A Randomized, Double-blind, Placebo-controlled Phase 3 Efficacy Study of an Ad26.RSV.preF-based Vaccine in the Prevention of Lower Respiratory Tract Disease Caused by RSV in Adults Aged 60 Years and Older
Phase: PHASE3
Conditions: Respiratory Syncytial Viruses, Lower Respiratory Tract Disease
Sponsor: Janssen Vaccines & Prevention B.V.

CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
1
Status: Approved, Date: 11 October 2022
Janssen Vaccines & Prevention B.V.*
Clinical Protocol
A Randomized, Double-blind, Placebo-controlled Phase 3 Efficacy Study of an
Ad26.RSV.preF-based Vaccine in the Prevention of Lower Respiratory Tract Disease
Caused by RSV in Adults Aged 60 Years and Older
EVERGREEN
Protocol VAC18193RSV3001; Phase 3
AMENDMENT 5
VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
* Janssen Vaccines & Prevention B.V. is a Janssen pharmaceutical company of Johnson & Johnson and is
hereafter referred to as the sponsor of the study. The sponsor is identified on the Contact Information page
that accompanies the protocol.
United States (US) sites of this study will be conducted under US Food & Drug Administration
Investigational New Drug (IND) regulations (21 CFR Part 312).
EudraCT NUMBER:2020‐005458‐97
Status: 
Approved
Date: 
11 October 2022
Prepared by: 
Janssen Vaccines & Prevention B.V.
EDMS number: 
EDMS-ERI-207539578, 10.0
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.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
2
Status: Approved, Date: 11 October 2022
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE
DOCUMENT HISTORY
Document 
Date
Amendment 5 
11 October 2022
Amendment 4 
8 April 2022
Amendment 3 
10 November 2021
Amendment 2 
19 July 2021
Amendment 1 
3 May 2021
Original Protocol 
30 November 2020
Amendment 5 (11 October 2022)
Overall Rationale for the Amendment:
The protocol is amended to provide clarification around the timing of the end-of-study analyses and
population included, to align risk language with the most recent safety data available, and to provide
additional clarification around follow-up that is conducted via phone call versus onsite visit. The changes
made to this clinical protocol as part of Protocol Amendment 5 are listed below, including the rationale of
each change and a list of all applicable sections. Changes made in previous protocol amendments are listed
in Section 10.15, Appendix 15: Protocol Amendment History.
Section Number
and Name
Description of Change 
Brief Rationale 
1.1 Synopsis, 1.3.1 Schedule of 
Activities, 4.1 Overall Design, 7.2 
Participant Discontinuation/Withdrawal 
from the Study, 8 Study Assessments 
and Procedures
The Month 24 telephone call or
telemedicine will be an onsite visit
for participants who need to return
eDevices to the site.
In addition, participants who
withdraw before study completion
will be encouraged to return the
eDevice provided by the site, if
applicable.
To allow participants to return
eDevices to the site.
1.1 Synopsis, 4.1 Overall Design  
The total number of participants was
updated from approximately 27,500
participants (with up to
approximately 4,500 participants in
specific Asian countries/territories) to
approximately 27,200 participants
(with up to approximately 4,200
participants in specific Asian
countries/territories).
No participants will be
enrolled in South Korea,
resulting in a smaller total
number of participants for the
study.
1.1 Synopsis, 4.1 Overall Design, 9 
STATISTICAL CONSIDERATIONS, 
9.2.1 Efficacy, 9.3 Populations for 
Analysis, 9.5.2 Additional Analyses,
9.5.3 End-of-Study Analyses
The timing of the end-of-study
analysis and the population used was
clarified.
To clarify the data used for
the planned end-of-study
analysis.
1.1 Synopsis, 4.1 Overall Study Design, 
8.1 ARI Assessments and Procedures; 
Allowance has been made for use of
an equivalent version of the BioFire
Filmarray Respiratory panel in
To reflect local regulations.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
3
Status: Approved, Date: 11 October 2022
Section Number
and Name
Description of Change 
Brief Rationale
8.2.4 Diagnosis of RSV and Other
Respiratory Infections
regions where the panel is not
approved.
1.3.1 Schedule of Activities, Footnotes
a, b, and c, 8 STUDY ASSESSMENTS
AND PROCEDURES
The timing of the Month 6 (Day 182)
safety follow-up relative to the End
of first RSV season visit, based on
different enrollment scenarios, was
clarified.
To clarify the process for the
End of first RSV season/Day
182 follow-up.
1.3.1 Schedule of Activities, Footnote
o, 8.1 ARI Assessments and Procedures
The RiiQ, the PGI-H and the EQ-5D-
5L questionnaires do not need to be
completed at Month 6.
To clarify the timing of
assessments.
2.2 Background, Thrombosis with
Thrombocytopenia Syndrome
8.5.6.1 Thrombosis with
Thrombocytopenia Syndrome
The risk language around TTS has
been updated.
To reflect the most recent
safety data available with
regards to vaccine-induced
TTS in the RSV program as
well as to align on the
terminology used by
regulatory authorities.
11 REFERENCES  
Updated date of the Adenoviral
Vaccine Safety Database Report
(from V6.0 to V7.0).
Reference to the 2021 Investigator
Brochure was removed.
The Adenoviral Vaccine
Safety Database Report
reference was updated to
reflect the most current report
available.
A reference to the latest
Investigator Brochure was
included in text.
Throughout 
Updated “country” to
“country/territory”.
Language was updated to
accurately reflect the various
geographies included in this
study.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
4
Status: Approved, Date: 11 October 2022
TABLE OF CONTENTS
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ............................................................... 2
TABLE OF CONTENTS ............................................................................................................................... 4
LIST OF IN-TEXT TABLES AND FIGURES................................................................................................ 7
1. 
PROTOCOL SUMMARY..................................................................................................................... 8
1.1. 
Synopsis........................................................................................................................................... 8
1.2. 
Schema.......................................................................................................................................... 23
1.3. 
Schedule of Activities..................................................................................................................... 24
1.3.1. 
Schedule of Activities –Assessments for All Participants.......................................................... 24
1.3.2. 
Schedule of Activities –Assessments for Participants with an ARI Episode ............................. 29
2. 
INTRODUCTION................................................................................................................................ 32
2.1. 
Study Rationale.............................................................................................................................. 32
2.2. 
Background .................................................................................................................................... 32
2.3. 
Benefit-Risk Assessment............................................................................................................... 35
2.3.1. 
Risks of Study Participation........................................................................................................ 35
2.3.2. 
Benefits of Study Participation.................................................................................................... 37
2.3.3. 
Benefit-Risk Assessment of Study Participation ........................................................................ 38
3. 
OBJECTIVES AND ENDPOINTS ..................................................................................................... 38
4. 
STUDY DESIGN ................................................................................................................................ 43
4.1. 
Overall Design................................................................................................................................ 43
4.2. 
Scientific Rationale for Study Design............................................................................................. 47
4.2.1. 
Study-Specific Ethical Design Considerations ........................................................................... 48
4.3. 
Justification for Dose...................................................................................................................... 48
4.4. 
End of Study Definition................................................................................................................... 49
5. 
STUDY POPULATION ...................................................................................................................... 49
5.1. 
Inclusion Criteria............................................................................................................................ 50
5.2. 
Exclusion Criteria........................................................................................................................... 51
5.3. 
Lifestyle Considerations................................................................................................................. 53
5.4. 
Screen Failures.............................................................................................................................. 54
5.5. 
Criteria for Temporarily Delaying Administration of Study Vaccine ............................................... 54
6. 
STUDY VACCINE AND CONCOMITANT THERAPY ...................................................................... 54
6.1. 
Study Vaccine Administration ........................................................................................................ 54
6.2. 
Preparation/Handling/Storage/Accountability ................................................................................ 55
6.3. 
Measures to Minimize Bias: Randomization and Blinding............................................................. 56
6.4. 
Study Vaccination Compliance ...................................................................................................... 58
6.5. 
Dose Modification........................................................................................................................... 58
6.6. 
Continued Access to Study Vaccine After the End of the Study ................................................... 58
6.7. 
Overdose........................................................................................................................................ 59
6.8. 
Concomitant Therapy..................................................................................................................... 59
7. 
DISCONTINUATION OF STUDY VACCINATION AND PARTICIPANT
DISCONTINUATION/WITHDRAWAL............................................................................................... 60
7.1. 
Discontinuation of Study Vaccination............................................................................................. 60
7.2. 
Participant Discontinuation/Withdrawal From the Study................................................................ 60
7.2.1. 
Withdrawal From the Use of Research Samples ....................................................................... 61
7.3. 
Lost to Follow-up............................................................................................................................ 61
8. 
STUDY ASSESSMENTS AND PROCEDURES ............................................................................... 62
8.1. 
ARI Assessments and Procedures ................................................................................................ 64
8.1.1. 
Respiratory Infection Intensity and Impact Questionnaire (RiiQ™v2)........................................ 70
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
5
Status: Approved, Date: 11 October 2022
8.1.2. 
EuroQoL, 5-Dimension, 5-Level Questionnaire.......................................................................... 72
8.1.3. 
Patient Global Impression Scores .............................................................................................. 72
8.2. 
Efficacy Assessments .................................................................................................................... 72
8.2.1. 
Case Definition for RT-PCR-confirmed RSV-mediated LRTD ................................................... 73
8.2.2. 
Case Definition for RT-PCR-confirmed RSV-mediated ARI....................................................... 74
8.2.3. 
Predefined Clinically Relevant Disease Associated with RT-PCR-confirmed RSV-
mediated ARI .............................................................................................................................. 74
8.2.4. 
Diagnosis of RSV and Other Respiratory Infections .................................................................. 75
8.3. 
Immunogenicity Assessments ....................................................................................................... 76
8.4. 
Safety Assessments....................................................................................................................... 77
8.4.1. 
Physical Examinations................................................................................................................ 79
8.4.2. 
Vital Signs................................................................................................................................... 79
8.5. 
Adverse Events, Serious Adverse Events, Adverse Events of Special Interest, and Other
Safety Reporting ............................................................................................................................ 79
8.5.1. 
Time Period and Frequency for Collecting Adverse Event, Serious Adverse Event, and
Adverse Event of Special Interest Information ........................................................................... 80
8.5.2. 
Method of Detecting Adverse Events, Serious Adverse Events, and Adverse Events of
Special Interest........................................................................................................................... 81
8.5.3. 
Follow-up of Adverse Events, Serious Adverse Events, and Adverse Events of Special
Interest........................................................................................................................................ 82
8.5.4. 
Regulatory Reporting Requirements for Serious Adverse Events ............................................. 82
8.5.5. 
Pregnancy................................................................................................................................... 82
8.5.6. 
Adverse Events of Special Interest............................................................................................. 83
8.5.6.1. 
Thrombosis with Thrombocytopenia Syndrome...................................................................... 83
8.6. 
Medical Resource Utilization and Health Economics .................................................................... 85
8.7. 
Participant Medical Information Prior to, During and After the Study (Real-world Data)............... 86
9. 
STATISTICAL CONSIDERATIONS.................................................................................................. 86
9.1. 
Statistical Hypotheses.................................................................................................................... 86
9.2. 
Sample Size Determination ........................................................................................................... 87
9.2.1. 
Efficacy ....................................................................................................................................... 87
9.2.2. 
Immunogenicity........................................................................................................................... 88
9.2.3. 
Safety.......................................................................................................................................... 89
9.3. 
Populations for Analyses................................................................................................................ 90
9.4. 
Statistical Analyses ........................................................................................................................ 91
9.4.1. 
Efficacy Analysis......................................................................................................................... 91
9.4.1.1. 
Primary Endpoint..................................................................................................................... 91
9.4.1.2. 
Secondary Efficacy Endpoints................................................................................................. 93
9.4.1.3. 
Testing Strategy for Primary and Confirmatory Secondary Endpoints ................................... 94
9.4.1.4. 
Exploratory Endpoints ............................................................................................................. 94
9.4.2. 
Immunogenicity Analyses........................................................................................................... 96
9.4.3. 
Safety Analyses.......................................................................................................................... 97
9.4.4. 
Other Analyses ........................................................................................................................... 98
9.4.4.1. 
Patient-reported Outcomes ..................................................................................................... 98
9.4.4.2. 
Medical Resource Utilization Analyses ................................................................................... 98
9.5. 
Planned Analyses .......................................................................................................................... 98
9.5.1. 
Analysis Plan for the Interim and Primary Efficacy Analyses..................................................... 98
9.5.2. 
Additional Analyses .................................................................................................................. 101
9.5.3. 
End-of-Study Analysis .............................................................................................................. 101
9.6. 
Committees.................................................................................................................................. 101
9.6.1. 
Independent Data Monitoring Committee................................................................................. 101
9.6.2. 
Clinical Event Adjudication Committee..................................................................................... 102
10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS .......................... 103
10.1. 
Appendix 1: Abbreviations ........................................................................................................... 103
10.2. 
Appendix 2: Regulatory, Ethical, and Study Oversight Considerations....................................... 105
10.2.1. 
Regulatory and Ethical Considerations .................................................................................... 105
10.2.2. 
Financial Disclosure.................................................................................................................. 108
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
6
Status: Approved, Date: 11 October 2022
10.2.3. 
Informed Consent Process ....................................................................................................... 108
10.2.4. 
Data Protection ......................................................................................................................... 109
10.2.5. 
Long-Term Retention of Samples for Additional Future Research .......................................... 110
10.2.6. 
Committees Structure............................................................................................................... 110
10.2.6.1. 
Independent Data Monitoring Committee.............................................................................. 110
10.2.6.2. 
Clinical Event Adjudication Committee.................................................................................. 110
10.2.7. 
Publication Policy/Dissemination of Clinical Study Data.......................................................... 111
10.2.8. 
Data Quality Assurance............................................................................................................ 112
10.2.9. 
Case Report Form Completion................................................................................................. 112
10.2.10. Source Documents ................................................................................................................... 113
10.2.11. Monitoring ................................................................................................................................. 113
10.2.12. On-Site Audits........................................................................................................................... 114
10.2.13. Record Retention...................................................................................................................... 114
10.2.14. Study and Site Start and Closure ............................................................................................. 115
10.3. 
Appendix 3: Adverse Events, Serious Adverse Events, Adverse Event of Special Interest,
Product Quality Complaints, and Other Safety Reporting: Definitions and Procedures for
Recording, Evaluating, Follow-up, and Reporting ....................................................................... 116
10.3.1. 
Adverse Event Definitions and Classifications ......................................................................... 116
10.3.2. 
Attribution Definitions................................................................................................................ 117
10.3.3. 
Severity Criteria........................................................................................................................ 117
10.3.4. 
Special Reporting Situations .................................................................................................... 118
10.3.5. 
Procedures ............................................................................................................................... 118
10.3.6. 
Product Quality Complaint Handling......................................................................................... 120
10.3.7. 
Contacting Sponsor Regarding Safety, Including Product Quality........................................... 120
10.4. 
Appendix 4: Toxicity Grading Scale............................................................................................. 121
10.5. 
Appendix 5: Definition of Acute Respiratory Infection for Participants Aged ≥60 Years ............. 123
10.6. 
Appendix 6: Medically-attended ARI Form .................................................................................. 124
10.7. 
Appendix 7: ARI Surveillance Assessment.................................................................................. 128
10.8. 
Appendix 8: Respiratory Infection Intensity and Impact Questionnaire (RiiQ™v2) –
Symptom Scale and Impact on Daily Activity Scale .................................................................... 129
10.9. 
Appendix 9: EuroQoL, 5-Dimension, 5-Level Questionnaire (EQ-5D-5L).................................. 130
10.10. Appendix 10: Patient Global Impression Scales.......................................................................... 133
10.11. Appendix 11: Medical Resources Utilization Questionnaire ........................................................ 134
10.12. Appendix 12: Missed Working Days ............................................................................................ 136
10.13. Appendix 13: Guidance on Study Conduct During a Natural Disaster........................................ 137
10.14. Appendix 14: Thrombotic Events to be Reported as Potential AESIs ......................................... 139
10.15. Appendix 15: Protocol Amendment History................................................................................. 140
11. REFERENCES................................................................................................................................. 154
INVESTIGATOR AGREEMENT............................................................................................................... 156
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
7
Status: Approved, Date: 11 October 2022
LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1: 
Clinical Studies with RSV PreF Protein and/or Ad26.RSV.preF in the Adult Population ......... 34
Table 2: 
Study Design: VAC18193RSV3001.......................................................................................... 44
Table 3: 
Strategy for Local Site and Central Testing of the Nasal Swabs and Sputum Samples.......... 76
Table 4: 
Laboratory Tests That May Be Performed Upon Sponsor Request on Immunogenicity
Samples Collected on Day 1 and 15 After Potential AESI Reporting....................................... 84
Table 5: 
Laboratory Tests That May Be Requested by the Sponsor to be Performed at the
Central Laboratory After Potential AESI Reporting .................................................................. 84
Table 6: 
Distance from the Mean to the Limits of 95% CI Around the Actual Value at Day 15 for
Pre-F ELISA, VNA, and ELISpot .............................................................................................. 89
Table 7: 
Probability of Observing at Least One Adverse Event or Serious Adverse Event at a
Given True Adverse Event Rate in the Active Vaccine Group (Group 1)................................. 90
Table 8: 
Secondary Endpoints: Overview of the Testing Order, Timing of the Testing in the
Testing Strategy and the Corresponding Alpha........................................................................ 94
Table 9: 
Alpha-spending at the Prespecified Analysis Timepoints......................................................... 99
FIGURES
Figure 1: Schematic Overview of the Study for all Participants............................................................... 23
Figure 2: Schematic Overview of the ARI Assessments and Procedures............................................... 65
Figure 3: Interim and Primary Analysis Plan.......................................................................................... 100
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
8
Status: Approved, Date: 11 October 2022
1. 
PROTOCOL SUMMARY
1.1. 
Synopsis
A Randomized, Double-blind, Placebo-controlled Phase 3 Efficacy Study of an Ad26.RSV.preF-based
Vaccine in the Prevention of Lower Respiratory Tract Disease Caused by RSV in Adults Aged 60 Years
and Older
Therespiratorysyncytialvirus (RSV) vaccine that will be investigated in this study, Ad26/protein preF RSV
vaccine, includes 2 components that are being mixed prior to administration as a single intramuscular (IM)
injection:
 
Ad26.RSV.preF (JNJ-64400141), a replication-incompetent adenovirus serotype 26 (Ad26)
containing a deoxyribonucleic acid (DNA) transgene encoding the pre-fusion conformation-stabilized
F protein (preF) derived from the RSV A2 strain, and
 
RSV preF protein (JNJ-64213175), a pre-fusion conformation-stabilized F protein derived from the
RSV A2 strain.
OBJECTIVES AND ENDPOINTS
The primary objective of this study is to demonstrate efficacy of the Ad26.RSV.preF-based study vaccine
in the prevention ofreverse transcriptase polymerase chain reaction (RT-PCR)-confirmed RSV-mediated
lower respiratory tract disease (LRTD) when compared to placebo in adults aged 60 years and above.
Interim analyses to evaluate the primary objective will be performed by the Independent Data Monitoring
Committee (IDMC). The primary, secondary and exploratory endpoints and objectives of the study are
presented below.
Primary Objective, Secondary Efficacy Objectives and Exploratory Objectives
Objectives 
Endpoints
PRIMARY
 To demonstrate the efficacy of the active
Ad26.RSV.preF-based study vaccine in the
prevention of RT-PCR-confirmed RSV-mediated
LRTD when compared to placebo in adults aged
60 years and above
 First occurrence of RT-PCR-confirmed, RSV-
mediated LRTD with onset at least 14 days after
dosing of study vaccine
CONFIRMATORY SECONDARY*
 To demonstrate the efficacy of active study vaccine
in the prevention of any RT-PCR-confirmed RSV-
mediated acute respiratory infection (ARI) when
compared to placebo
 First occurrence of any RT-PCR-confirmed
RSV-mediated ARI with onset at least 14 days
after dosing of study vaccine
 To demonstrate the efficacy of active study vaccine
in the prevention of RT-PCR-confirmed
RSV-mediated LRTD during the second year when
compared to placebo in adults aged 60 years and
above
 First occurrence of RT-PCR-confirmed RSV-
mediated LRTD during the second year, with onset
after study Day 365
 To demonstrate the efficacy of active study vaccine
in the prevention of any RT-PCR-confirmed RSV-
mediated ARI during the second year when
compared to placebo
 First occurrence of any RT-PCR-confirmed
RSV-mediated ARI during the second year, with
onset after study Day 365
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
9
Status: Approved, Date: 11 October 2022
Objectives 
Endpoints
 To demonstrate the efficacy of active study vaccine 
in the prevention of predefined clinically relevant 
disease associated with RT-PCR-confirmed RSV- 
mediated ARI over the whole study when 
compared to placebo
 First occurrence of predefined clinically relevant
disease associated with RT-PCR-confirmed
RSV-mediated ARI over the whole study with
onset at least 14 days after dosing of study vaccine
NON-CONFIRMATORY SECONDARY
 To evaluate safety in terms of serious adverse 
events (SAEs) and adverse events of special 
interest (AESIs) until 6 months after vaccination
 Occurrence and relationship of vaccination to
SAEs and AESIs until 6 months after vaccination
 In the Safety Subset and in subgroups ofthe Safety
Subset (including but not limited to participants at
increased risk of severe RSV disease), to evaluate
the safety and reactogenicity in terms of solicited
local and systemic adverse events (AEs) during
7days after vaccination, and in terms of
unsolicited AEs during 28 days after vaccination
 Occurrence, intensity, duration and relationship to
vaccination of solicited local and systemic AEs
during 7 days after vaccination and of unsolicited
AEs during 28 days after vaccination
 In the Immuno Subset and in subgroups ofthe
Immuno Subset (including but not limited to
participants at increased risk of severe
RSV disease), to evaluate the immunogenicity of
active study vaccine when compared to placebo
 Characterization of the humoral and cellular
immune responses in the Immuno Subset with
emphasis on neutralizing and binding antibodies
and antigen-specific cytokine production by
T-cells
 To assess the reduction of symptom severity in
participants with an RT-PCR-confirmed RSV-
mediated ARI when compared to placebo over the
whole study
 In participants with an RT-PCR-confirmed RSV-
mediated ARI over the whole study: the area under
the curve (AUC) of the change from baseline in
Respiratory Infection Intensity and Impact
Questionnaire (RiiQa) Total Symptom score
EXPLORATORY
 To demonstrate the efficacy of active study vaccine
in the prevention of RT-PCR-confirmed
RSV-mediated LRTD during the first year when
compared to placebo in adults aged 60 years and
above
 First occurrence of RT-PCR-confirmed RSV-
mediated LRTD during the first year, with onset at
least 14 days after dosing of study vaccine, and
prior to study Day 365
 To demonstrate the efficacy of active study vaccine
in the prevention of RT-PCR-confirmed
RSV-mediated ARI during the first year when
compared to placebo
 First occurrence of RT-PCR-confirmed RSV-
mediated ARI during the first year, with onset at
least 14 days after dosing of study vaccine, and
prior to study Day 365
 To explore the effect of active study vaccine on
RSV A and B infection when compared to placebo
 Assessment of the RSV A and B viral load by
quantitative RT-PCR
a 
The Respiratory Infection Intensity and Impact Questionnaire used in this study is the RiiQ Symptom Scale and the RiiQ
Impact on DailyActivities Scale of the RiiQ™ Version 2 (hereafter referred to as RiiQ).
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
10
Status: Approved, Date: 11 October 2022
Objectives 
Endpoints
 To explore the efficacy of active study vaccine in 
the prevention of any RT-PCR-confirmed RSV- 
mediated LRTD caused by an RSV A and/or B 
strain when compared to placebo 
o during the first year 
o during the second year 
o over the whole study  
 First occurrence of any RT-PCR-confirmed
RSV-mediated LRTD caused by an RSV A strain
and/or RSV B strain, respectively, during the
considered years
o with onset at least 14 days after dosing of study
vaccine and prior to study Day 365 (first year
comparison)
o with onset after study Day 365 (second year
comparison)
o with onset at least 14 days after dosing of study
vaccine (whole study comparison)
 To explore the efficacy of active study vaccine in 
the prevention of any RT-PCR-confirmed RSV- 
mediated ARI caused by an RSV A and/or B strain 
when compared to placebo 
o during the first year 
o during the second year 
o over the whole study  
 First occurrence of any RT-PCR-confirmed
RSV-mediated ARI caused by an RSV A strain
and/or RSV B strain, respectively, during the
considered years
o with onset at least 14 days after dosing of study
vaccine and prior to study Day 365 (first year
comparison)
o with onset after study Day 365 (second year
comparison)
o with onset at least 14 days after dosing of study
vaccine (whole study comparison)
 To explore the efficacy of active study vaccine in 
the prevention of at least mild, at least moderate, 
and at least severe RT-PCR-confirmed RSV LRTD 
as assessed by the Clinical Event Adjudication 
Committee (CEC) compared to placebo 
o during the first year 
o during the second year
o over the whole study
 First occurrence of any RT-PCR-confirmed RSV
LRTD assessed by the CEC as:
- at least mild lower respiratory tract infection
(LRTI)
- at least moderate LRTI
- at least severe LRTI
during the considered year:
o with onset at least 14 days after dosing of study
vaccine and prior to study Day 365 (first year
comparison)
o with onset after study Day 365 (second year
comparison)
o with onset at least 14 days after dosing of study
vaccine (whole study comparison)
 To explore the reduction of symptom severity and 
time to return to usual health in participants with 
an RT-PCR-confirmed RSV-mediated ARI and in 
participants with RT-PCR-confirmed RSV- 
mediated LRTD when compared to placebo 
o during the first year 
o during the second year 
o over the whole study  
 In participants with an RT-PCR-confirmed RSV-
mediated ARI and in participants with RT-PCR-
confirmed RSV-mediated LRTD (during the first
year, the second year, or over the whole study,
respectively):
o the AUC of the change from baseline in RiiQ
Total Symptom score
o the time to return to usual health
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
11
Status: Approved, Date: 11 October 2022
Objectives 
Endpoints
 To explore the reduction of disease severity in 
participants with an RT-PCR-confirmed RSV- 
mediated ARI and in participants with RT-PCR- 
confirmed RSV-mediated LRTD when compared 
to placebo, by subtype (RSV A, RSV B) 
o during the first year 
o during the second year 
o over the whole study 
 In participants with an RT-PCR-confirmed RSV-
mediated ARI and in participants with RT-PCR-
confirmed RSV-mediated LRTD (during the first
year, the second year or over the whole study
respectively), by subtype (RSV A, RSV B):
o the AUC of the change from baseline in RiiQ
Total Symptom score
o the time to return to usual health
 To explore the impact of active study vaccine on 
the course of an RT-PCR-confirmed RSV- 
mediated ARI and of human metapneumovirus 
(hMPV)- and influenza-mediated respiratory 
infections, general health status and health-related 
quality of life (HRQoL) measures when compared 
to placebo
 HRQoL and health status reported by participants
on the RiiQ, patient global impression scales, and
EuroQoL, 5-Dimension, 5-Level (EQ-5D-5L) in
participants with an RT-PCR-confirmed RSV-
mediated ARI or hMPV and influenza-mediated
respiratory infections
 To explore the effect of active study vaccine on
each of the following separately: the potential
complications (including pneumonia),
hospitalizations, emerging therapeutic use and
medical resource utilization (MRU) of an RT-PCR-
confirmed RSV-mediated ARI, an RT-PCR-
confirmed RSV-mediated LRTD, and of hMPV
and respiratory infections when compared to
placebo
o during the first year
o during the second year
o over the whole study
For influenza, the objective is to explore the
incidence of these endpoints.
 For each of the following separately:
(1) complications, (2) pneumonia,
(3) hospitalizations, (4) emerging therapeutic
interventions and (5) MRU, all associated with
RT-PCR-confirmed RSV-mediated ARI or RT-
PCR-confirmed RSV-mediated LRTD during the
first year, the second year and over the whole
study
o with onset at least 14 days after dosing of study
vaccine and prior to study Day 365 (first year
comparison)
o with onset after study Day 365 (second year
comparison)
o with onset at least 14 days after dosing of study
vaccine (whole study comparison)
 Complications, pneumonia, hospitalizations,
emerging therapeutic use and MRU associated
with hMPV and influenza-mediated respiratory
infections will be defined similarly
 To explore the efficacy of active study vaccine in
the prevention of RT-PCR-confirmed
hMPV-mediated ARI and RT-PCR-confirmed
hMPV-mediated LRTD when compared to placebo
in adults aged 60 years and above
 First occurrence of RT-PCR-confirmed, hMPV-
mediated ARI and RT-PCR-confirmed hMPV-
mediated LRTD with onset at least 14 days after
dosing of study vaccine
 To explore the immune response biomarkers in
study participants as correlates of risk of RSV
disease and as correlates of protection induced by
the active study vaccine
 Assessment of the correlation of immune
responses with emphasis on neutralizing and
binding antibodies with the risk of RSV disease
and protection induced by the vaccine
 To explore biomarkers for the diagnosis of RSV
infection, RSV-mediated LRTD and hMPV and
influenza- mediated respiratory infections
 Assessment of blood samples collected during ARI
episodes for biomarkers that correlate with RSV
infection, RSV-mediated LRTD and hMPV and
influenza-mediated respiratory infections
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
12
Status: Approved, Date: 11 October 2022
Objectives 
Endpoints
 To explore additional vaccine-elicited immune
responses in the Immuno Subset
 Assays that may be used include, but are not
limited to:
o RSV cross-neutralization of B and/or other A
strain(s)
o Antigen specific antibody functional and
molecular characterization
o Analysis of neutralizing antibodies to Ad26
o Antigen-specific T-cell immune responses using
detailed immunoprofiling
 To increase the information on prior medical
history (electronic health records, claims,
laboratory data from other care settings) in order to
further evaluate its potential effect on the response
to immunization and the impact of immunization
on efficacy and duration of efficacy as well as AEs
that may occur during and after completion of the
study
 Utilization of tokenization and matching
procedures for exploratory analysis of participant’s
medical data prior to, during, and following
participation in the study (real-world data).
Analysis will be performed to relate real-world
data to vaccine immune responses, efficacy and
duration of protection, and AEs
*Included in the testing strategy
Hypotheses
The study is designed to test the primary hypothesis of VE against RT-PCR-confirmed RSV-mediated
LRTD in the PPE population.
 
The hypothesis for the primary endpoint is:
- 
Null hypothesis: the VE against RT-PCR-confirmed RSV-mediated LRTD of Group 1 vs placebo
is ≤20%.
- 
Alternative hypothesis: the VE against RT-PCR-confirmed RSV-mediated LRTD ofGroup 1 vs
placebo is >20%.
The study is successful if:
 
The lower limit (LL) of the 95% 2-sided confidence interval (CI, potentially corrected as described in
Section 9.4.1.3) around the VE (1-relative risk rate) calculated from the Exact Poisson regression
model is above 20% and additionally a point-estimate of VE >50% is observed for Group 1
OVERALL DESIGN
This is a multicenter, randomized, double-blind, placebo-controlled Phase 3 confirmatory efficacy study in
participants aged 60 years and older. The primary objective of the study is to further establish the efficacy
of the active Ad26.RSV.preF-based study vaccine in the prevention of RT-PCR-confirmed RSV-mediated
LRTD.
Up to approximately 27,200 participants (with up to approximately 23,000 in the Global cohort, and up to
approximately 4,200 participants in specific Asian countries/territories under local protocols) will be
enrolled and randomized in parallel in a 2:1 ratio to receive active study vaccine or placebo.
Note that some additional local cohort enrollment beyond the Global cohort enrollment may be allowed if
required by local health authorities for the purpose of local health authority consideration.
 
The Global cohort is defined as all participants (including the Safety subset and the Immuno subset)
who are recruited up to the point that global enrollment is stopped.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
13
Status: Approved, Date: 11 October 2022
 
Local cohorts are defined as participants from the considered country/territory  and under local
protocols.
For analyses purposes, data from the Global cohort and the local cohorts may be aggregated. Analyses for
local cohort enrollment will be described separately, but they will also be included in the primary analysis
and final analysis if their enrollment started prior to the database cut-off of the primary analysis or final
analysis, respectively.
The study includes 1 dose of study vaccine at Day 1.
The study will be discontinued if the primary analysis is performed by the sponsor and the outcome is
negative; however, if at that timepoint, some participants have not completed 6 months of follow-up after
their vaccination, the study will continue until this follow-up period is complete.
Study Design: VAC18193RSV3001
Group  
N 
Day 1
1 
15,340 
Ad26/protein preF RSV vaccine (1×1011 vp/150 μg)
2 
7,670 
Placebo
N number of participants, vp viral particles
ARI ASSESSMENTS AND PROCEDURES
From the study vaccination until 24 months after vaccination (ie, the full duration of the study), participants
will be followed up to identify potential cases of RSV infection. After administration of study vaccine, ARI
surveillance will be conducted twice weekly via the participant’s eDevice (or desktop computer, where
applicable) for the duration of the study. The surveillance questions ask participants if they have
experienced any ARI symptoms, or for participants who have one or more of these symptoms at baseline,
if they have experienced any additional ARI symptoms or a worsening of their baseline symptoms.
Participants who experience any symptoms suggestive of an ARI (new onset or worsening, in the setting
that baseline symptoms are present) are instructed to indicate this (refer to Appendix 7: ARI Surveillance
Assessment) and start completing the required ARI episode questionnairesa on a daily basis (preferably in
the evening). Ideally within the next 24 hours, the site and participant should have telephone or telemedicine
contact with each other in order for the site to confirm that the participant is experiencing symptoms
consistent with an ARIb and to give instructions to the participant on the further ARI episode procedures to
be followed. Participants will collect a nasal swab at home on the day of symptom onset or the day thereafter
(ARI Day 1-2).
On ARI Day 3-5, participants will present to the site, where vital signs will be measured, and a nasal swab,
a sputum sample (in participants with a productive cough, when possible), and blood samples (to measure
the immune responses at the time of exposure and for exploration of biomarkers that correlate with
respiratory infection and disease severity) may be taken by a member of the study staff(see Section 8.1 to
a 
The following questionnaires will need to be completed on a daily basis: the RiiQ Symptom Scale and the RiiQ Impact on
Daily Activities Scale, the European Quality of Life, 5 Dimension, 5 Level (EQ 5D 5L), the Patient Global Impression of
Health (PGI H) scale, the Patient Global Impression of Severity (PGI S) scale, the Patient Global Impression of Change
(PGI C) scale, and the Return to Usual Health question. Note that the PGI C scale and Return to Usual Health question will
not be completed on ARI Day 1.
b 
This will be assessed by the site by confirming that at least one of the symptoms used to confirm the ARI from the RiiQ
Symptom Scale is worse than baseline. As defined in Appendix 5, symptoms used to confirm an ARI episode are: nasal
congestion, sore throat, cough, short of breath, coughing up phlegm (sputum), and wheezing (from the RiiQ Symptom Scale).
As it is possible that the participants will make errors when they answer the RiiQ Symptom Scale, the telephone or telemedicine
contact will be used by the sites to also confirm the correctness of the answers provided by the participant and to confirm the
ARI episode was correctly triggered.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
14
Status: Approved, Date: 11 October 2022
determine if the blood samples can be omitted). Ideally within 24 hours after the ARI Day 3-5 visit (but no
later than 48 hours after the ARI Day 3-5 visit), a qualified member of the study staff will perform a local
RT-PCR of all available nasal swabs with the BioFire® Filmarray Respiratorypanel, which will be provided
to all sites (both US and non-US); changes to the process might be implemented at the local level based on
local requirements. Participants will subsequently be contacted by telephone and given further instructions,
as detailed below, on how to further proceed based on the outcome of the RT-PCR tests. Sputum samples
(where applicable) will be sent to the central laboratory for testing using the BioFire Filmarray Pneumonia
(PN) panel. For all ARI episodes where a sputum sample is collected, the ARI episode will be followed up
until ARI resolution (ie, with daily questionnaires and an ARI Day 29 visit) (refer to the procedures in the
first bullet point below), independent of the test results from the collected nasal swabs. Participants who
are under self-isolation because of a (possible) positive test for SARS-CoV-2 will not come to the site for
ARI Day 3-5 assessments but will self-collect the nasal swab.
 
In the unlikely event where at least one nasal swab from an ARI episode cannot be tested at the site
with the BioFire Filmarray  Respiratory  panel (eg, in the setting of instrument malfunction,
unavailability of the device in the country/territory or at the site, or shortage of testing reagents at the
site), this sample(s) should be sent to the central laboratory for testing with the BioFire Filmarray
Respiratory  panel, and the ARI episode will be followed up until ARI resolution (ie, with daily
questionnaires and an ARI Day 29 visit) (refer to the procedures in the first bullet point below),
independent of the results from other collected samples for that ARI episode. Further details on the
strategy for local site and central testing of the nasal swabs and sputum samples are provided in
Section 8.2.4.
 
