessment in RSV-seronegative toddlers before progressing to 
younger age groups, and performing dose-response assessments, in future studies.
Blinding, Control, Study Phase/Periods, Vaccine Groups
Controls (Nimenrix or placebo) will be used to establish the frequency and magnitude of changes 
in endpoints that may occur in the absence of Ad26.RSV.preF vaccine. Randomization will be 
used to minimize bias in the assignment of subjects to vaccine groups, to increase the likelihood 
that known and unknown subject attributes (eg, demographic and baseline characteristics) are 
evenly balanced across vaccine groups, and to enhance the validity of statistical comparisons 

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across vaccine groups. Blinded treatment will be used to reduce potential bias during data 
collection and evaluation of endpoints.
The incorporation of a licensed vaccine as an alternative to placebo offers a more accepted 
approach to this pediatric vaccine study. Nimenrix has been selected for incorporation in the 
design of this study as the recommended one-dose vaccination in the targeted age group matches 
the existing study design, which is essential to preserve the blind in the current study.
3.3.
Risk/Benefit Section
3.3.1.
Known Benefits
The clinical benefits of vaccination with Ad26.RSV.preF have yet to be established.
In countries where the commercial vaccine Nimenrix q is licensed, Nimenrix will be incorporated 
as the Day 57 vaccination for subjects in the control group, in accordance with the local label and 
local regulations, and unless contra-indicated. Nimenrix will be administered, only if permitted 
by the subject’s parent/legal guardian and following PI assessment on a case-by-case basis as 
vaccination with Nimenrix outside this study might be preferred (joint parent/legal guardian and 
PI decision). See Attachment 2 for further details.
Vaccination with Nimenrix may provide protection against invasive meningococcal disease 
caused by N. meningitidis.
3.3.2.
Potential Benefits
Ad26.RSV.preF is under development for prophylaxis of RSV, however vaccine efficacy has not 
yet been investigated. There is no direct medical benefit to the subject for participation in this 
clinical study. Although study subjects 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.
3.3.3.
Known Risks
Single doses of 5×1010 vp of Ad26.RSV.preF are under investigation in the ongoing FIH Phase 1 
study VAC18193RSV1003 in elderly subjects. Safety data from the unblinded interim analyses 
at 28 days post-Dose 1 and at 6 months post-Dose 1 in all subjects did not reveal safety concerns. 
The unblinded interim analysis 6 months post-Dose 1 also confirmed the immunogenicity seen at 
28 days post-Dose 1 over time.
The most common side effects from initial vaccination with Nimenrix (seen in more than 
1 patient in 10) are loss of appetite, irritability, drowsiness, tiredness, headache, fever, swelling, 
and pain and redness at the site of injection.12
                                                
q
Nimenrix is a vaccine used to protect adults, adolescents, and children from the age of 6 weeks against invasive 
meningococcal disease caused by 4 groups of the bacterium Neisseria meningitidis (group A, C, W-135, and Y).12

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For further details, see the Nimenrix Summary of Product Characteristics.
3.3.4.
Potential Risks
The following potential risks for Ad26.RSV.preF will be monitored during the study.
Risks Related to Vaccination
In general, intramuscular injection may cause local itching, warmth, pain, tenderness, 
erythema/redness, induration/swelling, arm discomfort or bruising of the skin at vaccine 
injection sites.
Subjects may exhibit general signs and symptoms associated with administration of a vaccine, or 
vaccination with placebo, including (in pediatric subjects:) loss of appetite, vomiting, diarrhea, 
decreased activity/lethargy, irritability/crying. These side effects will be monitored, but are 
generally short-term and do not require treatment.
Subjects 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. Subjects with 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) will be excluded from the study. Sites should have medical treatment and 
medically qualified staff 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 2.5×1010 vp, 5×1010 vp or 1×1011 vp.21,22
Local AEs (moderate injection site pain and tenderness, and moderate to severe redness at the 
injection site) and systemic AEs (headache, chills, joint pain, muscle pain, tiredness/generally 
not feeling well/fatigue and fever) have been reported after vaccination with Ad26-vectored 
vaccines. In a few subjects, transient laboratory abnormalities have been seen, 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 subjects.
For further details on the safety profiles of other Ad26-vectored vaccine candidates, refer to the 
Ad26.RSV.preF Investigator’s Brochure.1
An Ad35-vectored vaccine (AERAS-402) has been tested in two completed clinical studies in 
infants: data from these studies indicate acceptable safety at doses from 1×108 vp to 1×1011 vp in 
infants aged 14 weeks and older.

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Risks Related to RSV Vaccines
In the 1960s, an FI-RSV vaccine was associated with ERD in young children, characterized by 
an increased rate of RSV-mediated, severe LRTI in the vaccinated individuals compared to a
control group.8,13,26,27 Children aged between 2 months and 7 years were vaccinated; the risk of 
ERD was highest among children under 6 months of age. In the study with the most severe 
outcomes, RSV infection was confirmed in 20/31 (65%) children who received the FI-RSV 
vaccine, with 16/20 children requiring hospitalization due to severe LRTI (52% of all FI-RSV 
vaccinees, representing 80% of those being RSV-infected). In contrast, while RSV infection was 
observed in 21/40 (53%) children who received a control vaccine, only one hospitalization due to 
severe LRTI (2.5% of all control vaccinees, representing 5% of those being RSV-infected) was 
required. Two FI-RSV vaccinated children died.27 ERD is characterized by increased pulmonary 
inflammatory response and mucin production leading to reduced oxygen exchange in the lungs.
Although the mechanisms for ERD are not fully understood, it is thought that FI-RSV: 1) may 
have failed to induce adequate neutralizing antibody titers; 2) may have led to overproduction of 
binding antibodies promoting immune complex deposition and hypersensitivity reactions; 3) may 
have failed to induce adequate numbers of memory CD8+ T-cells important for viral clearance; 
or 4) may have induced a Th2-skewed allergic type T-cell response.35
In general, adenoviral-vectored vaccines have been shown to promote a Th1-biased response.41
Single immunization with low doses of Ad26.RSV.preF protects cotton rats from challenge with 
the vaccine-homologous RSV-A2 and the heterologous B Wash strain, without induction of any 
histopathological signs of ERD. This Th1 profile of Ad26.RSV.preF reduces the likelihood of 
disease enhancement in RSV-seronegative infants.
Risks from Collection of Nasal Samples
Collection of nasal samples may cause a nosebleed.
Risks from Blood Draws
As with all clinical studies requiring blood sampling, there are risks associated with venipuncture
and multiple blood sample collection. Blood drawing may cause pain, tenderness, bruising, 
bleeding, dizziness, vasovagal response, syncope, and, rarely, infection at the site where the 
blood is taken. The total blood volume to be collected is considered to be an acceptable amount 
of blood over this time period from the population in this study (see Section 16.1, Study-Specific 
Design Considerations).
Subjects 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 as in immunocompetent 
individuals. However, the magnitude, breadth, and persistence of the immune response to 
vaccination may be reduced or absent in immunocompromised persons. Subjects with abnormal 
function of the immune system will be excluded from the study.

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Concomitant Vaccination
Concomitant vaccination might have an influence on both safety profile and immunogenicity of 
Ad26.RSV.preF. Likewise, Ad26.RSV.preF might have an influence on both safety profile and 
immunogenicity of any concomitant vaccination. As a result, vaccination with live attenuated 
vaccines within 28 days of a study vaccination (ie, before and after) is prohibited. Other vaccines 
(eg, influenza, tetanus, hepatitis A, hepatitis B, rabies) should be given at least 14 days before (or 
at least 14 days after) administration of study vaccine. If a vaccine is indicated in a post-exposure 
setting (eg, rabies or tetanus), it must take priority over the study vaccine. Note: Planning for 
routine childhood vaccinations will be available from the site to ensure that these can be taken at 
appropriate times during the study.
Unknown Risks
There may be other risks that are not known. If any significant new risks are identified, the PI(s) 
and parent(s)/legal guardian(s) of subjects will be informed.
3.3.5.
Overall Benefit/Risk Assessment
Based on the available data and proposed safety measures, the overall benefit/risk assessment for 
this clinical study is considered acceptable for the following reasons:
Preliminary safety data from the ongoing clinical studies and safety data generated with the 
related vaccines containing different inserts revealed no significant safety issues.
Only subjects who meet all inclusion criteria and none of the exclusion criteria (specified in 
Section 4) will be allowed to participate in this study. The selection criteria include adequate 
provisions to minimize the risk and protect the well-being of subjects in the study.
Safety will be closely monitored throughout the study:
After each vaccination, subjects will be closely observed by study staff for a minimum of
30 minutes (or 60 minutes, depending on local or study-site requirements) post-
vaccination, or longer if deemed necessary by the investigator, to monitor the development 
of any acute reactions. Any unsolicited and solicited local or systemic AEs will be 
documented during this period. The subject’s parent/legal guardian or caregiver will use a 
diary to document solicited local and systemic AEs in the evening after each vaccination 
and then daily for the next 7 days at approximately the same time each day.
Subjects will undergo safety follow-up by study staff 72 hours after each vaccination by 
telephone.
Unsolicited AEs will be documented from immediately prior to until 28 days after each 
vaccination. SAEs will be recorded from first dose administration through the end of the 
study.

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Any clinically significant abnormalities (including those persisting at the end of the study
or at early withdrawal) will be followed by the investigator until resolution or until a 
clinically stable endpoint is reached.
Several safety measures are included in this protocol to minimize the potential risk to subjects, 
including the following:
Safety review by the PI(s) or designee and SRP/S of 7-day safety data in the first 8 subjects 
after the first dose; safety review by the IDMC of 7-day safety data in the first 12 subjects 
after the first dose. These safety assessments at 7 days post-first dose are described in 
Section 3.1.
For all subjects, there are pre-specified rules that would result in pausing of further study 
vaccinations if predefined conditions occur, preventing exposure of new subjects to study 
vaccine until the PI(s) or designee/SRP/S and IDMC reviews all safety data (see
Section 11.10).
Subjects will discontinue study vaccine for the reasons included in Section 10.2.
If acute illness (excluding minor illnesses such as diarrhea) or fever (body temperature 
≥38.0°C) occur at the scheduled time for the first vaccination, the subject may be enrolled 
at a later dater, or be withdrawn at the discretion of the investigator and after consultation 
with the sponsor.
If acute illness (excluding minor illnesses such as diarrhea) or fever (body temperature 
≥38.0 °C) occur at the scheduled time for the second or third vaccination, the subject may 
be vaccinated up to 10 days beyond the scheduled vaccination, or be withdrawn from 
further vaccination at the discretion of the investigator and after consultation with the 
sponsor. In the event of an ongoing AE or other situation precluding subject vaccination 
within 10 days, subjects may be vaccinated beyond the 10-day window at the discretion of 
the sponsor.

Contraindications to vaccination are included in Section 10.3.

During the RSV season, careful monitoring will be in place to check for the occurrence of 
RTI/otitis media s. The subject’s parent/legal guardian or caregiver will record any signs 
and symptoms of RTI (eg, runny nose, fever, severe cough, wheezing, rapid breathing, or 
difficulty breathing) on a daily basis using the study-specific RTI Symptoms Form, starting 
on the first day their child experiences symptoms, including the day on which symptoms 
resolve. Nasal samples will be collected by the site staff and analyzed for identification and 
confirmation of RSV infection. The presence of severe LRTI and RSV infection will be 
determined by the CEC. The IDMC will be informed of any case of severe RSV-LRTI as 
assessed by the CEC. For such cases, a monitoring rule is applied (see Section 11.3.1.3).
                                                
r
If within the screening window. Otherwise, rescreening is required.
s
Note: The RTI procedures (see Section 9.2.2) also apply to all otitis media cases.