Participants with an ARI and a RT-PCR positive for RSV, hMPV, or influenza-mediated ARI will
continue filling out the ARI episode questionnaires daily until resolution of the ARI episode (defined
as 2 consecutive days with no symptoms listed on the RiiQ Symptom Scale, or, for participants who
have RiiQ symptoms at baseline [assessed prevaccination], 2 consecutive days where all symptoms on
the RiiQ Symptom Scale have returned to the same severity level as reported at baseline [or lower]).
After resolution of the ARI episode, the participant will return to ARI surveillance with twice weekly
reminders.
 
On ARI Day 29 (±7 days), regardless of whether the ARI episode has resolved, participants with
a RT-PCRpositive for RSV, hMPV, or influenza-mediated ARI will be asked to return to the site.
During this visit, the MRU questionnaire will be completed based on interview with the
participant, participants will complete the RiiQ, the EQ-5D-5L and each of the Patient Global
Impression (PGI)scales and the Return to Usual Health question, and the site staff will also collect
information on days missed from work and on complications, hospitalizations and concomitant
medications related to the ARI and record in the electronic case report form (eCRF). The ARI
Day 29 visit can also take place by telephone or telemedicine contact.
 
For medically-attended RT-PCRpositive forRSV, hMPV, or influenza-mediatedARIs, including
those resulting in hospitalization, a standard question list will be provided to collect additional
information on any other diagnostic tests (eg, chest x-rays, spirometry, pulmonary function tests,
etc.) or on any interventions during the clinical course of the ARI.
Note: the same procedures apply for participants with a sputum sample taken and for participants
with at least one nasal swab that cannot be tested at the site with the BioFire Filmarray Respiratory
panel.
Participants will remain blinded as to the outcome of RSV, hMPV and influenza RT-PCR test results
until study unblinding and the test results should only be disclosed in the event of safety concerns.
RT-PCR test results related to the detection of other respiratory pathogens can be communicated to
the participants. The RT-PCR results that are obtained with the BioFire Filmarray testing under the
study procedures will be used for research purposes only and will not be used by the investigator for
therapeutic decisions. A locally approved diagnostic test external to the study procedures, including
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
15
Status: Approved, Date: 11 October 2022
the RSV RT-PCR, should be obtained in case the participant’s own healthcare provider considers it
warranted (eg, based on symptoms and/or risk of severe disease) and/or according to local/site specific
guidelines. If a sample tests positive for SARS-CoV-2, the participant will be referred to their own
healthcare provider for locally approved diagnostic test and further management, in accordance with
local/site specific guidelines.
 
Participants with negative RT-PCRresults for RSV, hMPV, or influenza will be informed by telephone
or telemedicine contact that they can stop filling out the daily ARI episode questionnaires and the site
will end the ARI episode and return the participant to ARI surveillance.
 
For participants with a positive SARS-CoV-2 test and a negative test for RSV, hMPV, and influenza,
the collection of ARI data by the study site will be stopped for the ARI episode. The participant will
be informed by telephone or telemedicine contact that they can stop filling out the daily ARI episode
questionnaires, and the site will end the ARI episode and return the participant to ARI surveillance
with twice weekly reminders. Participants who have a positive SARS-CoV-2 RT-PCR test as part of
the study procedures should be referred to their own healthcare provider for locally approved
diagnostic test and further management, in accordance with local/site specific guidelines. Participants
whose standard-of-care testing during an ARI episode is positive for SARS-CoV-2, or who have been
in contact with someone that tested positive for SARS-CoV-2 and therefore must self-isolate according
to the local guidelines, will not come to the site for ARI Day 3-5 assessments but will self-collect the
nasal swab. In this circumstance, other ARI Day 3-5 assessments (vital signs, sputum sample and blood
samples) might not be performed.
Participants with positive RT-PCR results for RSV (or hMPV or influenza) should keep on filling out
the daily ARI episode questionnaires until resolution of the ARI episode independently of any other
co-infection (including SARS-CoV-2).
When the end of RSV season one telephone call or telemedicine contact occurs within 6 months after
vaccination, the participants will be contacted again by telephone or telemedicine at 6 months
post-vaccination to collect information on SAEs and AESIs (applies to Visit 3 [end of season 1/6-month
follow-up]).
At Month 24, all participants will be contacted by telephone or telemedicine (or come to the site if they
have eDevices to return) to ensure the participants complete the RiiQ, the PGI-H and the EQ-5D-5L.
NUMBER OF PARTICIPANTS
Up to approximately 27,200 participants (with up to approximately 23,000 in the Global cohort, and up to
approximately 4,200 participants in specific Asian countries/territories under local protocols) will be
enrolled and randomized in parallel in a 2:1 ratio to receive active study vaccine or placebo.
VACCINE GROUPS AND DURATION
The investigational medicinal products to be administered to participants in this study are Ad26.RSV.preF,
RSV preF protein, and placebo. The Ad26/protein preF RSV vaccine to be used in this study is composed
of Ad26.RSV.preF and RSV preF protein, to be administered as a single injection in the deltoid muscle.
Participants will be randomized to receive active vaccine or placebo as described in section “OVERALL
DESIGN” above. All injections will be 1 mL in volume.
The study duration for an individual participant will be approximately 24 months.
EFFICACY EVALUATIONS
Throughout the study, nasal swabs and sputum samples will be collected when an ARI occurs. Confirmation
of RSV infection by RT-PCR for the primary endpoint will be done in nasal swabs or sputum samples.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
16
Status: Approved, Date: 11 October 2022
 
Confirmation of RSV infection by RT-PCR in nasal swabs will be performed at the site laboratory
with the BioFire® Filmarray Respiratory panel, which will be provided to all sites (both US and non-
US). Both the home swab and the site swab will be analyzed at the site. The central RSV confirmation
of the nasal swab with the BioFire Filmarray Respiratory panel will not be taken into account for the
primary endpoint, unless in the unlikely event where at least one nasal swab from an ARI episode
cannot be tested at the site (eg, in the setting of instrument malfunction, unavailability of the device in
the country/territory or at the site, or shortage of testing reagents at the site).
 
Confirmation of RSV infection by RT-PCR in sputum samples (when collected) will be performed in
the central laboratory with the BioFire Filmarray PN panel.
 
For participants hospitalized with symptoms of an ARI, confirmation of RSV infection using a locally
approved RT-PCR test at the hospital laboratory can also be used. These results will be used in the
primary analysis only if approved by an independent expert with expertise in diagnostic testing. The
approval of the RT-PCR results by the expert will be based on the specifications of the test performed,
the qualifications of the testing laboratory and the procedures followed in the laboratory.
One positive sample (defined as any sample with a value above the limit of detection) is sufficient.
The first occurrence of a considered endpoint is defined as the start of the first episode of the endpoint in
the study (regardless of RSV A or B strain, unless otherwise specified).
Case Definition for RT-PCR-confirmed RSV-mediated LRTD
A participant will be considered to have RT-PCR-confirmed RSV-mediated LRTD if the following criteria
are met:
 
New onset or worsening from baseline of 3 or more of the below symptoms as captured on the RiiQ
at the same assessment time point:
- 
Cough
- 
Short of breath
- 
Coughing up phlegm (sputum)
- 
Wheezing
AND
 
Confirmation of RSV by RT-PCR in one or more of the nasal swabs, or in the sputum sample (when
available)
Counting of the number of symptoms with new onset or worsening will be done per assessment. If a
participant completed the RiiQ more than once per day, the case definitions cannot be met by combining
symptoms from different assessments on that day, the required number of symptoms must be attained at
one assessment.
This definition will be programmed. The CEC will review all available data of all RSV-mediated ARIs and
will confirm if the above criteria are met. If the CEC confirms that the above criteria for LRTD are met, the
case will be counted as a primary endpoint in the statistical analysis.
Case Definition for RT-PCR-confirmed RSV-mediated ARI
A participant will be considered to have RT-PCR-confirmed RSV-mediated ARI if the following criteria
are met:
 
ARI episode initiated by the participant and confirmed by the site with symptoms consistent with an
ARI (new symptoms or worsening from baseline of at least one of the symptoms as captured on the
RiiQ):
- 
Sore throat
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
17
Status: Approved, Date: 11 October 2022
- 
Nasal congestion
- 
Cough
- 
Short of breath
- 
Coughing up phlegm (sputum)
- 
Wheezing
AND
 
Confirmation of RSV by RT-PCR in one or more of the nasal swabs, or in the sputum sample (when
available)
Predefined Clinically Relevant Disease Associated with RT-PCR-confirmed RSV-mediated ARI
A participant will be considered to have clinically relevant disease with specific parameters associated with
an RT-PCR-confirmed RSV-mediated ARI if the following criteria are met:
 
The participant has an RT-PCR-confirmed RSV-mediated ARI as defined above.
 
Any of the following is associated with the ARI:
- 
Hospitalization
- 
Emergency department visit
- 
Per clinical judgement, at least one of the following complications: asthma exacerbation, chronic
obstructive pulmonary disease (COPD) exacerbation, respiratory distress, bronchitis, bronchial
hyperreactivity, congestive heart failure (CHF) exacerbation, cardiac arrhythmia, renal
impairment or the presence of X-ray or radiological confirmed pneumonia, respiratory arrest
and/or failure, pulmonary embolism, pleural effusion, atelectasis, acute coronary events, acute
cerebrovascular events, altered mental status, seizure, syncope, systemic inflammatory response
syndrome (SIRS), new neurological deficit, asthenia, dehydration or metabolic disturbances
- 
For measurements at the site, decreased oxygen saturation is defined as oxygen saturation of <92%
for participants with a baseline oxygen saturation of ≥92% at randomization; for participants with
baseline oxygen saturation <92%, decreased oxygen saturation is defined as a ≥3% decrease in
their oxygen saturation from baselinea.
Decreased oxygen saturation based on measurements during medically-attended ARIs (ie,
hospitalization) is defined as oxygen saturation of <92% supporting LRTD.
- 
Tachypnea (at least emerging Grade 2, see Appendix 4: Toxicity Grading Scale)
- 
Need of supplemental oxygen
- 
Hypotension (emerging Grade 3, see Appendix 4: Toxicity Grading Scale)
- 
Pulmonary function test results supporting diagnosis of LRTD
- 
Arterial blood gas results supporting diagnosis of LRTD
IMMUNOGENICITY EVALUATIONS
Blood samples will be collected from all participants for immunogenicity assessments before and 14 days
after vaccination, and at 1 year after vaccination for the analysis of correlates of risk of RSV disease and
correlates of protection.
For participants in the Immuno Subset (consisting of at least 360 participants, of whom ~50% will be at
increased risk for severe RSV disease and ~50% will be 75 years or older), blood will be collected for
analysis of humoral and cellular immune responses before study vaccination and at 2, 12 and 24 weeks, and
1 and 1.5 years after vaccination.
Immunogenicity assessments may include (but are not limited to) the assays summarized below.
a 
Based on vital signs collected at baseline and during the ARI at the site.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
18
Status: Approved, Date: 11 October 2022
Humoral Assays 
Purpose
Secondary endpoints
RSV neutralization A 
Analysis of neutralizing antibodies to an A strain
F protein antibodies 
(ELISA; pre F and/or post F)
Analysis of antibodies binding to RSV F protein in pre fusion and/or post fusion form
Exploratory endpoints
RSV strain cross neutralization 
Analysis of cross neutralizing antibodies to B and/or a different A strain(s) using virus
neutralization assays and other surrogate antibody binding assays
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, epitope mapping, Ig isotype, functional VNAs to other respiratory viruses, and
antibody assessments for antibody repertoire
ADCC=antibody dependent cell mediated cytotoxicity, ADCP=antibody dependent cellular phagocytosis,
ELISA =enzyme linked immunosorbent assay, F=fusion, Ig=immunoglobulin, VNA=virus neutralizing antibody
Note: Antibody analyses may be performed in nasosorption samples and serum.
Cellular Assays a 
Purpose
Secondary endpoints
IFN γ ELISpot 
T cell IFN γ responses to RSV F protein peptides
Exploratory endpoints
Immunophenotyping 
May include analysis of T cell and B cell responses to RSV F protein peptide
stimulated PBMC (including, but not limited to, CD4+/CD8+, Th1/Th2, IL 2, IFN γ,
TNF α, activation markers and memory) using flow cytometry or mass cytometry
Immune repertoire analysis 
May include using antigen specific single cell sequencing or bulk sequencing in
order to assess T cell and B cell repertoire analysis
a Cellular assays will be performed in the Immuno Subset only where PBMCs are collected.
ELISpot=enzyme linked immunospot, F=fusion; IFN γ=interferon gamma, IL 2 =interleukin 2, PBMC=peripheral blood
mononuclear cells, TNF α=tumor necrosis factor alpha
Nasosorption samples using synthetic absorptive matrix (SAM) will be collected from Immuno Subset
participants prior to vaccination and at the 2 weeks and 1-year post-vaccination visits and will be used for
immunogenicity assessments that may include antigen-specific immunoglobulins (ie, IgG and IgA),
microbiome, and other viral pathogen analyses.
The blood samples that are collected between 2 and 4 days after symptom onset (ARI Day 3-5) from
participants with an RSV, hMPV, or influenza-mediated ARI episode will be assayed by serology (which
may include pre-F/post-F enzyme-linked immunosorbent assay (ELISA) and RSV virus neutralizing
antibodies [VNA], as available and applicable) to assess immune responses and correlates that are
associated with RSV infection. The samples will also be used for exploration of biomarkers that correlate
with RSV infection and RSV disease severity (which may include RT-PCR for RSV, ribonucleic acid
[RNA] transcriptomics to assess gene regulation [clusters] and expression patterns, cytokine/chemokine-
dependent immunophenotyping, and immune repertoire analysis, as available and applicable).
SAFETY EVALUATIONS
For All Participants
All (S)AEs and special reporting situations related to study procedures or to non-investigational
(concomitant) Janssen products will be collected from informed consent form (ICF) signature onwards until
the end of the study for all participants. All other SAEs and AESIs will be collected from administration of
study vaccine (Day 1) until 6 months after vaccination. AEs leading to discontinuation from the study will
be collected for the duration of the study. All COVID-19 cases will be collected for all participants for the
duration of the study.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
19
Status: Approved, Date: 11 October 2022
ARIs and complications related to RSV, hMPV, and influenza-mediated ARIs that classify as SAE will be
captured in all participants and reported as SAEs in the eCRF continuously from the time of vaccination
until 24 months after vaccination.
All participants will be closely observed for a minimum of 15 minutes after vaccination to monitor for the
development of any acute reactogenicity. This post-vaccination observation period should be extended for
participants whom in the investigator’s opinion would require further observation or for any occurrence of
a localized reaction or (minor) systemic symptoms during the post-vaccination observation that require
monitoring for any progression.
Vital signs will be collected prior to vaccination for all participants. At non-vaccination visits, vital signs
will be measured if deemed necessary by the investigator.
For Participants in the Safety Subset
Additional procedures will be carried out in the Safety  Subset participants (consisting of at least
1,050 participants, of whom ~50% of all participants in each region will be at increased risk of severe RSV
disease and ~50% of all participants in the Safety Subset in each region will be 75 years or older). Safety
Subset participants will have provided consent for the additional study proceduresa:
 
At the end of the 15-minute observation period, vital signs (body temperature, blood pressure, heart
rate, respiratory rate, oxygen saturation) will be obtainedb, and any unsolicited and solicited local and
systemic AEs will be documented in the eCRF by study personnel.
 
Participants will record solicited local (at the injection site) AEs, solicited systemic AEs, and body
temperatures in the eDiary, beginning on the evening of the vaccine dosing day and on a daily basis
for the following 7 days. If a solicited local or systemic AE is not resolved within 7 days after
vaccination (Day 8), safety follow-up should be performed until the symptom resolves. The study-site
personnel will be instructed to record the date of last symptoms and maximum severity until resolution
in the source document and eCRF.
 
All other AEs (unsolicited) and special reporting situations will be reported from the time of
vaccination through the following 28 days. Participants will be contacted by telephone or telemedicine
at 28 days (+3 days) after vaccination to collect information on unsolicited AEs and associated
concomitant medications.
 
All ARIs and all complications related to RSV, hMPV, and influenza-mediated ARIs that do not
classify as SAEs will be reported as AEs in the eCRF from the time of vaccination through the
following 28 days.
MEDICAL RESOURCE UTILIZATION
Medical resource utilization (MRU) data associated with medical encounters will be collected by the
investigator and study site personnel at 28 days after onset of each ARI episode (ARI Day 29 ±7 days) for
all ARIs that are followed until their resolution (ie, for RSV, hMPV, or influenza-positive ARIs, for ARIs
with sputum collection, and for ARIs where at least one nasal swab cannot be tested at the site with the
BioFire Filmarray Respiratory panel). Protocol-mandated procedures, tests, and encounters are excluded.
The data collected may be used to conduct exploratory economic analyses and will include:
 
Number and type of medical consultations (including primary care and specialist visits), whether these
consultations were related to ARIs and a reason for each medical encounter
a 
Note that participants can participate in both the Immuno Subset and the Safety Subset.
b 
Actual values (normal and abnormal) will only be documented in the eCRF for body temperature.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
20
Status: Approved, Date: 11 October 2022
 
Number and duration of hospital and/or institutional care admissions (total days length of stay,
including duration by wards; eg, intensive care unit), whether these admissions were related to ARIs,
and a reason for each admission
 
Number and type of emergency department visits and whether these emergency department visits were
related to ARIs
 
Where applicable, information on whether supplemental oxygen or mechanical ventilation was used
 
Whether participation in the study (ie, contact with healthcare providers during study visits and
procedures) increased or decreased the participant’s use of medical resources outside of the study
PARTICIPANT MEDICAL INFORMATION PRIOR TO, DURING AND AFTER THE STUDY
(REAL-WORLD DATA)
For participants (from the US only) who have provided consent for this, medical data (electronic health
records, claims and laboratory data from other care settings) from 5 years prior to study enrollment until
5 years after study completion may be accessed utilizing tokenization and matching procedures (ie, the
generation of anonymous identifiers or “tokens” [hashed and encrypted combinations of identifying
elements] to allow linking of participant data from different sources without compromising the participant’s
confidentiality). These data may be used for exploratory analyses to enhance our understanding of the
impact of prior medical history on the response to immunization and the impact of immunization on efficacy
and duration of efficacy as well as adverse events that may occur during and after completion of the study.
The analyses will be described in detail in a dedicated analysis plan.
STATISTICAL METHODS
Sample Size Determination
The required sample size was determined using the following assumptions:
 
a VE for RT-PCR-confirmed RSV-mediated LRTD of 65% during the first year and during the second
year,
 
an incidence of RT-PCR-confirmed RSV-mediated LRTD of at least 0.2% during the first RSV season
(2021-2022) and an incidence of 0.5% in later RSV seasons in 60+-year-old placebo recipients,
 
a randomization ratio of 2:1 (active vaccine: placebo),
 
an analysis plan as described in Section 9.5.1,
 
a 1-sided α of 2.5% (potentially corrected for multiplicity), and
 
10% of exclusions (due to dropout, major protocol violations, etc.) per year
Simulations performed in R show that with ~15,340 participants in the active vaccine group (Group 1) and
~7,670 participants in the placebo group (Group 2) the study has at least 90% total power to demonstrate
VE against the primary endpoint statistically significant >20% and a point-estimate for VE >50%. This
leads to a sample size of ~23,000 participants.
This sample size is also required to reach approximately 80% power for the secondary endpoint of first
occurrence of RT-PCR-confirmed RSV-mediated LRTD during the second year.
Efficacy Analysis
Primary Endpoint
The analysis of the primary endpoint will evaluate the first occurrence of RT-PCR-confirmed RSV-
mediated LRTD with onset of at least 14 days after vaccination in the active vaccine group compared to the
placebo group in the PPE population. The null hypothesis of LL ≤20% for RT-PCR-confirmed RSV-
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
21
Status: Approved, Date: 11 October 2022
mediated LRTD will be tested versus the alternative hypothesis of LL >20%. Additionally, the observed
VE should be >50%.
Exact Poisson regression will be fitted with the event rate, defined as the number of cases (with onset at
least 14 days after vaccination) over the follow-up time (off-set) as dependent variable and the vaccination
group, being at increased risk of RSV disease, and age stratum (both variables as stratified) as independent
variables. This model will be based on the PPE population.
The study is successful if:
 
The LL of the 95% 2-sided CI (potentially corrected as described in Section 9.4.1.3) around the VE
(1-relative risk rate) calculated from the Exact Poisson regression model is above 20% and additionally
a point-estimate of VE >50% is observed for Group 1
As a sensitivity analysis, the above model will be repeated based on the Full Analysis Set (FAS), not taking
into account the restriction on the onset (at least 14 days). Additional sensitivity analyses will be performed
as well.
Secondary Endpoints
The following confirmatory secondary endpoints will only be tested when the primary endpoint shows
statistical significance.
1. 
First occurrence of any RT-PCR-confirmed RSV ARI, with onset at least 14 days after dosing of study
vaccine
2. 
First occurrence of any RT-PCR-confirmed RSV-mediated LRTD during the second year with onset
after study Day 365
3. 
First occurrence of any RT-PCR-confirmed RSV ARI during the second year with onset after study
Day 365
4. First occurrence of predefined clinically relevant disease associated with RT-PCR-confirmed RSV-
mediated ARI over the whole study, with onset at least 14 days after dosing of study vaccine
The testing strategy will test those endpoints hierarchically. A similar Exact Poisson regression model as
for the primary endpoint will be used for the analyses of the secondary endpoints #1, #2, #3, and #4 (see
Section 9.4.1.2). For those secondary endpoints, the null hypothesis of VE ≤0% will be tested versus the
alternative hypothesis VE >0%. Formal inference for secondary endpoint #1, as part of the testing strategy,
will occur at the time of the primary analysis. For secondary endpoints 2, 3, and 4, the formal inference as
part of the testing strategy will only occur at study end.
Immunogenicity Analyses
Immunogenicity Subset
No formal hypothesis on immunogenicity will be tested. Descriptive statistics (such as geometric mean and
95% CI for ELISA and RSV neutralization assay, and median and quartiles for interferon gamma [IFN-γ]
enzyme-linked immunospot [ELISpot]) will be calculated for continuous immunogenicity parameters at all
available timepoints. For the humoral assays, geometric mean fold rises from baseline with 95% Cis may
additionally be calculated. Baseline is considered as the last available assessment before vaccination.
Graphical representations of immunogenicity parameters will be made as applicable.
Correlates of Protection
If VE is demonstrated, correlates of protection will be further explored in  samples collected from all
participants. Immunogenicity markers are considered correlates of protection if VE is explained through
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
22
Status: Approved, Date: 11 October 2022
the effect of the vaccine on the immunogenicity markers. More details with appropriate methods will be
provided in a separate analysis plan.
Safety Analyses
No formal statistical testing of safety data is planned. The safety analysis will include the descriptive
summary of solicited local AEs, solicited systemic AEs, unsolicited AEs, AESIs, SAEs, and COVID-19
infections. The overall frequencies per group as well as frequencies according to severity will be calculated
for solicited and unsolicited AEs. The analysis of solicited, and unsolicited AEs will be restricted to a subset
of the FAS (Safety Subset). For the analyses of AESIs, SAEs, and COVID-related AEs, the entire FAS
population will be used.
Independent Data Monitoring Committee
The study will be formally monitored by the IDMC. In general, the IDMC will monitor the safety data on
a regular basis to ensure the continuing safety of the participants. The IDMC will also formally monitor the
primary efficacy endpoint. The IDMC will evaluate in an unblinded fashion if the success criteria have
been met.
Clinical Event Adjudication Committee
Prior to database lock for all planned analyses, the CEC will review in a blinded manner all available data
of all RSV-mediated ARIs and will confirm if the RT-PCR-confirmed RSV LRTD definition criteria were
met. Further for all RT-PCR-confirmed RSV LRTD cases the CEC will assess their severity (mild,
moderate or severe).
Details on the review approach will be provided in the CEC Charter.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
23
Status: Approved, Date: 11 October 2022
1.2. 
Schema
Figure 1: 
Schematic Overview of the Study for all Participants
Additional assessments will be performed for participants in the Safety and Immuno Subsets.
Refer to the Schedule of Activities for assessments to be performed for participants with an ARI episode.
Schematic overviews for participants in specific Asian countries/territories are provided in their respective local protocols
*Refer to Section 1.3.2, footnote j to determine whether a blood sample is required during an ARI Day 3-5 visit
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
26
Status: Approved, Date: 11 October 2022
pre-dose
Note: At any clinic visit, an abbreviated, symptom directed physical examination may be performed if deemed necessary by the investigator based on any clinically
relevant issues, clinically relevant symptoms, and medical history.
Footnotes:
a. For Immuno Subset participants, where the timing of the 24-week post-vaccination visits and end offirst RSV season or Month 6 (Day 182) visits may overlap,
procedures can be combined.
b. For the Northern Hemisphere (NH), the end of the first RSV season is defined as 15 April 2022. For the Southern Hemisphere (SH), the end of the first RSV season
is defined as 30 September 2022. This visit (Visit 3) is then referred to as “End of first RSV season” visit. End of first RSV season procedures may be conducted on
the same day as Visit 1, or before Visits 2, 2a, 2b, and 2c depending on the date of enrollment of the participant. If a participant is enrolled after the maximum
window of the “End of first RSV season” visit (ie, after 29 Apr 2022 for NH and after 14 Oct 2022 for SH), only a “Month 6” (182 days, -7/+14 days post
vaccination) safety follow-up call is required to collect information on SAEs and potential AESIs.
c. If the “End of first RSV season” visit for a participant is at least 6 months (or more) post-vaccination, the SAE and potential AESI safety follow-up is collected at
the “End of first RSV season” visit. In this scenario, no additional Safety follow-up is required at Month 6 (Day 182 -7/+14 days). If the “End of first RSV
season” visit for a participant occurs less than 6 months (-7 days) post-vaccination, a separate Safety follow-up call is required (182 days, -7/+14 days post
vaccination) to collect additional information on SAEs and potential AESIs. This Safety follow-up call is in addition to the “End of first RSV season” visit.
d. Visit 4 through Visit 5 will only take place if the study is not discontinued earlier. At Visit 5 (Month 24), participants may be required to come to the site to return
their eDevices, if applicable.
e. The timings of the post-vaccination visits will be determined relative to the actual day of vaccination using the “Visit Timing” from the upper part of the table.
f. 
Screening and vaccination may be split into 2 visits after consultation with the sponsor or its delegate. Every effort should be made for split visits to occur
preferably within 3 to 5 days and no later than 14 days, and pre-vaccination vital signs should be repeated on the day of vaccination if this visit is split.
g. Signing of the ICF must be done before any study-related activity. Participants in the Immuno Subset and/or Safety Subset will need to consent for the additional
study procedures in these subsets.
h. Participants (from the US only) will be asked for optional consent to allow access to their medical data (electronic health records, claims, laboratory data from other
care settings) from 5 years prior to study enrollment until 5 years after study completion utilizing tokenization and matching procedures (see Section 8.7).
Participants will be informed that consent can be withdrawn at any given time. The sponsor will then remove the token generated and any associated linked real-
world data.
i. 
Only relevant medical history is to be collected, in particular: congenital abnormalities, history of cancer, history of immunodeficiency or conditions treated with
immunomodulators, major psychiatric illness, major cardiovascular or lung diseases, type 2 diabetes and chronic kidney diseases (CKD), history of an allergy to
vaccination, ongoing comorbidities, history of any comorbidity known to be associated with an increased risk of progression to severe RSV disease, history of
hepatitis B or hepatitis C infection, and history of any thrombotic events and/or thrombocytopenia. Participants with stable/well-controlled HIV infection are
allowed to enroll in the study. These participants will be encouraged to have HIV RNA viral load and CD4 cell count assessed at least twice a year and to provide
these data for inclusion in the eCRF.
j. 
Therapies administered up to 30 days before vaccination will be recorded.
k. Any seasonal influenza vaccination must occur at least 14 days before or after study vaccination. Live-attenuated SARS-CoV-2 vaccines and viral-vectored SARS-
CoV-2 vaccines must occur at least 28 days before or after study vaccination; non-live SARS-CoV-2 vaccines must occur at least 14 days before or after study
vaccination. If seasonal influenza vaccination or SARS-CoV-2 vaccination occurs after Day 15, the information will be recorded at the next site contact or at the
end of the RSV season, whichever comes first.
l. 
Vital signs (sitting systolic and diastolic blood pressure, heart rate, respiratory rate, oxygen saturation [after at least 5 minutes rest] weight and body temperature).
At non-vaccination visits, vital signs will be measured if deemed necessary by the investigator. Height will only be collected at screening.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
27
Status: Approved, Date: 11 October 2022
m. A cap will be installed to ensure that ~50% of participants enrolled in the Immuno Subset and ~50% of participants enrolled in the Safety Subset will be at
increased risk of severe RSV disease, ie, have underlying chronic heart disease (congestive heart failure [CHF], coronary artery disease [eg, angina pectoris,
ischemic cardiomyopathy, history of myocardial infarct, history of coronary artery bypass graft, or coronary artery stent]) and chronic lung disease (asthma and
chronic obstructive pulmonary disease [COPD]). A cap will also be installed to ensure that ~50% of participants in these subsets will be 75 years or older.
n. Participants will be randomized at Day 1 in a 2:1 ratio to receive active vaccine (Group 1) or placebo (Group 2) (see Section 6.3).
o. The RiiQ, EQ-5D-5L, and the PGI-H will be completed by the participant in the eDiary. The questionnaires need to be completed at the “End of first RSV season”
visit but not at the Month 6 (Day 182) follow-up.
p. Participants may use their own eDevice (or desktop computer, where applicable) using a study-specific application instead if their device (smartphone or tablet) is
compatible. eDevices provided to the participant should be returned to the site at the end of the study.
q. Participants will be re-trained on how to use the eDiary, if needed, and on how to collect a nasal swab. Participants will be provided with 2 nasal swab kits.
r. All participants will be closely observed for a minimum of 15 minutes post-vaccination to monitor for the development of any acute reactogenicity. This post-
vaccination observation period should be extended for participants whom in the investigator’s opinion would require further observation or for any occurrence of a
localized reaction or (minor) systemic symptoms during the post-vaccination observation that require monitoring for any progression.
s. All (S)AEs and special reporting situations related to study procedures or to non-investigational (concomitant) Janssen products will be collected from ICF
signature onwards until the end of the study for all participants. All other SAEs will be collected from administration of study vaccine (Day 1) until 6 months after
vaccination. AEs leading to discontinuation from the study will be collected for the duration of the study.
t. 
AESIs, including potential AESIs, are to be reported to the sponsor within 24 hours of awareness from the moment of vaccination until 6 months after vaccination
(See Section 8.5.6).
u. All COVID-19 cases will be collected for all participants for the duration of the study. COVID-19 cases reported by the participant to the investigator and any ARI
positive for SARS-CoV-2 will be reported in the eCRF by the investigator.
v. Concomitant medications will be collected for all participants for the duration of the study when associated with any SAEs and AESIs and/or with any AEs leading
to discontinuation from the study.
w. ARI surveillance will be via the eDiary which participants must complete at least twice weekly. Procedures in the event of an ARI are described in the Schedule of
Activities for participants with an ARI episode.
x. Aliquots of serum samples collected for immunogenicity tests can be reconverted for participant’s safety purposes upon sponsor request. Please refer to Table 4 for
a non-exhaustive list of tests that may be requested to be performed on these samples in case of potential AESI reporting.
y. Solicited local and solicited systemic AEs will be documented by study site personnel following the 15 minutes post-vaccination observation period and will be
collected via the eDiary from vaccination until 7 days after vaccination for Safety Subset participants. If a solicited local or systemic AE is not resolved within 7
days after vaccination (Day 8), safety follow-up should be performed until the symptom resolves. The study-site personnel will be instructed to record the date of
last symptoms and maximum severity until resolution in the source document and eCRF.
z. All AEs and special reporting situations related to study procedures or to non-investigational (concomitant) Janssen products will be reported from ICF signature
onwards until the end of the study for all participants. All other AEs (unsolicited) and special reporting situations will be reported from vaccination through the
following 28 days for Safety Subset participants only.
aa. Vital signs (sitting systolic and diastolic blood pressure, heart rate, respiratory rate, oxygen saturation [after at least 5 minutes rest] and body temperature) will be
obtained prior to vaccination and at the end of the observation period. Emerging vital sign abnormalities will be summarized based on the planned visits. Clinically
relevant abnormalities for systolic and diastolic blood pressure, heart rate, respiratory rate, and oxygen saturation collected during unscheduled visits will be
documented as AEs.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
28
Status: Approved, Date: 11 October 2022
AE=adverse event, AESI=adverse event of special interest, ARI=acute respiratory infection, d=day, eCRF=electronic case report form, EQ-5D-5L= EuroQoL, 5-
Dimension, 5-Level, HIV=human immunodeficiency virus, ICF=informed consent form, NH=Northern Hemisphere, PGI-H=Patient Global Impression of Health,
RiiQ=Respiratory Infection Intensity and Impact Questionnaire (RiiQ™) v2, RNA=ribonucleic acid, RSV=respiratory syncytial virus, SAE=serious adverse event,
SAM=synthetic absorptive matrix, SH-Southern Hemisphere, vac=vaccination, we=week
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
30
Status: Approved, Date: 11 October 2022
episode. For all ARIs, a start date of the ARI should be entered into eCRF; for all RSV, hMPV, or influenza-mediated ARIs, an end date of the ARI should be
entered in the eCRF. For ARIs that are RSV, hMPV and influenza negative, the date that the site ends the ARI (after the RT-PCR test results are known) should
also be entered in the eCRF.
c. 
Home visits by a healthcare professional are allowed in the event that the participant is unable to come to the site.
d. 
Participants will be asked to return to the site if a sputum sample was provided by the participant at ARI Day 3-5 visit, regardless of the swab RT-PCR test results,
AND/OR at least one of the nasal swab samples collected could not be tested at the study site with the BioFire Filmarray Respiratory panel (RT-PCR test) and had
to be shipped for a central laboratory test AND/OR at least one nasal swab sample had a positive RT-PCR result for either RSV, hMPV, or influenza when tested at
the study site.
e. 
The nasal swab collected by the participant at home should preferably be taken between 12 to 24 hours after onset of symptoms. Participants who are under self-
isolation because of a (possible) positive test for SARS-CoV-2 will not come to the site for ARI Day 3-5 assessments but will self-collect the nasal swab. In this
circumstance the other planned assessments for ARI Day 3-5 visit may be omitted.
f. 
The nasal swab collected by the study staff at the site or at home should ideally be taken at least 24 hours after the nasal swab collected by the participant at home.
g. 
For participants hospitalized with symptoms of an ARI, confirmation of RSV infection using a locally approved RT-PCR test at the hospital laboratory can also be
used. These results will be used in the primary analysis only if approved by an independent expert with expertise in diagnostic testing. The approval of the RT-PCR
results by the expert will be based on the specifications of the test performed, the qualifications of the testing laboratory and the procedures followed in the
laboratory.
h. 
Vital signs (sitting systolic and diastolic blood pressure, heart rate, respiratory rate, oxygen saturation [after at least 5 minutes rest] and body temperature).
i. 
For exploration of biomarkers correlating with RSV infection.
j. 
To reduce the burden on the participant and to avoid collection of blood samples (ie, serology blood sample, whole blood PAXgene sample and whole blood
sample with PROT1 stabilizer), not related to an RSV/hMPV/influenza related ARI, participants and investigators can choose the preferred option during each
Day 3-5 visit between: 1) Collecting blood samples before the nasal swab samples are tested or in the setting where sputum sample is collected, independent of the
RT-PCR results; and 2) Collecting blood samples after the nasal swab RT-PCR results are available, according to nasal swab test results, and for ARIs where there
is no sputum sample collection. If this is the preferred option by the participant and investigator, the participant will wait at the site for the time needed to test the
swab samples (estimated time: 2 hours). In this scenario, if the swab samples are negative for RSV, hMPV and influenza AND if no sputum sample can be
collected, the blood samples collection at the ARI Day 3-5 timepoint can be omitted. If the swab samples are positive for RSV, hMPV or influenza OR if sputum
sample is collected, the blood samples collection must be performed. Whenever a sputum sample is collected during the ARI Day 3-5 visit, the blood samples must
still be collected as the RT-PCR test on the sputum sample will be performed at the central laboratory and not on site.
k. 
Participants complete the eDiary to respond to the ARI Surveillance Assessment, the RiiQ Symptom Scale and the RiiQ Impact on Daily Activity Scale, the
EQ-5D-5L, PGI-H, the PGI-S, the PGI-C, and the Return to Usual Health question once daily (ie, either at home or during the site visit, ifapplicable). (Note: the
PGI-C scale and the Return to Usual Health question will not be completed on ARI Day 1). Participants with a RT-PCR positive for RSV, hMPV, or influenza-
mediated ARI will continue filling out the questionnaires until resolution of the ARI episode. Participants with negative RT-PCR results for RSV, hMPV, or
influenza will be informed by telephone or telemedicine that they can stop filling out the questionnaires and the site will end the ARI episode and return the
participant to ARI surveillance. Participants with a sputum sample taken and participants with at least one nasal swab that cannot be tested at the site with the
BioFire Filmarray Respiratory panel will follow the same procedures as participants with a RT-PCR positive for RSV, hMPV, or influenza-mediated ARI. Further
details are provided in Appendix 7: ARI Surveillance Assessment.
l. 
All ARIs will be captured in the eCRF for all participants who experience an ARI episode for the duration of the study. All complications (including pneumonia),
hospitalizations, concomitant medications, and MRU data associated with medical encounters, and whether they were related to ARIs will be captured in the eCRF
for all participants who experience an ARI episode for the duration of the study. ARIs and complications related to ARIs that classify as SAEs will be captured in
all participants and reported as SAEs in the eCRF continuously from the time of vaccination until 6 months after vaccination. In addition, ARIs and complications
related to ARIs that do not classify as SAEs will be reported as AEs in the eCRF from the time of vaccination through the following 28 days for Safety Subset
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
31
Status: Approved, Date: 11 October 2022
participants only.
m. For medically-attended RT-PCR positive for RSV, hMPV, or influenza-mediated ARIs, including those resulting in hospitalization, a standard question list will be
provided (Appendix 6: Medically-attended ARI Form) to collect additional information on any other diagnostic tests (eg, chest x-rays, spirometry, pulmonary
function tests, etc.) or on any interventions during the clinical course of the ARI.
n. 
Concomitant medications associated with RSV, hMPV, and influenza-mediated ARI episodes and with complications of RSV, hMPV, and influenza-mediated
ARIs will be recorded for all participants for the duration of the study.
AE=adverse event, ARI=acute respiratory infection, eCRF=electronic case report form, EQ-5D-5L= EuroQoL, 5-Dimension, 5-Level, hMPV=human metapneumovirus,
MRU=Medical Resource Utilization, PGI-C=Patient Global impression of Change, PGI-H=Patient Global Impression of Health, PGI-S=Patient Global Impression of
Severity, RiiQ=Respiratory Infection Intensity and Impact Questionnaire (RiiQ™) v2, RNA=ribonucleic acid, RSV=respiratory syncytial virus, RT-PCR=reverse
transcriptase polymerase chain reaction, SAE=serious adverse event
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
32
Status: Approved, Date: 11 October 2022
2. 
INTRODUCTION
Therespiratorysyncytialvirus (RSV) vaccine that will be investigated in this study, Ad26/protein
preF RSV vaccine, includes 2 components that are being mixed prior to administration as a single
intramuscular (IM) injection:
 
Ad26.RSV.preF (JNJ-64400141), a replication-incompetent adenovirus serotype 26 (Ad26)
containing a deoxyribonucleic acid (DNA) transgene encoding the pre-fusion conformation-
stabilized F protein (preF) derived from the RSV A2 strain, and
 
RSV preF protein (JNJ-64213175), a pre-fusion conformation-stabilized F protein derived
from the RSV A2 strain.
For the most comprehensive nonclinical and clinical information regarding Ad26/protein preF
RSV vaccine, refer to the latest version of the Investigator’s Brochure (IB) for Ad26/protein preF
RSV vaccine.
The term ‘study vaccine’ throughout the protocol refers to the Ad26/protein preF RSV vaccine or
placebo as defined in Section 6.1, Study Vaccine Administration.
The term ‘sponsor’ throughout the protocol refers to the entities listed in the Contact Information
page, which will be provided as a separate document.
The term ‘participant’ throughout the protocol refers to the common term ‘subject’.
2.1. 
Study Rationale
Following successful demonstration of efficacy in preventing lower respiratory tract disease
(LRTD) due to RSV after one season in the Phase 2b proof-of-concept efficacy study
VAC18193RSV2001, the current study will further investigate the efficacy of Ad26/protein preF
RSV vaccine in participants aged 60 years and older, with surveillance for acute respiratory
infection (ARI) from the time of study vaccination until 24 months after vaccination. The primary
endpoint is based on a case definition that was demonstrated to be relevant in  study
VAC18193RSV2001 as it encompassed both moderate and severe forms of RSV LRTD (see
Section 2.2).
The primary objective of this study is to demonstrate efficacy of the Ad26.RSV.preF-based study
vaccine in the prevention of reverse transcriptase polymerase chain reaction (RT-PCR)-confirmed
RSV-mediated LRTD when compared to placebo in adults aged 60 years and above, as outlined
in Section 9.5, Planned Analyses. Recruitment will be conducted both in the Northern Hemisphere
(NH) and Southern Hemisphere (SH). Interim analyses to evaluate the primary objective will be
performed by the IDMC (see Section 9.5.1).
2.2. 
Background
RSV is an important cause of serious respiratory infections in adults aged 60 years and older, in
immunocompromised individuals, and in individuals with underlying chronic cardiopulmonary
conditions (Falsey 2005). Exact numbers on the burden of RSV disease in adults aged 60 years
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
33
Status: Approved, Date: 11 October 2022
and older are limited. In long-term care facilities, RSV has been estimated to infect 5% to 10% of
the residents per year, with significant rates of pneumonia (10% to 20%) and death (2% to 5%) as
a consequence (Falsey 2000).
In the United States (US), about 177,000 hospital admissions and 10,000 to 14,000 deaths per year
are due to severe RSV infections in adults aged 65 years and older (Thompson 2003). In Europe
(data available from 14 studies for 8 countries), RSV accounted for 1% to 11% of all influenza-
like illness in patients of all ages (Htar 2020). In adults (aged 50 years and older), RSV accounted
for 2% to 18% of influenza-like illness. Even though data on the burden of RSV disease in older
adults remain scarce in Europe, statistical modelling indicates that RSV is associated with
substantial hospitalization and mortality in this population  (Fleming 2015, Hardelid 2013,
Jansen 2007, van Asten 2012). In Japan, a prospective cohort study of adults aged ≥65 showed
that the attack rate of RSV infection is 2.4%  (study VAC18193RSV0002), and the rate is
comparable to other countries (Falsey 2000). These data support the importance of developing a
safe and effective vaccine for certain adult populations, such as those aged ≥60 years. Currently,
there are no licensed vaccines or treatments available for RSV in the adult population.
Ad26.RSV.preF and RSV preF Protein Nonclinical Data
Both Ad26.RSV.preF and the RSV preF protein have been evaluated for induction of immune
responses in multiple species (mice, cotton rats, bovine calves [Ad26.RSV.preF only], and non-
human primates [NHPs]). Ad26.RSV.preF induced RSV-specific cellular and humoral immune
responses, whereas the RSV preF protein mainly induced humoral immunity. The combination of
both vaccine components improved the humoral and/or cellular immune response over each
vaccine component individually.
Efficacy of the Ad26.RSV.preF-induced immune response was shown in mice, cotton rats, and the
bovine RSV challenge model, and it was shown for the RSV preF protein alone and the
combination of both vaccine components in the cotton rat RSV challenge model. In the cotton rat
RSV challenge model, efficacy was higher in Ad26.RSV.preF vaccinated animals compared to the
RSV preF protein. A combination of Ad26.RSV.preF and the RSV preF protein further improved
efficacy in the upper respiratory tract.
Ad26.RSV.preF and RSV preF Protein Clinical Data
The clinical studies completed or currently ongoing are included in Table 1.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
34
Status: Approved, Date: 11 October 2022
Table 1: 
Clinical Studies with RSV PreF Protein and/or Ad26.RSV.preF in the Adult Population
Study Identifier 
Clinical 
Phase
Description 
Vaccine
Completed
VAC18193RSV1003 
1 
First-in-human  
Ad26.RSV.preF
VAC18193RSV1005 
1 
Shedding assessment 
Ad26.RSV.preF
VAC18193RSV2002 
2a 
Challenge study  
Ad26.RSV.preF
VAC18193RSV2003 
2a 
Influenza vaccine co-administration  Ad26.RSV.preF
Ongoing
VAC18193RSV1006 
1 
Phase 1 study in Japanese 
Ad26/protein preF RSV vaccine
VAC18193RSV1004* 
1/2a 
Regimen selection 
Ad26.RSV.preF
RSV preF protein
Ad26/protein preF RSV vaccine
VAC18193RSV2005 
2a 
Dose ranging 
Ad26/protein preF RSV vaccine
VAC18193RSV2001*  
2b 
Proof-of-concept 
Ad26/protein preF RSV vaccine
* Primary analysis has been completed
Theresults from the first-in-human study VAC18193RSV1003 confirmed the immunogenicity of
a single Ad26.RSV.preF immunization. The 1×1011 vp (viral particles) dose of Ad26.RSV.preF
was subsequently evaluated in the human challenge study VAC18193RSV2002. These results
showed a reduction in the nasal wash viral load compared to placebo. The reduction was associated
with a major reduction in the total clinical symptom score.
Theimmunologicalbenefit of combining Ad26.RSV.preF with RSV preF protein was first shown
in study VAC18193RSV1004. A significant increase in virus neutralizing titers was observed at
28 days post dose 1 in the groups combining Ad26.RSV.preF and RSV preF protein compared to
Ad26.RSV.preF 1×1011 vp alone. Based on this study, a vaccine combining Ad26.RSV.preF with
RSV preF protein was selected for future clinical development.
This vaccine is currently being tested in studyVAC18193RSV2001, a multicenter, randomized,
double-blind, placebo-controlled Phase 2b proof-of-concept efficacy study in ~5,800 participants
aged ≥65 years, with and without comorbidities. The study is designed to demonstrate efficacy of
the Ad26.RSV.preF/ RSV preF protein  vaccine (1×1011 vp/150µg) for at least 1 of the 3 case
definitions of RSV-mediated LRTD. The primary analysis after the end of the first RSV season
showed high, statistically significant VE against RSV-mediated LRTD for all case definitions,
ranging from 80% for the most severe endpoint (case definition #1) to 69.8% for the mildest
endpoint (case definition #3). The vaccine was safe and well-tolerated. Based on these data, case
definition #1 (see Section 8.2.1) was selected for use as primary endpoint in the present Phase 3
study. Study VAC18193RSV2001 is currently ongoing to evaluate the duration of protection and
immune responses beyond 1 year in a subset of participants.
Clinical Safety Experience With Ad26-based Vaccines
Safety data of Ad26-vectored vaccines from the adenoviral vaccine safety database (Advac Safety
Database 2022), including vaccines against Ebola virus (Ad26.ZEBOV), HIV (Ad26.ENVA.01,
Ad26.Mos.HIV, and Ad26.Mos4.HIV), malaria (Ad26.CS.01), RSV (Ad26.RSV.FA2 and
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
35
Status: Approved, Date: 11 October 2022
Ad26.RSV.preF), filovirus (Ad26.Filo), zikavirus (Ad26.ZIKV.001), and HPV (Ad26.HPV16 and
Ad26.HPV18) have been evaluated in adults.
All the above Ad26-based vaccines were found to be well tolerated in adults, without significant
safety issues identified. Several other studies are currently ongoing, and no safety concerns have
been raised to date.
Thrombosis With Thrombocytopenia Syndrome
Thrombosis with thrombocytopenia syndrome (TTS), in some cases accompanied by internal
bleeding, has been observed very rarely following vaccination with the Janssen COVID-19
(Ad26.COV2.S) vaccine. Reports of vaccine-induced TTS, also known as vaccine-induced
immune thrombotic thrombocytopenia (VITT), include severe cases of venous thrombosis at
unusual sites such as cerebral venous sinus thrombosis (CVST), splanchnic vein thrombosis and
arterial thrombosis, in combination with thrombocytopenia. The associated symptoms began
approximately 1 to 2 weeks after vaccination, mostly in women under 60 years of age. Vaccine-
induced TTS can be fatal. The exact pathophysiology of the syndrome is unclear. As of 21 July
2022, no cases of vaccine-induced TTS have been identified following vaccination with any other
Janssen Ad26-based vaccines. Participants should be instructed to seek immediate medical
attention if they develop symptoms such as shortness of breath, chest pain, leg swelling, persistent
abdominal pain, severe or persistent headaches, blurred vision, skin bruising or petechiae beyond
the site of vaccination.
2.3. 
Benefit-Risk Assessment
More detailed information about the known and expected benefits and risks of Ad26/protein preF
RSV vaccine may be found in the Investigator’s Brochure for Ad26/protein preF RSV vaccine.
2.3.1. 
Risks of Study Participation
The following potential risks for Ad26/protein preF RSV vaccine will be monitored during this
study:
Risks Related to Ad26/Protein preF RSV Vaccine
As of October 27, 2021, the Ad26/protein preF RSV vaccine has been studied for its safety and/or
its ability to prevent RSV disease in ongoing trials in 8,499 participants with and without
underlying medical conditions, primarily in adults aged 60 years and above. Of the above
participants, 137 were aged 18-59 years of age. The vaccine is being further studied in several
ongoing trials.
In adults, the most commonly reported local symptom was injection site pain/tenderness and
swelling (mild to moderate). The reported body symptoms were mostly mild to moderate; the most
frequently seen were fatigue, muscle pain, headache, chills, joint pain and nausea. In all
participants, these symptoms were short-lived and resolved within days. Results from the trials
show that the vaccine is tolerated well and there were no safety concerns.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
36
Status: Approved, Date: 11 October 2022
General Risks Related to Vaccination
In general, IM injection may cause local itching, warmth, pain, tenderness, erythema or redness,
induration, swelling, arm discomfort, or bruising of the skin. Participants may exhibit general signs
and symptoms associated with IM injection of a vaccine and/or placebo, including fever, chills,
rash, myalgia, nausea or vomiting, headache, dizziness, arthralgia, general itching, and fatigue.
These side effects will be monitored, but they are generally short-term and do not require
treatment.
Syncope can occur in association with administration of injectable vaccines. Syncope can be
accompanied by falls. Procedures should be in place to avoid falling injury. If syncope develops,
participants should be observed until symptoms resolve. Fear of injection might lead to fainting
and fast breathing.
Participants may have an allergic reaction to the vaccination. An allergic reaction may cause a
rash, urticaria, or even anaphylaxis. Severe reactions are rare. Participants with a known or
suspected allergy, or with a history of anaphylaxis or other serious adverse reactions to vaccines
or their excipients (including specifically the excipients of the study vaccine) will be excluded
from the study.
After vaccination, participants will remain at the study site for at least 15 minutes and will be
closely observed by the study staff. Necessary emergency equipment and medications must be
available in the clinic to treat severe allergic reactions.
Pregnancy and Birth Control
The effect of the Ad26/protein preF RSV vaccine on a fetus or nursing baby is unknown.
Participants may therefore only participate if they are postmenopausal (defined as no menses for
12 months without an alternative medical cause) and not intending to conceive by any methods.
Participants who are surgically sterile are also eligible for the study. Follow-up information
regarding the outcome of the pregnancy will be required.
Because the effect on sperm is unknown, participants must inform the study-site personnel if their
partner becomes pregnant during the study. Follow-up information regarding the outcome of the
pregnancy will be requested upon the consent provided by the partner.
Participants with Immunosuppression/Reduced Immune Response
Participants with abnormal function of the immune system will be excluded from the study.
Limited evidence indicates that inactivated vaccines (or nonreplicating 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.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
37
Status: Approved, Date: 11 October 2022
Risks from Collection of Nasal Swabs and Nasosorption Samples
Collection of a nasal swab may cause a nosebleed.
Nasosorption sampling is more comfortable and less invasive than using a conventional swab.
Risks from Blood Draws
Blood draws may cause pain, tenderness, bruising, bleeding, dizziness, vasovagal response,
syncope, and rarely, infection at the site where the blood is taken. Participants with
contraindications to IM injections and blood draws (eg, bleeding disorders) will be excluded.
Concomitant Vaccination
Concomitant vaccination might have an influence on both the safety profile and immunogenicity
ofthe Ad26/protein preF RSV vaccine. Likewise, the Ad26/protein preF RSV vaccine might have
an influence on both the safety profile and immunogenicity of any concomitant vaccination. As a
result, licensed live attenuated vaccines should be given at least 28 days before or after study
vaccination. Other licensed (not live) vaccines (eg, tetanus, hepatitis A, hepatitis B, rabies) should
be given at least 14 days before or after study vaccination to avoid potential confusion of adverse
reactions and potential immune interference. If a vaccine is indicated in a postexposure setting (eg,
rabies or tetanus), it must take priority over the study vaccine.
For SARS-CoV-2 vaccines either licensed or available under Emergency Use Authorization: live
attenuated vaccines should be given at least 28 days before or after study vaccination; non-live
vaccines should be given at least 14 days before or afterstudy vaccination. A viral-vectored SARS-
CoV-2 vaccine is not to be given within 28 days before or after study vaccination.
Unknown Risks
There may be other risks that are not known. If any significant new risks are identified, the
investigators and participants will be informed.
2.3.2. 
Benefits of Study Participation
Participants may benefit from clinical testing.
The clinical benefits of Ad26/protein preF RSV vaccine are yet to be established.
The Ad26/protein preF RSV vaccine is under development for prophylaxis of RSV and VE is
being evaluated in ongoing studies. Results from the primary analysis of study
VAC18193RSV2001 with approximately 5,800 participants showed the potential for the vaccine
to prevent lower respiratory tract disease caused by RSV in participants 65 years and older.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
38
Status: Approved, Date: 11 October 2022
2.3.3. 
Benefit-Risk Assessment of Study Participation
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:
 
The primary analysis after the end of the first RSV season in the ongoing proof-of-concept
efficacy study  VAC18193RSV2001 showed high, statistically significant VE of
Ad26.RSV.preF/ RSV preF protein vaccine (1×1011 vp/150µg) against all RSV for all case
definitions, ranging from 80% for the most severe endpoint to 69.8% for the mildest endpoint.
The vaccine was safe and well-tolerated (see Section 2.2).
 
Only participants who meet all inclusion criteria and none of the exclusion criteria (specified
in Section 5, Study Population) will be allowed to participate in this study. The selection
criteria include adequate provisions to minimize the risk and to protect the well-being of the
participants in the study.
 
Safety will be closely monitored throughout the study:
 
In general, safety evaluations will be performed at scheduled visits during the study, as
indicated in the Schedule of Activities.
 
After vaccination, participants will remain at the study site for at least 15 minutes and
will be closely observed by the study staff. Necessary emergency equipment and
medications must be available in the clinic to treat severe allergic reactions.
 
Participants in the Safety Subset will use an eDiaryto document solicited signs and symptoms.
Details are provided in Section 8.4, Safety Assessments.
 
The investigator or designee will document unsolicited AEs as indicated in Section 8.4,
Safety Assessments, Section 8.5, Adverse Events, Serious Adverse Events, and Other
Safety Reporting, and Appendix 3: Adverse Events, Serious Adverse Events, Adverse
Event of Special Interest, Product Quality Complaints, and Other Safety Reporting:
Definitions and Procedures for Recording, Evaluating, Follow-up, and Reporting .
 
Any clinically significant abnormalities (including those persisting at the end of the study
or upon early withdrawal) will be followed by the investigator until resolution or until
clinically stable.
 
Safety measures are included in this protocol to minimize the potential risk to participants,
including the following:
 
Temporary contraindications to study vaccination are included in Section 5.5, Criteria for
Temporarily Delaying Administration of Study Vaccine.
3. 
OBJECTIVES AND ENDPOINTS
The primary objective of this study is to demonstrate efficacy of the Ad26.RSV.preF-based study
vaccine in the prevention of RT-PCR-confirmed RSV-mediated LRTD when compared to placebo
in adults aged 60 years and above. Interim analyses to evaluate the primary objective will be
performed by the Independent Data Monitoring Committee (IDMC). The primary, secondary and
exploratory objectives and endpoints of the study are presented below.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
39
Status: Approved, Date: 11 October 2022
Primary Objective, Secondary Efficacy Objectives and Exploratory Objectives
Objectives 
Endpoints
PRIMARY
 To demonstrate the efficacy of the active
Ad26.RSV.preF-based study vaccine in the
prevention of RT-PCR-confirmed RSV-mediated
LRTD when compared to placebo in adults aged
60 years and above
 First occurrence of RT-PCR-confirmed, RSV-
mediated LRTD with onset at least 14 days after
dosing of study vaccine
CONFIRMATORY SECONDARY*
 To demonstrate the efficacy of active study
vaccine in the prevention of any RT-PCR-
confirmed RSV-mediated acute respiratory
infection (ARI) when compared to placebo
 First occurrence of any RT-PCR-confirmed
RSV-mediated ARI with onset at least 14 days
after dosing of study vaccine
 To demonstrate the efficacy of active study
vaccine in the prevention of RT-PCR-confirmed
RSV-mediated LRTD during the second year
when compared to placebo in adults aged 60 years
and above
 First occurrence of RT-PCR-confirmed RSV-
mediated LRTD during the second year, with onset
after study Day 365
 To demonstrate the efficacy of active study
vaccine in the prevention of any RT-PCR-
confirmed RSV-mediated ARI during the second
year when compared to placebo
 First occurrence of any RT-PCR-confirmed
RSV-mediated ARI during the second year, with
onset after study Day 365
 To demonstrate the efficacy of active study
vaccine in the prevention of predefined clinically
relevant disease associated with RT-PCR-
confirmed RSV-mediated ARI over the whole
study when compared to placebo
 First occurrence of predefined clinically relevant
disease associated with RT-PCR-confirmed
RSV-mediated ARI over the whole study with
onset at least 14 days after dosing of study vaccine
NON-CONFIRMATORY SECONDARY
 To evaluate safety in terms of serious adverse
events (SAEs) and adverse events of special
interest (AESIs) until 6 months after vaccination
 Occurrence and relationship of vaccination to
SAEs and AESIs until 6 months after vaccination
 In the Safety Subset and in subgroups of the
Safety Subset (including but not limited to
participants at increased risk of severe RSV
disease), to evaluate the safety and reactogenicity
in terms of solicited local and systemic adverse
events (AEs) during 7days after vaccination, and
in terms of unsolicited AEs during 28 days after
vaccination
 Occurrence, intensity, duration and relationship to
vaccination of solicited local and systemic AEs
during 7 days after vaccination and of unsolicited
AEs during 28 days after vaccination
 In the Immuno Subset and in subgroups of the
Immuno Subset (including but not limited to
participants at increased risk of severe
RSV disease), to evaluate the immunogenicity of
active study vaccine when compared to placebo
 Characterization of the humoral and cellular
immune responses in the Immuno Subset with
emphasis on neutralizing and binding antibodies
and antigen-specific cytokine production by
T-cells
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
40
Status: Approved, Date: 11 October 2022
Objectives 
Endpoints
 To assess the reduction of symptom severity in 
participants with an RT-PCR-confirmed RSV- 
mediated ARI when compared to placebo over the 
whole study  
 In participants with an RT-PCR-confirmed RSV-
mediated ARI over the whole study: the area under
the curve (AUC) of the change from baseline in
Respiratory Infection Intensity and Impact
Questionnaire (RiiQa) Total Symptom score
EXPLORATORY
 To demonstrate the efficacy of active study 
vaccine in the prevention of RT-PCR-confirmed 
RSV-mediated LRTD during the first year when 
compared to placebo in adults aged 60 years and 
above
 First occurrence of RT-PCR-confirmed RSV-
mediated LRTD during the first year, with onset at
least 14 days after dosing of study vaccine, and
prior to study Day 365
 To demonstrate the efficacy of active study
vaccine in the prevention of RT-PCR-confirmed
RSV-mediated ARI during the first year when
compared to placebo
 First occurrence of RT-PCR-confirmed RSV-
mediated ARI during the first year, with onset at
least 14 days after dosing of study vaccine, and
prior to study Day 365
 To explore the effect of active study vaccine on
RSV A and B infection when compared to placebo
 Assessment of the RSV A and B viral load by
quantitative RT-PCR
 To explore the efficacy of active study vaccine in
the prevention of any RT-PCR-confirmed RSV-
mediated LRTD caused by an RSV A and/or B
strain when compared to placebo
o during the first year
o during the second year
o over the whole study
 First occurrence of any RT-PCR-confirmed
RSV-mediated LRTD caused by an RSV A strain
and/or RSV B strain, respectively, during the
considered years
o with onset at least 14 days after dosing of study
vaccine and prior to study Day 365 (first year
comparison)
o with onset after study Day 365 (second year
comparison)
o with onset at least 14 days after dosing of study
vaccine (whole study comparison)
 To explore the efficacy of active study vaccine in
the prevention of any RT-PCR-confirmed RSV-
mediated ARI caused by an RSV A and/or B strain
when compared to placebo
o during the first year
o during the second year
o over the whole study
 First occurrence of any RT-PCR-confirmed
RSV-mediated ARI caused by an RSV A strain
and/or RSV B strain, respectively, during the
considered years
o with onset at least 14 days after dosing of study
vaccine and prior to study Day 365 (first year
comparison)
o with onset after study Day 365 (second year
comparison)
o with onset at least 14 days after dosing of study
vaccine (whole study comparison)
a 
The Respiratory Infection Intensity and Impact Questionnaire used in this study is the RiiQ Symptom Scale and the RiiQ
Impact on DailyActivities Scale of the RiiQ™ Version 2 (hereafter referred to as RiiQ).
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
41
Status: Approved, Date: 11 October 2022
Objectives 
Endpoints
 To explore the efficacy of active study vaccine in 
the prevention of at least mild, at least moderate, 
and at least severe RT-PCR-confirmed RSV 
LRTD as assessed by the Clinical Event 
Adjudication Committee (CEC) compared to 
placebo
o during the first year
o during the second year
o over the whole study
 First occurrence of any RT-PCR-confirmed RSV
LRTD assessed by the CEC as:
- at least mild lower respiratory tract infection
(LRTI)
- at least moderate LRTI
- at least severe LRTI
during the considered year:
o with onset at least 14 days after dosing of study
vaccine and prior to study Day 365 (first year
comparison)
o with onset after study Day 365 (second year
comparison)
o with onset at least 14 days after dosing of study
vaccine (whole study comparison)
 To explore the reduction of symptom severity and 
time to return to usual health in participants with 
an RT-PCR-confirmed RSV-mediated ARI and in 
participants with RT-PCR-confirmed RSV- 
mediated LRTD when compared to placebo 
o during the first year 
o during the second year 
o over the whole study  
 In participants with an RT-PCR-confirmed RSV-
mediated ARI and in participants with RT-PCR-
confirmed RSV-mediated LRTD (during the first
year, the second year, or over the whole study,
respectively):
o the AUC of the change from baseline in RiiQ
Total Symptom score
o the time to return to usual health
 To explore the reduction of disease severity in 
participants with an RT-PCR-confirmed RSV- 
mediated ARI and in participants with RT-PCR- 
confirmed RSV-mediated LRTD when compared 
to placebo, by subtype (RSV A, RSV B) 
o during the first year 
o during the second year 
o over the whole study 
 In participants with an RT-PCR-confirmed RSV-
mediated ARI and in participants with RT-PCR-
confirmed RSV-mediated LRTD (during the first
year, the second year or over the whole study
respectively), by subtype (RSV A, RSV B):
o the AUC of the change from baseline in RiiQ
Total Symptom score
o the time to return to usual health
 To explore the impact of active study vaccine on 
the course of an RT-PCR-confirmed RSV- 
mediated ARI and of human metapneumovirus 
(hMPV)- and influenza-mediated respiratory 
infections, general health status and health-related 
quality of life (HRQoL) measures when compared 
to placebo
 HRQoL and health status reported by participants
on the RiiQ, patient global impression scales, and
EuroQoL, 5-Dimension, 5-Level (EQ-5D-5L) in
participants with an RT-PCR-confirmed RSV-
mediated ARI or hMPV and influenza-mediated
respiratory infections
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
42
Status: Approved, Date: 11 October 2022
Objectives 
Endpoints
 To explore the effect of active study vaccine on 
each of the following separately: the potential 
complications (including pneumonia), 
hospitalizations, emerging therapeutic use and 
medical resource utilization (MRU) of an RT- 
PCR-confirmed RSV-mediated ARI, an RT-PCR- 
confirmed RSV-mediated LRTD, and of hMPV 
and respiratory infections when compared to 
placebo 
o during the first year 
o during the second year 
o over the whole study  
For influenza, the objective is to explore the 
incidence of these endpoints. 
 For each of the following separately:
(1) complications, (2) pneumonia,
(3) hospitalizations, (4) emerging therapeutic
interventions and (5) MRU, all associated with
RT-PCR-confirmed RSV-mediated ARI or RT-
PCR-confirmed RSV-mediated LRTD during the
first year, the second year and over the whole
study
o with onset at least 14 days after dosing of study
vaccine and prior to study Day 365 (first year
comparison)
o with onset after study Day 365 (second year
comparison)
o with onset at least 14 days after dosing of study
vaccine (whole study comparison)
 Complications, pneumonia, hospitalizations,
emerging therapeutic use and MRU associated
with hMPV and influenza-mediated respiratory
infections will be defined similarly
 To explore the efficacy of active study vaccine in 
the prevention of RT-PCR-confirmed 
hMPV-mediated ARI and RT-PCR-confirmed 
hMPV-mediated LRTD when compared to 
placebo in adults aged 60 years and above
 First occurrence of RT-PCR-confirmed, hMPV-
mediated ARI and RT-PCR-confirmed hMPV-
mediated LRTD with onset at least 14 days after
dosing of study vaccine
 To explore the immune response biomarkers in
study participants as correlates of risk of RSV
disease and as correlates of protection induced by
the active study vaccine
 Assessment of the correlation of immune
responses with emphasis on neutralizing and
binding antibodies with the risk of RSV disease
and protection induced by the vaccine
 To explore biomarkers for the diagnosis of RSV
infection, RSV-mediated LRTD and hMPV and
influenza- mediated respiratory infections
 Assessment of blood samples collected during ARI
episodes for biomarkers that correlate with RSV
infection, RSV-mediated LRTD and hMPV and
influenza-mediated respiratory infections
 To explore additional vaccine-elicited immune
responses in the Immuno Subset
 Assays that may be used include, but are not
limited to:
o RSV cross-neutralization of B and/or other A
strain(s)
o Antigen specific antibody functional and
molecular characterization
o Analysis of neutralizing antibodies to Ad26
o Antigen-specific T-cell immune responses using
detailed immunoprofiling
 To increase the information on prior medical
history (electronic health records, claims,
laboratory data from other care settings) in order
to further evaluate its potential effect on the
response to immunization and the impact of
immunization on efficacy and duration of efficacy
as well as AEs that may occur during and after
completion of the study
 Utilization of tokenization and matching
procedures for exploratory analysis of participant’s
medical data prior to, during, and following
participation in the study (real-world data).
Analysis will be performed to relate real-world
data to vaccine immune responses, efficacy and
duration of protection, and AEs
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
43
Status: Approved, Date: 11 October 2022
*Included in the testing strategy
Refer to Section 8, Study Assessments and Procedures for evaluations related to endpoints.
HYPOTHESIS
The study is designed to test the primary hypothesis of VE against RT-PCR-confirmed RSV-
mediated LRTD in the PPE population.
 
The hypotheses are:
 
Null hypothesis: the VE against RT-PCR-confirmed RSV-mediated LRTD of Group
1 vs placebo is ≤20%.
 
Alternative hypothesis: the VE against RT-PCR-confirmed RSV-mediated LRTD of
Group 1 vs placebo is >20%.
Refer to Section 9.3, Populations for Analyses, for a definition of the PPE population.
4. 
STUDY DESIGN
4.1. 
Overall Design
This isamulticenter, randomized, double-blind, placebo-controlled Phase 3 confirmatory efficacy
study in participants aged 60 years and older. The primary objective of the study is to further
establish the efficacy of the active Ad26.RSV.preF-based study vaccine in the prevention of RT-
PCR-confirmed RSV-mediated LRTD.
Up to approximately 27,200 participants (with up to approximately 23,000 in the Global cohort
and up to approximately 4,200 participants in specific Asian countries/territories under local
protocols) will be enrolled and randomized in parallel in a 2:1 ratio to receive active study vaccine
or placebo (Table 2).
Note that some additional local cohort enrollment, beyond the global cohort enrollment may be
allowed if required by local health authorities for the purpose of local health authority
consideration.
 
The Global cohort is defined as all participants (including the Safety subset and the Immuno
subset) who are recruited up to the point that global enrollment is stopped.
 
Local cohorts are defined as participants from the considered country/territory and under local
protocols.
For analyses purposes, data from the Global cohort and the local cohorts may be aggregated.
Analyses for local cohort enrollment will be described separately, but they will also be included
in the primary analysis and final analysis if their enrollment started prior to the database cut-off of
the primary analysis or final analysis, respectively.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
44
Status: Approved, Date: 11 October 2022
Table 2: 
Study Design: VAC18193RSV3001
Group  
N 
Day 1
1 
15,340 
Ad26/protein preF RSV vaccine (1×1011 vp/150 μg)
2 
7,670 
Placebo
Note: The study will be discontinued if the primary analysis is performed by the sponsor and the outcome is negative;
however, if at this timepoint, some participants have not completed 6 months of follow up after their vaccination, the study
will continue until this follow up period is complete.
N number of participants, vp viral particles
ARI ASSESSMENTS AND PROCEDURES
From study vaccination until 24 months after vaccination (ie, the full duration of the study),
participants will be followed up to identify potential cases of RSV infection as further detailed in
Section 8.1. After administration of study vaccine, ARI surveillance will be conducted twice
weekly via the participant’s eDevice (or desktop computer, where applicable) for the duration of
the study. The surveillance questions ask participants if they have experienced any ARI symptoms,
or for participants who have one or more of these symptoms at baseline, if they have experienced
any additional ARI symptoms or a worsening of their baseline symptoms. Participants who
experience any symptoms suggestive of an ARI (new onset or worsening, in the setting that
baseline symptoms are present) are instructed to indicate this (refer to Appendix 7) and start
completing the required ARI episode questionnaires on a daily basis (preferably in the evening)
(Appendix 8, Appendix 9, and Appendix 10).a Ideally within the next 24 hours, the site and
participant should have telephone or telemedicine contact with each other in order for the site to
confirm that the participant is experiencing symptoms consistent with an ARIb and to give
instructions to the participant on the further ARI episode procedures to be followed. Participants
will collect a nasal swab at home on the day of symptom onset or the day thereafter (ARI Day 1-2).
On ARI Day 3-5, participants will present to the site, where vital signs will be measured, and a
nasal swab, a sputum sample (in participants with a productive cough, when possible), and blood
samples (to measure the immune responses at the time of exposure and for exploration of
biomarkers that correlate with respiratory infection and disease severity) may  be taken by a
member of the study staff (see Section 8.1 to determine if the blood samples can be omitted).
Ideally within 24 hours after the ARI Day 3-5 visit (but no later than 48 hours after the ARI Day
3-5 visit), a qualified member of the study staff will perform a local RT-PCR of all available nasal
swabs with the BioFire® Filmarray Respiratory panel, which will be provided to all sites (both US
and non-US); changes to the process might be implemented at the local level based on local
requirements. Participants will subsequently be contacted by telephone and given further
instructions, as detailed below, on how to further proceed based on the outcome of the RT-PCR
a
Note that the PGI-C scale and Return to Usual Health question will not be completed on ARI Day 1.
b
This will be assessed by the site by confirming that at least one of the symptoms used to confirm the ARI from the
RiiQ Symptom Scale is worse than baseline. As defined in Appendix 5, symptoms used to confirm an ARI episode
are: nasal congestion, sore throat, cough, short of breath, coughing up phlegm (sputum), and wheezing (from the
RiiQ Symptom Scale). As it is possible that the participants will make errors when they answer the RiiQ Symptom
Scale, the telephone or telemedicine contact will be used by the sites to also confirm the correctness of the answers
provided by the participant and to confirm the ARI episode was correctly triggered.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
45
Status: Approved, Date: 11 October 2022
tests. Sputum samples (where applicable) will be sent to the central laboratory for testing using the
BioFire Filmarray Pneumonia (PN) panel. For all ARI episodes where a sputum sample is
collected, the ARI episode will be followed up until ARI resolution (ie, with daily questionnaires
and an ARI Day 29 visit) (refer to the procedures in the first bullet point below), independent of
the test results from the collected nasal swabs. Participants who are under self-isolation because
of a (possible) positive test for SARS-CoV-2 will not come to the site for ARI Day 3-5 assessments
but will self-collect the nasal swab.
 