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Assuming all subjects are recruited before the season, if 4 severe RSV-LRTI events are 
observed and all occur in the Ad26.RSV.preF group, enrollment in all pediatric studies 
with Ad26.RSV.preF will be halted and monitoring of all enrolled subjects will be 
increased (see Section 11.3.1.3).
Nimenrix has been shown to be at least as effective as comparable vaccines at stimulating an 
immune response to the 4 groups of the N. meningitidis bacterium in people of different age 
groups. Nimenrix offered the benefits of conjugated vaccines over conventional vaccines, 
including producing a strong immune response in young children. Nimenrix is well-tolerated and 
it can be safely given together with other routinely used vaccines in the different age groups.12
4.
SUBJECT POPULATION
Screening for eligible subjects will be performed within 42 days before administration of the first 
dose of study vaccine.
The inclusion and exclusion criteria for enrolling subjects 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 subject in the study. Waivers are not allowed.
Note: Investigators should ensure that all study enrollment criteria have been met at screening. If 
a subject’s clinical status changes (including 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 subject 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 subject must satisfy all of the following criteria to be enrolled in the study:
1.
Criterion amended per Amendment 5:
1.1
Each subject’s parent(s)/legal guardian(s) must sign an informed consent form (ICF)
indicating that he/she understands the purpose of and procedures required for the 
study, are willing for his/her child to participate in the study and attend all scheduled 
visits, and are willing and able to comply with all study procedures, including 
maintaining contact with the site for 2 RSV seasons following the first dose, and 
adhere to the prohibitions and restrictions specified in this protocol.
Note: For each subject, at least one parent or legal guardian, according to local 
regulations, must give written consent. In countries where regulation requires that 
both parents/legal guardians give consent, this will be applicable.

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2.
Criterion amended per Amendment 4:
2.1
Subject is male or female, whose age on the day of ICF signature is ≥12 months to 
≤24 months and who is seronegative for RSV within 42 days prior to dosing.
Note: Serostatus may be assessed via the RSV EIA if available from a different study
of the sponsor (VAC18194RSV2001). If done within 42 days of first dose, this 
assessment would not have to be repeated in the absence of a history of respiratory 
infection during that period.
3.
Subject is the product of a normal term pregnancy ≥37 weeks, with a minimum birth 
weight of 2.5 kg.
4.
Subject must be in good health without any significant medical illness on the basis of 
physical examination, medical history, and vital signs performed at screening.
5.
Subject has received all routine immunizations appropriate for his or her age according to 
local guidelines.
6.
Each subject’s parent(s)/legal guardian(s) must have access to a consistent means of 
contact either by telephone contact or email/computer.
4.2.
Exclusion Criteria
Any potential subject who meets any of the following criteria will be excluded from participating 
in the study:
1.
Criterion amended per Amendment 4:
1.1
Subject has moderate or severe illness (this does not include minor illnesses such as 
diarrhea) or temperature ≥38.0 ºC within 24 hours prior to the first dose of study 
vaccine; the subject may be enrolled at a later datet, or be withdrawn at the discretion 
of the investigator and after consultation with the sponsor.
2.
Any subject who has had an RTI between screening and randomization that the PI(s) feels 
would make them ineligible.
3.
Subject’s weight is below 10th percentile according to World Health Organization (WHO) 
pediatric growth and weight charts.7
4.
Subject has any clinically significant acute or chronic medical condition (eg, history of 
seizure disorders, bleeding/clotting disorder, autoimmune disease, active malignancy, 
systemic infections, congenital heart disease, history of any pulmonary condition requiring 
medication, 
atopy, 
reactive 
airway 
disease, 
medically-confirmed 
wheezing, 
bronchoconstriction or treatment with a β2 agonist, cystic fibrosis, bronchopulmonary 
dysplasia, chronic pulmonary disease, medically-confirmed apnea, hospitalization for 
respiratory illness, or mechanical ventilation for respiratory illness) that, in the opinion of 
                                                
t
If within the screening window. Otherwise, rescreening is required.

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the investigator, would preclude participation.
5.
Subject has major congenital anomalies (after discussion with the SRP/S) or known 
cytogenetic disorders (eg, Down’s syndrome).
6.
Subject has had major surgery within the 4 weeks prior to randomization or has planned 
major surgery through the course of the study.
7.
Subject is in receipt of, or planning to receive, live attenuated vaccine (eg, measles, mumps 
and rubella [MMR] or varicella, but excluding rotavirus vaccine) within 28 days of each 
study vaccination (ie, before and after); other vaccines (eg, influenza, pertussis, polio or 
rotavirus) should be given at least 14 days before or 14 days after each study vaccination.
Note: Planning for routine childhood vaccinations will be available from the site to ensure 
that these can be taken at appropriate times during the study.
8.
Subject has known or suspected immunodeficiency, such as known HIV infection.
9.
Subject 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 this study.
Note: Participation in an observational clinical study (ie, with no intervention) is allowed 
upon approval of the sponsor.
10.
Criterion amended per Amendment 2:
10.1 Subject has a known allergy to vaccines or vaccine components (including any of the 
constituents of the study vaccine), or history of anaphylaxis or other serious adverse 
reactions to vaccines or vaccine components (including any of the constituents of the 
study vaccine). Note: subjects with egg allergies can be enrolled.
11.
Criterion amended per Amendment 3:
11.1 Subject has a history of the following moderate to severe chronic conditions: 
urticaria (recurrent hives), eczema and/or atopic dermatitis. 
12.
Subject has a history of acute polyneuropathy (eg, Guillain-Barré syndrome).
13.
Subject has chronic or recurrent use of immunomodulators/suppressors, eg, cancer 
chemotherapeutic agents, oral or parenteral corticosteroids for at least 5 days within 42
days prior to randomization, or planned during the study.
14.
Subject has a history of receipt of blood products or immunoglobulin within 3 months of 
randomization. 
15.
Subject has been in receipt of palivizumab/Synagis® or received any other vaccine or 
monoclonal/polyclonal antibody in a previous RSV study at any time prior to 
randomization.
16.
Subject has a contraindication to intramuscular injections and blood draws, eg, bleeding 
disorders.

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17.
Subject has a history of an underlying clinically significant acute or chronic medical 
condition or physical examination findings for which, in the opinion of the investigator, 
participation would not be in the best interest of the subject (eg, compromise the well-
being) or that could prevent, limit, or confound the protocol-specified assessments.
18.
Subject’s parent(s)/legal guardian(s) cannot communicate reliably with the investigator.
19.
Criterion amended per Amendment 4:
19.1 Subject is a family member of either the investigator, 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, or employee of the sponsor.
4.3.
Prohibitions and Restrictions
Potential subjects must be willing and able to adhere to the following prohibitions and 
restrictions during the study to be eligible for participation:
1.
See Section 8, Pre-study and Concomitant Therapy, for details on prohibited and restricted 
therapy during the study.
2.
Agree to follow all requirements that must be met during the study as noted in the 
Inclusion and Exclusion Criteria.
3.
Vaccination with live attenuated vaccines within 28 days of a study vaccination (ie, before 
and after) is prohibited. Other vaccines (eg, influenza, tetanus, hepatitis A, hepatitis B, 
rabies) should be given at least 14 days before (or at least 14 days after) administration of 
study vaccine in order 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 study vaccine.
4.
Subjects should receive all routine immunizations according to applicable national 
guidelines. A subject will not postpone, forego or delay the receipt of any recommended 
vaccine according to local schedules (eg, in Europe, the applicable national immunization 
schedules,10 and the equivalent in other countries) due to participation in the current study. 
All subjects should receive routine immunizations according to schedule.
5.
STUDY VACCINE ALLOCATION AND BLINDING
Study Vaccine Allocation
Central randomization will be implemented in this study. Subjects will be randomly assigned to a 
treatment 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. No stratification will be applied.
The randomization ratio is 1:1.

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The interactive web response system (IWRS) will assign a unique code, which will dictate the 
group assignment for the subject. The requestor must use his or her own user identification and 
personal identification number when contacting the IWRS, and will then give the relevant 
subject details to uniquely identify the subject.
If randomized subjects are withdrawn from vaccination before the first dose is administered, 
additional subjects may be recruited to replace these subjects at the discretion of the sponsor. 
Any replacement subject will be assigned to the same group as the original (discontinued) 
subject. The replacement subject’s randomization number will equal the randomization number 
of the discontinued subject +1000 (for example subject 0001 would be replaced by subject 
1001). These additional subjects should also be randomized through IWRS.
Any randomized subject 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 subject will be assigned to the same group as the original (discontinued) 
subject. The replacement subject’s randomization number will equal the randomization number 
of the discontinued subject +2000.
Every effort will be made to determine the serostatus of subjects. During the study, any subject 
who was assessed as seronegative at screening and who subsequently shows an anamnestic 
response at Day 8 will be replaced if possible.
Blinding
The investigator will not be provided with randomization codes until the final analysis is 
performed. The codes will be maintained within the IWRS, which has the functionality to allow 
the investigator to break the blind for an individual subject.
Unblinding will occur at the time of the primary analysis. The results will only be available to a 
selected group of sponsor personnel, excluding personnel involved in data collection and data 
management and clinical immunology laboratory personnel. From the primary analysis onwards, 
group level results may be shared with the investigator or other blinded clinical staff, as needed, 
however, efforts will be made to preserve the blinding to the individual subject allocation.
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 electronic case report form (eCRF), and in the source document. 
Documentation received from the IWRS indicating the code break must be retained with the 
subject’s source documents in a secure manner.

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The subjects, the subject’s parent/legal guardian or caregiver, study-site personnel and 
investigator, as well as sponsor personnel involved in data collection and data management and 
clinical immunology laboratory personnel, will be blinded to study vaccine allocation throughout 
the study, except for the pharmacist or qualified staff member with primary responsibility for 
study vaccine preparation and dispensing. The pharmacy and the preparation of study vaccines 
will be monitored by an independent study 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.
In general, randomization codes will be disclosed fully only if the study is completed and the 
clinical database is closed. If the randomization code is broken by the investigator or the study-
site personnel, the subject 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 subject should not discontinue further study vaccine 
administration and may remain in the study (if the randomization code is still blinded to the 
study-site personnel and the subject’s parent/legal guardian or caregiver).
6.
DOSAGE AND ADMINISTRATION
Every effort will be made to administer the first 2 doses before the start of the RSV season.
Ad26.RSV.preF (JNJ-64400141) will be supplied in single-use vials. The dose of 2.5×1010 vp 
will be administered in a volume of 0.25 mL by intramuscular injection. Placebo will be supplied 
as sterile 0.9% saline for intramuscular injection. Nimenrix u will be supplied as Nimenrix 
powder and solvent for solution for injection in pre-filled syringe or ampoule and administered 
as 0.5 mL solution for intramuscular injection.
The unblinded pharmacist, or other qualified individual, may also perform
vaccine
administration, but will have no other study function following dosing.
To ensure that the site staff or qualified professional staff who will do the observation as well as 
the subjects (and their parents/legal guardians) will be blinded, the necessary precautions will be 
taken as documented by the clinical sites and agreed upon by the sponsor.
Details on study vaccine preparation will be provided in the Investigational Product Preparation 
Instructions.
                                                
u
In countries where the commercial vaccine Nimenrix is licensed, placebo (0.9% saline) can be replaced with Nimenrix as the 
Day 57 vaccination for the study subjects in the control group, in accordance with the local label and local regulations, and 
unless contra-indicated. Nimenrix will be administered, only if permitted by the subject’s parent/legal guardian and following 
PI assessment on a case-by-case basis as vaccination with Nimenrix outside this study might be preferred (joint parent/legal 
guardian and PI decision). In the US, Nimenrix will not be used unless it has been licensed for use or an IND has been 
submitted.