Participants with an ARI and a RT-PCR positive for RSV, hMPV, or influenza-mediated ARI
will continue filling out the ARI episode questionnaires daily (Appendix 8, Appendix 9, and
Appendix 10) until resolution of the ARI episode (defined as 2 consecutive days with no
symptoms listed on the RiiQ Symptom Scale, or, for participants who have RiiQsymptomsat
baseline [assessed pre-vaccination], 2 consecutive days where all symptoms on the RiiQ
Symptom Scale have returned to the same severity level as reported at baseline [or lower]).
After resolution of the ARI episode, the participant will return to ARI surveillance with twice
weekly reminders.
 
On ARI Day 29 (±7 days), regardless of whether the ARI episode has resolved,
participants with a RT-PCR positive for RSV, hMPV, or influenza-mediated ARI will be
asked to return to the site. During this visit, the MRU questionnaire will be completed
(Appendix 11) based on interview with the participant, participants will complete the
RiiQ  (Appendix 8), the EQ-5D-5L (Appendix 9) and each of the Patient Global
Impression (PGI) scales and the Return to Usual Health question (Appendix 10), and the
site staff will also collect information on days missed from work (Appendix 12) and on
complications, hospitalizations and concomitant medications related to the ARI and
record in the electronic case report form (eCRF). The ARI Day 29 visit can also take
place by telephone or telemedicine contact.
 
For medically-attended RT-PCR positive for RSV, hMPV, or influenza-mediated ARIs,
including those resulting in hospitalization, a standard question list will be provided
(Appendix 6) to collect additional information on any other diagnostic tests (eg, chest
x-rays, spirometry, pulmonary function tests, etc.) or on any interventions during the
clinical course of the ARI.
Note: the same procedures apply for participants with a sputum sample taken and for
participants with at least one nasal swab that cannot be tested at the site with the BioFire
Filmarray Respiratory panel.
Participants will remain blinded as to the outcome of RSV, hMPV and influenza RT-PCR test
results until study unblinding and the test results should only be disclosed in the event of safety
concerns. RT-PCR test results related to the detection of other respiratory pathogens can be
communicated to the participants. The RT-PCR results that are obtained with the BioFire
Filmarray testing under the study procedures will be used for research purposes only and will
not be used by the investigator for therapeutic decisions. A locally approved diagnostic test
external to the study procedures, including the RSV RT-PCR, should be obtained in case the
participant’s own healthcare provider considers it warranted (eg, based on symptoms and/or
risk of severe disease) and/or according to local/site specific guidelines. If a sample tests
positive for SARS-CoV-2, the participant will be referred to their own healthcare provider for
locally approved diagnostic test and further management, in accordance with local/site
specific guidelines.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
46
Status: Approved, Date: 11 October 2022
 
Participants with negative RT-PCR results for RSV, hMPV, or influenza will be informed by
telephone or telemedicine contact that they can stop filling out the daily ARI episode
questionnaires and the site will end the ARI episode and return the participant to ARI
surveillance.
 
For participants with a positive SARS-CoV-2 test and a negative test for RSV, hMPV, and
influenza, the collection of ARI data by the study site will be stopped for the ARI episode.
The participant will be informed by telephone or telemedicine contact that theycan stop filling
out the daily ARI episode questionnaires, and the site will end the ARI episode and return the
participant to ARI surveillance with twice weekly reminders. Participants who have a positive
SARS-CoV-2 RT-PCR test as part of the study procedures should be referred to their own
healthcare provider for locally approved diagnostic test and further management, in
accordance with local/site specific guidelines. Participants whose standard-of-care testing
during an ARI episode is positive for SARS-CoV-2, or who have been in contact with
someone that tested positive for SARS-CoV-2 and therefore must self-isolate according to the
local guidelines, will not come to the site for ARI Day 3-5 assessments but will self-collect
the nasal swab. In this circumstance, other ARI Day 3-5 assessments (vital signs, sputum
sample and blood samples) might not be performed.
Participants with positive RT-PCR results for RSV (or hMPV or influenza) should keep on
filling out the daily ARI episode questionnaires until resolution of the ARI episode
independently of any other co-infection (including SARS-CoV-2).
When the end of RSV season one telephone call or telemedicine contact occurs within 6 months
after vaccination, the participants will be contacted again by telephone or telemedicine at 6 months
post-vaccination to collect information on SAEs and AESIs (applies to Visit 3 [end of
season one/6-month follow-up]).
At Month 24, all participants will be contacted by telephone or telemedicine (or come to the site
if they have eDevices to return) to ensure the participants complete the RiiQ, the PGI-H and the
EQ-5D-5L.
Additional study procedures and assessments for efficacy, immunogenicity, safety, and MRU will
be performed as described in Section 8.
Throughout the study, RT-PCR results from the nasal swabs and sputum sample (where available)
will be used to determine whether the infection was caused by RSV. If at least one of these samples
is positive for RSV, the collected information will be applied against the clinical case definition.
The study will be discontinued if the primary analysis is performed by the sponsorand the outcome
is negative; however, if at that timepoint, some participants have not completed 6 months of
follow-up after their vaccination, the study will continue until this follow-up period is complete.
The study duration for an individual participant is approximately 24 months.
An IDMC will be commissioned for this study. Refer to Committees Structure in Appendix 2:
Regulatory, Ethical, and Study Oversight Considerations for details.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
47
Status: Approved, Date: 11 October 2022
A Clinical Event Adjudication Committee (CEC) will be constituted. The CEC will review all
available data of all RSV-mediated ARIs and will confirm if the RT-PCR-confirmed RSV LRTD
definition criteria were met. Further for all RT-PCR-confirmed RSV LRTD cases the CEC will
assess their severity (mild, moderate or severe). Further details are provided in Section 9.6.2.
A diagram of the study design is provided in Section 1.2, Schema.
4.2. 
Scientific Rationale for Study Design
Blinding, Control, Study Phase/Periods, Vaccine Groups
A placebo control will be used to establish the frequency and magnitude of changes in clinical
endpoints that may occur in the absence of active vaccination. Randomization will be used to
minimize bias in the assignment of participants to vaccine groups (active vaccine or placebo), to
increase the likelihood that known and unknown participant attributes (eg, demographic and
baseline characteristics) are evenly balanced across vaccine groups, and to enhance the validity of
statistical comparisons across the vaccine groups. Blinded vaccination will be used to reduce
potential bias during data collection and evaluation of clinical endpoints.
Medical Resource Utilization Data Collection
Prophylaxis of RSV infection may reduce the need for and duration of supportive care (such as
hospitalization, oxygen supplementation, etc.). The study will evaluate the impact of active study
vaccine versus placebo on the development and clinical course of RSV disease.
Participant Medical Information Prior to, During and After the Study (Real-world Data)
Real-world data plays a critical role in improving understanding of factors that may influence
response to immunization and the effectiveness and safety of a vaccine product during and after
completion of the study. This may be important in gaining insight in terms of duration of efficacy
and incidence of AEs after study completion. This may be especially important in the event that
efficacy of Ad26/protein preF RSV vaccine or another vaccine is shown and follow-up in a
randomized manner is compromised.
To allow the linking of participant records from different sources, ie, data collected as part of the
study as specified in the Schedule of Activities and longitudinal real-world data (from 5 years prior
to enrollment in the study until 5 years after study completion) such as electronic health records,
claims, and laboratory data from other care settings, without compromising the participant’s
confidentiality, tokenization and matching procedures will be utilized (for participants from the
US only). The tokenization process starts with each data provider generating a token behind the
firewall via a proprietary software. Personal information such as names and dates of birth from
study participants are removed from real-world data sources and replaced with encrypted, one-
way, hashed identifiers, and then further encrypted using asymmetric keys in compliance with
Health Insurance Portability and Accountability Act (HIPAA 1996). This encrypted anonymized
information is sent for matching to the anonymized participant master index. While it is not
possible to reverse the hash, source-specific tokens can be decrypted and re-encrypted so that
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
48
Status: Approved, Date: 11 October 2022
records can be linked across sources. The result of the process is a unique anonymized identifier
for each participant, which can be used to link participant records across sources.
4.2.1. 
Study-Specific Ethical Design Considerations
Potential participants will be fully informed of the risks and requirements of the study and, during
the study, participants will be given any new information that may affect their decision to continue
participation. They will be told that their consent to participate in the study is voluntary and may
be withdrawn at any time with no reason given and without penalty or loss of benefits to which
they would otherwise be entitled. Only participants who are fully able to understand the risks,
benefits, and potential AEs of the study, and provide their consent voluntarily will be enrolled.
The primary ethical concern is that this study will be performed in adult participants who will
receive no direct benefit from participation in the study, except for participant reimbursement for
the time and inconveniences that may arise from participation in the study. See Section 2.3 for
details on potential and known benefits and risks, and for the safety measures taken to minimize
risk to participants.
The total blood volume to be collected is considered to be an acceptable amount of blood to be
collected over this time period from the population in this study based upon the standard of the US
Department of Health and Human Services Office for Human Research Protections, and US FDA
guidelines of 550 mL in any 8-week period (OHRP 1998, FDA 1998).
For participants (from the US only) who consent to the optional collection of real-world medical
data, the sponsor is committed to protect their data and privacy. Tokenization and matching
procedures will be utilized to allow for those participant’s medical data to be obtained without
violation of participant confidentiality. Participants will be informed that consent to this part of the
study is completely optional and that they can withdraw their consent at any given time. In the
event of withdrawal of consent, the sponsor will remove the token generated and any associated
linked real-world data. Participation in or withdrawal from this optional part of the study will not
affect the participation in the main study.
4.3. 
Justification for Dose
The dose levels for Ad26.RSV.preF and RSV preF protein used in this study were determined
from the primary analysis of Cohort 2 in Study VAC18193RSV1004. From the primary analysis,
a significant increase in virus neutralizing antibodies (VNA) A2 titers was observed in the groups
combining Ad26.RSV.preF and RSV preF protein compared to Ad26.RSV.preF 1×1011 vp alone.
No relevant differences between the mixture groups and Ad26.RSV.preF alone were observed for
other immunogenicity assays available at the time of the primary analysis. All regimens had
acceptable safety and reactogenicity profiles, which were similar across groups. Based on these
data, and on the outcome of the primary analysis of the proof-of-concept efficacy study
VAC18193RSV2001 (see Section 2.2), the mixture of Ad26.RSV.preF 1×1011 vp and 150 µg of
the RSV preF protein was selected for the present study.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
49
Status: Approved, Date: 11 October 2022
4.4. 
End of Study Definition
End of Study Definition
The end of study is considered as the last visit for the last participant in the Global cohort ofthe
study.
The final data from the study site will be sent to the sponsor (or the designee) after completion of
the final participant visit at that study site, in the time frame specified in the Clinical Trial
Agreement.
Study Completion Definition
A participant will be considered to have completed study vaccination if the participant has received
a vaccination.
A participant will be considered to have completed the study if the participant has completed all
assessments at the final visit.
5. 
STUDY POPULATION
Participants will be adult men and women ≥60 years of age on the day of signing the Informed
Consent Form (ICF). Participants must be in stable health (on the basis of medical history and vital
signs measurement performed at Day 1).
Participants in this age range with congestive heart failure (CHF), coronary artery disease (such as
angina pectoris, ischemic cardiomyopathy, history of myocardial infarct, or history of coronary
artery bypass graft or coronaryarterystent), and chronic lung disease (suchas asthma and chronic
obstructive pulmonary disease [COPD]) are generally at higher risk for severe RSV disease
(CDC 2020); hereafter, this population will be referred to as “increased risk”. Although no required
minimum is set in the overall population, it is expected that ~25% of the participants enrolled in
the study will have medical conditions that place them in this “increased risk” group.
The randomization will be set-up to ensure that ~50% of participants in the Safety Subset, and
~50% of participants in the Immuno Subset will be at increased risk of severe RSV disease and
~50% of them will be 75 years or older (refer to Section 6.3, Measures to Minimize Bias:
Randomization and Blinding).
A cap will be installed on the number of participants in the 60-64 year age group (see Section 6.3
for information related to caps).
Screening and vaccination may be split into 2 visits after consultation with the sponsor or its
delegate. Every effort should be made for split visits to occur preferably within 3 to 5 days and no
later than 14 days, and pre-vaccination vital signs should be repeated on the day of vaccination if
this visit is split.
The inclusion and exclusion criteria for enrolling participants in this study are described below. If
there is a question about these criteria, the investigator must consult with the appropriate sponsor
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
50
Status: Approved, Date: 11 October 2022
representative and resolve any issues before enrolling a participant in the study. Waivers are not
allowed.
For a discussion of the statistical considerations of participant selection, see Section 9.2, Sample
Size Determination.
5.1. 
Inclusion Criteria
Each potential participant must satisfy all of the following criteria to be enrolled in the study:
1. Must sign an ICF indicating that the participant understands the purpose, procedures and
potential risks and benefits of the study, and is willing to participate in the study.
2. Willing and able to adhere to the prohibitions and restrictions specified in this protocol.
3. Must be ≥60 years old on the day of signing the ICF and expected to be available for the
duration of the study.
4. Before randomization, a participant must be:
 postmenopausal (postmenopausal state is defined as no menses for 12 months without an
alternative medical cause); and
 not intending to conceive by any methods.
Note: Hysterectomized participants are also eligible for the study.
5. Criterion modified per Amendment 3
5.1 Criterion modified per Amendment 4
5.2 In the investigator’s clinical judgment, the participant must be in stable health at the time
of vaccination. Participants may have underlying illnesses such as hypertension, CHF,
COPD, type 2 diabetes, hyperlipoproteinemia, or hypothyroidism, as long as their
symptoms and signs are stable and medically controlled in the judgement of the
investigator at the time of vaccination, and these conditions receive routine follow-up by
the participant’s healthcare provider. Participants will be included on the basis of medical
history and vital signsa taken between ICF signature and vaccination.
6. From the time of vaccination through 3 months after vaccination, participant agrees not to
donate blood.
7. Must be able to read, understand, and complete questionnaires in the eDiary.
8. Must be willing to provide verifiable identification, has means to be contacted and to contact
the investigator during the study.
9. Must be able to work with smartphones/tablets/computers.
a 
Participants can be enrolled with ≤Grade 3 values for vital signs measurements (other than temperature), if these are deemed
not clinically significant by the investigator (refer to Appendix 4: Toxicity Grading Scale). Confirmation of investigator’s
clinical assessment must be provided in the participant’s medical record.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
51
Status: Approved, Date: 11 October 2022
5.2. 
Exclusion Criteria
Any potential participant who meets any  of the following criteria will be excluded from
participating in the study:
1. Has a serious clinically unstable condition, (eg, end-stage renal disease with or without
dialysis, clinically unstable cardiac disease), Alzheimer’s disease, or any other condition for
which, in the opinion of the investigator, participation would not be in the best interest of the
participant (eg, compromise well-being) or that could prevent, confound, or limit the protocol-
specified assessments.
2. History of malignancy within 5 years before screening not in the following categories:
a. Participants with squamous and basal cell carcinomas of the skin and carcinoma in situ of
the cervix may be enrolled at the discretion of the investigator.
b. Participants with a history of malignancy within 5 years, which is considered cured with
minimal risk of recurrence per investigator’s judgement, can be enrolled.
3. Had major surgery (eg, major cardiopulmonary or abdominal operations) as per the
investigator’s judgment within 4 weeks before vaccination, or will not have fully recovered
from surgery, or has major surgery planned during the time the participant is expected to
participate in the study.
4. Criterion modified per Amendment 1
4.1 Criterion modified per Amendment 3
4.2 Has abnormal function of the immune system resulting from:
a. Clinical conditions (eg, autoimmune disease or immunodeficiency) expected to have
an impact on the immune response elicited by the study vaccine.
Participants with autoimmune disease (eg, autoimmune-mediated thyroid disease,
autoimmune inflammatory rheumatic disease such as rheumatoid arthritis, and type 1
diabetes) that is stable and inactive without the use of systemic immunomodulators
and glucocorticoids may be enrolled at the discretion of the investigator.
b. Chronic or recurrent use of systemic corticosteroids within 2 months before
administration of study vaccine and during the study. A substantially
immunosuppressive steroid dose is considered to be ≥2 weeks of daily receipt of
20 mg of prednisone or equivalent.
Note: Ocular, topical, intra-articular, or inhaled steroids are allowed.
c. Administration of antineoplastic and immunomodulating agents, eg, cancer
chemotherapeutic agents, or radiotherapy within 6 months before administration of
study vaccine and during the study.
Note: Ocular and topical antineoplastic and immunomodulating agents are allowed.
5. Criterion modified per Amendment 1
5.1 Received or plans to receive:
a. Licensed live-attenuated vaccines within 28 days before or after planned
administration of study vaccination
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
52
Status: Approved, Date: 11 October 2022
b. Other licensed (not live) vaccines within 14 days before or after planned
administration of study vaccination.
6. Has an acute illness (including acute respiratory illnesses) or body temperature of ≥38.0ºC
(≥100.4ºF) within 24 hours prior to administration of study vaccine.
Note: Enrollment at a later date is permitted.
7. Has had major psychiatric illness and/or drug or alcohol abuse which in the investigator’s
opinion would compromise the participant’s safety and/or compliance with the study
procedures.
8. Known or suspected allergy or history of anaphylaxis or other serious adverse reactions to
vaccines or vaccine components (including any of the constituents of the study vaccine). Refer
to the latest version of the Investigator’s Brochure for Ad26/protein preF RSV vaccine.
9. History of acute polyneuropathy (eg, Guillain-Barré syndrome) or chronic idiopathic
demyelinating polyneuropathy (CIDP).
10. Criterion modified per Amendment 1
10.1 Received hematopoietic stem cell transplant in medical history, immunoglobulins in the
2 months, immunoglobulins specific to RSV, hMPV, or parainfluenza viruses in the
12 months, apheresis therapies in the 4 months, or blood products in the 4 months before
the planned administration of the study vaccine or has any plans to receive such treatment
during the study.
Note: Use of monoclonal antibodies (mAbs) before administration of study vaccine and
during the study conduct is permitted with the exception of those targeting T cells (anti-
CD3, CD4, CD33, and CD52), B cells (anti-CD45, CD19, CD20, CD22, CD27, CD38,
and CD138) and check point inhibitors (PD-1, PDL-1 and CTLA-4). Examples of not
allowed MABS are: muromonab-CD3, gemtuzumab ozogamicin, alemtuzumab,
bevacizumab, rituximab, ofatumumab, ocrelizumab, tositumomab, veltuzumab,
obinutuzumab, epratuzumab, pembrolizumab, nivolumab, atezolizumab, avelumab,
durvalumab and CTLA-4 targeting ipilimumab. Participants receiving these mAbs in the
2 months before the planned administration of the study vaccine or who plan to receive
these mAbs during the study will be excluded from participating in the study.
11. Criterion modified per Amendment 3
11.1 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 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, without intervention) or in the
observational phase of interventional studies is allowed upon approval of the sponsor or its
delegate.
12. Contraindication to IM injections and blood draws (eg, bleeding disorders).
13. Criterion modified per Amendment 1
13.1 Received an RSV vaccine in a previous RSV vaccine study.
14. Criterion deleted per Amendment 1
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
53
Status: Approved, Date: 11 October 2022
15. Employee of the investigator or study site, with direct involvement in the proposed study or
other studies under the direction of that investigator or study site, as well as family members
of the employees or the investigator, or an employee of the sponsor.
16. Criterion modified per Amendment 4
16.1 Who, in the opinion of the investigator, is unlikely to adhere to the requirements of the
study, or is unlikely to complete the vaccination and observation.
17. Cannot communicate reliably with the investigator.
18. For participants in the Safety  Subset only: Participants who have significant scarring,
tattoos, abrasions, cuts, or infections over the deltoid region of both arms that, in the
investigator’s opinion, could interfere with evaluation of injection site local reactions.
19. Criterion added per Amendment 1
19.1 Criterion modified per Amendment 4
19.2 Received or plans to receive a SARS-CoV-2 vaccine:
a. Live-attenuated SARS-CoV-2 vaccine within 28 days before or after planned
administration of the study vaccine.
b. Non-live SARS-CoV-2 vaccine within 14 days before or after planned administration of
the study vaccine.
c. A viral-vectored SARS-CoV-2 vaccine within 28 days before or after planned
administration of the study vaccine.
20. Criterion added per Amendment 1
20.1 Criterion modified per Amendment 4
20.2 Received or plans to receive an Ad26-vectored vaccine at any time prior to
randomization until 28 days after study vaccination (this does not apply to SARS-CoV-
2 vaccines; please refer to exclusion criterion 19).
21. Criterion added per Amendment 2
21.1 History of TTS or heparin-induced thrombocytopenia and thrombosis (HITT).
NOTE: Investigators must ensure that all study enrollment criteria have been met prior to the first
dose. If a participant’s clinical status changes (including any available laboratory results or receipt
of additional medical records) after screening but before vaccination such that the participant no
longer meets all eligibility criteria, then the participant must be excluded from participation. The
required documentation to support meeting the enrollment criteria is described under Source
Documents in Appendix 2: Regulatory, Ethical, and Study Oversight Considerations.
5.3. 
Lifestyle Considerations
Potential participants must be willing and able to adhere to the following lifestyle restrictions
during the study to be eligible for participation:
1. See Section 6.8, Concomitant Therapy for details onprohibited and restricted therapy during
the study.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
54
Status: Approved, Date: 11 October 2022
2. Agree to follow all requirements that must be met during the study as noted in the Inclusion
and Exclusion Criteria.
5.4. 
Screen Failures
Participant Identification, Enrollment, and Screening Logs
The investigator agrees to complete a participant identification and enrollment log to permit easy
identification of each participant during and after the study. This document will be reviewed by
the sponsor study site contact for completeness.
The participant identification and enrollment log will be treated as confidential and will be filed
by the investigator in the study file. To ensure participant confidentiality, no copy will be made.
All reports and communications relating to the study will identify participants by participant
identification and age at initial informed consent. In cases where the participant is not randomized
into the study, the date seen and age at initial informed consent will be used.
The investigator must also complete a participant screening log, which reports on all participants
who were seen to determine eligibility for inclusion in the study.
Individuals who do not meet the criteria for participation in this study (screen failure) but at some
point in the future are expected to meet the eligibility criteria may be rescreened. Individuals who
are rescreened will be assigned a new participant number and will undergo the informed consent
process, and then restart a new screening phase.
5.5. 
Criteria for Temporarily Delaying Administration of Study Vaccine
The following events constitute a temporary contraindication to study vaccination:
 
Clinically significant acute illness at the time of vaccination.
 
Fever (body temperature ≥38.0°C) within 24 hours prior to the planned time of vaccination.
If any of these events occur at the scheduled time for the vaccination, randomization at a later date
is permitted at the discretion of the investigator and after consultation with the sponsor (refer to
the Schedule of Activities).
If the vaccination visit cannot be rescheduled within the allowed window or the contraindications
to vaccination persist, the sponsor should be contacted for further guidance.
6. 
STUDY VACCINE AND CONCOMITANT THERAPY
6.1. 
Study Vaccine Administration
The investigational medicinal products to be administered to participants in this study are
Ad26.RSV.preF, RSV preF protein, and placebo. The Ad26/protein preF RSV vaccine to be used
in this study is composed of Ad26.RSV.preF and RSV preF protein, to be administered as a single
injection (1.0 mL) in the deltoid muscle:
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
55
Status: Approved, Date: 11 October 2022
 Ad26.RSV.preF (JNJ-64400141) will be supplied at a concentration of 2×1011 vp/1 mL in
single-use vials. A dose level of1×1011 vp will be used.
 RSV preF protein (JNJ-64213175) will be supplied at a concentration of 0.3 mg/1 mL in
single-use vials. A dose level of150 µg will be used.
 Placebo for Ad26.RSV.preF and for RSV preF protein.
The unblinded pharmacist, or other qualified individual, who will have no other study function
will prepare the appropriate syringe, labeled with the participant’s study identification number,
and provide the syringes for Ad26/protein preF RSV vaccine and placebo in a blinded manner to
the blinded study vaccine administrator who will perform the injection.
Study vaccine administration must be captured in the source documents and the eCRF.
The full details of study vaccine preparation will be provided in the Site Investigational Product
Procedures Manual and in the Investigational Product Preparation Instruction.
6.2. 
Preparation/Handling/Storage/Accountability
Ad26.RSV.preF/RSV preF protein will be manufactured and provided under the responsibility of
the sponsor. Refer to the Investigator’s Brochure for Ad26/protein preF RSV vaccine for a list of
excipients.
Preparation/Handling/Storage
All study vaccine must be stored in a secured location with no access for unauthorized personnel and
at controlled temperatures as indicated on the clinical labels. 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 supplies 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.
Refer to the Site Investigational Product Procedures Manual and to the Investigational Product
Preparation Instruction for additional guidance on study vaccine preparation, handling, and
storage.
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 participant must be
documented on the vaccine accountability form. All study vaccine will be stored and disposed of
according to the sponsor’s instructions. Study site personnel must not combine contents of the
study vaccine containers.
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 Investigational Product Destruction Form. When the
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
56
Status: Approved, Date: 11 October 2022
study site is an authorized destruction unit and study vaccine supplies are destroyed on-site, this
must also be documented on the Investigational Product Destruction Form.
Potentially hazardous materials containing hazardous liquids, such as used ampules, needles,
syringes and vials, should be disposed of immediately in a safe manner and therefore will not be
retained for vaccine accountability purposes.
Study vaccine must be dispensed under the supervision of the investigator or a qualified member
of the study site personnel. Study vaccine will be supplied only to participants participating in the
study. Study vaccine may not be relabeled or reassigned for use by other participants. 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.
Refer to the Investigational Product Preparation Instructions and Study Site Investigational
Product and Procedures Manual for additional guidance on the final disposition of unused study
vaccines.
6.3. 
Measures to Minimize Bias: Randomization and Blinding
Study Vaccine Allocation
Central randomization will be implemented in this study. On Day 1, participants will be randomly
assigned in a 2:1 ratio to 1 of 2 groups (active vaccine or placebo) based on a computer-generated
randomization algorithm prepared before the study by or under the supervision of the sponsor.
Participants who have provided additional informed consent will be enrolled in the Safety Subset
and/or in the Immuno Subset.
The interactive web response system (IWRS) will assign a unique code, which will dictate the
group assignment and matching study vaccine kit for the participant. The requestors must use their
own user identification and personal identification number when contacting the IWRS and will
then give the relevant participant details to uniquely identify the participant.
To ensure balance across arms, the randomization will be stratified by age category  (ie,
60-64 years, 65-74 years, 75-84 years, ≥85 years), and by being at increased risk of severe RSV
disease (yes/no). Within strata, minimization will be applied for subset (being part of the Safety
Subset only, the Immuno Subset only, both subsets or none), region (North America, Europe, SH),
site, and stratum combination. The following caps will be installed for the global cohort:
 
The total number of 60-64 year old participants will be a maximum of 2,000 participants.
Depending on recruitment, caps might be installed with the aim to have ~10% 60-64 year old
participants per region.
 
The Safety Subset (including participants who are only in the Safety Subset and who are in
both the Safety and Immuno Subset) will include at least 1,050 participants, ~50% of them
will be at increased risk for severe RSV disease, ~50% of them will be 75 years or older.
 
The Safety Subset should contain ~750 participants from North America and ~300 from
each of the other regions in the setting that these are part of the study. In each region,
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
57
Status: Approved, Date: 11 October 2022
~50% of the Safety Subset will be at increased risk of severe RSV disease and ~50% will
be 75 years or older.
 
The Immuno Subset (including participants who are only in the Immuno Subset and who are
in both the Safety and Immuno Subset) will include at least 360 participants, ~50% of them
will be at increased risk for severe RSV disease and ~50% will be 75 years or older.
 
The Immuno Subset should contain at least 180 participants from North America, at least
180 from Europe, and ~120 from each of the other regions in the setting that these are
part of the study. In each region, ~50% of the Immuno Subset will be at increased risk of
severe RSV disease and ~50% will be 75 years or older.
No other caps are installed for the Global cohort.
In each of the regions, the non-increased risk Safety Subset must be fully enrolled before further
enrollment of non-increased risk participants. Also, the 60-74 years Safety Subset must be fully
enrolled before further enrollment of participants aged 60-74 years. Similarly, in each region, the
increased risk Safety Subset must be fully enrolled before further enrollment of increased risk
participants. Also, the 75-years-and-older Safety Subset must be fully enrolled before further
enrollment of participants aged 75 years and older. Immuno Subset participants will be enrolled
only at a selection of sites.
Additional local cohort enrollment, beyond the Global cohort enrollment, may be allowed if
required by local health authorities for the purpose of local regulatory approval consideration. This
will also be handled via the IWRS and will follow the same randomization ratio as the Global
cohort. Stratification and minimization will be done in a similar way as for the Global cohort. The
number of 60-64 year old participants in those local cohorts will be a maximum 10% of the total
cohort. Caps for the Immuno Subset and the Safety Subset will depend on local requirements.
Blinding
The investigator will not be provided with randomization codes. The codes will be maintained
within the IWRS, which has the functionality to allow the investigator to break the blind for an
individual participant.
In general, for the Global cohort, randomization codes will be disclosed fully only if the study is
completed and the clinical database is closed. The participants, study site personnel (except for
those with primary responsibility for study vaccine preparation and dispensing), and investigator
will be blinded to the study vaccine allocation until the end of the study. The sponsor will be
blinded to Day 1 study vaccine allocation until the database lock for the primary efficacy analysis
except for the sponsor representatives involved in independent drug monitoring.
From the primary efficacy analysis onwards, group level results may be shared externally as
needed, however, efforts will be made to preserve the blinding to the individual participant
allocation until the end of the study.
For local cohorts, similar blinding principles hold. The randomization codes will be disclosed fully
if the study of the local cohort is completed and the respective clinical database is closed, but not
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
58
Status: Approved, Date: 11 October 2022
before the global clinical database is closed. Local study teams will be blinded to study vaccination
until the primary analysis as specified per local requirements, but this cannot be conducted prior
to the primary analysis of the Global cohort.
For countries/territories that contribute to both the Global and the local cohorts, the randomization
codes will be disclosed fully if the study of the local cohort is completed and the respective clinical
database is closed, but not before the global clinical database is closed. The global study team of
the sponsor will be unblinded. The local study teams will be blinded to study vaccination until the
primary analysis as specified per local requirements, but this cannot be conducted prior to the
primary analysis of the Global cohort.
The investigator may in an emergency determine the identity of the vaccination by contacting the
IWRS. While the responsibility to break the vaccination code in emergency situations resides
solely with the investigator, it is recommended that the investigator contact the sponsor or its
designee if possible, to discuss the particular situation before breaking the blind. Telephone contact
with the sponsor or its designee will be available 24 hours per day, 7days per week. In the event
the blind is broken, the sponsor must be informed as soon as possible. The date, time, and reason
for the unblinding must be documented by the IWRS, in the appropriate section of the eCRF, and
in the source document. The documentation received from the IWRS indicating the code break
must be retained with the participant’s source documents in a secure manner. The investigator is
advised not to reveal the study vaccine assignment to the study site personnel or sponsor
personnel/sponsor representative.
If the randomization code is broken by the sponsor for safety reporting purposes, the participant
may remain in the study (if the randomization code is still blinded to the study site personnel and
the participant).
Participants who withdraw will not be replaced.
6.4. 
Study Vaccination Compliance
Study vaccine (active or placebo) will be administered IM by a blinded vaccine administrator a
trained and qualified study nurse, medical doctor, or otherwise qualified healthcare professional.
Details of study vaccine administration will be recorded in the eCRF (including date and time of
injection and deltoid).
For details on blinding procedures, see Section 6.3, Measures to Minimize Bias: Randomization
and Blinding.
6.5. 
Dose Modification
Not applicable.
6.6. 
Continued Access to Study Vaccine After the End of the Study
Participants will be instructed that study vaccine will not be made available to them after they have
completed study vaccination.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
59
Status: Approved, Date: 11 October 2022
6.7. 
Overdose
For this study, any dose of vaccine greater than the assigned dose will be considered an overdose.
The sponsor does not recommend specific treatment for an overdose. In the event of a known
overdose, the investigator should:
 
Contact the medical monitor immediately.
 
Closely monitor the participant for AE/SAE/AESI/medically-attended AE (MAAE) (ie, the
participant will remain at the study site for at least 1 hour and will be closely monitored for
allergic or other reactions by study staff. Follow-up telephone calls or telemedicine contacts
12 hours and 24 hours post-dose will be made).
 
Document the quantity of the excess dose in the source document.
 
Report as a special reporting situation.
6.8. 
Concomitant Therapy
For All Participants
Prestudy specific therapies such as analgesics/antipyretics and non-steroidal anti-inflammatory
drugs (NSAIDs) administered up to 30 days before the dose of study vaccine must be recorded at
screening. Use of analgesics/antipyretics and NSAIDs for routine prophylaxis prior to study
vaccine administration is discouraged, however, should be used only in case of medical need and
in line with local standard of care.
Concomitant therapies associated with SAEs, AESIs, and with AEs leading to discontinuation
from study will be collected and recorded in the eCRF from the time of vaccination through the
end of the study. Concomitant medications associated with RSV, hMPV, and influenza-mediated
ARI episodes and with complications of RSV, hMPV, and influenza-mediated ARIs will be
captured in the eCRF for the duration of the study.
The use ofsystemic corticosteroids must be documented throughout the study. Antineoplastic and
immunomodulating agents, eg, cancer chemotherapeutic agents or chronic or recurrent use of
systemic corticosteroids, or radiotherapy are prohibitedthroughout the study. If the use of systemic
corticosteroids, antineoplastic or immunomodulating agents becomes medically indicated during
the study for any participant, the sponsor should be contacted.
Vaccination with licensed live-attenuated vaccines within 28 days of the study vaccination (ie,
before or after) is prohibited. Other licensed (not live) vaccines (eg, tetanus, hepatitis A or 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.
For SARS-CoV-2 vaccines either licensed or available under Emergency Use Authorization: live-
attenuated vaccines should be given at least 28 days before or after study vaccination; non-live
vaccines should be given at least 14 days before or afterstudy vaccination. A viral-vectored SARS-
CoV-2 vaccine is not to be given within 28 days before or after study vaccination. Any history of
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
60
Status: Approved, Date: 11 October 2022
SARS-COV-2 vaccination (name/manufacturer of the vaccine and date of administration,
whenever possible) prior to and during the study will be collected in the eCRF.
Seasonal influenza vaccination is recommended, but must occur at least 14 days before or at least
14 days after the study vaccine administration. Any history of influenza vaccination
(name/manufacturer of the vaccine and date of administration, whenever possible) within 3 months
prior to enrolment in the study to and during the study will be collected in the eCRF.
The sponsor must be notified in advance (or as soon as possible thereafter) of any instances in
which prohibited therapies are administered.
For Participants in the Safety Subset
For participants in the Safety Subset, concomitant therapies associated with unsolicited AEs will
be collected and recorded in the eCRF from the time of the study vaccine administration through
28 days after vaccination. Concomitant therapies associated with solicited AEs will be collected
by the participants and recorded in the eCRF from the time of vaccine administration through
7days after vaccination.
Information on concomitant use of herbal supplements or vitamins will not be collected.
7. 
DISCONTINUATION OF STUDY VACCINATION AND PARTICIPANT
DISCONTINUATION/WITHDRAWAL
7.1. 
Discontinuation of Study Vaccination
Not applicable.
7.2. 
Participant Discontinuation/Withdrawal From the Study
A participant will be withdrawn from the study for any of the following reasons:
 
Lost to follow-up
 
Withdrawal of consent
 
Death
 
Repeated failure to comply with protocol requirements
 
Any AE that requires discontinuation from the study
 
Decision by the sponsor or the investigator to stop or cancel the study
 
Decision by local regulatory authorities and Institutional Review Board (IRB)/ Independent
Ethics Committee (IEC) to stop or cancel the study
 
If the randomization code is broken by the investigator or the study site personnel.
Note: If the randomization code is broken by the sponsor for safety reporting purposes, the
participant may remain in the study (if the randomization code is still blinded to the study site
personnel and the participant).
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
61
Status: Approved, Date: 11 October 2022
When a participant withdraws before study  completion, the reason for withdrawal is to be
documented in the eCRF and in the source document. All efforts should be made for the participant
to return the eDevice provided by the site, as applicable. If the reason for withdrawal from the
study is withdrawal ofconsent then no additional assessments are allowed.
Withdrawal of Consent
A participant declining to return for scheduled visits does not necessarily constitute withdrawal of
consent. Alternate follow-up mechanisms that the participant agreed to when signing the consent
form apply as local regulations permit.
7.2.1. 
Withdrawal From the Use of Research Samples
Withdrawal From the Use of Samples in Future Research
The participant may withdraw consent for use of samples for research (refer to Long-Term
Retention of Samples for Additional Future Research in  Appendix 2: Regulatory, Ethical, and
Study Oversight Considerations). 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.
7.3. 
Lost to Follow-up
To reduce the chances of a participant being deemed lost to follow-up, prior to randomization,
attempts should be made to obtain contact information from each participant, eg, home, work, and
mobile telephone numbers and email addresses for both the participant as well as appropriate
family members.
A participant will be considered lost to follow-up if the participant repeatedly fails to return for
scheduled visits and is unable to be contacted by the study site. A participant cannot be deemed
lost to follow-up until all reasonable efforts made by the study site personnel to contact the
participant are deemed futile. The following actions must be taken if a participant fails to return to
the study site for a required study visit:
 
The study site personnel must attempt to contact the participant to reschedule the missed visit
as soon as possible, to counsel the participant on the importance of maintaining the assigned
visit schedule, to ascertain whether the participant wishes to or should continue in the study.
 
Before a participant is deemed lost to follow up, the investigator or designee must make every
reasonable effort to regain contact with the participant (where possible, 3 telephone calls,
telemedicine contacts, e-mails, fax, and, if necessary, a certified letter to the participant’s last
known mailing address, or local equivalent methods. These contact attempts should be
documented in the participant’s medical records.
 
Should participants continue to be unreachable, they will be considered to have withdrawn
from the study.
Should a study site close, eg, for operational, financial, or other reasons, and the investigator cannot
reach the participant to inform them, their contact information will be transferred to another study
site.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
62
Status: Approved, Date: 11 October 2022
8. 
STUDY ASSESSMENTS AND PROCEDURES
Overview
The Schedule of Activities summarizes the frequency and timing of all measurements applicable
to this study. Unscheduled visits may be performed based on the investigator’s clinical judgment
and may include further evaluations, as needed.
If multiple assessments are scheduled for the same timepoint, it is recommended that procedures
be performed in the following sequence: electronic patient-reported outcomes (ePROs), nasal
swabbing and/or nasosorption sampling, blood draws. If needed, assessments may be performed
on another day within the applicable visit window. Actual dates and times of assessments will be
recorded in the source documents and/or eCRF and/or eDevice.
eDevices will be provided for participants who require them. Instructions for completing eDiaries
on the provided eDevice or the participant’s own eDevicea (or desktop computer, where
applicable) will be provided to all participants on the day of study vaccination, together with a
nasal swab sample kit. Participants in the Safety Subset will receive additional instructions for
completing safety eDiaries on the eDevice (to record body temperature and solicited local [at the
injection site] and systemic signs and symptoms), and these participants will also be provided with
a thermometer (to measure body temperature) and a ruler (to measure local injection site reactions).
The eDiary instructions on how to capture the data and grading scales to assess severity of the
signs and symptoms will be provided to participants. The study staff is responsible for providing
appropriate (re)training to the participant to avoid missing or incorrect data. The eDiary will be
reviewed by study personnel at the visits indicated in the Schedule of Activities. If the eDiary
review is missed, the eDiary will be reviewed during the next visit.
If a participant is unable to complete the eDiary, as a fall back option, a study staff member can
collect information by contacting the participant by telephone or telemedicine (or visit the
participant at home in the event that the participant is unable to come to the site), reading the
questions aloud to the participant and entering the participant’s responses on the participant’s
behalf. If the participant requires it, the participant’s caregiver can assist the participant to complete
the eDiary assessment by reading the eDiary questions aloud to the participant and recording the
participant’s responses in the eDiary following the procedures for caregivers (using the caregiver’s
unique identifier and PIN). Procedures for caregivers to collect and report the participant’s
responses to the eDiary questions will be detailed in the instructions for caregivers.
Participants will also be trained on when and how to collect a nasal swab if they experience any
symptoms that could indicate an ARI. Participants will be provided with 2 nasal swab kits.
Over the entire study, the total blood volume scheduled to be collected from each participant in
the Immuno Subset will be approximately 366 mL when the study is continued to Month 24, and
a 
Participants may access the eDiary via their own eDevice if their device (smartphone or tablet) is compatible.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
63
Status: Approved, Date: 11 October 2022
244 mL when the study does not progress beyond the first year. For all other participants, the total
blood volume scheduled to be collected will be 51 mL when the study is continued to Month 24,
and 34 mL when the study does not progress beyond the first year. The maximum volume of blood
to be drawn at any given visit would be 62 mL for participants in the Immuno Subset and 17 mL
for all other participants. During each ARI episode, 21.5 mL additional blood will be sampled.
Repeat or unscheduled samples may be taken for safety reasons or for technical issues with the
samples.
Patient-reported Outcomes
Participants will complete self-assessments of their health, symptoms, and functional status in
questionnaires as well as ARI surveillance in an eDiary on their own eDevice or one provided for
this study or desktop computer (where applicable).
Requirements for investigators and study monitors will be detailed in separate documents.
All ePRO instruments will be provided in the local language in accordance with local guidelines.
The ePRO and AE data will not be reconciled with one another.
Visit Windows
The timings of post-vaccination visits will be determined relative to the actual day of vaccination.
The following visit windows will be allowed as indicated:
Visit #  
Visit Day/
Visit Week  
Visit Window  
Primary Purpose
2
15/
2
+3 days 
2 weeks after vaccination, Safety and Immuno visit
2aa 
29/ 
4 
+3 days
4 weeks after vaccination, Safety visit by telephone
or telemedicine contact
2bb 
85/
12
±7 days 
12 weeks after vaccination, Immuno visit
2cb 
169/
24
±14 days 
24 weeks after vaccination, Immuno visit
3c 
182/“End of first 
RSV season”/26 
-7/+14 days
26 weeks after vaccination (Month 6)/End of
season 1 assessments. Safety and efficacy visit
4
365/
52 
-7/+14 days
52 weeks after vaccination (Month 12). Safety and
Immuno visit
4a b
533/
76
±14 days 
76 weeks after vaccination. Immuno visit
5
730//
104 
-7/+14 days
104 weeks after vaccination (Month 24) assessments.
Follow-up visit
a. Safety Subset only.
b. Immuno Subset only.
c. Please refer to the Schedule of Activities for the exact timing of visits and assessments to be performed.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
64
Status: Approved, Date: 11 October 2022
Sample Collection and Handling
The actual dates and times of sample collection for the immunogenicity assessments must be
recorded in the eCRF or laboratory requisition form.
Refer to the Schedule of Activities for the timing and frequency of all sample collections.
Instructions for the collection, handling, storage, and shipment of the samples can be found in the
Laboratory Manual that will be provided. Collection, handling, storage, and shipment of the
samples must be under the specified, and where applicable, controlled temperature conditions as
indicated in the Laboratory Manual.
Study-Specific Materials
The investigator will be provided with the following supplies:
 
Investigator’s Brochure for Ad26/protein preF RSV vaccine
 
Site Investigational Product Procedures Manual
 
Investigational Product Preparation Instruction
 
Laboratory Manual
 
IWRS Manual
 
Electronic Data Capture (eDC) Manual/eCRF completion guidelines
 
Sample ICF
 
ePRO completion guides
 
ePRO participant information sheets
 
eDiaries and instructions for use
 
Rulers (to measure diameter of any erythema and swelling)
 
Thermometers
 
Nasal swab sample kits, including cooling bags
 
RT-PCR machines and supplies for performing respiratory panel tests
 
Pulse oximeters
 
Laboratory kits
 
Contact information page(s)
8.1. 
ARI Assessments and Procedures
From study vaccination until 24 months after vaccination (ie, full duration of the study),
participants will be followed up to identify potential cases of RSV infection (referto Appendix 7).
After administration of study vaccine, ARI surveillance will be conducted for the duration of the
study. To help participants remember to report symptoms of a possible ARI, ideally on the day of
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
65
Status: Approved, Date: 11 October 2022
symptom onset, written instructions are provided. A reminder will be sent to the participants twice
every week until the end of the study, to remind participants to fill out the ARI surveillance
question, which is always available, and to answer the question if they have experienced any ARI
symptoms, or for participants who have one or more of these symptoms at baseline, if they have
experienced any additional ARI symptoms or a worsening of their baseline symptoms. It is
expected that the participants answer these questions at least twice a week, preferably on the days
that the reminder is sent. Participants who experience any symptoms suggestive of an ARI are
instructed to indicate this (refer to Appendix 7) and start completing the required ARI episode
questionnaires on a daily basis (preferably in the evening) (Appendix 8, Appendix 9, and
Appendix 10). Ideally within the next 24 hours, the site and participant should have telephone or
telemedicine contact with each other in order for the site to confirm that the participant is
experiencing symptoms consistent with an ARIa and to give instructions to the participant on the
ARI episode procedures to be followed (detailed in the subsequent section).
Figure 2: 
Schematic Overview of the ARI Assessments and Procedures
Participants with a sputum sample taken and participants with at least one nasal swab that cannot be tested at the site with the
BioFire Filmarray Respiratory panel will follow the same procedures as participants with a RT PCR positive for RSV, hMPV, or
influenza mediated ARI. Participants will remain blinded as to the outcome of RT PCR test results until study unblinding and the
test results should only be disclosed in the event of safety concerns. RT PCR test results related to the detection of other respiratory
pathogens can be communicated to the participants. The RT PCR results that are obtained with the BioFire Filmarray testing under
the study procedures will be used for research purposes only and will not be used by the investigator for therapeutic decisions. A
locally approved diagnostic test external to the study procedures, including the RSV RT PCR, should be obtained in case the
participant’s own healthcare provider considers it warranted (eg, based on symptoms and/or risk of severe disease) and/or according
a 
This will be assessed by the site by confirming that at least one of the symptoms used to confirm the ARI from the RiiQ
Symptom Scale is worse than baseline. As defined in Appendix 5, symptoms used to confirm an ARI episode are: nasal
congestion, sore throat, cough, short of breath, coughing up phlegm (sputum), and wheezing (from the RiiQ Symptom Scale).
As it is possible that the participants will make errors when they answer the RiiQ Symptom  Scale, the telephone or
telemedicine contact will be used by the sites to also confirm the correctness of the answers provided by the
participant and to confirm the ARI episode was correctly triggered.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
66
Status: Approved, Date: 11 October 2022
to local/site specific guidelines. If a sample tests positive for SARS CoV 2, the participant will be referred to their own healthcare
provider for locally approved diagnostic test and further management, in accordance with local/site specific guidelines.
In the setting that the site confirms that the reported symptoms do not qualify as an ARIepisode,
or that an ARI episode has ended despite long-term ongoing symptoms above baseline, the site
staff can manually end an ARI episode. For all ARIs, a start date of the ARI should be entered into
the eCRF. For all RSV, hMPV, or influenza-mediated ARIs, an end date of the ARI should be
entered in the eCRF. For ARIs that are RSV, hMPV and influenza negative, the date that the site
ends the ARI (after the RT-PCR test results are known) should also be entered in the eCRF.
Procedures for Participants who Experience an ARI Episode
When any participant experiences any symptoms of an ARI (see Appendix 5 Definition of Acute
Respiratory Infection for Participants Aged ≥60 Years), the following will take place:
 
The participant should indicate on the ARI Surveillance Assessment that the participant is
experiencing new onset or worsening (in setting that baseline symptoms are present)
symptoms of an ARI, ideally on the day of symptoms onset.
 
The participant will contact the site as soon as possible if the participant experiences any
symptoms suggestive of an ARI (ie, sore throat, nasal congestion, cough, short of breath,
coughing up phlegm [sputum], wheezing), or the site will contact the participant by telephone
or telemedicine, ideally within 24 hours if new onset or worsening of ARI symptoms are
recorded in the eDiary and the participant has not called the site. During this telephone or
telemedicine contact, the site may confirm if the reported symptoms qualify as ARI episode,
in order to determine whether to proceed with the ARI procedures. The site should enter an
ARI start date in the eCRF. The participant will then be reminded to:
 
On ARI Days 1 and 2 (day of ARI onset and day thereafter)
Complete the RiiQ (Appendix 8) in the eDiary every evening (preferably), beginning on the
evening of the day of symptom onset (ARI Day 1).
In addition to the RiiQ on those days, the eDiary will also ask participants to complete the
following scales:
o EuroQoL, 5-Dimension, 5-Level (EQ-5D-5L) (Appendix 9)
o Patient Global Impression of Health (PGI-H) scale,
o Patient Global Impression of Severity (PGI-S) scale,
o Patient Global Impression of Change (PGI-C) scale, and
o Return to Usual Health question (Appendix 10).
Note that the PGI-C scale and Return to Usual Health question will not be completed on
ARI Day 1.
Collect a nasal swab at home on the day of symptom onset or the day thereafter (ARI
Day 1-2). If the participant requires it, the participant’s caregiver can assist the participant
to collect the nasal swab. Ensure the nasal swab collected at home is provided to the study
staff within 4 days (preferably) after collection.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
67
Status: Approved, Date: 11 October 2022
 
From ARI Day 3 Until the Diagnostic Results Are Known
Continue completing the RiiQ (Appendix 8) (until RT-PCR results known, see below), in
the eDiary every evening (preferably).
Note that the RiiQ needs to be completed only once per day, ie, either at home or during the
site visit, if applicable.
Continue completing the following scales (until RT-PCR results known, see below),
consisting of:
o EuroQoL, 5-Dimension, 5-Level (EQ-5D-5L) (Appendix 9)
o Patient Global Impression of Health (PGI-H) scale,
o Patient Global Impression of Severity (PGI-S) scale,
o Patient Global Impression of Change (PGI-C) scale, and
o Return to Usual Health question (Appendix 10).
Note that the scales need to be completed only once per day, ie, either at home or during the
site visit, if applicable.
 
The site should schedule a clinical visit with the participant between 2 and 4 days after ARI
symptom onset (ARI Day 3-5), or if a site visit is not feasible, a member of the study staff
could visit the participant at home (or at the hospital, if needed) during this time frame.
 
To reduce the burden on the participant and to avoid collection of blood samples (ie, serology
blood sample, whole blood PAXgene sample and whole blood sample with PROT1 stabilizer),
not related to an RSV/hMPV/influenza related ARI, participants and investigators can choose
the preferred option during each Day 3-5 visit between: 1) Collecting blood samples before
the nasal swab samples are tested or in the setting where a sputum sample is collected,
independent of the RT-PCR results; and 2) Collecting blood samples after the nasal swab RT-
PCR results are available, according to nasal swab test results, and for ARIs where there is no
sputum sample collection. If this is the preferred option by the participant and investigator,
the participant will wait at the site for the time needed to test the swab samples (estimated
time: 2 hours). In this scenario, if the swab samples are negative for RSV, hMPV and influenza
AND if no sputum sample can be collected, the blood sample collection at the ARI Day 3-5
timepoint can be omitted. If the swab samples are positive for RSV, hMPV or influenza OR
if sputum sample is collected, the blood samples collection must be performed. Whenever a
sputum sample is collected during the ARI Day 3-5 visit, the blood sample must still be
collected as the RT-PCR test on the sputum sample will be performed at the central laboratory
and not on site.
 
During the ARI Day 3-5 visit, vital signs will be measured, and a nasal swab, a sputum sample
(in participants with a productive cough, when possible), and blood samples (to measure the
immune responses at the time of exposure and for exploration of biomarkers that correlate
with respiratory infection and disease severity) may be taken by a member of the study staff.
 
Ideally within 24 hours after the ARI Day 3-5 visit (but no later than 48 hours after the ARI
Day 3-5 visit), a qualified member of the study staff will perform a local RT-PCR of all
available nasal swabs with the BioFire® Filmarray Respiratory panel, which will be provided
to all sites (both US and non-US); changes to the process might be implemented at the local
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
68
Status: Approved, Date: 11 October 2022
level based on local requirements. Participants will subsequently be contacted by telephone
or telemedicine and given further instructions, as detailed below, on how to further proceed
based on the outcome of the RT-PCR tests.
Sputum samples (where applicable) will be sent to the central laboratory for testing using the
BioFire Filmarray Pneumonia (PN) panel. For all ARI episodes where a sputum sample is
collected, the ARI episode will be followed up until ARI resolution (ie, with daily
questionnaires and an ARI Day 29 visit), independent of the test results from the collected
nasal swabs. Participants who are under self-isolation because of a (possible) positive test for
SARS-CoV-2 will not come to the site for ARI Day 3-5 assessments but will self-collect the
nasal swab.
 
In the unlikely event where at least one nasal swab from an ARI episode cannot be tested at
the site with the BioFire Filmarray  Respiratory  panel (eg, in the setting of instrument
malfunction, unavailability of the device in the country/territory or at the site, or shortage of
testing reagents at the site), this sample(s) should be sent to the central laboratory for testing
with the BioFire Filmarray Respiratory panel, and the ARI episode will be followed up until
ARI resolution (ie, with daily questionnaires and an ARI Day 29 visit), independent of the
results from other collected samples for that ARI episode. Further details on the strategy for
local site and central testing of the nasal swabs and sputum samples are provided in
Section 8.2.4 below.
 
For participants with a positive SARS-CoV-2 test and a negative test for RSV, hMPV, and
influenza, the collection of ARI data by the study site will be stopped for the ARI episode.
The participant will be informed by telephone or telemedicine contact that they can stop filling
out the daily ARI episode questionnaires, and the site will end the ARI episode and return the
participant to ARI surveillance with twice weekly reminders. Participants who have a positive
SARS-CoV-2 RT-PCR test as part of the study procedures should be referred to their own
healthcare provider for follow-up diagnostics and further management, in accordance with
local/site specific guidelines. Participants whose standard-of-care testing during an ARI
episode is positive for SARS-CoV-2, or who have been in contact with someone that tested
positive for SARS-CoV-2 and therefore must self-isolate according to the local guidelines,
will not come to the site for ARI Day 3-5 assessments but will self-collect the nasal swab. In
this circumstance, other ARI Day 3-5 assessments (vital signs, sputum sample and blood
samples) might not be performed.
Participants with positive RT-PCR results for RSV (or hMPV or influenza) should keep on
filling out the daily ARI episode questionnaires until resolution of the ARI episode
independently of any other co-infection (including SARS-CoV-2).
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
69
Status: Approved, Date: 11 October 2022
Further Procedures for Participants with an RSV, hMPV, or Influenza-mediated ARIa
Continue completing the RiiQ (Appendix 8) until resolution* of the ARI episode in the
eDiary every evening (preferably).
Continue completing the following scales until resolution* of the ARI episode:
o EuroQoL, 5-Dimension, 5-Level (EQ-5D-5L) (Appendix 9),
o Patient Global Impression of Health (PGI-H) scale,
o Patient Global Impression of Severity (PGI-S) scale,
o Patient Global Impression of Change (PGI-C) scale, and
o Return to Usual Health question (Appendix 10).
* A resolved ARI episode is defined as 2 consecutive days with no symptoms listed on the
RiiQ Symptom Scale, or, for participants who have RiiQ symptoms at baseline (assessed
pre-vaccination), 2 consecutive days where all symptoms on the RiiQ Symptom Scale have
returned to the same severity level as reported at baseline (or lower). After resolution of
the ARI episode, the participant will return to ARI surveillance with twice weekly
reminders.
On ARI Day 29 (±7 days), participants will be asked to return to the site if a sputum sample
was provided by the participant at ARI Day 3-5 visit, regardless of the swab RT-PCR test
results, AND/OR at least one of the nasal swab samples collected could not be tested at the
study site with the BioFire Filmarray Respiratory panel (RT-PCR test) and had to be shipped
for central laboratory test AND/OR at least one nasal swab sample had a positive RT-PCR
result for either RSV, hMPV, or influenza when tested at the study site. The ARI Day 29
visit can take place by telephone or telemedicine contact. During this visit:
o The MRU questionnaire will be completed (Appendix 11) based on interview with the
participant.
o Participants will complete the RiiQ (Appendix 8), the EQ-5D-5L (Appendix 9) and each
of the PGI scales and the Return to Usual Health question (Appendix 10) on the
participant’s eDiary.
o The site staff will also collect information on days missed from work (Appendix 12) and
on complications, hospitalizations and concomitant medications related to the ARI and
record in the eCRF.
o If the ARI episode is resolved by the time of the ARI Day 29 visit, the investigator should
enter the end date in the CRF during the ARI Day 29 visit.
o If the ARI episode is ongoing at the time of the ARI Day 29 visit, the participant should
continue filling in the ARI questionnaires until the end of the ARI episode. The
a 
Participants with a sputum sample taken and participants with at least one nasal swab that cannot be tested at the site with a
BioFire Filmarray Respiratorypanel will follow the same procedures as participants with a RT PCR positive for RSV, hMPV,
or influenza mediated ARI.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
70
Status: Approved, Date: 11 October 2022
investigator should follow up with the participant to collect the ARI end date and enter it
in the CRF.
 
For medically-attended RT-PCR  positive for RSV, hMPV, or influenza-mediated ARIs,
including those resulting in hospitalization, a standard question list will be provided
(Appendix 6) to collect additional information on any other diagnostic tests (eg, chest x-rays,
spirometry, pulmonary function tests, etc.) or on interventions during the clinical course of
the ARI.
Further Procedures for Participants with an ARI that is Negative for RSV, hMPV, and
Influenza
 
The site will end the ARI episode and inform the participant by telephone or telemedicine that
they can stop filling out the daily ARI episode questionnaires.
 
The date that the site ends the ARI (after the RT-PCR test results are known) should also be
entered in the eCRF.
 
The participant will return to ARI surveillance with twice weekly reminders 10 days after the
day of onset of this ARI.
All Participants
At the “End of first RSV season” visit, all participants will complete the RiiQ, the PGI-H and the
EQ-5D-5L in their eDiary.
Throughout the study, if an expected eDiary recording has been missed by a participant, the
participant or the participant’s caregiver should be contacted the next morning to confirm that the
eDiary is being completed as required.
Throughout the study, RT-PCR results from the nasal swabs and sputum sample (where available)
will be used to determine whether the infection was caused by RSV. If at least one of these samples
is positive for RSV, the collected information will be applied against the clinical case definition.
Local RT-PCR testing will be performed using the BioFire Filmarray Respiratory panel. In case
the BioFire Filmarray Respiratory panel cannot be performed at the site (eg, in the setting of
instrument malfunction, unavailability of the device in the country/territory  or at the site, or
shortage of testing reagents at the site), central RT-PCR testing with the BioFire Filmarray
Respiratory panel will be used as a backup option.
For participants hospitalized with symptoms of an ARI, confirmation of RSV infection using a
locally approved RT-PCR test at the hospital laboratory can also be used. These results will be
used in the primary analysis only if approved by an independent expert with expertise in diagnostic
testing. The approval of the RT-PCR results by the expert will be based on the specifications of
the test performed, the qualifications of the testing laboratory and the procedures followed in the
laboratory.
8.1.1. 
Respiratory Infection Intensity and Impact Questionnaire (RiiQ™v2)
The RiiQ will be used to identify possible ARI episodes, to define cases of RSV-mediated LRTD
(for participants with RT-PCR-confirmed RSV infection), to evaluate severity of RSV disease
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
71
Status: Approved, Date: 11 October 2022
episodes and assess the impact of an ARI episode on the participant’s daily life (see Appendix 8).
The RiiQ was adapted for RSV based on the Flu-iiQ™ originally developed and validated for the
monitoring of influenza symptoms and their impact in vaccine studies (Osborne 2011, van
Essen 2014).The RiiQ includes 3 additional lower respiratory tract symptoms common in patients
with RSV-related illness and 1 additional daily activity item to address limitations in opportunity
for activity for patients hospitalized for treatment of RSV disease.
The RiiQ asks participants to rate level of severity or impairment on a 4-point scale with higher
scores indicating greater severity or negative impact of an ARI episode. The questions ask the
participants to report symptoms at their worst during the past 24 hours to monitor the severity of
RSV-related illness, but also identify pre-existing symptoms and functional limitations at baseline
associated with comorbidities common in adults at risk for more severe illness due to RSV
infection.
The RiiQ consists of 4 scales that are scored separately:
 
RiiQ Symptom Scale (Question 1). Each symptom is rated on the following scale: 0 None,
1 Mild, 2 Moderate, and 3 Severe. The RiiQ Symptom scale can be scored as a mean of all
scores (Total Symptom Score) or 2 subscales scores, Respiratory Symptoms and Systemic
Symptoms:
 
The RiiQ Respiratory Symptoms Subscale score is the mean of 6 symptoms, ie, 2 upper
respiratory tract infection (URTI) symptoms (Nasal congestion and Sore throat) and
4 lower respiratory tract infection (LRTI) symptoms (Cough, Wheezing, Shortness of
breath, and Coughing up phlegm/sputum)
 
The RiiQ Systemic Symptom subscale score is the mean of 7 systemic symptoms
(Headache, Feeling feverish, Neck pain, Body aches and pain, Fatigue/tiredness,
Interrupted sleep, and Loss of appetite).
 
RiiQ Impact Scales (Questions 2 to 4):
 
RiiQ Impact on Daily Activity scale (Question 2) consists of 7activities. Ability to
perform each activity item is rated on the following scale: 0 No difficulty, 1 Some
difficulty, 2 Moderate Difficulty, and 3 Great difficulty. Scale scores are calculated as
the mean of all 7 items (range 0-3).
 
RiiQ Impact on Emotions scale (Question 3) consists of rating 4 negative emotions, rated
on the following scale: 0 Not at all, 1 Somewhat, 2 Moderately, and 3 Extremely.
Scale scores are calculated as the mean of all 4 items (range 0-3).
 
RiiQ Impact on Relationships scale (Question 4) consists of 5 problems that a respiratory
infection may cause in relationships with others, rated on the following scale: 0 Not at
all concerned, 1 Somewhat concerned, 2 Moderately concerned, and 3 Extremely
concerned) with scale scores calculated as the mean of all 5 items (range 0-3).
In the setting of the present study, only the RiiQ Symptom Scale (Question 1) and the RiiQ Impact
on DailyActivities Scale (Question 2) are being used (Appendix 8).
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
72
Status: Approved, Date: 11 October 2022
8.1.2. 
EuroQoL, 5-Dimension, 5-Level Questionnaire
The EQ-5D-5L questionnaire is a standardized instrument for use as a measure of health outcome,
primarily designed for self-completion by the participant. It consists of the EQ-5D-5L descriptive
system and EQ visual analogue scale (VAS) (see Appendix 9). The descriptive system includes
the following dimensions: mobility, self-care, usual activities, pain/discomfort, and
anxiety/depression. Each of these 5 dimensions is divided into 5 levels of perceived problems
(1 no problem, 2 slight problems, 3 moderate problems, 4 severe problems; 5 extreme
problems) (https://euroqol.org/eq-5d-instruments/).
8.1.3. 
Patient Global Impression Scores
Patient Global Impression scores (Appendix 10) developed for this study will be collected. The
questions will be used to evaluate overall health.
 
Patient Global Impression of Health (PGI-H). Participants report their overall impression of
their health status today on the following scale: 0 Very good, 1 Good, 2 Fair, 3 Poor,
4 Very poor.
 
Patient Global Impression of Severity (PGI-S). Participants rate the severity of their
respiratory illness on the following scale: 0 None, 1 Mild, 2 Moderate, 3 Severe.
 
Patient Global Impression of Change (PGI-C). Participants rate the amount of change in their
health each day during an ARI episode on the following scale: -3 Much better, -2 Somewhat
better, -1 A little better, 0 About the same, 1 A little worse, 2 Somewhat worse, 3 Much
worse
 
Return to Usual Health. Participants are being asked whether they have returned to their usual
health after developing symptoms suggesting an ARI.
8.2. 
Efficacy Assessments
In the below sections, new onset or worsening of symptoms is defined as follows:
 
Symptoms present during an ARI episode but not at the baseline assessment will be considered
as symptoms with a new onset.
 
Symptoms present at the baseline assessment that become worse (higher severity) during the
ARI episode will be considered as worsening symptoms.
The Day 1 assessment is considered the baseline.
Confirmation of RSV infection by RT-PCR for the primary endpoint will be done in nasal swabs
or sputum samples.
 
Confirmation of RSV infection by RT-PCR in nasal swabs will be performed at the site
laboratory with the BioFire Filmarray Respiratory panel, which will be provided to all sites
(both US and non-US). Both the home swab and the site swab will be analyzed at the site. The
central RSV confirmation of the nasal swab with the BioFire Filmarray Respiratory panel,
will not be taken into account for the primary endpoint, unless in the unlikely event where at
least one nasal swab from an ARI episode cannot be tested at the site (eg, in the setting of
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
73
Status: Approved, Date: 11 October 2022
instrument malfunction, unavailability of the device in the country/territory or at the site, or
shortage of testing reagents at the site).
 
Confirmation of RSV infection by RT-PCR in sputum samples (when collected) will be
performed in the central laboratory with the BioFire Filmarray PN panel.
 
For participants hospitalized with symptoms of an ARI, confirmation of RSV infection using
a locally approved RT-PCR test at the hospital laboratory can also be used. These results will
be used in the primary analysis only if approved by an independent expert with expertise in
diagnostic testing. The approval of the RT-PCR results by the expert will be based on the
specifications of the test performed, the qualifications of the testing laboratory and the
procedures followed in the laboratory.
One positive sample (defined as any sample with a value above the limit of detection) is sufficient.
The first occurrence of a considered endpoint is defined as the start of the first episode of the
endpoint in the study (regardless of RSV A or B strain, unless otherwise specified).
8.2.1. 
Case Definition for RT-PCR-confirmed RSV-mediated LRTD
A participant will be considered to have RT-PCR-confirmedRSV-mediated LRTD if the following
criteria are met:
 
New onset or worsening from baseline of 3 or more of the below symptoms as captured on
the RiiQ at the same assessment time point:
 
Cough
 
Short of breath
 
Coughing up phlegm (sputum)
 
Wheezing
AND
 
Confirmation of RSV by RT-PCR in one or more of the nasal swabs, or in the sputum sample
(when available)
Counting of the number of symptoms with new onset or worsening will be done per assessment.
If a participant completed the RiiQ more than once per day, the case definitions cannot be met by
combining symptoms from different assessments on that day, the required number of symptoms
must be attained at one assessment.
This definition will be programmed. Prior to database lock  for all planned analyses (see
Section 9.5), the CEC will review in a blinded manner all available data of all RSV-mediated ARIs
and will confirm if the above criteria are met. If the CEC confirms that the above criteria for LRTD
are met, the case will be counted as a primary endpoint in the statistical analysis.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
74
Status: Approved, Date: 11 October 2022
8.2.2. 
Case Definition for RT-PCR-confirmed RSV-mediated ARI
A participant will be considered to have RT-PCR-confirmed RSV-mediated ARI if the following
criteria are met:
 ARI episode initiated by the participant and confirmed by the site with symptoms consistent
with an ARI (new symptoms or worsening from baseline of at least one of the symptoms as
captured on the RiiQ):
 
Sore throat
 
Nasal congestion
 
Cough
 
Short of breath
 
Coughing up phlegm (sputum)
 
Wheezing
AND
 Confirmation of RSV by RT-PCR in one or more of the nasal swabs, or in the sputum sample
(when available)
8.2.3. 
Predefined Clinically Relevant Disease Associated with RT-PCR-
confirmed RSV-mediated ARI
A participant will be considered to have clinically  relevant disease with specific parameters
associated with an RT-PCR-confirmed RSV-mediated ARI if the following criteria are met:
 The participant has an RT-PCR-confirmed RSV-mediated ARI as defined in Section 8.2.2
 Any of the following is associated with the ARI:
 
Hospitalization
 
Emergency department visit
 
Per clinical judgement, at least one of the following complications: asthma exacerbation,
COPD  exacerbation, respiratory distress, bronchitis, bronchial hyperreactivity, CHF
exacerbation, cardiac arrhythmia, renal impairment or the presence of X-ray or
radiological confirmed pneumonia, respiratory arrest and/or failure, pulmonary
embolism, pleural effusion, atelectasis, acute coronary events, acute cerebrovascular
events, altered mental status, seizure, syncope, systemic inflammatory response
syndrome (SIRS), new neurological deficit, asthenia, dehydration or metabolic
disturbances
 
For measurements at the site, decreased oxygen saturation is defined as oxygen saturation
of <92% for participants with a baseline oxygen saturation of≥92% at randomization; for
participants with baseline oxygen saturation <92%, decreased oxygen saturation is
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
75
Status: Approved, Date: 11 October 2022
defined as a ≥3% decrease in their oxygen saturation from baselinea.
Decreased oxygen saturation based on measurements during medically-attended ARI (ie,
hospitalization) is defined as oxygen saturation of <92% supporting LRTD.
 