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Injections should be administered in the anterolateral aspect of the thigh. Only if required by local 
health authority guidance, injections may be administered in the deltoid muscle v. Alternating 
injection sites will be used for all study vaccinations unless there is a medically justifiable reason 
in the judgment of the PI(s).
A play assistant may be present to distract the infant/toddler while the subject’s parent/legal 
guardian or caregiver holds the child to receive the vaccination.
7.
STUDY VACCINE COMPLIANCE
Study vaccine will be administered intramuscularly by a study 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 administered 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 time of each vaccine 
administration through 28 days after each vaccination, and additionally outside of these periods 
when associated with SAE(s), RTI or OM case that meet the criteria outlined in Section 12.3.2.
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.
Subjects can receive medications such as acetaminophen, non-steroidal anti-inflammatory drugs, 
or antihistamines as needed, although their use must be documented and use of these medications 
as routine prophylaxis prior to study vaccination is discouraged, unless if specified by the 
sponsor. (Note: The use of EMLA® Cream [2.5% lidocaine and 2.5% prilocaine] as a topical 
anesthetic will not be prohibited during the study.)
Chronic or recurrent use of immunomodulators/suppressors, eg, cancer chemotherapeutic agents, 
oral or parenteral corticosteroids for at least 5 days is prohibited within 42 days prior to 
randomization, or planned during the study.
If chronic use of prohibited therapies becomes medically indicated during the study for any 
subject, the sponsor should be contacted.
                                                
v
For each vaccination, a record should be made in the eCRF of which leg (or arm) was injected.

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Vaccination with live attenuated vaccines within 28 days of a study vaccination (ie, before and 
after) is prohibited. Other licensed vaccines (ie, not live) should be given at least 14 days before 
or at least 14 days after administration of study vaccine in order 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 study vaccine.
Planning for routine childhood vaccinations will be available from the site to ensure that these 
can be taken at appropriate times during the 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 EVALUATIONS
9.1.
Study Procedures
9.1.1.
Overview
Evaluation of safety and reactogenicity will include physical assessment by study-site personnel, 
and the subject’s parent/legal guardian or caregiver reports on signs and symptoms post-
vaccination. Additional visits may be required if in the investigator’s opinion, further clinical or 
laboratory evaluation is needed.
Each subject’s parents/legal guardian or caregiver will be provided with a thermometer, ruler, 
and subject diary to measure and record body temperature and solicited local (at the injection 
site) and solicited systemic AEs.
The diary includes instructions how to capture the data and grading scales to assess severity of 
the symptoms. Study staff are responsible for providing appropriate training for diary completion 
to avoid missing or incorrect data. The diary will be reviewed by study personnel at visits 
indicated on the Time and Events Schedule.
At each visit or telephone call during the RSV season, each subject’s parent/legal guardian or 
caregiver should be informed that, if their child develops any symptoms of RTI (such as runny 
nose, fever, severe cough, wheezing, rapid breathing, or difficulty breathing) or otitis media, they
should record signs and symptoms of RTI and contact the site as soon as possible w.
The Time and Events Schedule summarizes frequency and timing of safety and immunogenicity 
measurements applicable to this study. Additionally, a summary of Procedures in the Event of an 
RTI is provided showing procedures applicable for both parents/guardians and for the study site.
The total blood volume to be collected from each subject over approximately 36 to 40 weeks 
from screening will be approximately 13.5 mL.
                                                
w
Note: The RTI procedures (see Section 9.2.2) also apply to all otitis media cases.

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9.1.2.
Visit Windows
For the following visits, windows will be allowed as indicated:

Second vaccination: ±3 days

Third vaccination: ±3 days

3 days post-vaccination safety only visit: ±1 day

7 days post-vaccination safety and immunogenicity visit: after first dose: –1/+3 days; after 
second and third doses: ±2 days

28 days post-final vaccination safety and immunogenicity visit: ±3 days

6 months post-final vaccination safety visit: ±14 days

End of RSV season safety and immunogenicity visit: +28 days
9.1.3.
Screening and Study Visits
Note: It is possible for any visit to be conducted in the subject’s home if the site has an 
established Standard Operating Procedure as such.
9.1.3.1.
Screening Phase: Days -42 to 1
Only healthy subjects without acute illness or fever and complying with the inclusion and 
exclusion criteria specified in Section 4.1 and Section 4.2, respectively, will be included into the 
study. The investigator will provide detailed information on the study to the subject’s 
parent(s)/legal guardian(s) and will obtain his/her written informed consent prior to the subject’s 
participation in the study. All the procedures described in the Time and Events Schedule will 
only take place after written informed consent has been obtained. Note: In countries where 
regulation requires that both parents/legal guardians give consent, this will be applicable.
The following evaluations will be performed to determine eligibility requirements as specified in
the inclusion and exclusion criteria:

Physical examination including vital signs measurement (respiratory rate, heart rate, body 
temperature, oxygen saturation [SpO2]) and length and weight

Demographic information

Medical history

Review of pre-study medications

Review of inclusion/exclusion criteria

Blood sample for immunogenicity testing*

Nasal sample for immunogenicity testing*

Blood sample for RSV serostatus testing**

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* Collection of blood samples and nasal samples for baseline immunogenicity assessments can 
be either at screening or pre-dose on Day 1, at the discretion of the investigator, however both 
samples should be collected on the same day. Note: If blood is collected by fingerstick for RSV 
serostatus at screening, baseline blood draw for immunogenicity should be on Day 1.
** By venous blood sample or fingerstick, at the discretion of the investigator.
Note: At screening, information will also be collected whether the toddler is currently breastfed, 
with breastfeeding history, number and ages of siblings, and whether family members smoke in 
the home environment, with smoking history.
RSV seropositivity will be assessed by RSV EIA at screening. The cut-off for seronegativity is a 
titer <1 EIA unit. Note: Serostatus may be assessed via this assay if available from a different 
study of the sponsor (VAC18194RSV2001). If done within 42 days of first dose, this assessment 
would not have to be repeated in the absence of a history of respiratory infection during that 
period. Every effort will be made to determine the serostatus of subjects. Any subject who was 
assessed as seronegative at screening and who subsequently shows an anamnestic response at 
Day 8 will be replaced if possible.
The seronegative status will be confirmed by the absence of an anamnestic humoral immune 
response from blood samples taken 7 days after the first dose. An anamnestic response is defined 
as a >4-fold increase in pre-F ELISA within 7 days post Dose 1. The criteria for assessment of 
the anamnestic response will be specified in the SAP.
General eligibility for this clinical study will be dependent on results of the medical assessment. 
Study subjects who qualify for inclusion based on the medical history and physical examination 
will be scheduled for enrollment and first vaccination (Visit 2) within 42 days. If necessary, the 
screening visit may be split into several visits.
After medical history and physical examination data have been reviewed for completeness and 
adherence to inclusion and exclusion criteria, the subject can be deemed eligible for the study.
The sponsor collects AEs, whether serious or non-serious, related to the study procedures or non-
investigational (concomitant) Janssen products from ICF signature onwards. SAEs (and any 
associated concomitant medications) 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.
Between screening and Day 1, only MA-RTIs (including severe LRTIs) will be collected. Any 
MA-RTI or severe LRTI which occurs during this period will be recorded on the Medical 
History page of the eCRF.

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9.1.3.2.
Vaccination Phase: Day 1 to Day 239
9.1.3.2.1.
Vaccination (Days 1, 29, and 57)
Visit 2: Day 1/Day of Randomization/Vaccination 1
After re-check of the inclusion and exclusion criteria,x abbreviated physical examination (at the 
discretion of the investigator) and measurement of vital signs, length and weight, eligible 
subjects will be randomized as described in Section 5. If medical status and/or physical 
examination suggests significant changes have occurred since screening, either the Day 1 visit 
can be re-scheduled, or the subject excluded from the study if he/she fails to meet the inclusion 
and exclusion criteria. Before the first vaccination, the investigator must check for any symptoms 
of an acute illness or body temperature ≥38.0 °C. In such a situation, the subject may be enrolled 
at a later datey, or be withdrawn at the discretion of the investigator and after consultation with 
the sponsor.
Collection of blood samples and nasal samples for baseline immunogenicity assessments can be 
either at screening or pre-dose on Day 1, at the discretion of the investigator, however both 
samples should be collected on the same day. If fingerstick sampling for RSV serology is done at 
screening, blood draw for immunogenicity should be on Day 1.
Administration of first dose of study vaccine.
Subjects will be closely observed for a minimum of 30 minutes (or 60 minutes, depending on 
local or study-site requirements) 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 and vital signs will be documented in the eCRF by study-site personnel 
following this observation period.
A subject diary, thermometer, and ruler will be provided to measure and record body temperature 
and solicited local and systemic AEs for 7 days post-vaccination.
RTI Symptoms Forms will be distributed to each subject’s parent/legal guardian or caregiver.
See Section 9.2.2 for details on completion of the RTI Symptoms Form.
Visits 5 and 8: Day 29/Vaccination 2 and Day 57/Vaccination 3
After verification of selected eligibility criteria,a abbreviated physical examination (at the 
discretion of the investigator) and measurement of vital signs, length and weight will be 
performed for all subjects pre-vaccination. Before the second or third vaccination, the 
investigator must check for any symptoms of an acute illness. In such a situation, the subject may 
be vaccinated up to, and no later than 10 days after the scheduled vaccination, or be withdrawn at 
                                                
x
Exclusion criterion 1, 2, 3, 4, 6, 7, 9, 10, 11, 13, 14, 15, 16, 17, and 18.
y
If within the screening window. Otherwise, rescreening is required.

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the discretion of the investigator and after consultation with the sponsor. In the event of an 
ongoing AE or other situation precluding subject vaccination within 10 days, subjects may be 
vaccinated beyond the 10-day window at the discretion of the sponsor.
Administration of study vaccine.
Subjects will be closely observed for a minimum of 30 minutes (or 60 minutes, depending on 
local or study-site requirements) 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 and vital signs will be documented in the eCRF by study-site personnel 
following this observation period.
A subject diary, thermometer, and ruler will be provided to measure and record body temperature 
and solicited local and systemic AEs for 7 days post-vaccination.
RTI Symptoms Forms will be distributed to each subject’s parent/legal guardian or caregiver.
9.1.3.2.2.
Post-vaccination Follow-Up
9.1.3.2.2.1.
Post-first, Post-second and Post-third Vaccination Follow-Up
Visits 3 and 4 (3 and 7 Days Post-first Vaccination), Visits 6 and 7 (3 and 7 Days Post-
second Vaccination) and Visits 9 and 10 (3 and 7 Days Post-third Vaccination)
Visits 3, 6 and 9 at 3 days post-vaccination will be a telephone call to check subject diaries and 
to collect safety information (solicited and unsolicited AEs, SAEs, concomitant medications, and 
RTIs).
Visits 4, 7 and 10 at 7 days post-vaccination will include an abbreviated physical examination 
(at the discretion of the investigator), vital signs measurement, and recording of any (serious) 
AEs, concomitant medications and RTIs. The subject diary will be reviewed and collected. If 
Visit 4 occurs before the end of Day 8, Visit 7 occurs before the end of Day 36 or Visit 10 occurs 
before the end of Day 64 (ie, before the end of the post-vaccination diary period), review of the 
diary will still take place, but the diary will be returned by the subject’s parent/guardian or 
caregiver at the next visit (ie, Visit 5, Visit 8 or Visit 11, respectively).
A blood sample for immunogenicity assessments will be collected from all subjects 7 days post-
first vaccination.
Note: If any subject comes in earlier than Day 8 for Visit 4, Day 36 for Visit 7 or Day 64 for 
Visit 10 (allowed windows are -1/+3, ±2 days, and ±2 days, respectively), 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 (ie, Day 8, Day 36 or Day 64, 
respectively).

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9.1.3.2.2.2.
Post-last Vaccination Follow-Up
Visits 11 and 12 (28 Days and 6 Months Post-third Vaccination)
Visits 11 and 12 will include an abbreviated physical examination including vital signs 
measurement (at the discretion of the investigator), measurement of length and weight, recording 
of unsolicited AEs (Visit 11 only), any RTIs, any SAEs, concomitant medications, and any MA-
RTIs.
Samples for immunogenicity assessments will be collected at Visit 11.
A nasal sample will be collected 28 days post-final vaccination from all subjects at Visit 11.
Parents/legal guardians or caregivers (where allowed by local regulations) will be invited to 
complete an Institutional Review Board/Independent Ethics Committee (IRB/IEC) approved 
Participant Experience Survey at Visit 12 (See Section 9.2.4).
9.1.3.2.3.
End of RSV Season Visit
The end of season visit will include an abbreviated physical examination including vital signs 
measurement (at the discretion of the investigator), measurement of length and weight, any RTIs, 
any SAEs, concomitant medications, and any MA-RTIs.
Samples for immunogenicity (humoral) assessments will be collected.
Subjects’ parents/legal guardians 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 (if 
available) or the local surveillance at the site (standard of care assessments, if available).
9.1.3.2.4.
Early Withdrawal: Early Exit Visit
For those subjects who are unable to continue participation in the study up to the visit at the end 
of the RSV season, but for whom consent is not withdrawn, an early exit visit will be conducted 
as soon as possible. In the event of early withdrawal from the study, all procedures required at 
Visit 12 will be performed (see Section 9.1.3.2.2.2). Samples for immunogenicity assessments 
will be collected at the early exit visit as follows: if the early exit visit is before Day 85, 4 mL for 
cellular assessments and 1 mL for humoral assessments will be collected; if the early exit visit is 
after Day 85, only 2 mL for humoral assessments will be collected.
If the early exit visit occurs within 7 days of the last vaccination, solicited AEs will be recorded; 
if the early exit visit occurs within 28 days of the last vaccination, unsolicited AEs will be 
recorded.
Note: Subjects for whom consent is withdrawn only for blood draws may remain in the study and 
continue to receive study vaccine and undergo safety follow-up.

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9.1.3.3.
Safety Follow-up 
Each subject’s parent/legal guardian or caregiver will be contacted by telephone (or other 
communication, or clinic visit) through 2 RSV seasons after the first dose, including during the 
vaccination phase and safety follow-up phase (every 30 days ±7 days outside of the RSV season, 
and every 14 days ±3 days within the RSV season, unless the timing coincides with a visit).
During the RSV season, these calls will remind the parents/legal guardians or caregivers to 
contact the site if their child develops any symptoms of RTI/otitis media; during and outside the 
RSV season, these calls will be to check for any SAEs and associated concomitant medications, 
any MA-RTIs/medically-attended otitis media cases, and any subsequent medical care that may 
have been sought, since the previous visit or telephone contact (this includes contacts with 
subjects who received at least one dose of study vaccine but withdrew from further dosing).
The follow-up phase will include all subjects who received at least one dose of study vaccine.
9.2.
Study Evaluations
9.2.1.
Immunogenicity
Venous blood samples will be collected for the determination of humoral and cellular responses 
according to the Time and Events Schedule. Sample collection and processing will be performed 
by the staff at clinical sites according to current and approved Standard Operating Procedures.
The humoral and cellular immunogenicity assays that may be used in this study (as available and 
applicable) are summarized in Table 5 and Table 6, respectively.
Immunogenicity samples will be prioritized as outlined in the Laboratory Manual.
Table 5:
Summary of Immunogenicity Assays (Humoral)
Assay 
Purpose
Secondary endpoints
RSV neutralization A strain
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-F and post-F specificity by binding or functional assays as ELISA, 
and/or competition ELISA, epitope mapping, and functional VNAs
Nasal Ig antibodies to RSV F 
protein 
Analysis includes, but not limited to, IgA or IgG antibodies to RSV pre-F 
and/or post-F
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
ADCC = antibody-dependent cell-mediated cytotoxicity; ADCP = antibody-dependent cellular phagocytosis; 
ELISA = enzyme-linked immunosorbent assay; F = fusion; Ig = immunoglobulin; RSV = respiratory syncytial 
virus; VNA = virus neutralizing antibody

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Table 6:
Summary of Immunogenicity Assays (Cellular)
Assay 
Purpose
Secondary endpoints
Flow cytometry (ICS)
Analysis of T-cell responses to RSV F protein peptides for Th1/Th2 subtyping
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)
Cytokine analysis
Analysis of secreted cytokines (eg, IFN-γ, IL-2, IL-4, IL-5, IL-13, and TNF-α) in RSV 
F peptide-stimulated PBMC supernatant, including, but not limited to, measurement of 
Th1/Th2 cytokine balance
IFN-γ ELISpot
T-cell IFN-γ responses to RSV F protein peptides
ELISpot = enzyme-linked immunospot; F = fusion; ICS = intracellular cytokine staining; IFN-γ = interferon gamma; IL = 
interleukin; PBMC = peripheral blood mononuclear cell; Th = T-helper (cell); RSV = respiratory syncytial virus; TNF-α = 
tumor necrosis factor alpha
Note: Cytokine analysis for Th1/Th2 profiling will be done if no ICS data can be generated due to insufficient PBMCs for ICS 
assay.
In addition to RT-PCR performed on RTI nasal samples, any immunogenicity blood sample 
collected from all subjects may also be assayed by serology (eg, ELISA specific to RSV protein 
G and/or N as available and applicable) to confirm exposure to RSV at the end of the season if 
the sample volumes allow.
Instructions for collection, handling, storage, and shipment of blood and nasal samples for 
immunogenicity assay can be found in the Laboratory Manual that will be provided. Collection, 
handling, storage, and shipment of blood and nasal 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
All RTIs and otitis media cases will be collected during the RSV seasonz. Outside the RSV 
season, only MA-RTIs (including severe LRTIs; see Section 11.3.1.1) and medically-attended 
otitis media cases will be collected.
During the RSV season, the subject’s parent/legal guardian or caregiver should record any signs 
and symptoms of RTI (eg, runny nose, fever, severe cough, wheezing, rapid breathing, difficulty 
breathing) or otitis media on a daily basis using a specific RTI Symptoms Form, starting on the 
first day their child experiences symptoms. Outside the RSV season, parents/guardians or 
caregivers should likewise record signs and symptoms of RTI or otitis media on a daily basis 
using the RTI Symptoms Form as soon as possible for any MA-RTI or medically-attended otitis 
media case until resolution of symptoms. A new form should be completed each day the subject 
has symptoms, including the day on which the symptoms resolve. RTI Symptoms Forms will be 
distributed at the timepoints as indicated in the Time and Events Schedule. Completed RTI forms 
can either be mailed to the site or brought to the site at the next visit.
                                                
z
Note: The RTI procedures also apply to all otitis media cases.

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In the event of an RTI, MA-RTI, or (medically-attended) otitis media, parents/legal guardians or 
caregivers should contact the site. Parents/legal guardians or caregivers will themselves be 
contacted periodically during the study. During the RSV season, these calls are to remind them 
to complete the RTI Symptoms Form in the event of any signs or symptoms of RTI or otitis 
media, and to contact the site at the time of symptom onset; during and outside the RSV season, 
these calls will check for SAEs and associated concomitant medications, MA-RTIs, medically-
attended otitis media cases, and any subsequent medical care that may have been sought, since 
the previous visit or telephone contact (this includes contacts with subjects who received at least 
one dose of study vaccine but withdrew from further dosing).
During the season, and where possible outside the season (for MA-RTIs, including severe LRTIs 
or for medically-attended otitis media cases), site staff will conduct a physical examination (with 
vital signs, including oxygen saturation), and collect nasal samples, preferably within 72 hours 
after onset of symptoms. For suspected severe RTI cases, nasal swabs should be shipped on the 
day of collection to enable timely assessment of samples for the presence of RSV infection by 
central laboratory RT-PCR. To evaluate the safety of the Ad26.RSV.preF vaccine, nasal samples 
may also be assessed for the presence of other respiratory pathogens. The actual dates and times 
of sample collection and physical examination data must be recorded in the eCRF, preferably 
within 24 hours of sample collection. Any suspected case of severe RSV-LRTI should be 
recorded in the eCRF within 24 hours of knowledge of the event. (Note: Nasal samples will not 
be collected if less than 7 days after the previous sample collection.) Note: A nasal swab for RSV 
RT-PCR testing will also be collected from any subject with otitis media (as recorded on the RTI 
Symptoms Form) during the study, independent of other RTI symptoms.
For all RTIs, every effort should be made to collect data on the clinical course of infection 
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.
In all RTI or otitis media cases where results from the physical examination during the RTI site 
visit conclude that the RTI is not severe, and the RTI episode is still ongoing, a follow-up phone 
call (or other communication) to the parents/legal guardians or caregivers will be made once 
every 2 working days (±1 day) until symptom resolution. In the event of a worsening RTI, a 
follow-up RTI visit will be scheduled. (Note: In the event of a worsening RTI, a repeat nasal 
sample may be collected if less than 7 days after the previous sample collection at the discretion 
of the investigator.) The data from this second RTI visit must be recorded in a separate eCRF 
page and will have a separate conclusion (severe/non-severe). Further follow-up visits to assess 
additional reported worsening of an RTI episode may be scheduled at the discretion of the 
investigator.
Signs and symptoms of RTI or otitis media recorded by the subject’s parent/legal guardian on the 
RTI Symptoms Form will be transferred onto the applicable RTI symptoms page in the eCRF, 
preferably within 24 hours of receipt of the form.