Tachypnea (at least emerging Grade 2, see Appendix 4: Toxicity Grading Scale)
 
Need of supplemental oxygen
 
Hypotension (emerging Grade 3, see Appendix 4: Toxicity Grading Scale)
 
Pulmonary function test results supporting diagnosis of LRTD
 
Arterial blood gas results supporting diagnosis of LRTD
8.2.4. 
Diagnosis of RSV and Other Respiratory Infections
After initiation of an ARI episode, the nasal swabs taken after symptom onset (ARI Day 1-2 and
ARI Day 3-5) will be analyzed at the local study site using an FDA -approved rapid RT-PCR based
assay (BioFire Filmarray  Respiratory  panel) to determine any positivity for RSV, hMPV, or
influenza virus. In the unlikely event where at least one nasal swab from an ARI episode cannot
be tested at the site with the BioFire Filmarray Respiratory panel (eg, in the setting of instrument
malfunction, unavailability of the device in the country/territoryor at the site, or shortage of testing
reagents at the site), this sample(s) should be sent to the central laboratory for testing with the
BioFire Filmarray Respiratory panel.
For ARIs where the optional sputum sample is collected at ARI Day 3-5, this sputum sample will
be shipped for central testing using the FDA-approved rapid RT-PCR-based assay (BioFire
Filmarray PN panel) to determine any positivity for RSV, hMPV, or influenza virus.
All nasal swabs tested at the local study sites which are positive for RSV will be shipped to the
central laboratory for positive confirmation of RSV, using the BioFire Filmarray  Respiratory
panel.
For all RSV positive samples (based on the results from both local testing for nasal swabs and
central testing on sputum samples and nasal swabs), the RSV subtype and viral load will be also
determined using the DDL qRT-PCR assay for RSV. For nasal swabs and sputum samples, the
presence of other respiratory pathogens will also be determined by the BioFire Filmarray
Respiratory panel and the BioFire Filmarray PN panel, respectively.
Table 3 shows strategy for local study site and centralized testing of the nasal swabs and sputum
samples collected.
a 
Based on vital signs collected at baseline and during the ARI at the site.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
76
Status: Approved, Date: 11 October 2022
Table 3: 
Strategy for Local Site and Central Testing of the Nasal Swabs and Sputum Samples
Centrala/ 
Local Site Testing
Purpose of the Test 
Type of Samples
BioFire Filmarray RP2.1 EZd 
Local site 
Presence of RSV, hMPV or 
influenza virus
All nasal swab samples
BioFire Filmarray Pneumonia panel Central 
Presence of RSV, hMPV or 
influenza virus
All sputum samples
BioFire Filmarray 2.0 
Central 
Presence of RSV, hMPV or 
influenza virus
Nasal swab samplesb
BioFire Filmarray 2.0 
Central 
Confirmation of RSV  
Nasal swab samplesc
DDL qRT PCR  
Central 
RSV subtype, viral load 
RT PCR+ nasal swabs
and sputum samples
Note: The BioFire Respiratory panel and Pneumonia panel will test for a panel of viral and bacterial infections.
a 
DDL Diagnostic Laboratory (Rijswijk, The Netherlands)
b 
Test will be performed on nasal swab samples that cannot be tested at the site only
c 
Confirmation will be performed on local site RSV positive nasal swab samples only
d 
When the BioFire Filmarray RP2.1 EZ panel is not locally approved in a region and its use under research use only is not
approved in that region, another locally approved version may be used at the local site, provided that it has an equivalent
performance for detecting the pathogens of interest (ie, RSV, hMPV and influenza) with the BioFire Filmarray RP2.1 EZ
panel.
Participants will remain blinded as to the outcome of RSV, hMPV and influenza RT-PCR test
results until study unblinding and the test results should only be disclosed in the event of safety
concerns, with the exception of SARS-CoV-2 infection. If a sample tests positive for
SARS-CoV-2, the participant will be referred to their own healthcare provider for locally approved
diagnostic test and further management, in accordance with local/site specific guidelines. RT-PCR
test results related to the detection of other respiratory pathogens can be communicated to the
participants.
For participants hospitalized with symptoms of an ARI, confirmation of RSV infection using a
locally approved RT-PCR test at the hospital laboratory can also be used. These results will be
used in the primary analysis only if approved by an independent expert with expertise in diagnostic
testing. The approval of the RT-PCR results by the expert will be based on the specifications of
the test performed, the qualifications of the testing laboratory and the procedures followed in the
laboratory. In these instances, attempts will be made to obtain a sample to ship to the central
laboratory for positive confirmation of the RSV infection with the BioFire Filmarray Respiratory
assay, RSV subtyping, viral load using the DDL qRT-PCR assay, and, if applicable, viral
sequencing.
8.3. 
Immunogenicity Assessments
Blood samples will be collected from all participants for humoral immunogenicity assessments
before and 14 days after vaccination, and at 1 year after vaccination for the analysis of correlates
of risk of RSV disease and correlates of protection.
For participants in the Immuno Subset (consisting of at least 360 participants, of whom ~50% will
be at increased risk for severe RSV disease and ~50% will be 75 years or older), blood will be
collected for analysis of humoral and cellular immune responses before study vaccination and at
2, 12, and 24 weeks, and 1 and 1.5 years after vaccination.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
77
Status: Approved, Date: 11 October 2022
Immunogenicity assessments may include (but are not limited to) the assays summarized below.
Humoral Assays 
Purpose
Secondary endpoints
RSV neutralization A 
Analysis of neutralizing antibodies to an A strain
F protein antibodies 
(ELISA; pre F and/or post F)
Analysis of antibodies binding to RSV F protein in pre fusion and/or post fusion form
Exploratory endpoints
RSV strain cross neutralization 
Analysis of cross neutralizing antibodies to B and/or a different A strain(s) using virus
neutralization assays and other surrogate antibody binding assays
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, epitope mapping, Ig isotype, functional VNAs to other respiratory viruses, and
antibody assessments for antibody repertoire
ADCC=antibody dependent cell mediated cytotoxicity, ADCP=antibody dependent cellular phagocytosis,
ELISA =enzyme linked immunosorbent assay, F=fusion, Ig=immunoglobulin, VNA=virus neutralizing antibody
Note: Antibody analyses may be performed in nasosorption samples and serum.
Cellular Assays a 
Purpose
Secondary endpoints
IFN γ ELISpot 
T cell IFN γ responses to RSV F protein peptides
Exploratory endpoints
Immunophenotyping 
May include analysis of T cell and B cell responses to RSV F protein peptide
stimulated PBMC (including, but not limited to, CD4+/CD8+, Th1/Th2, IL 2, IFN γ,
TNF α, activation markers and memory)
Immune repertoire analysis 
May include using antigen specific single cell sequencing or bulk sequencing in
order to assess T cell and B cell repertoire analysis
a 
Cellular assays will be performed in the Immuno Subset only where PBMCs are collected.
ELISpot=enzyme linked immunospot, F=fusion; IFN γ=interferon gamma, IL 2 =interleukin 2, PBMC=peripheral blood
mononuclear cells, TNF α=tumor necrosis factor alpha
Nasosorption samples using synthetic absorptive matrix (SAM) will be collected from Immuno
Subset participants prior to vaccination and at the 2 weeks and 1-year post-vaccination visits and
will be used for immunogenicity assessments that may include antigen-specific immunoglobulins
(ie, IgG and IgA), microbiome, and other viral pathogen analyses.
The blood samples that are collected between 2 and 4 days after symptom onset (ARI Day 3-5)
from participants with an RSV, hMPV, or influenza-mediated ARI episode will be assayed by
serology (which may include pre-F/post-F enzyme-linked immunosorbent assay [ELISA] and
RSV VNA, as available and applicable) to assess immune responses and correlates that are
associated with RSV infection. The samples will also be used for exploration of biomarkers that
correlate with RSV infection and RSV disease severity (which may include RT-PCR for RSV,
ribonucleic acid [RNA] transcriptomics to assess gene regulation [clusters] and expression
patterns, cytokine/chemokine-dependent immunophenotyping, and immune repertoire analysis, as
available and applicable).
8.4. 
Safety Assessments
For All Participants
All (S)AEs and special reporting situations related to study procedures or to non-investigational
(concomitant) Janssen products will be collected from ICF signature onwards until the end of the
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
78
Status: Approved, Date: 11 October 2022
study for all participants. All other SAEs and AESIs (see Section 8.5.6) will be collected from
administration of study vaccine (Day 1) until 6 months after vaccination. AEs leading to
discontinuation from the study will be collected for the duration of the study. All COVID-19 cases
will be collected for all participants for the duration of the study.
ARIs and complications related to RSV, hMPV, and influenza-mediated ARIs that classify as
SAEs will be captured in all participants and reported as SAEs in the eCRF continuously from the
time ofvaccination until 24 months after vaccination.
All participants will be closely observed for a minimum of 15 minutes after vaccination to monitor
for the development of any acute reactogenicity. This post-vaccination observation period should
be extended for participants whom in the investigator’s opinion would require further observation
or for any occurrence of a localized reaction or (minor) systemic symptoms during the post-
vaccination observation that require monitoring for any progression.
For Participants in the Safety Subset
Additional procedures will be carried out in the Safety  Subset participants; ~50% of the
participants in the Safety Subset will be at increased risk of severe RSV disease and ~50% will be
75 years or older (Section 6.3, Measures to Minimize Bias: Randomization and Blinding). Safety
Subset participants will have provided consent for the additional study proceduresa:
 
At the end of the 15-minute observation period, vital signs (body temperature, blood pressure,
heart rate, respiratory rate, oxygen saturation) will be obtainedb, and any unsolicited and
solicited localand systemic AEs will be documented in the eCRF by study personnel.
 
Participants will record solicited local (at the injection site) AEs, solicited systemic AEs, and
body temperatures in the eDiary, beginning on the evening of the vaccine dosing day and on
a daily basis for the following 7 days. If a solicited local or systemic AE is not resolved within
7 days after vaccination (Day 8), safety follow-up should be performed until the symptom
resolves. The study-site personnel will be instructed to record the date of last symptoms and
maximum severity until resolution in the source document and eCRF.
 
All other AEs (unsolicited) and special reporting situations will be reported from the time of
vaccination through the following 28 days. Participants will be contacted by telephone or
telemedicine at 28 days (+3 days) after vaccination to collect information on unsolicited AEs
and associated concomitant medications.
 
All ARIs and all complications related to RSV, hMPV, and influenza-mediated ARIs that do
not classify as SAEs will be reported as AEs in the eCRF from the time ofvaccination through
the following 28 days.
For more details on AE reporting, refer to Section 8.5, Adverse Events, Serious Adverse Events,
and Other Safety Reporting. In addition to AE reporting, the study includes the following safety
evaluations of safety according to the timepoints provided in the Schedule of Activities.
a 
Note that participants can participate in both the Immuno Subset and the Safety Subset.
b 
Actual values (normal and abnormal) will only be documented in the eCRF for body temperature.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
79
Status: Approved, Date: 11 October 2022
8.4.1. 
Physical Examinations
At any clinic visit, an abbreviated, symptom-directed physical examination may be performed if
deemed necessary by the investigator based on any clinically relevant issues, clinically relevant
symptoms, and medical history.
Physical examinations will be performed bythe investigator or appropriately trained delegate. Any
clinically relevant abnormalities or changes in severity noted during the review of body systems
should be documented in the eCRF as an AE or SAE if it meets the criteria for an AE or SAE
according to the protocol reporting requirements.
8.4.2. 
Vital Signs
Vital signs will be collected prior to vaccination for all participants:
 
Heart rate, respiratory rate, sitting systolic blood pressure, sitting diastolic blood pressure
Note: vital signs will also be collected post-vaccination from participants in the Safety Subset.
 
Body temperature (oral route preferred, or in accordance with the local standard of care).
Note: Additional temperature recordings will be collected from participants in the Safety
Subset (until 7 days post-vaccination in the eDiary).
 
Oxygen saturation (SpO2)
 
Height (at screening only) and weight
At non-vaccination visits, vital signs will be measured if deemed necessary by the investigator.
Any clinically relevant abnormalities or changes in severity should be documented in the eCRF as
an AE or SAE if it meets the criteria for an AE or SAE according to the protocol reporting
requirements.
8.5. 
Adverse Events, Serious Adverse Events, Adverse Events of Special
Interest, and Other Safety Reporting
Timely, accurate, and complete reporting and analysis of safety information, including (S)AEs,
AESIs (including potential AESIs, refer to Section 8.5.6) and Product Quality Complaints (PQCs),
from clinical studies are crucial for the protection of participants, investigators, and the sponsor,
and are mandated by regulatory agencies worldwide. The sponsor has established Standard
Operating Procedures in conformity with regulatory requirements worldwide to ensure appropriate
reporting of safety information; all clinical studies conducted by the sponsor or its affiliates will
be conducted in accordance with those procedures.
Further details on AEs, SAEs, AESIs, and PQCs can be found in Appendix 3: Adverse Events,
Serious Adverse Events, Adverse Event of Special Interest, Product Quality Complaints, and Other
Safety Reporting: Definitions and Procedures for Recording, Evaluating, Follow-up, and
Reporting.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
80
Status: Approved, Date: 11 October 2022
8.5.1. 
Time Period and Frequency for Collecting Adverse Event, Serious
Adverse Event, and Adverse Event of Special Interest Information
All Adverse Events
AEs and special reporting situations, whether serious or non-serious, that are related to study
procedures or that are related to non-investigational sponsor products will be reported from the
time a signed and dated ICF is obtained until the end of the study/early withdrawal.
Clinically relevant medical events not meeting the above criteria and occurring between signing
of ICF and moment of vaccination will be collected on the Medical History eCRF page as
pre-existing conditions.
Solicited AEs, collected through an eDiary, will be recorded from the time of vaccination until 7
days post-vaccination for Safety Subset participants.
All other unsolicited AEs and special reporting situations, whether serious or non-serious, will be
reported from the time of vaccination until 28 days post-vaccination for Safety Subset participants.
Unsolicited AEs with the onset date outside the timeframe defined above (>28 days after study
vaccination), which are ongoing at Month 12, should be recorded as such  for Safety Subset
participants only.
All AEs leading to discontinuation from the study (regardless of the causal relationship) are to be
reported from administration of study vaccine until the end of the study. The sponsor will evaluate
any safety information that is spontaneously reported by an investigator beyond the time frame
specified in the protocol.
All COVID-19 cases will be collected for all participants for the duration of the study.
All AEs will be followed until resolution or until clinically stable.
Serious Adverse Events
All SAEs within 6 months after vaccination, as well as PQCs, occurring during the study must be
reported to the appropriate sponsor contact person by study site personnel within 24 hours of their
knowledge of the event.
SAEs, including those spontaneously reported to the investigator within 6 months after vaccination
must be reported. The sponsor will evaluate any safety information that is spontaneously reported
by an investigator beyond the time frame specified in the protocol.
Information regarding SAEs will be transmitted to the sponsor using the SAE form and Safety
Report form of the eCRF, 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). Telephone reporting should be the
exception and the reporter should be asked to complete the appropriate form(s) first.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
81
Status: Approved, Date: 11 October 2022
AESIs
TTS is considered to be an AESI. Thrombotic events and/or thrombocytopenia (defined as platelet
count below the lower limit of normal [LLN] range for the testing lab) are considered to be
potential AESIs. All AESIs, including potential AESIs, will be reported to the sponsor within
24 hours of awareness from the moment of first study vaccination until 6 months after study
vaccination (see Section 8.5.6).
8.5.2. 
Method of Detecting Adverse Events, Serious Adverse Events, and
Adverse Events of Special Interest
Care will be taken not to introduce bias when detecting (S)AEs or AESIs. Open-ended and
nonleading verbal questioning of the participant is the preferred method to inquire about AE
occurrence.
Solicited Adverse Events (for Participants in the Safety Subset Only)
Solicited AEs are used to assess the reactogenicity of the study vaccine and are predefined local
(at injection site) and systemic events for which the participant is specifically questioned and
which are noted by participants in their eDiary.
After vaccination, participants will remain under observation at the study site for at least
15 minutes and will be closely observed by the study staff. Solicited AEs will be documented by
study site personnel following the 15 minutes post-vaccination observation period for participants
in the Safety Subset.
In addition, participants in the Safety Subset will record solicited signs and symptoms in an eDiary
for 7days post-vaccination. Participants will be provided with an eDiary and instructions on how
to complete the eDiary (refer to Overview in Section 8, Study Assessments and Procedures).
Electronic diary information will be transferred from the eDiary source to the sponsor. After
review and verbal discussion of the initial eDiary entries with the participant, the investigators will
complete their own assessment in the relevant sections of the eCRF. Once a solicited sign or
symptom from an eDiary is considered to be of severity Grade 1 or above, it will be recorded as a
solicited AE.
Solicited Injection Site (Local) Adverse Events
Participants in the Safety Subset will be asked to note in the eDiary occurrences of injection site
pain/tenderness, erythema and swelling at the study vaccine injection site daily for 7 days post-
vaccination (day of vaccination  and the subsequent 7days). The extent (largest diameter) of
erythema and swelling should be measured (using the ruler supplied) and recorded daily. Case
definitions for solicited injection site events can  be found in the references (Gidudu 2012,
Kohl 2007).
Solicited Systemic Adverse Events
Participants in the Safety Subset will be instructed on how to record daily temperature using a
thermometer provided for home use. Participants should record the temperature in the eDiary in
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
82
Status: Approved, Date: 11 October 2022
the evening of the day of vaccination, and then daily for the next 7days approximately at the same
time each day. 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° C, as recorded in at least one
measurement (Marcy 2004).
Participants in the Safety Subset will also be instructed on how to note signs and symptoms in the
eDiary on a daily basis for 7days post-vaccination (day of vaccination and subsequent 7days) for
the following events: fatigue, headache, nausea, and myalgia.
Unsolicited Adverse Events
Unsolicited AEs are all AEs for which the participant is not specifically questioned in the
participant eDiary.
For details regarding AESIs, refer to Section 8.5.6.
8.5.3. 
Follow-up of Adverse Events, Serious Adverse Events, and Adverse
Events of Special Interest
The investigator is obligated to perform or arrange for the conduct of supplemental measurements
and evaluations as medically indicated to elucidate the nature and causality of the (S)AE, AESI,
or PQC as fully as possible. This may include additional laboratory tests or investigations,
histopathological examinations, or consultation with other healthcare professionals.
AEs, including pregnancy, will be followed by the investigator as specified in Appendix 3:
Adverse Events, Serious Adverse Events, Adverse Event of Special Interest, Product Quality
Complaints, and Other Safety Reporting: Definitions and Procedures for Recording, Evaluating,
Follow-up, and Reporting.
8.5.4. 
Regulatory Reporting Requirements for Serious Adverse Events
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 suspected unexpected serious adverse reactions (SUSARs). The investigator (or
sponsor where required) must report SUSARs to the appropriate IEC/IRB that approved the
protocol unless otherwise required and documented by the IEC/IRB. A SUSAR will be reported
to regulatory authorities unblinded. Participating investigators and IEC/IRB will receive a blinded
SUSAR summary, unless otherwise specified.
8.5.5. 
Pregnancy
All initial reports of pregnancy in participants or partners of male participants must be reported to
the sponsor by the study site personnel within 24 hours of their knowledge of the event using the
appropriate pregnancy notification form. Abnormal pregnancy outcomes (eg, spontaneous
abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy) are considered SAEs and
must be reported using an SAE reporting form.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
83
Status: Approved, Date: 11 October 2022
If a participant becomes pregnant during the study, follow-up information regarding the outcome
of the pregnancy will be required. If the partner of a male participant becomes pregnant during the
study, follow-up information regarding the outcome of the pregnancy will be requested upon the
consent provided by the partner.
8.5.6. 
Adverse Events of Special Interest
AESIs (including potential AESIs) are significant AEs that are judged to be of special interest
because of clinical importance, known or suspected class effects, or based on nonclinical signals.
AESIs and potential AESIs will be carefully monitored during the study by the sponsor. AESIs
and potential AESIs must be reported to the sponsor within 24 hours of awareness irrespective
regardless of seriousness (ie, serious and nonserious AEs) or causality following the procedure
described above for SAEs.
AESIs must be reported using the AESI form in the eCRF using the eCRF completion guidelines.
Specific requirements for the AESI are described below.
8.5.6.1. 
Thrombosis with Thrombocytopenia Syndrome
TTS is a syndrome characterized by a combination of both a thrombotic event and
thrombocytopenia. (American Society of Hematology 2021, Brighton Collaboration 2021). As
described in Section 2.2, vaccine-induced TTS has been observed very rarely following
vaccination with the Janssen COVID vaccine.
TTS is considered to be an AESI in this study. Because this syndrome is very rare and not
completely understood, all cases of thrombosis and/or thrombocytopenia should be reported to the
sponsor within 24 hours of awareness using the AESI form. Each case will be reviewed to identify
a vaccine-induced TTS case. A potential TTS case is defined as:
 
Thrombotic events: suspected deep vessel venous or arterial thrombotic events as detailed in
Section 10.14, Appendix 14,
and/or
 
Thrombocytopenia, defined as platelet count below LLN for the testing lab
Responsibilities and procedures for identification, review, and evaluation ofpotential TTS cases
are outlined in a separate Thrombosis with Thrombocytopenia Syndrome Adjudication Committee
Charter.
Symptoms, signs, or conditions suggestive of a thrombotic event or thrombocytopenia should be
recorded and reported as a potential AESI even if the final or definitive diagnosis has not yet been
determined, and alternative diagnoses have not yet been eliminated or shown to be less likely.
Follow-up information and final diagnoses, if applicable, should be submitted to the sponsor as
soon as they become available.
In the event of thrombocytopenia, study site personnel should report the absolute value for the
platelet count and the reference range for the laboratory test used.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
84
Status: Approved, Date: 11 October 2022
For either a thrombotic event or thrombocytopenia, complete blood count including platelet count
and a coagulation profile available from participant’s medical records should be entered in the
eCRF. In case these results are not available at the time of the event report in the eCRF, the study
site is recommended to obtain a complete blood count including platelet count and a coagulation
profile (to be performed at the local laboratory). Repeat testing at the local laboratory may be
requested for confirmation upon sponsor discretion.
Aliquots of serum samples collected for immunogenicity test can be reconverted for participant’s
safety purposes upon sponsor request (Table 4).
Table 4 provides non-exhaustive list(s) of laboratory tests that may be performed (upon sponsor
request).
In addition, the sponsor may request additional laboratory tests on additional blood samples
obtained as soon as possible after the potential AESI onset, either during an ad hoc unscheduled
visit or the next scheduled visit, whichever comes first. Table 5 provides a non-exhaustive list of
laboratory tests that may be requested by the sponsor in case of potential AESI reporting, for which
additional samples may be needed.
Table 4: 
Laboratory Tests That May Be Performed Upon Sponsor Request on Immunogenicity Samples
Collected on Day 1 and 15 After Potential AESI Reporting
Parameters 
Timepoints
 Serum samples for assay such as but not limited to:
o Heparin Induced Thrombocytopenia (HIT)/PF4 Ab, IgG·(HIT assay)
If the above test is positive, also consider:
 Anti-cardiolipin antibody
 Beta-2 glycoprotein
 Days 1 and 15 visits (aliquots
of serum samples collected for
immunogenicity test can be
reconverted for participant’s
safety purposes).
Note: results of the test should be reported in the narrative of the event and/or in the TTS AESI pages of the eCRF.
Table 5: 
Laboratory Tests That May Be Requested by the Sponsor to be Performed at the Central
Laboratory After Potential AESI Reporting
Parameters 
Timepoints
 Serum/plasma/whole blood samples for coagulation-related assays such as 
but not limited to: 
o Fibrinogen 
o D-dimer· 
o Lupus anticoagulant· 
o Anti-cardiolipin antibody
o Beta-2 glycoprotein·
o Heparin Induced Thrombocytopenia (HIT)/PF4 Ab, IgG·(HIT assay)
o Platelet activation assay (if HIT/PF4 is positive)
o Homocysteine·
o COVID-19 serological test
 As soon as possible after the
potential AESI onset upon
sponsor request (during an ad
hoc unscheduled visit or the
next scheduled visit, whichever
comes first). 
Note: results of the test should be reported in the narrative of the event and/or in the TTS AESI pages of the eCRF.
Irrespective on samples for central laboratory tests collection, relevant data for TTS assessment reported in the
medical records of the participant should be reported in eCRF narrative of the event and/or in the TTS AESI pages
of the eCRF.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
85
Status: Approved, Date: 11 October 2022
AESIs, including potential AESIs, will require enhanced data collection and evaluation. Every
effort should be made to report as much information as possible about the event to the sponsor in
a reasonable timeframe. Relevant laboratory results can be entered on the AESI form in the eCRF,
using the eCRF completion guidelines.
If the investigator is not the treating physician, every effort should be made to collect the
information requested in the form from the treating physician and enter the available information
in the eCRF.
If an event meets the criteria for an SAE (Section 10.3.1), it must be reported using the same
process as for other SAEs.
Treatment and Follow-up Recommendation
The medical management of thrombotic events with thrombocytopenia is different from the
management of isolated thromboembolic diseases. Study site personnel and/or treating physicians
should follow available guidelines for treatment of thrombotic thrombocytopenia (eg, American
Society of Hematology 2021, British Society for Haematology 2021, CDC 2021). The use of
heparin may be harmful and alternative treatments may be needed. Consultation with a
hematologist is strongly recommended.
8.6. 
Medical Resource Utilization and Health Economics
MRU data associated with medical encounters will be collected by the investigator and study site
personnel at 28 days after onset of each ARI episode (ARI Day 29 ±7 days) for all ARIs that are
followed until their resolution (ie, for RSV, hMPV, or influenza-positive ARIs, for ARIs with
sputum collection, and for ARIs where at least one nasal swab cannot be tested at the site with the
BioFire Filmarray Respiratory panel). Protocol-mandated procedures, tests, and encounters are
excluded. The data collected may be used to conduct exploratory economic analyses and will
include:
 
Number and type of medical consultations (including primary care and specialist visits),
whether these consultations were related to ARIs and a reason for each medical encounter
 
Number and duration of hospital and/or institutional care admissions (total days length of stay,
including duration by wards; eg, intensive care unit), whether these admissions were related
to ARIs, and a reason for each admission
 
Number and type of emergency department visits and whether these emergency department
visits were related to ARIs
 
Where applicable, information on whether supplemental oxygen or mechanical ventilation
was used
 
Whether participation in the study (ie, contact with healthcare providers during study visits
and procedures) increased or decreased the participant’s use of medical resources outside of
the study
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
86
Status: Approved, Date: 11 October 2022
8.7. 
Participant Medical Information Prior to, During and After the Study
(Real-world Data)
For participants (from the US only) who have provided consent for this, medical data (electronic
health records, claims and laboratory data from other care settings) from 5 years prior to study
enrollment until 5 years after study completion may be accessed utilizing tokenization and
matching procedures (ie, the generation of anonymous identifiers or “tokens” [hashed and
encrypted combinations of identifying elements] to allow linking of participant data from different
sources without compromising the participant’s confidentiality). These data may be used for
exploratory analyses to enhance our understanding of the impact of prior medical history on the
response to immunization and the impact of immunization on efficacy and duration of efficacy as
well as adverse events that may occur during and after completion of the study. The analyses will
be described in detail in a dedicated analysis plan.
9. 
STATISTICAL CONSIDERATIONS
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 efficacy, safety and immunogenicity
data is outlined below. Specific details will be provided in the Statistical Analysis Plan. This
section focusses on the key statistical considerations for the Global cohort. Analyses for local
cohort enrollment will be described separately, but local cohorts will also be included in the
primary analysis and final analysis if their enrollment started prior to the database cut-off of the
primary analysis or final analysis, respectively.
9.1. 
Statistical Hypotheses
The study is designed to test the primary hypothesis of VE against RT-PCR-confirmed
RSV-mediated LRTD in the PPE population.
 
The hypothesis for the primary endpoint is:
 
Null hypothesis: the VE against RT-PCR-confirmed RSV-mediated LRTD of Group 1 vs
placebo is ≤20%.
 
Alternative hypothesis: the VE against RT-PCR-confirmed RSV-mediated LRTD of
Group 1 vs placebo is >20%.
Refer to Section 9.3 for the definition of the PPE population and to Section 9.4.1.1 for details on
the primary endpoint. The analysis plan for the interim and primary analyses is provided in
Section 9.5.1.
The study is successful if:
 
The LL of the 95% 2-sided confidence interval (CI, potentially corrected as described in
Section 9.4.1.3) around the VE (1-relative risk rate) calculated from the Exact Poisson
regression model is above 20% and additionally a point-estimate of VE >50% is observed for
Group 1
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
87
Status: Approved, Date: 11 October 2022
IfVE for the primary endpoint is demonstrated, the following secondary endpoints will be tested:
1. First occurrence of any RT-PCR-confirmed RSV ARI, with onset at least 14 days after
dosing of study vaccine
2. First occurrence of any RT-PCR-confirmed RSV-mediated LRTD during the second year,
with onset after study Day 365
3. First occurrence of any RT-PCR-confirmed RSV ARI during the second year, with onset
after study Day 365
4. First occurrence of predefined clinically relevant disease associated with RT-PCR-
confirmed RSV-mediated ARI over the whole study, with onset at least 14 days after
dosing of study vaccine
The following null and alternative hypothesis will be used for those secondary endpoints:
 
The null hypothesis is that the VE for the considered secondary endpoint is ≤0%.
 
The alternative hypothesis is that the VE for the considered secondary endpoint is >0%.
Formal inference for secondary endpoint #1, as part of the testing strategy, will occur at the time
of the primary analysis. For secondary endpoints 2, 3, and 4, the formal inference as part of the
testing strategy will only occur at study end. For more details on the secondary endpoints and the
testing strategy, see Section 9.4.1.2 and Section 9.4.1.3.
9.2. 
Sample Size Determination
9.2.1. 
Efficacy
The required sample size was determined using the following assumptions:
 
a VE for RT-PCR-confirmed RSV-mediated LRTD of 65% during the first year and during
the second year,
 
an incidence of RT-PCR-confirmed RSV-mediated LRTD of at least 0.2% during the first
RSV season (2021-2022) and an incidence of 0.5% in later RSV seasons in 60+-year-old
placebo recipients,
 
a randomization ratio of2:1 (active vaccine: placebo),
 
an analysis plan as described in Section 9.5.1
 
a 1-sided α of 2.5% (potentially corrected for multiplicity), and
 
10% of exclusions (due to dropout, major protocol violations, etc.) per year
Simulations performed in R show that with ~15,340 participants in the active vaccine group
(Group 1) and ~7,670 participants in the placebo group (Group 2) the study has at least 90% total
power to demonstrate VE against the primary endpoint statistically significant >20% and a point-
estimate for VE >50%. This leads to a sample size of ~23,000 participants.
This sample size is also required to reach approximately 80% power for the secondary endpoint of
first occurrence of RT-PCR-confirmed RSV-mediated LRTD during the second year.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
88
Status: Approved, Date: 11 October 2022
Operating characteristics of the methods used with the sample size will be described in a separate
modeling and simulations report.
In the proof-of-concept study (VAC18193RSV2001), which was performed in participants of at
least 65 years of age, the observed VE for RSV-mediated LRTD (Case Definition 1) was 80% with
corresponding 94.211% CI (52.2%; 92.2%). To account for uncertainty, a VE of 65% is used for
the sample size determination. Further, an incidence of 1.1% for the primary endpoint selected for
Phase 3 (Case Definition 1) was observed in study VAC18193RSV2001. The assumed incidence
for the present study is decreased to 0.5% during the second RSV season to account for seasonal
variability (Belongia 2018), and the potential impact of social distancing measures (anti-COVID)
on the RSV incidence. As the impact of the anti-COVID measures on the first RSV season is
unknown, the study covers for an incidence of RSV-mediated LRTD during the first RSV season
of at least 0.2%.
Additional local cohort enrollment beyond the Global cohort enrollment, may be allowed if
required by local health authorities for the purpose of local regulatory approval consideration. Any
such local cohort enrollment, not part of the Global cohort, will be analyzed as a separate dataset
apart from the Global cohort, but they will also be included in the primary analysis and final
analysis if their enrollment started prior to the database cut-off of the primary analysis or final
analysis, respectively.
9.2.2. 
Immunogenicity
Immunogenicitywill be assessed in the Immuno Subset, including~360participants in Europe and
North America, of whom ~240 are active study vaccine participants. Additionally,
immunogenicity may be assessed in ~120 from each of the other regions in the setting that these
are part of the study. Approximately 50% of the participants in the Immuno Subset in each region
will be at increased risk of severe RSV disease and ~50% will be 75 years or older. If further local
immunogenicity data are needed per country/territory specific guidelines, this will be described in
a separate document.
Table 6 shows the actual distance from the mean to the limits of the 95% CI around the actual
value at Day 15 for the different assays, accounting for ~10% of discontinuations.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
89
Status: Approved, Date: 11 October 2022
Table 6: 
Distance from the Mean to the Limits of 95% CI Around the Actual Value at Day 15 for Pre-F
ELISA, VNA, and ELISpot
N 
(Active 
Group)* 
Pre-F ELISA  
(SD=1.3) 
VNA  
(SD=1.5) 
ELISpot
(SD=1.2)
Distancea
from 
Mean to 
Limits 
95% CI 
95% CI if 
Observed 
Mean is eg, 
6,000 
Distancea 
from Mean 
to Limits 
95% CI 
95% CI if 
Observed 
Mean is eg, 
6,500 
Distancea 
from Mean 
to Limits 
95% CI 
95% CI if
Observed
Mean is eg,
400
All 
240 
0,174 
(5318;6769) 
0,201 
(5655;7472) 
0,161 
(358;447)
Increased 
Risk  
120 
0,248 
(5052;7125) 
0,286 
(5331;
7925) 
0,229 
(341;469)
* Not yet including Southern Hemisphere and eventual other local 89ucces data.
CI=confidence interval, ELISA=enzyme-linked immunosorbent assay, ELISpot=enzyme-linked immunospot,
SD=standard deviation, VNA=virus neutralization assay
a 
Calculated on the log2-scale.
9.2.3. 
Safety
While mild to moderate reactogenicity (local injection site and systemic reactions) are expected,
AEs that preclude further vaccine administration (if applicable) are not anticipated.
Solicited and unsolicited AEs will be captured in the Safety Subset, including ~1,050 participants
from Europe and North America (~700 active and ~350 placebo participants). Additionally,
solicited and unsolicited AEs will be captured in ~300 participants from each of the other regions
in the setting that these are part of the study. Approximately 50% of all participants in the Safety
Subset in each region will be at increased risk of severe RSV disease and ~50% of all participants
in the Safety Subset in each region will be 75 years or older.
If further local solicited and unsolicited AE data are needed per country/territory  specific
guidelines, this will be described in separate documentation.
SAEs/AESIs will be captured in all participants. Outside the Safety Subset and Immuno Subset,
no cap is installed on the number of participants at increased risk of severe RSV disease. It is
expected that participants at increased risk of severe RSV disease will represent ~25% of the
overall population, so it is estimated that SAE/AESI information will be available for ~3,835
participants at increased risk of severe RSV disease in the active vaccine group (Group 1).
For SAEs/AESIs, the observation of 0 events in the database would be associated with 95%
confidence that the true rate is less than 0.025%. Assuming that ~3,835 participants in the total
active vaccine group (Group 1) are at increased risk of severe RSV disease, the observation of
0 SAEs/AESIs in participants at increased risk of severe RSV disease would be associated with
95% confidence that the true rate is less than 0.1%.
For unsolicited AEs, which are captured in the Safety Subset of at least 700 active participants
from Europe and North-America, the observation of 0 unsolicited AEs in the active group would
be associated with 95% confidence that the true rate is less than 0.5%. In active participants at
increased risk of severe RSV disease (~350 active participants from Europe and North-America),
this would be less than 1%.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
90
Status: Approved, Date: 11 October 2022
Table 7 shows the probabilities of observing at least one event (solicited, unsolicited or serious
AE) in one of the arms at given true AE rates (overall population and participants at increased risk
of severe RSV disease).
Table 7: 
Probability of Observing at Least One Adverse Event or Serious Adverse Event at a Given True
Adverse Event Rate in the Active Vaccine Group (Group 1)
Probability of Observing at Least One Adverse Event in N Participants
True
Adverse 
Overall 
Increased Risk
Event Rate 
Solicited and 
Unsolicited 
Adverse Events 
N=700a 
Serious 
Adverse Events 
in Group 1 
N=15,340 
Solicited and 
Unsolicited  
Adverse Events 
N=350a 
Serious
Adverse Events in
Group 1
N=3,835b
0.01%  
7%  
78%  
3% 
32%
0.1% 
50% 
100%  
30% 
98%
0.5% 
97%  
100%  
83%  
100%
1%  
100%  
100%  
97%  
100%
2.5% 
100%  
100%  
100%  
100%
9.3. 
Populations for Analyses
Vaccination assignment will follow the as-treated principle. Note that all analyses will focus on
the participants enrolled in the Global cohort. Any local cohort enrolment beyond what is included
in the Global cohort will be analyzed as a separate dataset apart from the Global cohort, but they
will also be included in the primary analysis and final analysis if their enrollment started prior to
the database cut-off of the primary analysis or final analysis, respectively.
For purposes of analysis, the following populations are defined:
 
Full Analysis Set (FAS): will include all participants with a documented vaccine
administration, regardless of the occurrence of protocol deviations. The FAS is the primary
safety population. The analysis of solicited and unsolicited AEs will be restricted to a subset
of the FAS (ie, the Safety Subset).a
 
Per-protocol Efficacy (PPE) population includes all randomized and vaccinated participants,
excluding those with major protocol deviations (MPDs) expecting to impact the efficacy
outcomes. Only data of the year (first year, second year) in which the MPD impacting efficacy
occurs and the data of later years are excluded. The list of MPDs to be excluded from efficacy
analyses will be specified in the Statistical Analysis Plan or major protocol violation criteria
document, which will be finalized before database lock and unblinding. Participants with an
RT-PCR-confirmed RSV-mediated ARI with onset within 14 days after vaccination,
participants who discontinue within 14 days after vaccination, and participants who received
vaccination within 14 days of the database cut-off date will be excluded from the PPE
a 
The specification of this subset for analysis of solicited and unsolicited AEs does not preclude the investigator from reporting
an AE in any participant if the investigator considers the event to be of clinical relevance and/or related to the study vaccine.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
91
Status: Approved, Date: 11 October 2022
population. This analysis set will be used for analyses over the whole study period (up to
database cut-off).
For analyses focusing on the first year, the PPE population is similar but only excludes MPDs
occurring during the first year.
For analyses focusing on the second year, participants with MPDs expecting to impact the
efficacy outcomes and occurring during the second year will be additionally excluded from
the PPE set defined above, as well as participants who discontinued prior to Day 365.
The PPE population is the primary efficacy population. Sensitivity efficacy analyses will be
performed on the FAS.
 