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Note: RTI procedures (completion of the RTI symptoms form at home, and an RTI visit to the 
site with associated procedures, including nasal sampling) are not applicable for a non-
medically-attended RTI that occurs outside the season, including those that started before the 
RSV season and continue into the season without worsening of symptoms.
Any RTI or otitis media case that is not due to RSV infection will be reported as an AE if it 
occurs between the time of any study vaccination through the following 28 days. During the 
study, any RTI or case of otitis media fulfilling the criterion of an SAE will be reported to the 
sponsor (and, when appropriate, extended to Regulatory Agencies). Any RTI or case of otitis 
media reported as an (S)AE that is found to be positive for RSV will be excluded from the 
analyses of (S)AEs. However, the case will remain in the clinical database and will be tabulated 
separately in the clinical study report.
Any MA-RTI (including any severe LRTI) or (medically-attended) otitis media case which 
occurs between screening and Day 1 will be recorded on the Medical History page of the eCRF
(RTI visit and RTI Symptoms Form completion is not required for these events prior to the first 
vaccination).
An overview of the RTI procedures is provided in Figure 2 below. Note: The RTI procedures 
also apply to all otitis media cases.
Any parent/legal guardian or caregiver who seeks medical attention for their child due to an RTI or 
otitis media should make the attending healthcare professional aware that their child is taking part 
in an RSV vaccine study. Each parent/legal guardian or caregiver will be given a wallet card with 
key study information and study-site contact details (see Section 12.3.1). These details should be 
shared with the attending healthcare professional.

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9.2.3.
Safety Evaluations
Any clinically relevant changes occurring must be recorded on the eCRF. Any clinically 
significant abnormalities, including those persisting at the end of the study/early withdrawal, will 
be followed by the investigator until resolution or until a clinically stable endpoint is reached.
The study will include the following evaluations of safety and reactogenicity according to the 
timepoints provided in the Time and Events Schedule.
Adverse Events
All AEs will be reported as specified in Section 12.3.1, All Adverse Events.
Unsolicited AEs
Unsolicited AEs will be reported by the subject (ie, by a caregiver, surrogate, or the subject’s 
legally acceptable representative) from the time of each vaccination through the following 28 
days, or early discontinuation. Relatedness of unsolicited AEs should be determined by the 
investigator. Additionally, AEs that are related to the study procedures or are related to non-
investigational (concomitant) Janssen products will be reported from ICF signature onwards.
Solicited AEs
Information related to solicited AEs as defined in Section 12.1.1, will be recorded by the 
subject’s parent/legal guardian or caregiver in a diary for 7 days after each vaccination. Each 
subject’s parent/legal guardian or caregiver 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 (or 60-minute, 
depending on local or study-site requirements) post-vaccination assessment of solicited events at 
the site. Diary information will be transcribed by the study personnel in the appropriate eCRF 
pages.
Injection Site (Local) Adverse Events
Each subject’s parent/legal guardian or caregiver will be asked to note in the diary occurrences 
of pain/tenderness, erythema and induration/swelling at the study vaccine injection site daily for 
7 days post-vaccination. The extent (largest diameter) of any erythema, and induration/swelling 
should be measured (using the ruler supplied) and recorded daily. Induration/swelling should 
also be graded using the functional scale.

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 and/or movement of the limb. Due to 
subjective nature of the reaction, the severity assessment of pain/tenderness is self-reported 
(if a subject is unable to provide self-report, other reporters include parent/care giver or 
healthcare provider).14

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
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 either 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 
healthcare professional’s assessment, both symptoms have been combined to allow self-
assessment by the subject’s parent/legal guardian or caregiver. Both 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.28,29
Systemic Adverse Events
The subject’s parent/legal guardian or caregiver will be instructed on how to record daily 
temperatureaa using a thermometer provided for home use. The subject’s parent/legal guardian or 
caregiver should record the temperature in the diary in the evening of the day of vaccination, and 
then daily for the next 7 days approximately at the same time each daybb. If more than one 
measurement is made on any given day, the highest temperature of that day will be used in the 
eCRF.
Fever is defined as endogenous elevation of body temperature ≥38.0 °C, as recorded in at least 
one measurement.32
The subject’s parent/legal guardian or caregiver s will also be instructed on how to note daily in 
the diary for 7 days post-vaccination symptoms of the following events: loss of appetite, 
vomiting, diarrhea, decreased activity/lethargy, irritability/crying and fever (ie, body temperature 
≥38.0 °C).
The severity of these solicited systemic AEs will be graded by the investigator according to the 
criteria presented in Section 12.1.3, Severity Criteria.
If a solicited local or systemic AE is not resolved by 7 days post-vaccination, the follow-up will 
be captured on the diary. The subject’s parent/legal guardian or caregiver will be instructed to 
record the date of last symptoms and maximum severity in the diary after resolution.
                                                
aa
Recommended to be measured axillary (actual routes to be recorded in the eCRF).
bb
All Day 8 post-vaccination diary assessments, including temperature measurements, may be collected earlier to coincide with 
the corresponding clinic visit.

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9.2.3.1.
Vital Signs
Pulse/heart rate measurements should be preceded by at least 5 minutes of rest in a quiet setting 
without distractions (eg, television, cell phones):

Heart rate (beats per minutes), and respiratory rate (breaths per minute)

Body temperature (the axillary route is recommended)

Oxygen saturation (SpO2)
Confirmatory vital signs measurement can be performed if inconsistent with a prior 
measurement. If any clinically significant changes in vital signs are noted, they will be reported 
as AEs and followed to resolution, or until reaching a clinically stable endpoint.
9.2.3.2.
Physical Examination
Full physical examination, including length and weight, will be carried out at screening. At all 
other visits, abbreviated, symptom-directed examinations 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.
9.2.4.
Other Evaluations
At Visit 12 (6 months post-Dose 3), parents/legal guardians or caregivers (where allowed by 
local regulations) of each study subject will be invited to complete an IEC/IRB approved 
Participant Experience Survey, to share to their experience in this study. The responses will be 
collected by an external party and anonymously provided to the sponsor.
10.
SUBJECT COMPLETION/DISCONTINUATION OF STUDY VACCINE/ 
WITHDRAWAL FROM THE STUDY
10.1.
Completion
A subject will be considered to have completed study vaccination if he or she has received all 
three study vaccinations. A subject will be considered to have completed the study if he or she 
has completed assessments through to the end of the study (see Section 17.9.1).
10.2.
Discontinuation of Study Vaccine/Withdrawal from the Study
Discontinuation of Study Vaccine
A subject 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.

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Subjects will be discontinued from study vaccination for the reasons listed below. These subjects 
must not receive any additional dose of study vaccine but should continue other study 
procedures, eg, safety follow-up:

Anaphylactic reaction following vaccination, not attributable to causes other than 
vaccination

Any related SAE

Any related AE, worsening of health status or intercurrent illness that, in the opinion of the 
investigator, requires study vaccine discontinuation

Repeated failure to comply with protocol requirements

Decision by the sponsor, investigator, local regulatory authorities or IRB/IEC
Note: A subject will not be automatically withdrawn from the study if consent is withdrawn only 
for blood draws; they may remain in the study and continue to receive study vaccine and undergo 
safety follow-up.
Withdrawal From the Study
Parents/legal guardians have the right to withdraw their child from the study at any time for any 
reason without affecting the right to treatment by the investigator. Although parents/legal 
guardians are 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 subject’s rights.
A subject will be withdrawn from the study for any of the following reasons:

Lost to follow-up

Withdrawal of consent

Death
Any unnecessary study discontinuation should be avoided. Should a subject be withdrawn, all 
efforts should be made to complete and report the observations as thoroughly as possible. 
Whenever a subject is withdrawn from the study, independent of the reason, a final evaluation 
should be completed for that subject and the major reason for which the subject was withdrawn 
must be stated. If a subject is lost to follow-up, every reasonable effort must be made by the 
study-site personnel to contact the subject and determine the reason for discontinuation/ 
withdrawal. The measures taken to follow-up must be documented.
When a subject is withdrawn 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 
subject may not be assigned to another subject. In general, subjects who withdraw will not be 
replaced, unless the subject was randomized but did not receive any study vaccine. However, any 
randomized subject 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.

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If a subject withdraws early from the study, assessments for early withdrawal should be obtained 
(see Section 9.1.3.2.4).
Subjects 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 subject 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:

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 time of vaccination.
If any of these events occur at the scheduled time for the first vaccination, enrollment at a later 
date is permittedcc at the discretion of the investigator and after consultation with the sponsor. If 
any of these events occur at the scheduled time for the second or third vaccination, the subject 
may be vaccinated up to 10 days beyond the scheduled vaccination, or be withdrawn from 
further vaccination at the discretion of the investigator and after consultation with the sponsor. In 
the event of an ongoing AE or other situation precluding subject vaccination within 10 days, 
subjects may be vaccinated beyond the 10-day window at the discretion of the sponsor.
Note: Medically-indicated vaccines should be given at least 14 days before or 14 days after study 
vaccine administration. If a vaccine is indicated in a post-exposure setting (eg, rabies or tetanus), 
it must take priority over the study vaccine (see Section 4.3).
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 11.8.
11.1.
Analysis Sets
Vaccination assignment will follow the as-treated principle.
                                                
cc
If within the screening window. Otherwise, rescreening is required.

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The Full Analysis (FA) set includes all subjects who were randomized and received at least one 
dose of study vaccine, regardless of the occurrence of protocol deviations. All safety analyses 
will be based on the FA set. As a sensitivity analysis, key immunogenicity tables will also be 
based on the FA set.
The Per-protocol Immunogenicity (PPI) analysis set will include all randomized and vaccinated 
subjects for whom immunogenicity data are available, excluding subjects with major protocol 
deviations expecting to impact the immunogenicity outcomes. Any subject with an anamnestic 
response at Day 8 will not be included in the PPI analysis set.
In addition, the following samples will not be included in the PPI set:

If subjects miss one or more doses, but continue the planned visit schedule, samples taken 
after the planned but missed dose(s) will not be taken into account;

For subjects who experience a natural RSV infection (based on RT-PCR, or other sources), 
samples taken after the natural infection will not be taken into account.
The analysis of immunogenicity will be based on the PPI set.
Additionally, a modified intent-to-treat (mITT) analysis set is defined as a subset of the FA set 
excluding subjects who are seronegative at screening but for whom there is an anamnestic 
response at Day 8. The criteria for assessment of the anamnestic response will be specified in the 
SAP. The mITT set will be the primary analysis set for assessment of RSV infection in 
seronegative subjects.
11.2.
Sample Size Determination
The number of subjects chosen for this study will provide a preliminary safety and 
immunogenicity assessment. Control recipients (Nimenrix or placebo) are included for blinding 
and safety purposes and will provide additional control specimens for immunogenicity assays.
While mild to moderate vaccine reactions (local site and systemic responses) are expected, AEs
that preclude further dose administration or more serious ones that would limit product 
development are not anticipated.
Table 7 shows the probabilities of observing at least 1 AE at given true AE rates:

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Table 7:
Probability of Observing at Least One Adverse Event at a Given True Adverse Event Rate
True Adverse 
Probability of Observing at Least One Adverse Event in N 
Subjects
Event Rate
N=18
0.5%
9%
1%
17%
2.5%
37%
5%
60%
10%
85%
25%
99%
50%
100%
A monitoring rule for severe RSV-LRTI is described in Section 11.3.1.3. Based on this rule and
assuming an event rate in controls of 1%, there is at least 80% power to halt enrollment in this or 
the next study if the incidence in the Ad26.RSV.preF group is approximately 25% or more.
11.3.
Criteria for Endpoints of RSV Infection
11.3.1.
Definitions for Endpoints of RSV Infection
The endpoints of RSV infection shown below will be collected to assess the feasibility of, and 
gain expertise in the collection of such events for future studies.

Severe RSV-LRTI (secondary endpoint)

RSV MA-RTI (exploratory endpoint)

RSV-RTI (exploratory endpoint)

RSV-LRTI (exploratory endpoint)
11.3.1.1.
Definitions of Severe RSV-LRTI
Severe RSV-LRTI will be defined as the presence of severe LRTI as assessed by the CEC, and 
confirmation of RSV infection by nasal (mid-turbinate or nasopharyngeal) sample using 
independent RT-PCR by a central laboratory. See also Section 11.9.1. If no central laboratory 
RT-PCR result is available, a positive test result (including commercial test results) for RSV 
from a local laboratory (if available) could be used to confirm RSV infection upon evaluation by 
the CEC.
11.3.1.2.
Presence of Severe RSV-LRTI as Assessed by the Clinical Endpoint 
Committee (CEC)
For subjects with an RTI that is considered severe by the PI(s) (based on below-mentioned WHO 
criteria)34, the CEC will determine the presence or absence of severe LRTI by reviewing all 
available clinical information related to respiratory disease, with a special focus on the following 
characteristics (“WHO” criteria)34:

Respiratory infection defined as cough or difficulty breathing
AND

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
LRTI defined as fast breathing or peripheral capillary oxygen saturation (SpO2) <95%
AND

≥1 of the severe disease feature:

oximetry <93%

lower chest wall indrawing
Determination of RSV Infection
A subject is considered RSV positive if the subject has a positive RT-PCR for RSV on nasal
(mid-turbinate or nasopharyngeal) samples (central laboratory; see Section 9.2.2). If no central 
laboratory RT-PCR result is available, a positive test result (including commercial test results)
for RSV from a local laboratory (if available) could be used to confirm RSV infection upon 
evaluation by the CEC.
If a test result for RSV is missing (ie, not available or not conclusive), the RTI will not be 
considered RSV-related.
11.3.1.3.
Monitoring Rule for Severe RSV-LRTI
In this section ‘severe RSV-LRTI’ refers to the assessment made by the CEC.
With respect to the secondary endpoint ‘severe RSV-LRTI’, a monitoring rule for severe RSV-
LRTI is as follows.

If 1 event (regardless of group) of ‘severe RSV-LRTI’ is observed, no analysis will be done. 
Note: However, the IDMC will be informed and may convene.

As soon as 2 or more events (regardless of group) of ‘severe RSV-LRTI’ have been 
observed, confidence limits for the difference in proportions (using Wilson score method) 
between the Ad26.RSV.preF group and control group (pooling placebo/placebo/Nimenrix 
and placebo/placebo/placebo) will be constructed by the external statistician who is 
supporting the IDMC:

If the upper (one-sided) 95% confidence limit for the difference is <10%: continue the 
study; if study enrollment is still ongoing, continue enrollment.

If the upper (one-sided) 95% confidence limit is ≥10% and the lower (one-sided) 80% 
confidence limit is >0: more frequent active monitoring of subjects, including weekly 
calls within the RSV season and more frequent medical review will be initiated.

If the upper (one-sided) 95% confidence limit is ≥10% and the lower (one-sided) 95% 
confidence limit is >0: halt enrollment in this study or the next study; more frequent 
active monitoring of subjects, including weekly calls within the RSV season and more 
frequent medical review for all enrolled subjects should be initiated.
For example: assuming complete enrollment, if 2 or 3 severe RSV-LRTI events are observed and 
all occurred in the Ad26.RSV.preF group, the lower (one-sided) 80% (but not the 95%) 

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confidence limit will be >0 and monitoring will be increased. If 4 severe RSV-LRTI events are 
observed and all occurred in the Ad26.RSV.preF group, the lower (one-sided) 95% confidence 
limit will be >0 and enrollment in all pediatric studies with Ad26.RSV.preF will be halted and 
monitoring of all enrolled subjects will be increased.
More details on this monitoring rule are specified in the IDMC charter.
11.3.2.
Definitions of RSV MA-RTI
RSV MA-RTI includes all subjects with RSV-RTI that is medically-attended, ie, when the 
subject’s parent/legal guardian or caregiver seeks medical attention outside normal study 
procedures, including healthcare professional visits to the home, clinic visits, emergency room 
attendance, and hospital admission.
Determination of RSV Infection
A subject is considered RSV positive if the subject has a positive RT-PCR for RSV nasal (mid-
turbinate or nasopharyngeal) samples (central laboratory; see Section 9.2.2). If no central 
laboratory RT-PCR result is available, a positive test result (including commercial test results) 
for RSV from a local laboratory (if available) could be used to confirm RSV infection upon 
evaluation by the CEC.
If a test result for RSV is missing (ie, not available or not conclusive), the RTI will not be 
considered RSV-related.
11.4.
Subject Information
For all subjects, demographic characteristics (eg, age, weight and length percentiles according to 
WHO pediatric growth and weight charts,49 race, and gender), and other baseline characteristics 
(eg, physical examination, medical history, concomitant diseases) will be tabulated and 
summarized with descriptive statistics.
11.5.
Immunogenicity Analyses
No formal hypothesis on immunogenicity will be tested. Descriptive statistics (geometric mean 
and 95% confidence interval for ELISA and virus neutralization assays; median and quartiles for 
ELISpot and ICS) will be calculated for continuous immunologic parameters at all timepoints. 
Graphical representations of immunologic parameters will be made as applicable.
Frequency tabulations will be calculated for discrete (qualitative) immunologic parameters as 
applicable.
The primary analysis set for immunogenicity is the PPI set. As a sensitivity analysis, key tables 
will also be based on the FA set. Depending on their occurrence, the effect of missed doses or 
natural infections might be further explored. Note that they will be included in the tables 
showing the FA set.

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11.6.
RSV Infection
The presence of RSV infection, as described in Section 9.2.2, will be assessed by RT-PCR. The 
presence of RSV infection will be summarized by descriptive statistics.
Any RTI or otitis media case recorded as an AE in the eCRF that is subsequently found to be 
RSV positive by RT-PCR (central laboratory or based on CEC assessment if available) will be 
excluded from the safety analysis and tabulated separately (refer to Section 11.7).
The mITT set is the primary analysis set for assessment of RSV infection in seronegative 
subjects.
11.7.
Safety Analyses
No formal statistical testing of safety data is planned. 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 after 
vaccination up to 28 days post-vaccination, and SAEs from first dose administration onwards, 
will be included in the analysis. For each AE, the percentage of subjects who experience at least 
1 occurrence of the given event will be summarized by group.
Summaries, listings, datasets, or subject narratives may be provided, as appropriate, for those 
subjects who die, who discontinue 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 time frame (eg, beyond 28 days post-vaccination) and that were reported pre-dose at the 
moment of subsequent vaccinations for studies using multiple doses.
Solicited local (at injection site) and 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 subjects with at least one 
solicited local (at injection site) or systemic AE will be presented. Frequencies of unsolicited 
AEs, separately for all and vaccination-related only, will be presented by System Organ Class 
and preferred term. Note: Frequencies of post-dose 3 AEs in the control group will be presented 
separately for Nimenrix and placebo.
Any RTI or otitis media case recorded as an AE in the eCRF that is subsequently found to be 
RSV positive by RT-PCR (central laboratory or based on CEC assessment if available) will be 
excluded from the safety analysis and tabulated separately.

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Vital Signs
A tabulation of the distribution of temperatures per half degree intervals will be provided. For 
heart rate and respiratory rate, the percentage of subjects with values beyond clinically relevant 
limits will be summarized. Note: Vital signs data post-dose 3 in the control group will be 
presented separately for Nimenrix and placebo.
Physical Examination
Physical examination abnormalities will be listed.
11.8.
Planned Analyses
The following analyses will be performed:

Primary analysis 28 days post-final dose in all subjects, includes safety and immunogenicity; 
unblinded

Interim analysis performed when all subjects have data of 1 RSV season post-Dose 1, 
includes safety and immunogenicity; unblinded

Final analysis at the end of the study; unblinded
The primary analysis and interim analysis may be combined into one analysis. These analyses 
will also be shared with the IDMC.
Additional interim analyses (blinded or unblinded) may be performed during the study for the 
purpose of informing future vaccine-related decisions in a timely manner, or upon health 
authority request. 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, excluding sponsor personnel involved in data collection or 
data management and clinical immunology laboratory personnel.
11.9.
Data Review Committees
11.9.1.
Clinical Endpoint Committee (CEC)
The CEC is an independent panel consisting of external medical experts with relevant experience 
in RSV in children. At all times during the study, the CEC will stay blinded, hence CEC 
members will not be part of the IDMC. Full details of CEC responsibilities, authorities, and 
procedures will be documented in its charter.
The CEC will assess suspected cases of severe LRTI and the occurrence of RSV infection. If the 
RTI is assessed to be a severe RSV-LRTI by the CEC (see Section 11.3.1.2), this will be shared 
with the IDMC which then might convene to run the monitoring rule. 

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11.9.2.
Independent Data Monitoring Committee (IDMC)
An IDMC will be established to review safety data, and as needed on an ad hoc basis to ensure 
the continuing safety of the subjects enrolled in this study. The IDMC will convene to discuss 
any situation that meets a study vaccination pausing rule (see Section 11.10).
The presence of severe LRTI and the occurrence of RSV infection will be determined by the 
CEC, a separate committee (see Section 11.9.1).
The IDMC will monitor severe RSV-LRTI as assessed by the CEC according to the rule 
described in Section 11.3.1.3 and further detailed in the IDMC charter.
The IDMC will consist of members independent of the sponsor, including at least one medical 
expert in the relevant therapeutic area and at least one statistician. An immunologist may be 
included on an ad hoc basis, as needed. The IDMC responsibilities, authorities, and procedures 
will be documented in its charter. An external statistician independent of the sponsor and not 
involved in the interim, primary, and final analyses of the study will prepare the data and 
perform all analyses for review by the IDMC.
In any case(s) under review, the IDMC will review unblinded data.
Details on the intervals of the safety evaluations will be provided in the IDMC charter.
Safety data from the interim and primary analyses will be shared with the IDMC.
If any question arises related to safety, the IDMC will be convened.
11.10. Study Vaccination Pausing Rules
The PI(s) or designee and the SRP/S will monitor the study vaccination pausing rules. If study 
vaccination is considered to raise significant safety concerns, further vaccination of subjects will 
be suspended until IDMC review is carried out and subsequent communication between the 
sponsor and the investigators takes place.
The occurrence of any of the following events will lead to suspension of further vaccination, and 
trigger a meeting of the IDMC to discuss study suspension, adaptation or discontinuation of 
further vaccination:
1. One or more subjects experience an SAE or other potentially life-threatening (Grade 4) 
event that is determined to be related to study vaccine (ie, by the PI[s]); OR
2. One or more subjects experience anaphylaxis clearly not attributable to other causes than 
vaccination with study vaccine; OR
3. Two or more subjects 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