Per-protocol Immunogenicity (PPI) population: will include all randomized and vaccinated
participants who are part of the Immuno Subset and for whom immunogenicity data are
available. Samples taken after a participant experiences an MPD expected to impact the
immunogenicity outcomes will be excluded from the PPI analysis. The list of MPDs to be
excluded from the immunogenicity analysis will be specified in the Statistical Analysis Plan
or major protocol violation criteria document, which will be finalized before database lock
and unblinding.
In addition, for participants who experience an  RT-PCR-confirmed RSV-mediated ARI,
samples taken after the RSV infection will not be taken into account in the assessment of the
immunogenicity.
 The PPI population is the primary immunogenicity population. For key tables, sensitivity
immunogenicity analyses will be performed on the FAS, including participants who are part of
the Immuno Subset for whom immunogenicity measures are available. Excluded samples may
be taken into account as well in the sensitivity analysis.
9.4. 
Statistical Analyses
The Statistical Analysis Plan will be finalized prior to the first database lock (primary or interim
analysis) and it will include a more technical and detailed description of the statistical analyses
described in this section. This section is a summary of the planned statistical analyses of the most
important endpoints including primary and secondary endpoints.
The analysis plan for the interim and primary analyses is provided in Section 9.5.1.
9.4.1. 
Efficacy Analysis
9.4.1.1. 
Primary Endpoint
The analysis of the primary endpoint will evaluate the first occurrence of RT-PCR-confirmed
RSV-mediated LRTD (for the definition, see Section 8.2, Efficacy Assessments) with onset of at
least 14 days after vaccination in the active vaccine group compared to the placebo group in the
PPE population. Time at risk will also be taken into account. The null hypothesis of LL ≤20% for
RT-PCR-confirmed RSV-mediated LRTD will be tested versus the alternative hypothesis of LL
>20%. Additionally, the observed VE should be >50%.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
92
Status: Approved, Date: 11 October 2022
Exact Poisson regression will be fitted with the event rate, defined as the number of cases (with
onset at least 14 days after vaccination) over the follow-up time (off-set) as dependent variable
and the vaccination group, being at increased risk of RSV disease, and age stratum (both variables
as stratified; see Section 6.3) as independent variables. Each participant will be taken into account
in the model with one observation indicating whether they had a case or not, the vaccination group,
the stratification factors, and the follow-up time.
The follow-up time is defined as the time between 14 days post-vaccination and occurrence of the
first event. For non-cases, it is the time between 14 days post-vaccination and the database cut-off
date of the analysis. However, for participants who discontinued or completed the study before
that date and before having an event, follow-up time is defined as the time between 14 days post-
vaccination and the date of last contact.
For participants with an MPD impacting efficacy during the second year, only the first year data
are taken into account: for cases during the first year, the follow-up time is defined as the time
between 14 days post-vaccination and occurrence of the first event. For non-cases, it is the time
between 14 days post-vaccination and the Day 365 visit. Thus, all participants will be included in
the analysis according to their follow-up time.
The study is 92uccessfull if:
 
The LL of the 95% 2-sided CI (potentially corrected as described in Section 9.4.1.3) around
the VE (1-relative risk rate) calculated from the Exact Poisson regression model is above 20%
and additionally a point-estimate of VE >50% is observed for Group 1
Sensitivity Analyses
As a sensitivity analysis, the above model will be repeated based on the FAS, not taking into
account the restriction on the onset (at least 14 days). Additional sensitivity analyses will include:
 
An exact binomial test, which does not take into account strata or follow-up time, based on
the PPE population and the FAS. The VE ( 1-relative risk) and the corresponding corrected
2-sided CI based on the exact binomial will be calculated as well. The same alpha as in the
primary analysis will be used for calculating the CI.
 
If the primary analysis is performed in 2023, an exact Poisson model similar to the primary
analysis will be performed including an interaction term between the treatment group and the
year variables.
The analysis of the primary endpoint will be repeated, but participants with RSV infection and a
co-infection with at least one other respiratory virus (ie, confirmed using the BioFire Filmarray
Respiratory panel for nasal swabs, or the BioFire Filmarray PN panel for a sputum sample, when
available) will not be considered as a case for that episode, as the etiology of symptoms will be
indeterminate. Additionally, the analysis of the primary endpoint will be repeated, taking into
account onlythe RT-PCR test results fromthe study-specified BioFire Filmarray Respiratorypanel
for nasal swabs and the BioFire Filmarray PN panel for a sputum sample, when available (ie,
excluding hospital test results with a locally approved RT-PCR test for participants who were
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
93
Status: Approved, Date: 11 October 2022
hospitalized). Details on the strategy for local site and central testing of the nasal swabs and sputum
samples are provided in Section 8.2.4. Another sensitivity analysis will focus on the programmed
case definition of RT-PCR confirmed RSV-mediated LRTD, not taking into account the CEC
adjudication.
9.4.1.2. 
Secondary Efficacy Endpoints
The following endpoints are considered confirmatory secondary endpoints:
1. First occurrence of any RT-PCR-confirmed RSV ARI, with onset at least 14 days after dosing
of study vaccine
2. First occurrence of any RT-PCR-confirmed RSV-mediated LRTD during the second yearwith
onset after study Day 365
3. First occurrence of any RT-PCR-confirmed RSV ARI during the second year with onset after
study Day 365
4. First occurrence of predefined clinically relevant disease associated with RT-PCR-confirmed
RSV-mediated ARI over the whole study, with onset at least 14 days after dosing of study
vaccine
A similar Exact Poisson regression model as for the primary endpoint will be used for the analyses
of the secondary endpoints focusing on VE (secondary endpoints #1, #2, #3 and #4). For those
secondary endpoints that focus on VE during the second year (secondary endpoints #2 and #3) the
follow-up time is defined as follows: For cases occurring after Day 365, the follow-up time is
defined as the time between Day 365 and the occurrence of the event. For non-cases, the follow-up
time is the time between Day 365 and the minimum of the database cut-off date of the analysis
and the completion or discontinuation date. Participants who discontinue prior to the Month
12/Day 365 visit or have a major protocol deviation impacting efficacy during the first year are
excluded from this analysis.
For secondary endpoint #1 the follow-up time is defined similarly as for the primary endpoint.
The following non-confirmatory secondary endpoint will also be evaluated:
 
The AUC of the change from baseline in RiiQ Total Symptom score in participants with an
RT-PCR-confirmed RSV-mediated ARI over the whole study
Descriptive statistics will be calculated restricting to participants with RT-PCR-confirmed RSV-
mediated ARI during the whole study.
A Wilcoxon Rank Sum test will be performed to test the null hypothesis that the distribution in
both groups is the same versus the alternative hypothesis that the distribution shifted towards a
lower AUC in the change from baseline in RiiQ Total Symptom score (ie, more reduced symptom
scores). This is a non-confirmatory endpoint and will not be taken  into account in the testing
strategy, no alpha correction will be applied.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
94
Status: Approved, Date: 11 October 2022
9.4.1.3. 
Testing Strategy for Primary and Confirmatory Secondary Endpoints
The VE against the primary endpoint will be tested using the significance level α’ (1 or 2 or 3
orα4), as defined in Section 9.5.1. If the LL of the exact 2-sided CI (1-2×α’) for the VE (1-relative
risk rate) calculated from the Exact Poisson regression model, is above 20% and the observed VE
is above 50%, VE is demonstrated for the primary endpoint. If VE is demonstrated for the primary
endpoint, the above secondary endpoints will be tested according to the testing order displayed in
Table 8. The first secondary efficacy endpoint (first occurrence of any RT-PCR-confirmed RSV
ARI) is tested using the same significance level ’ as used for the primary endpoint. The Exact 2-
sided CI (1-2×α’) for the VE (1-relative risk rate) will be calculated from the Exact Poisson
regression model. If the LL of the CI is above 0%, VE will have been demonstrated for this
endpoint and the next endpoint in the testing strategy can be tested. The following secondary
endpoints (#2, #3, and #4) will be tested hierarchically at the end of the study at the full alpha
(α 2.5%), as indicated in the table below.
Table 8: 
Secondary Endpoints: Overview of the Testing Order, Timing of the Testing in the Testing
Strategy and the Corresponding Alpha
Secondary endpoint: first occurrence of  
Analysis timepoint in the 
testing strategy 
Alpha at which the endpoint is
tested
1. Any RT-PCR confirmed RSV ARI 
Time of primary analysis 
Alpha used at the primary
analysis
2. Any RT-PCR confirmed RSV LRTD  
during the second Year
End of the study  
2.5%
3. Any RT-PCR confirmed RSV ARI 
during the second Year
End of the study  
2.5%
4. Predefined clinically relevant disease 
associated with RT-PCR-confirmed
RSV-mediated ARI
End of the study  
2.5%
Second year starts at the D365 visit
9.4.1.4. 
Exploratory Endpoints
For the following exploratory endpoints, similar Exact Poisson regression models as for the
primary and secondary endpoints will be used and exact 2-sided 95% Cis for VE (1-relative risk
rate) will be calculated. For all exploratory endpoints related to influenza-mediated ARI and LRTD
only the proportion of participants meeting the respective endpoints will be summarized.
 
First occurrence of RT-PCR-confirmed RSV-mediated LRTD during the first year
 
First occurrence of RT-PCR-confirmed RSV-mediated ARI during the first year
 
First occurrence of RT-PCR-confirmed RSV-mediated LRTD by subtype (RSV A or RSV B)
 
First occurrence of RT-PCR-confirmed RSV-mediated ARIs by subtype (RSV A or RSV B)
 
First occurrence of complications associated with RT-PCR-confirmed RSV-mediated ARIs
RSV-mediated LRTD, influenza-mediated ARIs and hMPV-mediated ARIs
 
First occurrence of hospitalizations associated with RT-PCR-confirmed RSV-mediated ARIs
RSV-mediated LRTD, influenza-mediated ARIs and hMPV-mediated ARIs
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
95
Status: Approved, Date: 11 October 2022
 
First occurrence of pneumonia (radiological or X-ray confirmed) associated with RT-PCR-
confirmed RSV-mediated ARIs RSV-mediated LRTD, influenza-mediated ARIs and hMPV-
mediated ARIs
 
First occurrence of emerging therapeutic interventions of interest associated with RT-PCR-
confirmed RSV ARIs. The following are considered emerging therapeutic interventions of
interest:
 
New onset or increased dose (compared to baseline) of bronchodilator/nebulizer
treatment
 
New onset or increased dose (compared to baseline) of corticosteroid prescription
 
New onset or increased dose (compared to baseline) of antibiotic prescription
 
New onset or increased dose (compared to baseline) of antiviral prescription
 
First occurrence ofRT-PCR-confirmed hMPV-mediated ARI
 
First occurrence of RT-PCR-confirmed hMPV-mediated LRTD
Unless specifically mentioned otherwise, the Ves will be calculated for the above endpoints
occurring during the first year, and during the second year and over the whole study. The follow-
up time is determined in a similar way as for the primary and secondary endpoints.
If the primary analysis occurs before the end of the study, the secondary endpoints #2, #3 (provided
second year data are already available) and #4 might be analyzed descriptively at the time of the
primary analysis, VE with 95% CI will be calculated.
RSV A and RSV B viral load will be analyzed descriptively. More details on exploratory endpoints
will be provided in the Statistical Analysis Plan.
Exploratory endpoints related to disease severity in participants with RT-PCR-confirmed RSV-
mediated ARIs and in participants with RT-PCR-confirmed RSV-mediated LRTDs are:
 
The AUC of the change from baseline in RiiQ Total Symptom score*
* Note: Reduction of symptom severity in participants with an RT-PCR-confirmed RSV-
mediated ARI over the whole study is a non-confirmatory secondary endpoint.
 The time to return to usual health (based on this question from the PGI questionnaire).
The CEC review will also assess, independently and based on CRF/eDiary data, the severity of the
RT-PCR-confirmed RSV-mediated LRTDs. The CEC will use all information available for the
participants, including but not limited to MRU, presence of clinically relevant disease, use of
therapeutic interventions, and RiiQs, in order to make their adjudication.
The following endpoints will be calculated with similar Exact Poisson regression models as for
the primary and secondary endpoints:
 
First occurrence of an RT-PCR-confirmed RSV LRTDs assessed as at least mild, as at least
moderate and as at least severe by the CEC during the considered year:
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
96
Status: Approved, Date: 11 October 2022
 
with onset at least 14 days after dosing of study vaccine and prior to study Day 365 (first
year comparison)
 
with onset after study Day 365 (second year comparison)
 
with onset at least 14 days after dosing of study vaccine (whole study comparison)
For more details on these endpoints, see Section 8.1. These endpoints may be determined during
the first year, during the second year, and potentially over the whole study. For the AUC,
descriptive statistics will be calculated once restricting to participants with a RT-PCR-confirmed
RSV-mediated ARI in the considered period and once restricting to participants with RT-PCR-
confirmed RSV-mediated LRTD in the considered period. Additionally, these analyses will be
done by subtype (RSV A or RSV B).
For the time to return to usual health, a Kaplan Meier curve will be fitted and a hazard ratio with
corresponding 95% 2-sided CI will be calculated from a Cox proportional hazard model with group
as dependent variable. These analyses will be restricted once to participants with a RT-PCR-
confirmed RSV-mediated ARI in the considered period and once restricted to participants with
RT-PCR-confirmed RSV-mediated LRTD in the considered period. These analyses will be done
by subtype (RSV A or RSV B) as well.
9.4.2. 
Immunogenicity Analyses
No formal statistical testing of the immunogenicity data is planned. All immunogenicity analyses
will be performed on the PPI set. Key tables may be repeated for the FAS (including the samples
that are excluded from the PPI analysis).
Immunogenicity Subset
No formal hypothesis on immunogenicity will be tested. Descriptive statistics (such as geometric
mean and 95% CI for ELISA and RSV neutralization assay, andmedianand quartiles for interferon
gamma [IFN-γ] enzyme-linked immunospot [ELISpot]) will be calculated for continuous
immunogenicity parameters at all available timepoints. For the humoral assays, geometric mean
fold rises from baseline with 95% Cis may additionally be calculated. Baseline is considered as
the last available assessment before vaccination. Graphical representations of immunogenicity
parameters will be made as applicable.
The impact of baseline factors on the humoral and cellular responses will be explored graphically
or via descriptive statistics.
Correlates of Protection
If VE is demonstrated, correlates of protection will be further explored in samples collected from
all participants. Data from the current study will be used to confirm and refine the model found in
study VAC18193RSV2001. Immunogenicity markers are considered correlates of protection if
VE is explained through the effect of the vaccine on the immunogenicity markers. More details
with appropriate methods will be provided in a separate analysis plan.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
97
Status: Approved, Date: 11 October 2022
9.4.3. 
Safety Analyses
No formal statistical testing of safety data is planned. Safety data by vaccination group and based
on the FAS will be analyzed descriptively. The analysis of solicited and unsolicited AEs will be
restricted to a subset of the FAS (ie, the Safety Subset). For the analyses of AESIs, SAEs, and
COVID-related AEs, the entire FAS population will be used.
The impact of baseline factors (such as being at increased risk for severe RSV disease) may be
explored as well.
Adverse Events (Solicited and Unsolicited)
Solicited local (at injection site) and systemic AEs will be summarized descriptively. Solicited
AEs shown in the tables and listings will be based on the overall assessment of the investigator.
The overall frequencies by vaccine group as well as the frequencies according to severity and
duration will be described for solicited AEs. The number and percentages of participants with at
least one solicited local (at the injection site) or systemic AE will be presented. Frequencies of
unsolicited AEs, separately for all and vaccination-related only, will be shown by system organ
class and preferred term, while those of solicited AEs will be presented only by preferred term.
The verbatim terms used in the eCRF by investigators to identify AEs will be coded using the
Medical Dictionary for Regulatory Activities (MedDRA). Reported AEs with onset during the
active vaccination phase (ie, AEs occurring post vaccination up to 28 days post-vaccination) and
SAEs and AESIs will be included in the analysis. For each AE, the number and percentage of
participants who experience at least one occurrence of the given event will be summarized by
group.
Summaries, listings, datasets, or participant narratives may be provided, as appropriate, for those
participants who die, who discontinue the study (or vaccination, if applicable) due to an AE, or
who experience a severe AE or AESI or SAE or COVID-19 infection.
ARIs recorded as (S)AEs in the eCRF will be excluded from any (S)AE analysis if the laboratory
RT-PCR is subsequently found to be positive for RSV. ARIs 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.
Vital Signs
A tabulation of the distribution of body temperatures in the 7 days following vaccination will be
provided per half-degree intervals. Emerging vital sign abnormalities will be summarized based
on the planned visits. Clinically relevant abnormalities for systolic and diastolic blood pressure,
heart rate, respiratory rate, and oxygen saturation  collected during unscheduled visits will be
documented as AEs.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
98
Status: Approved, Date: 11 October 2022
9.4.4. 
Other Analyses
9.4.4.1. 
Patient-reported Outcomes
Changes from baseline in daily symptom severity reported by participants using the RiiQSymptom
Scale and changes from baseline functioning associated with ARI collected using the RiiQ Impact
Scales will be descriptively analyzed. The AUC of the change from baseline in Total Symptom
Score will be determined. For the analysis of this AUC, refer to Section 9.4.1.2. For other scores,
AUC may be calculated as well.
The Patient Global Impression Scales from ARI symptom onset to ARI symptom resolution will
be descriptively analyzed by group (active vaccine or placebo). AUCs may be calculated. For the
analysis of the time to return to usual health refer to Section 9.4.1.4.
EQ-5D-5L data will be analyzed descriptively by dimension (mobility, self-care, usual activities,
pain/discomfort, and anxiety/depression), single index value, and EQ-VAS, and summarized by
study vaccination group. Focus will be on participants with an RSV-confirmed ARI. This will be
further detailed in a Statistical Analysis Plan.
9.4.4.2. 
Medical Resource Utilization Analyses
MRU data will be descriptively summarized by vaccination group. A VE of emerging MRU
associated with an RT-PCR-confirmed RSV mediated ARI and of hMPV and influenza-mediated
respiratory infections may be calculated as well. This will be further detailed in the SAP.
9.5. 
Planned Analyses
9.5.1. 
Analysis Plan for the Interim and Primary Efficacy Analyses
The following describes the analysis plan for the interim analysis and the primary analysis. This
takes into account participants enrolled in the Global cohort. Any local cohort enrolment beyond
the Global cohort will be analyzed separately, except if individual participant enrollment started
before the database cut-off of the primary analysis.
The interim analysis plan is as follows:
 
Based on a database cut-offdate of15 September 2022, an IA by IDMC will be performed.
The IDMC will evaluate in an unblinded fashion if the LL of the (100-2×α1)% 2-sided CI
around the VE (1-relative risk rate) is above 20% and additionally a point-estimate of VE
>50% is observed for Group 1. If the success criteria are met, the sponsor will be notified.
The database used for the IDMC analysis will be unblinded for the sponsor and the primary
analysis will be performed by the sponsor at the same significance level (α1). If the success
criteria are not met, the participants will be followed further, and the same steps will be
performed at the following subsequent database cut-offs:
 
24 October 2022 with an alpha level α2
 
22 January 2023 with an alpha level α3
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
99
Status: Approved, Date: 11 October 2022
 
Provided no primary analysis occurred earlier, the primary analysis will be performed with
database cut-off30 April 2023 with alpha level α4
Figure 3 displays the interim and primary analysis plan.
If VE is not demonstrated to be significantly >20% with a point estimate >50% at the time of the
primary analysis, the study will be stopped.
The total alpha will be controlled at 2.5%. A Pocock-like alpha spending function as described by
DeMets (DeMets 1994) with a target number of events of 76 used to spend the alpha over the
different analyses. The different alphas to be used during every IA are shown above in Figure 3
and the calculations are explained below in Table 9.
Table 9: 
Alpha-spending at the Prespecified Analysis Timepoints
Alpha
Description ofhow to obtain alpha
α1 
Alpha obtained from Pocock-like alpha spending function with information fractions = [# RSV LRTD
events by 15 September 2022 / 76¥, 1]
α2 
Alpha obtained from Pocock-like alpha spending function with information fractions = [# RSV LRTD
events by 15 September 2022 / 76¥, # RSV LRTD events by 24 October 2022 / 76¥, 1]
α3 
Alpha obtained from Pocock-like alpha spending function with information fractions = [# RSV LRTD
events by 15 September 2022 / 76¥, # RSV LRTD events by 24 October 2022 / 76¥, # RSV LRTD
events by 22 Jan 2023 / 76¥, 1]
α4 
Alpha obtained from the remaining alpha to be spent (2.5% - total alpha spent during the interim
analyses) and the actual information fractions observed at all analyses. That is, the information fraction,
IF = [# RSV LRTD events by 15 September 2022 / # RSV LRTD events by 30 April 2023, # RSV
LRTD events by 24 October 2022 / # RSV LRTD events by 30 April 2023, # RSV LRTD events by 22
January 2023 /  # RSV LRTD events by 30 April 2023, 1]. The final alpha will be calculated using the
user-defined alpha spending function approach (Jennison 2000).
¥ 76  target sample size for 90% power with 65% VE. Note that if at any of the interim analyses 76 or more RSV LRTD events
have been observed, all remaining alpha will be spent and no further (interim) analyses for primary efficacy endpoint will be
performed.
At the time of the primary analysis, unblinded safety and efficacy data will be analyzed.
Immunogenicity data will be included if available.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
100
Status: Approved, Date: 11 October 2022
Figure 3: 
Interim and Primary Analysis Plan
For the first interim analysis, ARIs with an onset up to 1 September 2022 will be included and a database cut-off of 15 September 2022 will be used. For the second IA,
ARIs with an onset up to 10 October 2022 will be included and a database cut-off of 24 October 2022 will be used. For the third IA, ARIs with an onset up to 8 January
2023 will be included and a database cut-off of 22 January 2023 will be used. For the primary analysis, ARIs with an onset up to 15 April 2023 will be included and a
database cut-off of 30 April 2023 will be used.
DB= database, IA= interim analysis, IDMC = independent data monitoring committee, PA=primary analysis, PPE=Per-protocol Efficacy, POS= positive
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 11 October 2022
9.5.2. 
Additional Analyses
Provided the primary efficacy analysis has occurred earlier, the following exploratory analyses
might be performed depending on program needs:
 
Exploratory analysis with database cut-off of 31 January 2023: will include unblinded
efficacy data, including secondary endpoints #2, #3 and #4. The latter will be considered an
exploratory descriptive analysis. Formal inference of those endpoints as part of the testing
strategy will only occur at study end. Safety data will be included when needed.
Immunogenicity data will be included if available.
 
Exploratory analysis with database cut-off of 31 May 2023: will include unblinded efficacy
data, including secondary endpoints #2, #3 and #4. The latter will be considered an exploratory
descriptive analysis. Formal inference of those endpoints as part of the testing strategy will
only occur at study end. Safety data will be included when needed. Immunogenicity data will
be included if available.
Note: Analyses will include all participants enrolled prior to the primary analysis and participants
of local cohorts enrolled after the cut off of the primary analysis, provided that the local primary
analysis has already been conducted.
9.5.3. 
End-of-Study Analysis
The end of study analysis will include unblinded efficacy, safety and immunogenicity data. For
secondary endpoints #2, #3 and #4, formal inference as part of the testing strategy will occur during
this analysis.
Note:
The timing of the end-of-study analysis is based on last participant last visit of the Global cohort
but will include all participants of Global and local cohorts up to the cut-off of the end of study
analysis (see Section 4.1, Number of Participants, for cohort definitions).
9.6. 
Committees
9.6.1. 
Independent Data Monitoring Committee
An IDMC will be established as noted under Committees Structure in Appendix 2: Regulatory,
Ethical, and Study Oversight Considerations.
The study will be formally monitored by the IDMC. Ingeneral, the IDMC will monitor the safety
data on a regular basis to ensure the continuing safety of the participants. Enrollment will not be
paused during these safety reviews. The IDMC will review unblinded data. Conclusions from the
IDMC reviews will be communicated to the sponsor.
In addition, the IDMC will also formally monitor the primary efficacy endpoint at the timepoints
specified in Section 9.5, Planned Analyses. The IDMC will evaluate in an unblinded fashion if the
success criteria have been met.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 11 October 2022
The IDMC will assess the null hypothesis of LL ≤20% for VE against RT-PCR-confirmed RSV-
mediated LRTD versus the alternative hypothesis of LL >20%. For VE to be demonstrated for this
primary endpoint additionally, the observed VE should be >50%. Refer to Section 9.1 for details
on the hypothesis testing.
To maintain the blinding ofthe study to the clinical staff, investigators, and sponsor personnel, the
independent statistical support group will perform the IDMC safety analyses and will present the
results to the IDMC. A sponsor committee will be established for this study, which will be the
point of contact between IDMC and sponsor. After the review, the IDMC will make
recommendations regarding the continuation of the study.
The IDMC responsibilities, authorities, and procedures will be provided in its charter.
9.6.2. 
Clinical Event Adjudication Committee
Prior to database lock for all planned analyses (see Section 9.5), the CEC will review in a blinded
manner all available data of all RSV-mediated ARIs and will confirm if the RT-PCR-confirmed
RSV LRTD definition criteria were met. Further for all RT-PCR-confirmed RSV LRTD cases the
CEC will assess their severity (mild, moderate, severe or unable to assess). Details on the review
approach will be provided in the CEC Charter.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 11 October 2022
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Abbreviations
Ad26 
adenovirus serotype 26
ADCC  
antibody dependent cell mediated cytotoxicity
ADCP  
antibody dependent cellular phagocytosis
AE 
adverse event
AESI 
adverse event of special interest
ARI 
acute respiratory infection
AUC  
area under the curve
CEC  
Clinical Event Adjudication Committee
CHF  
congestive heart failure
CI 
confidence interval
COPD  
chronic obstructive pulmonary disease
COVID-19 
coronavirus disease 2019
CVST  
cerebral venous sinus thrombosis
CRF  
case report form(s) (paper or electronic as appropriate for this study)
DNA  
deoxyribonucleic acid
eCRF  
electronic case report form
eDC  
electronic data capture
ELISA  
enzyme-linked immunosorbent assay
ELISpot 
enzyme-linked immunospot (assay)
ePRO  
electronic patient-reported outcome
EQ-5D-5L 
EuroQoL, 5-Dimension, 5-Level (questionnaire)
EQ-VAS  
EQ visual analogue scale
F protein  
fusion protein
FAS  
Full Analysis Set
FDA  
(US) Food and Drug Administration
FOIA  
Freedom of Information Act
GCP  
Good Clinical Practice
GMT  
geometric mean titer
HITT  
heparin-induced thrombocytopenia and thrombosis
HIV  
human immunodeficiency virus
hMPV  
human metapneumovirus
HRQoL 
health-related quality of life
IA  
interim analysis
ICF  
informed consent form
ICH  
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for
Human Use
IDMC  
Independent Data Monitoring Committee
IEC  
Independent Ethics Committee
IF  
information fraction
IFN-γ 
interferon gamma
Ig 
immunoglobin
IL 
interleukin
IM  
intramuscularly
IRB  
Institutional Review Board
IWRS  
interactive web response system
LL 
lower limit
LRTD  
lower respiratory tract disease
LRTI 
lower respiratory tract infection
MAAE  
medically-attended adverse event
mAbs 
monoclonal antibodies
MedDRA  
Medical Dictionary for Regulatory Activities
MPD  
major protocol deviation
MRU  
medical resource utilization
NH  
Northern Hemisphere
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 11 October 2022
PBMC  
peripheral blood mononuclear cell
NSAIDs 
non-steroidal anti-inflammatory drugs
PGI-C 
Patient Global Impression of Change
PGI-H 
Patient Global Impression of Health
PGI-S 
Patient Global Impression of Severity
PPE 
Per-protocol Efficacy
PPI 
Per-protocol Immunogenicity
PQC  
Product Quality Complaint
preF  
pre-fusion conformation-stabilized F protein
PT  
preferred term
RiiQ™ 
Respiratory Infection Intensity and Impact Questionnaire (Version 2)
RNA  
ribonucleic acid
RSV  
respiratory syncytial virus
RT-PCR  
reverse transcriptase polymerase chain reaction
SAE 
serious adverse event
SAM  
synthetic absorptive matrix
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2
SH 
Southern Hemisphere
SUSAR  
suspected unexpected serious adverse reaction
TNF-α 
tumor necrosis factor alpha
TTS  
thrombosis with thrombocytopenia syndrome
URTI 
upper respiratory tract infection
US  
United States
VE 
vaccine efficacy
VITT  
vaccine-induced immune thrombotic thrombocytopenia
VNA  
virus neutralizing antibody
vp 
viral particles
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 11 October 2022
10.2. Appendix 2: Regulatory, Ethical, and Study Oversight Considerations
10.2.1. 
Regulatory and Ethical Considerations
Investigator Responsibilities
The investigator is responsible for ensuring that the study is performed in accordance with the
protocol, the current International Council for Harmonisation (ICH) guidelines on Good Clinical
Practice (GCP), and applicable regulatory and country/territory-specific requirements.
Good Clinical Practice is an international ethical and scientific quality standard for designing,
conducting, recording, and reporting studies that involve the participation of human participants.
Compliance with this standard provides public assurance that the rights, safety, and well-being of
study participants are protected, consistent with the principles that originated in the Declaration of
Helsinki, and that the study data are credible.
Protocol Clarification Communications
If text within a final approved protocol requires clarification (eg, current wording is unclear or
ambiguous) that does not change any aspect of the current study conduct, a protocol clarification
communication (PCC) may be prepared. The PCC Document will be communicated to the
Investigational Site, Site Monitors, Local Trial Managers (LTMs), Clinical Trial Managers
(CTMs), and/or Contract Research Organizations (CROs) who will ensure that the PCC
explanations are followed by the investigators.
The PCC Document may be shared by the sites with Independent Ethics Committees/Institutional
Review Boards (IECs/IRBs) per local regulations.
The PCC Documents must NOT be used in place of protocol amendments, but the content of the
PCC Document must be included in any future protocol amendments.
Protocol Amendments
Neither the investigator nor the sponsor will modify this protocol without a formal amendment by
the sponsor. All protocol amendments must be issued by the sponsor, and signed and dated by the
investigator. Protocol amendments must not be implemented without prior IEC/IRB approval, or
when the relevant competent authority has raised any grounds for non-acceptance, except when
necessary to eliminate immediate hazards to the participants, in which case the amendment must
be promptly submitted to the IEC/IRB and relevant competent authority. Documentation of
amendment approval by the investigator and IEC/IRB must be provided to the sponsor. When the
change(s) involve only logistic or administrative aspects of the study, the IEC/IRB (where
required) only needs to be notified.
During 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 must 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
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 11 October 2022
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.
Regulatory Approval/Notification
This protocol and any amendment(s) must be submitted to the appropriate regulatory authorities
in each respective country/territory, if applicable. A study may not be initiated until all local
regulatory requirements are met.
Required Prestudy 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 principal investigator
 
A copy of the dated and signed (or sealed, where appropriate per local regulations), written
IEC/IRB approval of the protocol, amendments, ICF, any recruiting materials, and if
applicable, participant compensation programs. This approval must clearly identify the
specific protocol by title and number and must be signed (or sealed, where appropriate per
local regulations) by the chairman or authorized designee.
 
Name and address of the IEC/IRB, including a current list of the IEC/IRB members and their
function, with a statement that it is organized and operates according to GCP and the
applicable laws and regulations. If accompanied by a letter of explanation, or equivalent, from
the IEC/IRB, a general statement may be substituted for this list. If an investigator or a
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 principal investigator, where
required
 
Signed and dated clinical trial agreement, which includes the financial agreement
 
Any other documentation required by local regulations
The following documents must be provided to the sponsor before enrollment of the first
participant:
 
Completed investigator financial disclosure forms from all sub-investigators
 
Documentation of sub-investigator qualifications (eg, curriculum vitae)
 
Name and address of any local laboratory conducting tests for the study, and a dated copy of
current laboratory normal ranges for these tests, if applicable
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 11 October 2022
 
Local laboratory documentation demonstrating competence and test reliability
(eg, accreditation/license), if applicable
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 participants)
 
Investigator Brochures (or equivalent information) and amendments/addenda
 
Sponsor-approved participant recruiting materials
 
Information on compensation for study-related injuries or payment to participants for
participation in the study, if applicable
 
Investigator’s curriculum vitae or equivalent information (unless not required, as documented
by the IEC/IRB)
 
Information regarding funding, name of the sponsor, institutional affiliations, other potential
conflicts of interest, and incentives for participants
 
Any other documents that the IEC/IRB requests to fulfill its obligation
This study will be undertaken only after the IEC/IRB has given full approval of the final protocol,
amendments (if any, excluding the ones that are purely administrative, with no consequences for
participants, data or study conduct, unless required locally), the ICF, applicable recruiting
materials, and participant compensation programs, and the sponsor has received a copy of this
approval. This approval letter must be dated and must clearly identify the IEC/IRB and the
documents being approved.
During the study the investigator (or sponsor where required) will send the following documents
and updates to the IEC/IRB for their review and approval, where appropriate:
 
Protocol amendments (excluding the ones that are purely administrative, with no
consequences for participants, data or study conduct)
 
Revision(s) to ICF and any other written materials to be provided to participants
 
If applicable, new or revised participant recruiting materials approved by the sponsor
 
Revisions to compensation for study-related injuries or payment to participants for
participation in the study, if applicable
 
New edition(s) of the Investigator Brochures 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
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 11 October 2022
 
New information that may adversely affect the safety of the participants or the conduct of the
study
 
Deviations from or changes to the protocol to eliminate immediate hazards to the participants
 