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4. Two or more subjects 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. Death of any subject, considered related to study vaccine or if the causal relationship to the 
study vaccine cannot be excluded.
Note: All cases of death will be sent to the IDMC. Upon their review, the IDMC may then 
decide whether a study pause is required.
Note: The count of subjects for each pausing rule will be across all study sites. After the first 
IDMC meeting triggered by the occurrence of a given pausing rule, the IDMC will convene 
thereafter for each additional subject meeting that pausing rule.
Note: The study will also be paused if specific severe RSV-LRTI monitoring criteria are met as 
described in Section 11.3.1.3.
To enable prompt response to a situation that would trigger pausing rules 3 or 4, the investigator 
should update the eCRF with information on any Grade 3 or 4 AE within 24 hours after the AE
is reported. Any suspected case of severe RSV-LRTI should be recorded in the eCRF within 
24 hours of knowledge of the event.
If any of the above specific pausing rules are met, the IDMC will make recommendations 
regarding continuation of the study or discontinuation to the sponsor. Study suspensions or 
terminations will occur within 5 working days after the decision is made, unless local regulations 
specify a shorter time frame. Local regulatory authorities including IECs/IRBs will be informed 
within appropriate regulatory-mandated time frames. The study may be resumed only upon the 
approval of a substantial amendment to the initial study application by the local regulatory 
authorities and IECs/IRBs. The sponsor will communicate conclusions regarding study 
continuation to the investigators, IECs/IRBs and national regulatory authorities as appropriate.
Vaccinations for an individual subject may be suspended for safety concerns other than those 
described above, at the discretion of the investigator if he/she feels the subject’s safety may be 
threatened. The investigator may ask for a review meeting to be held for any single event or 
combination of multiple events which, in his/her professional opinion, jeopardize the safety of 
the subjects 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 investigator, subject safety may be 
threatened. The sponsor should be notified that the IDMC will need to be convened.
Central randomization will be implemented in this study. Central randomization ensures that 
study recruitment and dosing can be effectively halted simultaneously across all sites in the event 
of a situation meeting any of the pausing rules. Sponsor activities and responsibilities related to 
temporary study suspension and restart are described in the sponsor’s applicable Standard 
Operating Procedures.19,20

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12.
ADVERSE EVENT REPORTING
Timely, accurate, and complete reporting and analysis of safety information from clinical studies 
are crucial for the protection of subjects, 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 
nonleading verbal questioning of the subject is the preferred method to inquire about AE
occurrence. For some studies, subjects are not always able to provide valid verbal responses to 
open-ended questions. In these circumstances, another method of detecting these events is
specified (ie, questioning of the subject’s parent/legal guardian or caregiver).
Solicited Adverse Events
Solicited AEs are predefined local (at the injection site) and systemic events for which the 
subject’s parent/legal guardian or caregiver is specifically questioned and which are noted by the 
subject’s parent/legal guardian or caregiver in their diary (see Section 9.1.1, Overview).
Unsolicited Adverse Events
Unsolicited AEs are all AEs for which the subject’s parent/legal guardian or caregiver is 
specifically not questioned in the subject 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 subject administered a medicinal 
(investigational or non-investigational) product. An AE does not necessarily have a causal 
relationship with the vaccine. 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 

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non-serious AEs and special reporting situations will be reported from each vaccination through 
the following 28 days on the Adverse Event eCRF page (refer to 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.
Any RTI or otitis media case that is not due to RSV infection will be reported as an AE if it 
occurs between the time of any study vaccination through the following 28 days. Any RTI or 
otitis media case 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 or otitis media 
cases 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.
Serious Adverse Event
A 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 subject 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 subject 
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 study 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.
During the study, any RTI or case of otitis media fulfilling the criterion of an SAE will be 
reported to the sponsor (and, when appropriate, extended to Regulatory Agencies). Any RTI or 

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case of otitis media reported as an (S)AE that is found to be positive for RSV by RT-PCR will be 
excluded from the analyses of (S)AEs. However, the case will remain in the clinical database and 
will be tabulated separately in the clinical study report.
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, the expectedness of an AE will be 
determined by whether or not it is listed in the Investigator’s Brochure Reference Safety 
Information for Assessment of Expectedness of Serious Adverse Reactions.1
For Nimenrix, the expectedness of an AE will be determined by whether or not it is listed in the 
Summary of Product Characteristics.
Adverse Event Associated With the Use of the Vaccine
An AE is considered associated with the use of the vaccine if the attribution is related by the 
definitions listed in Section 12.1.2, Attribution Definitions.
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 study vaccine or to alternative causes (eg, natural history 
of the underlying diseases, concomitant therapy). This applies to all AEs, whether 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 study vaccine and the AE
(without determining the extent of probability); there is a reasonable possibility that the study 
vaccine contributed to the AE.
Unrelated: there is no suspicion that there is a relationship between the study vaccine and the 
AE; there are other more likely causes and administration of the study 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 the study 
vaccine administration.
12.1.3.
Severity Criteria
All AEs will be coded for severity using the toxicity grading table in Attachment 1. For AEs not 
identified in the 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.

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Severe (Grade 3): Extreme distress, causing significant impairment of functioning or 
incapacitation. Prevents normal everyday activities.
Potentially life-threatening (Grade 4): Symptoms causing inability to perform basic self-care 
functions OR medical or operative intervention indicated to prevent permanent impairment, 
persistent disability.
The investigator should use clinical judgment in assessing the severity of events not directly 
experienced by the subject (eg, laboratory abnormalities).
The severity of solicited AEs will be graded in the diary by the subject’s parent/legal guardian or 
caregiver based on the severity assessment provided in the diary and then verified by the 
investigator.
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 subject/patient exposure to 
the sponsor study vaccine, eg, name confusion)

Exposure to a sponsor study vaccine from breastfeeding
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 
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 non-serious AEs and special reporting situations will be reported until 28 days (including 
relevant visit window, if applicable) after first dose of study vaccine and thereafter, pre-dose on 
the day of vaccination and for 28 days (including relevant visit window, if applicable) after each 
subsequent dose of study vaccine. Unsolicited AEs with the onset date outside the time frame 
defined above (>28 days after previous study vaccination), which are ongoing on the day of the 
subsequent vaccination, should be recorded on the eCRF AE page.
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 subject’s parent/legal guardian or caregiver in the subject 
diary for 7 days after each dosing. The investigator will review each subject’s diary at the 
subsequent in-clinic visit; diary information will be transcribed by the study personnel in
relevant 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 data, as they become 
available and will make determinations regarding the severity of the adverse experiences and 
their relation to study vaccine. All AEs will be deemed related to study vaccine or not related to 
study 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 study 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 study 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 Independent Ethics Committee/Institutional Review Board (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.
The subject’s parent/legal guardian or caregiver will be provided with a “wallet (study) card” and 
instructed that the subject will carry this card for the duration of the study indicating the 
following:

Study number

Statement, in the local language(s), that the subject 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

Subject number

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
Any other information that is required to do an emergency breaking of the blind
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. Information regarding SAEs will be transmitted to the 
sponsor using the SAE Form and Safety Report Form of the CRF, which must be completed and 
reviewed 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 transmitted electronically or by facsimile (fax; 
only when the electronic system is not available).
All SAEs that have not resolved by the end of the study, or that have not resolved upon 
discontinuation of the subject’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 study vaccine or to factors unrelated to 
study conduct

It becomes unlikely that any additional information can be obtained (subject 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 
subject’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 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 SAEs. Any AE that results in a prolongation of the originally planned 
hospitalization is to be reported as a new SAE.
The cause of death of a subject in a study during the entire study period, whether or not the event 
is expected or associated with the study vaccine, is considered an SAE and must be reported.

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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 subjects, 
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, Serious Adverse Events). 
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.
14.
STUDY VACCINE INFORMATION
14.1.
Physical Description of Study Vaccine
A human replication-incompetent adenovirus-vectored vaccine candidate, 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 for 
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.

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Ad26.RSV.preF will be supplied as a frozen liquid to be thawed prior to use, and will be filled in 
stoppered and sealed 2 mL single-use glass vials. The dose of 2.5×1010 vp will be administered 
in a volume of 0.25 mL by intramuscular injection.
Refer to the Investigator’s Brochure for details of the components of Ad26.RSV.preF and a list 
of excipients.1
Placebo
Placebo will be supplied as sterile 0.9% saline for intramuscular injection.
Nimenrix
Nimenrix will be supplied as Nimenrix powder and solvent for solution for injection in pre-filled 
syringe or ampoule and administered as 0.5 mL solution for intramuscular injection.
Nimenrix is a meningococcal group A, C, W-135 and Y conjugate vaccine for intramuscular 
injection (Pfizer) indicated to protect adults, adolescents, and children from the age of 6 weeks 
against invasive meningococcal disease caused by 4 groups of the bacterium Neisseria 
meningitidis (group A, C, W-135, and Y).
Nimenrix will be used in line with the licensed indication, and it will not be formally compared 
to either the study vaccine or placebo.
14.2.
Packaging and Labeling
All study vaccines were manufactured and packaged in accordance with Current Good 
Manufacturing Practice. All study vaccines will be packaged and labeled under the responsibility 
of the sponsor. Study vaccine labels will contain information to meet the applicable regulatory 
requirements.
No study vaccine can be repacked or relabeled without prior approval from the sponsor.
Further details for study vaccine packaging and labeling can be found in the Investigational 
Product Preparation Instructions.
14.3.
Storage and Handling
Vials 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. Study refrigerators/freezers should be equipped with back-up 
power systems. If study vaccine is exposed to temperatures outside the specified temperature 
range, all relevant data will be sent to the sponsor to determine if the affected study vaccine can 
be used or will be replaced. The affected study vaccine must be quarantined and not used until 
further instruction from the sponsor is received.

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Injections should be administered in the anterolateral aspect of the thigh. Only if required by local 
health authority guidance, injections may be administered in the deltoid muscle. Alternating 
injection sites will be used for all study vaccinations.
The study vaccine will be prepared and may also be administered by the unblinded site pharmacist,
or other qualified individual, who will have no other study function following dosing.
Further details for study 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 study vaccine received at the site is 
inventoried and accounted for throughout the study. The study vaccine administered to the 
subject must be documented on the vaccine accountability form. All study vaccine will be stored 
and disposed of according to the sponsor’s instructions.
Study vaccine 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 study vaccine must be available for verification by the 
sponsor’s study-site monitor during on-site monitoring visits. The return to the sponsor of unused 
study vaccine will be documented on the vaccine return form. When the study site is an 
authorized destruction unit and study vaccine supplies are destroyed on-site, this must also be 
documented on the vaccine return form.
Potentially hazardous materials such as used ampoules, 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.
Study vaccine should be dispensed under the supervision of the investigator or a qualified 
member of the study-site personnel, or by a hospital/clinic pharmacist. Study vaccine will be 
supplied only to subjects participating in the study. Returned study vaccine must not be 
dispensed again, even to the same subject. Study vaccine may not be relabeled or reassigned for 
use by other subjects. The investigator agrees neither to dispense the study vaccine from, nor 
store it at, any site other than the study sites agreed upon with the sponsor.
15.
STUDY-SPECIFIC MATERIALS
The investigator will be provided with the following supplies:

Investigator’s Brochure for Prophylactic RSV Vaccine1

Summary of Product Characteristics for Nimenrix

Investigational Product Preparation Instructions/Investigational Product Procedures Manual

Laboratory Manual (including procedures for collection of nasal samples)

IWRS Manual

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
Electronic Data Capture (eDC) Manual/eCRF completion guidelines and randomization 
instructions

Sample ICF

Subject diaries

Rulers

Thermometers

RTI Symptoms Forms for subject’s parents/legal guardian or caregiver

Contact information page(s)

Participant Experience Survey
16.
ETHICAL ASPECTS
16.1.
Study-Specific Design Considerations
The parents/legal guardians of potential subjects will be fully informed of the risks and 
requirements of the study and, during the study, will be given any new information that may 
affect their decision for their child to continue participation. They will be told that their consent 
for their child 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 parents/legal guardians who are fully able to understand the risks, benefits, and potential 
AEs of the study, and provide their consent voluntarily will be able to enroll their child in the 
study.
When referring to the signing of the ICF, the terms legal guardian/legally acceptable 
representative refer to the legally appointed guardian of the child with authority to authorize 
participation in research. For each subject, his or her parent(s) (preferably both parents, if 
available) or legally acceptable representative(s), as required by local regulations, must give 
written consent (permission) according to local requirements after the nature of the study has 
been fully explained and before the performance of any study-related assessments. For the 
purposes of this study, all references to subjects who have provided consent refers to the subjects 
and his or her parent(s) or the subject’s legal guardian(s) or legally acceptable representative(s) 
who have provided consent according to this process. Note: In countries where regulation 
requires that both parents/legal guardians give consent, this will be applicable
The total blood volume drawn from each subject will not exceed the most stringent (European 
Medicines Agency) guidelines for pediatric subjects in clinical studies: blood loss should not 
exceed 3% of total blood volume over 4 weeks, and it should not exceed 1% of total blood 
volume at any single time.11
See Section 3.3 for the benefit-risk assessment.

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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 subjects. Compliance 
with this standard provides public assurance that the rights, safety, and well-being of study 
subjects 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

Sponsor-approved ICF (and any other written materials to be provided to the subjects)

Investigator’s Brochure (or equivalent information) and amendments/addenda

Sponsor-approved subject recruiting materials

Information on compensation for study-related injuries or payment to subjects 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 subjects

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 subjects, data or study conduct, unless required locally), the ICF, applicable 
recruiting materials, and subject 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 subjects, data or study conduct)

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
Revision(s) to ICF and any other written materials to be provided to subjects

If applicable, new or revised subject recruiting materials approved by the sponsor

Revisions to compensation for study-related injuries or payment to subjects for participation 
in the study, if applicable

New edition(s) of the Investigator’s Brochure 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 study vaccine

New information that may adversely affect the safety of the subjects or the conduct of the 
study

Deviations from or changes to the protocol to eliminate immediate hazards to the subjects

Report of deaths of subjects under the investigator’s care

Notification if a new investigator is responsible for the study at the site

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 subjects, 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 subject’s parent(s)/legal guardian(s) 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 subject’s 
parent/legal guardian 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. Note: In countries where regulation 
requires that both parents/legal guardians give consent, this will be applicable.
Before enrollment in the study, the investigator or an authorized member of the study-site 
personnel must explain to potential subject’s parent/legal guardian the aims, methods, reasonably 
anticipated benefits, and potential hazards of the study, and any discomfort participation in the 

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study may entail. The subject’s parent/legal guardian 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 subject will receive. Finally, they will 
be told that the investigator will maintain a subject 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 subject, to the extent 
permitted by the applicable law(s) or regulations. By signing the ICF the subject’s parent/legal 
guardian is authorizing such access. It also denotes that the subject’s parent/legal guardian agrees 
to allow his or her study physician to recontact the subject for the purpose of obtaining consent 
for additional safety evaluations, if needed.
The subject’s parent/legal guardian 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 subject’s parent(s)/legal guardian(s) personally 
dated signature. After having obtained the consent, a copy of the ICF must be given to the 
subject’s parent/legal guardian.
All blood samples (venous blood and fingerstick) collected during the study, including samples 
from subjects who have been screened but not enrolled into the study, will be stored and used for 
future research if the subject’s parent(s)/legal guardian(s) consent (see also Section 16.2.5).
16.2.4.
Privacy of Personal Data
The collection and processing of personal data from subjects enrolled in this study will be 
limited to those data that are necessary to fulfill the objectives of the study.
These data will 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 will be 
put in place. Sponsor personnel whose responsibilities require access to personal data agree to 
keep the identity of subjects confidential.
The informed consent obtained from the subject’s parent(s)/legal guardian(s) 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 subject’s parent/legal guardian 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.

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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, to 
understand RSV, and to develop tests/assays related to Ad26.RSV.preF and RSV. The research 
may begin at any time during the study or the post-study storage period. Included are samples 
from subjects who were screened but not randomized which may also be used to develop 
tests/assays related to Ad26.RSV.preF and RSV.
Stored samples will be coded throughout the sample storage and analysis process and will not be 
labeled with personal identifiers. The subject’s parent(s)/legal guardian(s) 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.
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 subjects, 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.

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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 study vaccine 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, subject 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 
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

Genetically modified organism (GMO) and/or Institutional Biosafety Committee (IBC) 
approval, if applicable
The following documents must be provided to the sponsor before enrollment of the first subject:

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

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
Local laboratory documentation demonstrating competence and test reliability (eg,
accreditation/license), if applicable
17.3.
Subject Identification, Enrollment, and Screening Logs
The investigator agrees to complete a subject identification and enrollment log to permit easy 
identification of each subject during and after the study. This document will be reviewed by the 
sponsor study-site contact for completeness.
The subject identification and enrollment log will be treated as confidential and will be filed by 
the investigator in the study file. To ensure subject confidentiality, no copy will be made. All 
reports and communications relating to the study will identify subjects by subject identification
and date of birth. In cases where the subject is not randomized into the study, the date seen and 
date of birth will be used.
The investigator must also complete a subject screening log, which reports on all subjects 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: 
subject 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
receipt/dispensing/return records; study vaccine administration information; and date of study 
completion and reason for early discontinuation of study 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 subject 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 
subject diary will be reviewed by the investigator; diary information will be transcribed by study 
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 the electronic source system is utilized, 
references made to the eCRF in the protocol include the electronic source system but information 
collected through the electronic source system may not be limited to that found in the eCRF.

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17.5.
Case Report Form Completion
CRFs are prepared and provided by the sponsor for each subject 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 
electronic 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 subject’s source documents. Data must be entered into 
the eCRF in English. The eCRF must be completed as soon as possible after a subject visit and 
the forms should be available for review at the next scheduled monitoring visit (See 
Section 9.2.2 and Section 12.3.2).
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-site personnel.
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 subject, 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.

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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,
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 vaccination phase will be when the last subject completes the visit 6 months after 
the final dose. The end of the study will be the last subject’s last visit (by telephone) at the end of
the safety follow-up phase through 2 RSV seasons after the first dose. The study is considered 
completed with the last visit for the last subject participating in the study. The final data from the 

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study site will be sent to the sponsor (or designee) after completion of the final subject 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 subjects by the investigator

Discontinuation of further study vaccine development
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. Subject 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 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.

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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 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 subject 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.
Arrangements on publication policy will be addressed in the Clinical Trial Agreement.
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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Attachment 2: Vaccination of Subjects From the Control Group With the Licensed Vaccine 
Nimenrix
In countries where the commercial vaccine Nimenrix (Meningococcal group A, C, W-135, and Y 
conjugate vaccine) is licensed, Nimenrix can be administered to all consented pediatric subjects 
to replace the Day 57 vaccination with placebo (0.9% saline) in the control group, in accordance 
with the local label and local regulations, and unless contra-indicated. Nimenrix will be 
administered, only if permitted by the subject’s parent/legal guardian and following PI 
assessment on a case-by-case basis as vaccination with Nimenrix outside this study might be 
preferred (joint parent/legal guardian and PI decision). In the US, Nimenrix will not be used 
unless it has been licensed for use or an IND has been submitted.
Nimenrix would be used according to the terms of the marketing authorization and unless contra-
indicated, taking into account the specific subject’s age, and other childhood vaccines already 
received. Note: Required vaccination with Nimenrix depending on the judgment of the 
investigator or per national immunization schedule may be considered to be a contraindication
for vaccination with Nimenrix in this study.

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Attachment 3: 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 subjects 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 subject 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 subjects and site staff. If, at any time, a 
subject’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, subjects’ parents/legal guardians will be interviewed to collect safety data. Key 
efficacy endpoint assessments should be performed if required and as feasible. Subjects’ 
parents/legal guardians 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 subjects on study 
intervention, including follow up. Modifications to protocol-required assessments may be 
permitted after consultation between subjects’ parents/legal guardians, investigator, and 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. 
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 subject 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.

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GUIDANCE SPECIFIC TO THIS PROTOCOL:

End of RSV season visits (that include blood sampling for immunogenicity) may be delayed 
until the COVID-19 situation has resolved sufficiently for the subject to safely visit the site, 
in line with national/regional guidelines.

Follow-up of RTIs is of importance for the study since monitoring for severe RSV-LRTI is 
used as a preliminary indicator of ERD. Therefore, although a nasal sample might not be 
taken, it is important for any RTI to be followed to be aware of a severe RTI occurring 
during the study.

During the COVID-19 pandemic, in cases where a nasal swab is unable to be collected by 
site staff, and where local regulations allow, and with sponsor awareness, a trained 
parent/caregiver may obtain, store and transport the sample using instructions provided by 
the sponsor. Documentation of training completion and distribution of instructions should be 
noted in the subject’s record. Whenever possible, collection by site staff is preferred.

During the COVID-19 pandemic and at the impacted sites, clinical Site GCP audits with 
direct impact/engagement from the clinical investigator team will not be conducted, to 
comply with national, local and/or organizational social distancing restrictions. Additional 
quality assurance activities such as remote audits or focused review of study related 
documents may take place with limited impact/engagement, if possible.

If on-site monitoring visits are not possible, the site monitor may contact the investigator to 
arrange monitoring visits and activities remotely. Additional on-site monitoring visits may 
be needed in the future to catch up on source data verification.

Consent for remote visits (telephone or video consultation) of subjects will be performed as 
applicable for the measures taken and according to local guidance for informed consent 
applicable during the COVID-19 pandemic. Documentation of this consent should be noted 
in the subject’s record.

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Status: Approved, Date: 25 May 2020
INVESTIGATOR AGREEMENT
I have read this protocol and agree that it contains all necessary details for carrying out this study. I will 
conduct the study as outlined herein and will complete the study within the time designated.
I will provide copies of the protocol and all pertinent information to all individuals responsible to me who 
assist in the conduct of this study. I will discuss this material with them to ensure that they are fully 
informed regarding the study vaccine, the conduct of the study, and the obligations of confidentiality.
Coordinating Investigator (where required):
Name (typed or printed):
Institution and Address:
Signature:
Date:
(Day Month Year)
Principal (Site) Investigator:
Name (typed or printed):
Institution and Address:
Telephone Number:
Signature:
Date:
(Day Month Year)
Sponsor’s Responsible Medical Officer:
Name (typed or printed):
Institution:
Janssen Vaccines & Prevention B.V.
Signature:
electronic signature appended at the end of the protocol
Date:
(Day Month Year)
Note: If the address or telephone number of the investigator changes during the course of the study, written 
notification will be provided by the investigator to the sponsor, and a protocol amendment will not be required.
PPD

Signature
User
Date
Reason
25-May-2020
19:19:09
(GMT)
Document Approval
PPD