Report of deaths of participants under the investigator’s care
 
Notification if a new investigator is responsible for the study at the site
 
Development Safety Update Report and Line Listings, where applicable
 
Any other requirements of the IEC/IRB
For all protocol amendments (excluding the ones that are purely administrative, with no
consequences for participants, data or study conduct), the amendment and applicable ICF revisions
must be submitted promptly to the IEC/IRB for review and approval before implementation of the
change(s).
At least once a year, the IEC/IRB will be asked to review and reapprove this study, where required.
At the end of the study, the investigator (or sponsor where required) will notify the IEC/IRB about
the study completion.
Country/Territory Selection
This study will only be conducted in those countries/territories where the intent is to launch or
otherwise help ensure access to the developed product if the need for the product persists, unless
explicitly addressed as a specific ethical consideration in Section  4.2.1, Study-Specific Ethical
Design Considerations.
Other Ethical Considerations
For study-specific ethical design considerations, refer to Section 4.2.1.
10.2.2. 
Financial Disclosure
Refer to Required Prestudy Documentation (above) for details on financial disclosure.
10.2.3. 
Informed Consent Process
Each participant must give written consent according to the local requirements after the nature of
the study has been fully explained. Informed consent for additional study procedures will be
requested from participants in the Immuno Subset and/or the Safety Subset. The ICF(s) must be
signed before performance of any study-related activity. The ICF(s) that is/are used must be
approved by both the sponsor and by the reviewing IEC/IRB and be in a language that the
participant can read and understand. The informed consent must be in accordance with principles
that originated in the Declaration of Helsinki, current ICH and GCP guidelines, applicable
regulatory requirements, and sponsor policy.
Informed consent may be obtained remotely.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
109
Status: Approved, Date: 11 October 2022
Before enrollment in the study, the investigator or an authorized member of the study site personnel
must explain to potential participants the aims, methods, reasonably anticipated benefits, and
potential hazards of the study, and any discomfort participation in the study may entail.
Participants will be informed that their participation  is voluntary and that they may withdraw
consent to participate at any time. They will be informed that choosing not to participate will not
affect the care the participant will receive. Finally, they will be told that the investigator will
maintain a participant identification register for the purposes of long-term follow up if needed and
that their records may be accessed by health authorities and authorized sponsor personnel without
violating the confidentiality of the participant, to the extent permitted by the applicable law(s) or
regulations. By signing the ICF the participant is authorizing such access. It also denotes that the
participant agrees to allow the study physician to recontact the participant for the purpose of
obtaining consent for additional safety evaluations, if needed.
The participant will be given sufficient time to read the ICF and the opportunity to ask questions.
After this explanation and before entry into the study, consent must be appropriately recorded by
means of the participant’s personally dated signature. After having obtained the consent, a copy of
the ICF must be given to the participant.
Participants who are rescreened are required to sign a new ICF.
As described in Section 8, a caregiver may assist a participant who is unable to complete the
eDiary, by reading the questions aloud and recording the responses in the eDiary on the
participant’s behalf (using the caregiver’s unique identifier and PIN). For this purpose, a caregiver
consent form has been developed. Consent must be obtained according to local requirements and
must be obtained from the caregiver before the caregiver is allowed to complete the eDiary on
behalf of the participant. After having obtained the caregiver’s consent, a copy of the consent form
must be given to the caregiver. Of note, the caregiver is not intended to be a Legally Authorized
Representative who can provide informed consent for study participation on behalf of the
participant.
10.2.4. 
Data Protection
Privacy of Personal Data
The collection and processing of personal data from participants enrolled in this study will be
limited to those data that are necessary to fulfill the objectives of the study.
These data must be collected and processed with adequate precautions to ensure confidentiality
and compliance with applicable data privacy protection laws and regulations. Appropriate
technical and organizational measures to protect the personal data against unauthorized disclosures
or access, accidental or unlawful destruction, or accidental loss or alteration must be put in place.
Sponsor personnel whose responsibilities require access to personal data agree to keep the identity
of participants confidential.
The informed consent obtained from the participants includes explicit consent for the processing
of personal data and for the investigator/institution to allow direct access to their original medical
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
110
Status: Approved, Date: 11 October 2022
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/territories.
The participants have the right to request through the investigator access to their 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.
10.2.5. 
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/protein preF RSV vaccine,
to understand RSV and other respiratory pathogens, to understand differential vaccine responders,
and to develop tests/assays related to Ad26/protein preF RSV vaccine and RSV and other
respiratory pathogens. The research may begin at any time during the study or the post-study
storage period.
Stored samples will be coded throughout the sample storage and analysis process and will not be
labeled with personal identifiers. Participants may withdraw their consent for their samples to be
stored for research (refer to Section 7.2.1, Withdrawal From the Use of Research Samples).
10.2.6. 
Committees Structure
10.2.6.1. 
Independent Data Monitoring Committee
An IDMC will be established. In general, the IDMC will monitor safety data on a regular basis
throughout the study to ensure the continuing safety of the participants. In addition, the IDMC will
also formally monitor the primary efficacy endpoints. The IDMC will evaluate in an unblinded
fashion if the success criteria have been met.
This committee will consist of at least one medical expert in the relevant therapeutic area and at
least one statistician; committee membership responsibilities, authorities, and procedures will be
documented in its charter.
10.2.6.2. 
Clinical Event Adjudication Committee
Prior to database lock for all planned analyses (see Section 9.5), the CEC will review in a blinded
manner all available data of all RSV-mediated ARIs and will confirm if the RT-PCR-confirmed
RSV LRTD definition criteria were met. Further for all RT-PCR-confirmed RSV LRTD cases the
CEC will assess their severity (mild, moderate or severe).
The CEC will consist of independent medical experts in the relevant therapeutic area. A Charter
will be developed to describe the members, roles, and responsibilities of the CEC appointed to
perform this review.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
111
Status: Approved, Date: 11 October 2022
10.2.7. 
Publication Policy/Dissemination of Clinical Study Data
All information, including but not limited to information regarding Ad26/protein preF RSV
vaccine 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, including research data, generated as a
result of this study, are considered confidential and remain the sole property of the sponsor. The
investigator agrees to maintain this information in confidence and use this information only to
accomplish this study and will not use it for other purposes without the sponsor’s prior written
consent.
The investigator understands that the information developed in the study will be used by the
sponsor in connection with the continued development of Ad26/protein preF RSV vaccine, 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 for the study. Results of analyses
performed after the Clinical Study Report has been issued will be reported in a separate report and
will not require a revision of the Clinical Study Report.
Study participant identifiers will not be used in publication of results. Any work created in
connection with performance of the study and contained in the data that can benefit from copyright
protection (except any publication by the investigator as provided for below) shall be the property
of the sponsor as author and owner of copyright in such work.
Consistent with Good Publication Practices and International Committee of Medical Journal
Editors (ICMJE) guidelines, the sponsor shall have the right to publish such primary (multicenter)
data and information without approval from the investigator. The investigator has the right to
publish study site-specific data after the primary data are published. If an investigator wishes to
publish information from the study, a copy of the manuscript must be provided to the sponsor for
review at least 60 days before submission for publication or presentation. Expedited reviews will
be arranged for abstracts, poster presentations, or other materials. If requested by the sponsor in
writing, the investigator will withhold such publication for up to an additional 60 days to allow for
filing of a patent application. In the event that issues arise regarding scientific integrity or
regulatory compliance, the sponsor will review these issues with the investigator. The sponsor will
not mandate modifications to scientific content and does not have the right to suppress information.
For multicenter study designs and sub-study approaches, secondary results generally should not
be published before the primary endpoints of a study have been published. Similarly, investigators
will recognize the integrity of a multicenter study by not submitting for publication data derived
from the individual study site until the combined results from the completed study have been
submitted for publication, within 18 months after the study end date, or the sponsor confirms there
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
112
Status: Approved, Date: 11 October 2022
will be no multicenter study publication. Authorship of publications resulting from this study will
be based on the guidelines on authorship, such as those described in the ICMJE Recommendations
for the Conduct, Reporting, Editing and Publication of Scholarly Work in Medical Journals, which
state that the named authors must have made a significant contribution to the conception or design
of the work; or the acquisition, analysis, or interpretation of the data for the work; and drafted the
work or revised it critically for important intellectual content; and given final approval of the
version to be published; and agreed to be accountable for all aspects of the work in ensuring that
questions related to the accuracy or integrity of any part of the work are appropriately investigated
and resolved.
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. The disclosure of the final study results will be performed after the end of study in order
to ensure the statistical analyses are relevant.
10.2.8. 
Data Quality Assurance
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 may review the 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.
10.2.9. 
Case Report Form Completion
Case report forms are prepared and provided by the sponsor for each participant in electronic
format. All data relating to the study must be recorded in the eCRF. 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 participant’s source documents. Data must be entered into
the eCRF in English. The eCRF must be completed as soon as possible after a participant visit and
the forms must be available for review at the next scheduled monitoring visit.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
113
Status: Approved, Date: 11 October 2022
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.
10.2.10. 
Source Documents
At a minimum, source documents consistent in the type and level of detail with that commonly
recorded at the study site as a basis for standard medical care must be available for the following:
participant identification, eligibility, and study identification; study discussion and date of signed
informed consent; dates of visits; results of safety and efficacy parameters as required by the
protocol; record of all AEs and follow-up of AEs; concomitant medication; vaccination
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 must be identifiable.
Information from the participant eDiary will be reviewed by the investigator. The participant’s
eDiary used to collect information regarding solicited signs and symptoms after vaccination will
be considered source data.
Participant-completed scales and assessments designated by the sponsor (solicited AEs after
vaccination [including body temperature], RiiQ, and ARI surveillance responses) will be recorded
directly into an electronic device and will be considered source data.
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).
An eSource system may be utilized, which contains data traditionally maintained in a hospital or
clinic record to document medical care (eg, electronic source documents) as well as the clinical
study-specific data fields as determined by the protocol. This data is electronically extracted for
use by the sponsor. If eSource is utilized, references made to the eCRF in the protocol include the
eSource system but information collected through eSource may not be limited to that found in the
eCRF. Data in this system may be considered source documentation.
10.2.11. 
Monitoring
The sponsor will use a combination of monitoring techniques (central, remote, or on-site
monitoring) to monitor this study.
The sponsor or its designee 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
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
114
Status: Approved, Date: 11 October 2022
first post-initiation visit will be made as soon as possible after enrollment has begun. At these
visits, the monitor may compare data entered into the eCRF  with the source documents (eg,
hospital/clinic/physician’s office medical records); a sample may be reviewed. 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.
In addition to on-site monitoring visits, remote contacts can occur. It is expected that during these
remote contacts, study site personnel will be available to provide an update on the progress of the
study at the site.
Central monitoring will take place for data identified by the sponsor as requiring central review.
10.2.12. 
On-Site Audits
Representatives of the sponsor’s clinical quality assurance department may visit the study site at
any time during or after completion of the study to conduct an audit of the study in compliance
with regulatory guidelines and company policy. These audits will require access to all study
records, including source documents, for inspection. Participant privacy must, however, be
respected. The investigator and study site personnel are responsible for being present and available
for consultation during routinely scheduled study site audit visits conducted by the sponsor or its
designees.
Similar auditing procedures may also be conducted by agents of any regulatory body, either as part
of a national GCP compliance program or to review the results of this study in support of a
regulatory submission. The investigator must immediately notify the sponsor if the investigator
has been contacted by a regulatory agency concerning an upcoming inspection.
10.2.13. 
Record Retention
In compliance with the ICH/GCP guidelines, the investigator/institution will maintain all eCRF
and all source documents that support the data collected from each participant, as well as all study
documents as specified in ICH/GCP Section 8, Essential Documents for the Conduct of a Clinical
Trial, and all study documents as specified by the applicable regulatory requirement(s). The
investigator/institution will take measures to prevent accidental or premature destruction of these
documents.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
115
Status: Approved, Date: 11 October 2022
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.
10.2.14. 
Study and Site Start and Closure
First Act of Recruitment
The first site open is considered the first act of recruitment and it becomes the study start date.
Study/Site Termination
The sponsor reserves the right to close the study site or terminate the study at any time for any
reason at the sole discretion of the sponsor. Study sites will be closed upon study completion. A
study site is considered closed when all required documents and study supplies have been collected
and a study site closure visit has been performed.
The investigator may initiate study site closure at any time, provided there is reasonable cause and
sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a study site by the sponsor or investigator may include but are not
limited to:
 
Failure of the investigator to comply with the protocol, the requirements of the IEC/IRB or
local health authorities, the sponsor’s procedures, or GCP guidelines
 
Inadequate recruitment of participants by the investigator
 
Discontinuation of further study vaccine development
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
116
Status: Approved, Date: 11 October 2022
10.3. Appendix 3: Adverse Events, Serious Adverse Events, Adverse Event of
Special Interest, Product Quality Complaints, and Other Safety Reporting:
Definitions and Procedures for Recording, Evaluating, Follow-up, and
Reporting
10.3.1. 
Adverse Event Definitions and Classifications
Adverse Event
An AE is any untoward medical occurrence in a clinical study participant administered a
pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have
a causal relationship with the intervention. 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 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: For time period of sponsor’s AE collection, see All Adverse Events under Section 8.5.1,
Time Period and Frequency for Collecting Adverse Event and Serious Adverse Event Information.
Serious Adverse Event
An SAE based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for
Human Use is any untoward medical occurrence that at any dose:
 
Results in death
 
Is life-threatening
(The participant was at risk of death at the time of the event. It does not refer to an event that
hypothetically might have caused death if it were more severe.)
 
Requires inpatient hospitalization or prolongation of existing hospitalization
 
Results in persistent or significant disability/incapacity
 
Is a congenital anomaly/birth defect
 
Is a suspected transmission of any infectious agent via a medicinal product
 
Is Medically Important*
*Medical and scientific judgment must be exercised in deciding whether expedited reporting is
also appropriate in other situations, such as important medical events that may not be immediately
life threatening or result in death or hospitalization but may jeopardize the participant or may
require intervention to prevent one of the other outcomes listed in the definition above. These
should usually be considered serious.
If a serious and unexpected AE occurs for which there is evidence suggesting a causal relationship
between the study vaccine and the event (eg, death from anaphylaxis), the event must be reported
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
117
Status: Approved, Date: 11 October 2022
as a SUSAR by the sponsor to health authorities and by the investigator to the IRB/IEC according
to regulatory and local requirements.
Unlisted (Unexpected) Adverse Event/Reference Safety Information
An AE is considered unlisted if the nature or severity is not consistent with the applicable product
reference safety information. For Ad26.RSV.preF and RSV preF protein, expectedness of an AE
will be determined by whether or not it is listed in the Investigator’s Brochure.
10.3.2. 
Attribution Definitions
Assessment of Causality
The causal relationship to study vaccine is determined by the investigator. The following selection
must be used to assess all AEs.
Related
There is a reasonable causal relationship between study vaccine administration and the AE.
Not Related
There is not a reasonable causal relationship between study vaccine administration and the AE.
The term “reasonable causal relationship” means there is evidence to support a causal relationship.
By definition, all solicited AEs at the injection site (local) will be considered related to the study
vaccine administration.
10.3.3. 
Severity Criteria
All AEs will be coded for severity using a modified version of the FDA grading table, based on
version of September 2007 (https://www.fda.gov/media/73679/download), included in
Appendix 4: Toxicity Grading Scale. For AEs not identified in the grading table, the following
guidelines will be applied:
Grade 1 
Mild 
Symptoms causing no or minimal interference with usual social and
functional activities
Grade 2 
Moderate 
Symptoms causing greater than minimal interference with usual social
and functional activities
Grade 3 
Severe 
Symptoms causing inability to perform usual social and functional
activities and requires medical intervention
Grade 4 
Potentially 
life-threatening 
Symptoms causing inability to perform basic self-care functions,
or medical or operative intervention indicated to prevent permanent
impairment, persistent disability, or ER visit or hospitalization
The severity of solicited signs and symptoms will be graded in the eDiary by the participant based
on the severity assessment provided in the eDiary and then verified by the investigator using the
toxicity grading scale in Appendix 4: Toxicity Grading Scale. (Note: severity of the measured
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
118
Status: Approved, Date: 11 October 2022
events will be derived from the diameter [for erythema and swelling] and the temperature
measurements [for fever]).
10.3.4. 
Special Reporting Situations
Safety events of interest on a sponsor study vaccine in an interventional study that may require
expedited reporting or safety evaluation include, but are not limited to:
 
Overdose of a sponsor study vaccine
 
Suspected abuse/misuse of a sponsor study vaccine
 
Accidental or occupational exposure to a sponsor study vaccine
 
Medication error, intercepted medication error, or potential medication error involving a
Johnson & Johnson medicinal product (with or without patient exposure to the Johnson &
Johnson medicinal product, eg, product name confusion, product label confusion, intercepted
prescribing or dispensing errors)
Special reporting situations must be recorded in the eCRF. Any special reporting situation that
meets the criteria of an SAE must be recorded on the SAE page of the eCRF.
10.3.5. 
Procedures
All Adverse Events
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 the study vaccine. All measures required for AE management must be recorded in the source
document and reported according to sponsor instructions.
The participant will be provided with a “wallet (study) card” and instructed to carry this card with
them for the duration of the study indicating the following:
 
Study number
 
Statement, in the local language(s), that the participant is participating in a clinical study
 
Investigator’s name and 24hour contact telephone number
 
Local sponsor’s name and 24-hour contact telephone number (for medical personnel only)
 
Site number
 
Participant number
 
Any other information that is required to do an emergency breaking of the blind
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
119
Status: Approved, Date: 11 October 2022
Serious Adverse Events
All SAEs that have not resolved by the end of the study, or that have not resolved upon the
participant’s discontinuation from 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 (participant or healthcare
practitioner refusal to provide additional information, lost to follow-up after demonstration of
due diligence with follow-up efforts)
Any event requiring hospitalization (or prolongation of hospitalization) that occurs during
participation in the 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 participant in a study, whether or not the event is expected or associated
with the study vaccine, is considered an SAE.
Information regarding SAEs will be transmitted to the sponsor using an SAE reporting form and
safety report form of the eCRF, which must be completed and reviewed by a physician from the
study site, and transmitted in a secure manner to the sponsor within 24 hours. The initial and
follow-up reports of an SAE should be transmitted in a secure manner electronically or by
facsimile (fax). Telephone reporting should be the exception and the reporter should be asked to
complete the appropriate form(s) first.
Adverse Events of Special Interest
AESIs, including potential AESIs, will be carefully monitored during the study by the sponsor and
must be reported to the sponsor within 24 hours of awareness irrespective of seriousness (ie,
serious and nonserious AEs) or causality assessment, following the procedure described above for
SAEs and will require enhanced data collection.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
120
Status: Approved, Date: 11 October 2022
10.3.6. 
Product Quality Complaint Handling
Definition
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, reliability, or performance of a distributed product, including its labeling, drug delivery
system, or package integrity. A PQC may have an impact on the safety and efficacy of the product.
In addition, it includes any technical complaints, defined as any complaint that indicates a potential
quality issue during manufacturing, packaging, release testing, stability monitoring, dose
preparation, storage or distribution of the product or the drug delivery system.
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.
A sample of the suspected product should be maintained under the correct storage conditions until
a shipment request is received from the sponsor.
10.3.7. 
Contacting Sponsor Regarding Safety, Including Product Quality
The names (and corresponding telephone numbers) of the individuals who must be contacted
regarding safety issues, PQC, or questions regarding the study are listed in the Contact Information
page(s), which will be provided as a separate document.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
121
Status: Approved, Date: 11 October 2022
10.4. Appendix 4: Toxicity Grading Scale
Adapted from the FDA Guidance document “Toxicity Grading Scale for Healthy Adult and
Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials” (September 2007)
A: Tables for Clinical Abnormalities
Local Reaction to 
Injectable Product 
Mild  
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life-
threatening (Grade 4)
Pain/Tenderness# 
Aware of symptoms 
but easily tolerated; 
Does not interfere 
with activity; 
Discomfort only to 
touch  
Notable symptoms; 
Requires modification 
in activity or use of 
medications; 
Discomfort with 
movement 
Incapacitating 
symptoms; 
Inability to do work, 
school, or usual 
activities; Use of 
narcotic pain reliever
Hospitalization;
Pain/tenderness
causing inability to
perform basic self-care
function
Erythema# 
25-50 mm  
51-100 mm  
>100 mm  
Hospitalization;
Necrosis or exfoliative
dermatitis
Swelling# 
25-50 mm  
51-100 mm  
>100 mm  
Hospitalization;
Necrosis
# Revised by the sponsor.
Vital Signs * 
Mild  
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life-
threatening (Grade 4)
Fever (°C) **  
          (°F) ** 
38.0-38.4 
100.4-101.1 
38.5-38.9 
101.2-102.0 
39.0-40.0 
102.1-104.0 
>40
>104.0
Tachycardia –beats 
per minute 
101-115 
116-130 
>130 
Hospitalization for
arrhythmia#
Bradycardia –beats 
per minute*** 
50-54  
45-49 
<45 
Hospitalization for
arrhythmia#
Hypertension 
(systolic) –mm Hg 
141-150 
151-160# 
>160# 
Hospitalization for
malignant
hypertension#
Hypertension 
(diastolic) –mm Hg 
91-95 
96-100 
>100 
Hospitalization for
malignant
hypertension#
Hypotension 
(systolic) –mm Hg 
85-89 
80-84 
<80 
Hospitalization for
hypotensive shock#
Respiratory Rate – 
breaths per minute
17-20 
21-25 
>25 
Intubation
* Participant should be at rest for all vital sign measurements.
** For oral temperature: no recent hot or cold beverages or smoking.
***When resting heart rate is between 60 –100 beats per minute. Use clinical judgment when characterizing
bradycardia among some healthy participant populations, for example, conditioned athletes.
# Revised by the sponsor.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
122
Status: Approved, Date: 11 October 2022
Systemic
(General)
Mild
(Grade 1)
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life-
threatening (Grade 4)
Vomiting#
No interference with
activity or
1-2 episodes/24 hours
Some interference 
with activity or 
>2 episodes/24 hours 
Prevents daily  
activity, requires 
outpatient IV
hydration
Hospitalization;
Hypotensive shock
Nausea#
Minimal symptoms;
causes minimal or no
interference with
work, school, or self-
care activities
Notable symptoms; 
Requires modification 
in activity or use of 
medications; 
Does NOT result in 
loss of work, school, 
or cancellation of 
social activities
Incapacitating 
symptoms; 
Requires bed rest 
and/or results in loss 
of work, school, or
cancellation of social
activities
Hospitalization;
Inability to perform
basic self-care
functions
Diarrhea# 
2-3 loose stools or
<400 gms/24 hours
4-5 stools or 
400-800 gms/ 
24 hours 
6 or more watery  
stools or 
>800 gms/24 hours or 
oral rehydration 
necessary
Hospitalization;
Hypotensive shock OR
IV fluid replacement
indicated
Headache# 
Minimal symptoms;
causes minimal or no
interference with
work, school, or self-
care activities
Notable symptoms; 
Requires modification 
in activity or use of 
medications; 
Does NOT result in 
loss of work, school, 
or cancellation of 
social activities 
Incapacitating 
symptoms; 
Requires bed rest 
and/or results in loss 
of work, school, or
cancellation of social
activities;
Use of narcotic pain
reliever
Hospitalization;
Inability to perform
basic self-care
functions
Fatigue# 
Minimal symptoms;
causes minimal or no
interference with
work, school, or self-
care activities
Notable symptoms; 
Requires modification 
in activity or use of 
medications; 
Does NOT result in 
loss of work, school, 
or cancellation of 
social activities 
Incapacitating 
symptoms; 
Requires bed rest 
and/or results in loss 
of work, school, or
cancellation of social
activities;
Use of narcotic pain
reliever
Hospitalization;
Inability to perform
basic self-care
functions
Myalgia# 
Minimal symptoms;
causes minimal or no
interference with
work, school, or self-
care activities
Notable symptoms; 
Requires modification 
in activity or use of 
medications; 
Does NOT result in 
loss of work, school, 
or cancellation of 
social activities 
Incapacitating 
symptoms; 
Requires bed rest 
and/or results in loss 
of work, school, or
cancellation of social
activities;
Use of narcotic pain
reliever
Hospitalization;
Inability to perform
basic self-care
functions
# Revised by the sponsor.
Systemic Illness 
Mild
(Grade 1)
Moderate
(Grade 2)
Severe
(Grade 3)
Potentially Life-
threatening (Grade 4)
Illness or clinical 
adverse event (as 
defined according to
applicable regulations)
No interference with
activity
Some interference
with activity not
requiring medical
intervention
Prevents daily
activity and requires
medical intervention
Hospitalization#
# Revised by the sponsor.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
123
Status: Approved, Date: 11 October 2022
10.5. Appendix 5: Definition of Acute Respiratory Infection for Participants Aged
≥60Years
Acute respiratory infection (ARI) is defined as the occurrence of at least one respiratory symptom
that the participant reports is different or worse than the participant usually experiences:
 
Respiratory symptom: an upper respiratory tract infection (URTI) symptom (ie, nasal
congestion, sore throat) or a lower respiratory tract infection (LRTI) symptom (ie, cough, short
of breath, coughing up phlegm [sputum], wheezing) from the RiiQ™v2 Symptom Scale)
Resolution of an ARI episode is defined as 2 consecutive days with no symptoms listed on the
RiiQ™v2 Symptom Scale or, for participants who have RiiQ™v2 symptoms present at baseline
(assessed pre-vaccination), 2 consecutive days where all symptoms on the RiiQ™v2 Symptom
Scale have returned to same severity level as reported at baseline (or lower).
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
124
Status: Approved, Date: 11 October 2022
10.6. Appendix 6: Medically-attended ARI Form
Section 1: 
To be completed in all healthcare settings (e.g., family doctor, nurse practitioner, outpatient clinic,
emergency department visits and hospitalizations).
Participant ID (will be completed by study staff):
Date of visit:
Name and role of healthcare professional completing form:
Optional contact details:
DIAGNOSIS/DIAGNOSES
Please list diagnosis or diagnoses made during clinical interaction here.
MEDICATIONS
Please list any new medications prescribed or changes in medication dosing.
VITAL SIGNS
Temperature (oC/oF): ________________
Respiratory rate (breaths per minute): _________________
Does the measured respiratory rate support a diagnosis of lower respiratory tract disease (LRTD)?
□    Yes  
   □    No
Below question only to be completed if patient has history of COPD or asthma.
Does the measured respiratory rate support a diagnosis of a COPD or asthma exacerbation?
□    COPD exacerbation                     □    asthma exacerbation                            □    No
Oxygen saturation (SpO2): __________________
Does the measured oxygen saturation support a diagnosis of lower respiratory tract disease (LRTD)?
□    Yes    
□    No
Below question only to be completed if patient has history of COPD or asthma.
Does the measured oxygen saturation support a diagnosis of a COPD or asthma exacerbation?
□    COPD exacerbation                     □    asthma exacerbation                            □    No
WERE ADDITIONAL DIAGNOSTIC TESTS PERFORMED?                                    
□    Yes     □    No
If ‘yes’ selected, please fill out remaining questions in this section.
Was a chest x-ray performed?                                                                                                        
□    Yes     □    No
If yes, please indicate date performed:  ___________________
If yes, do the results support a diagnosis of lower respiratory tract disease (LRTD)?        
□    Yes     □    No
If LRTD diagnosis supported, further diagnosis by x-ray:                           □    Pneumonia    
□    Other LRTD
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
125
Status: Approved, Date: 11 October 2022
Was a peak flow measurement made?                                                                                          □    Yes     □   No
If yes, please indicate date performed:  ___________________
Peak flow (L/min): ______________
If yes, do the results support a diagnosis of LRTD?                                                                      □   Yes     □    No
Below question only to be completed if patient has history of COPD or asthma.
Do the results support a diagnosis of a COPD or asthma exacerbation?
□    COPD exacerbation                     □    asthma exacerbation                            □    No
Was spirometry performed?                                                                                                          □    Yes     □   No
If yes, please indicate date performed:  ___________________
Specify results:
Only indicate results for measurements made.
FEV1 (L): ________
FEV6 (L): ________
FVC (L): _________
If yes, do the results support a diagnosis of LRTD?                                                                     □    Yes     □   No
Below question only to be completed if patient has history of COPD or asthma.
Do the results support a diagnosis of a COPD or asthma exacerbation?
□    COPD exacerbation                     □    asthma exacerbation                            □    No
Was another diagnostic method used?                                                                                           □    Yes     □    No
If yes, please specify diagnostic method:  ________________________________________________________
Date performed: ______________
Specify results: __________________________________________________________________
Do the results support a diagnosis of LRTD?                                                                               □    Yes     □   No
WAS ANY MANAGEMENT PRESCRIBED OTHER THAN MEDICATION?                     □    Yes     □    No
(including nebulizer treatments, IV fluids, etc.)
If ‘yes’ selected, please fill out remaining questions in this section.
If yes, please specify:  
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
126
Status: Approved, Date: 11 October 2022
Section 2: 
Additional questions only to be completed if patient seen in emergency department or is hospitalized.
WERE ADDITIONAL DIAGNOSTIC TESTS PERFORMED?                                                            □    Yes     □    No
If ‘yes’ selected, please fill out remaining questions in this section.
Was a CT-scan performed?                                                                                                            □    Yes     □    No
If yes, please indicate date performed:  ___________________
If yes, do the results support a diagnosis of LRTD?                                                                    □    Yes     □    No
If LRTD diagnosis supported, further diagnosis by CT:                              □    Pneumonia     □    Other LRTD
Was an MRI performed?                                                                                                                  □    Yes     □    No
If yes, please indicate date performed:  ___________________
If yes, do the results support a diagnosis of LRTD?                                                                     □    Yes     □    No
If LRTD diagnosis supported, further diagnosis by MRI:                            □    Pneumonia     □    Other LRTD
Was bronchoscopy performed?                                                                                                      □    Yes     □    No
If yes, please indicate date performed:  ___________________
Specify results: __________________________________________________________________
If yes, do the results support a diagnosis of LRTD?                                                                     □    Yes     □   No
Was an arterial blood gas measured?                                                                                            □    Yes     □   No
If yes, please indicate date performed:  ___________________
Specify results: pH: _________, pCO2 (mmHg): _________, pO2 (mmHg): _________, HCO3 (mEq/L): _________, 
O2 saturation (%): _________
If yes, do the results support a diagnosis of LRTD?                                                                     □    Yes     □    No
Below question only to be completed if patient has history of COPD or asthma.
Do the results support a diagnosis of a COPD or asthma exacerbation?
□    COPD exacerbation                     □    asthma exacerbation                            □    No
Was another diagnostic method used?                                                                                           □    Yes     □    No
If yes, please specify diagnostic method:  ________________________________________________________
Date performed: ______________
Specify results: __________________________________________________________________
Do the results support a diagnosis of LRTD?                                                                                □    Yes     □   No
SUPPLEMENTAL OXYGEN
Was supplemental oxygen administered?                                                                                     □    Yes     □   No
If ‘yes’ selected, please fill out remaining questions in this section.
Type of supplemental oxygen administration:
□   Invasive Mechanical Ventilation   
□   Venturi Mask
□   Non-Invasive Mechanical Ventilation 
□   Simple Face Mask
□   Nasal Cannula 
□   Reservoir Cannulas
□   Nonrebreathing Face Mask with Reservoir and One-Way Valve
□   Other: _______________________
If invasive mechanical ventilation, specify:
□   Through endotracheal tube                               □   Through tracheostomy tube
If non-invasive mechanical ventilation, specify:
□   Continuous positive airway pressure               □   Bilevel positive airway pressure
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
127
Status: Approved, Date: 11 October 2022
Oxygen concentration and units: _________________________
Start date and time: ______________________
End date and time (if applicable): ____________________
Has supplemental oxygen administration returned to that level provided prior to the current respiratory illness?
□    Yes     □    No
Below question only to be completed if patient has history of COPD or asthma.
If applicable, does requirement for oxygen supplementation or increased oxygen supplementation support a diagnosis of
a COPD or asthma exacerbation?
□    COPD exacerbation                     □    asthma exacerbation                            □    No
ADDITIONAL COMMENTS
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
128
Status: Approved, Date: 11 October 2022
10.7. Appendix 7: ARI Surveillance Assessment
Since the last time you completed your eDiary, have you had any symptoms of a cold or respiratory infection such as
nasal congestion (a stuffy or runny nose), a sore throat, a cough, coughing up phlegm (sputum), trouble breathing
(short of breath), or whistling sounds when you breathe (wheezing)?
If you usually have some of these symptoms even when you do not have a cold, please only answer “yes” if you have
more symptoms than usual or your symptoms are worse than usual.
Responses:
No cold symptoms 
The participant will be referred to AE reminder screen (below)
Yes, I had cold symptoms The participant completes ARI assessment as follows:
1. Date ARI symptoms started or became worse than usual
2. RiiQ™v2 Symptom Scale
The ePRO system will compare reported symptoms/severity to values reported during the vaccination visit.
If symptoms are the same or less severe than the participant reported during the vaccination visit, the symptoms
indicate no ARI has occurred according to protocol definition. Therefore, the remainder of the ARI assessment is not
collected. The participant will be referred to AE reminder screen (below).
If symptoms are worse than baseline, the remaining ARI assessments are presented in the following order:
3. RiiQ™v2 Impact on Daily Activities
4. EQ-5D-5L
5. PGI-H
6. PGI-S
7. PGI-C
(Note that the PGI C will not be completed on ARI Day 1)
8. Return to Usual Health
(Note that the Return to Usual Health question will not be completed on ARI Day 1)
The participant will then be referred to AE reminder screen (below). A final screen reminds participants to collect a
nasal swab and to contact site to schedule a site visit.
Adverse Event Reminder Screen:
Thank you for completing your eDiary.
If you are having any severe symptoms, health issues, or other concerns about your health, please contact your study
doctor to discuss these.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
130
Status: Approved, Date: 11 October 2022
10.9. Appendix 9: EuroQoL, 5-Dimension, 5-Level Questionnaire (EQ-5D-5L)
Note: This appendix provides a representative example of the questionnaire that will be used in
this study. The site should always use the most recently provided version of the questionnaire.
Health Questionnaire
English version for the UK
UK (English) © 2009 EuroQol Group. EQ 5D™ is a trade mark of the EuroQol Group
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
131
Status: Approved, Date: 11 October 2022
Under each heading, please check the ONE box that best describes your health TODAY.
MOBILITY
I have no problems in walking about 

I have slight problems in walking about 

I have moderate problems in walkingabout 

I have severe problems in walking about 

I am unable to walk about 

SELF-CARE
I have no problems washing or dressing myself 

I have slight problems washing or dressing myself 

I have moderate problems washing or dressing myself 

I have severe problems washing or dressing myself 

I am unable to wash or dress myself 

USUAL ACTIVITIES (e.g. work, study, housework,
family or leisure activities)
I have no problems doing my usual activities 

I have slight problems doing my usual activities 

I have moderate problems doing my usual activities 

I have severe problems doing my usual activities 

I am unable to do my usual activities 

PAIN / DISCOMFORT
I have no pain or discomfort 

I have slight pain or discomfort 

I have moderate pain or discomfort 

I have severe pain or discomfort 

I have extreme pain or discomfort 

ANXIETY / DEPRESSION
I am not anxious or depressed 

I am slightly anxious or depressed 

I am moderately anxious or depressed 

I am severely anxious or depressed 

I am extremely anxious or depressed 

UK (English) © 2009 EuroQol Group. EQ 5D™ is a trade mark of the EuroQol Group
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
132
Status: Approved, Date: 11 October 2022
 We would like to know how good or bad your health is TODAY.
 This scale is numbered from 0 to 100.
 100 means the best health you can imagine.
0 means the worst health you can imagine.
 Mark an X on the scale to indicate how your health is TODAY.
 Now, please write the number you marked on the scale in the box
below.
YOUR HEALTH TODAY 
UK (English) © 2009 EuroQol Group. EQ 5D™ is a trade mark of the EuroQol Group
10
0
20
30
40
50
60
80
70
90
100
5
15
25
35
45
55
75
65
85
95
The best health
you can imagine
The worst health
you can imagine
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
133
Status: Approved, Date: 11 October 2022
10.10. Appendix 10: Patient Global Impression Scales
Patient Global Impression of Health (PGI-H)
Overall, how would you rate your health today?
Very good
Good
Fair
Poor
Very poor
Patient Global Impression of Severity (PGI-S)
Overall, how would you rate your respiratory illness today?
None
Mild
Moderate
Severe
Patient Global Impression of Change (PGI-C)
How was your respiratory illness today compared to when you first entered this study?
Much better
Somewhat better
A little better
About the same
A little worse
Somewhat worse
Much worse
Return to Usual Health
Have you returned to your usual health today?
Yes
No
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
134
Status: Approved, Date: 11 October 2022
10.11. Appendix 11: Medical Resources Utilization Questionnaire
Participant ID: 
Date (dd-mmm-yyyy): 
During your ARI, did the interactions you had with healthcare providers for study-related visits and procedures affect the number of times you sought medical care outside
of the study?
Yes    
No
If yes, what was the effect on the medical consultations that you sought outside of the study?
  interactions with healthcare providers increased  
  interactions with healthcare providers decreased
1. Medical consultations
Since onset of acute respiratory infection, how many times have you had medical consultations?
No 
Yes 
Specify number of
visits (include home
visits, telephone
consults, telemedicine 
consults, and 
in-person visits) 
For each visit, please indicate:
if this was
preplanned prior to
ARI onset
if this was related to
an ARI or its
complications 
a reason
if this was a home visit, an
appointment by telephone,
a telemedicine consult or an
in-person visit
General Practitioner
Nurse
Internal Medicine
Pulmonologist
Respiratory Physiotherapy
Other (Please specify)
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
136
Status: Approved, Date: 11 October 2022
10.12. Appendix 12: Missed Working Days
Participant ID: 
Date (dd-mmm-yyyy): 
Missed working days
Do you normally work*?                                                                                                                                      
 yes
                                                                                                                                                                              
 no
* Either paid or volunteer work
If yes, how many days from work* did you miss due to the ARI or its complications?                                       
 days
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
137
Status: Approved, Date: 11 October 2022
10.13. Appendix 13: Guidance on Study Conduct During a Natural Disaster
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, isolation or quarantine of participants and
study-site personnel; travel restrictions/limited access to public places, including hospitals; study
site personnel being reassigned to critical tasks.
The sponsor is providing options for study related participant management in the event of
disruption to the conduct of the study. This guidance does not supersede any local or government
requirements or the clinical judgement of the investigator to protect the health and well-being of
participants and site staff. If, at any time, a participant’s travel to the study site is considered to be
dangerous, study participation may be interrupted, and study follow-up conducted. If it becomes
necessary to discontinue participation in the study, the procedures outlined in the protocol for
discontinuing study intervention will be followed.
If, as a result of the COVID-19 pandemic, scheduled visits cannot be conducted in person at the
study site, they will be performed to the extent possible remotely/virtually or delayed until such
time that on-site visits can be resumed. At each contact, participants will be interviewed to collect
safety data. Key immunogenicity endpoint assessments should be performed if required and as
feasible. Participants will also be questioned regarding general health status to fulfill any physical
examination requirement.
Every effort should be made to adhere to protocol-specified assessments for participants on study
intervention, including follow up. Modifications to protocol-required assessments may be
permitted using the examples contained in this appendix, after consultation with the participant,
investigator, and the sponsor. Missed assessments/visits will be captured in the clinical trial
management system for protocol deviations. Discontinuations of study interventions and
withdrawal from the study should be documented with the prefix “COVID-19-related” in the case
report form CRF.
If a participant has tested positive for COVID-19, the investigator should contact the sponsor’s
responsible medical officer to discuss plans for administration of study intervention, performing
study assessments, and follow-up. Modifications made to the study conduct as a result of the
COVID-19 pandemic should be summarized in the clinical study report.
Guidance Specific to this Protocol
 
Depending on the ongoing incidence of COVID-19 infection and subject to availability of
SARS-CoV-2 point-of-care testing, participants may receive COVID-19 screening at home or
clinical visits. Informed consent may be obtained remotely.
 
When site visits are not possible due to local/national guidelines, sites should collect the
assessments via telephone or telemedicine contact or home-based visits, if the participant
allows. The actual visit date and the type of visit (ie, telephone/ telemedicine or home-based
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
138
Status: Approved, Date: 11 October 2022
visit) should be captured in the eCRF according to the eCRF completion guidelines.
Procedures that require an on-site visit should be excluded.
 
For participants with an ARI episode: nasal swabs and a sputum sample (when available) still
need to meet the case definition for RSV-mediated LRTD. The ARI Day 1-2 nasal swab is a
self-swab collected at home by the participant, and the ARI Day 3-5 nasal swab and sputum
sample (when available) may also need to be collected at home, when site visits may not be
possible.
 
In the setting that on-site visits are not possible, a courier service will need to be arranged to
transport the samples to the site in a timely manner.
 
Questionnaires to be completed at the Day 365 visit, and additionally for participants with an
ARI episode on ARI Days 3-5 and 29, will be completed by the participant in the eDiary or
via a telephone or telemedicine interview with the participant, as applicable.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
139
Status: Approved, Date: 11 October 2022
10.14. Appendix 14: Thrombotic Events to be Reported as Potential AESIs
At the time of protocol writing, the list of thrombotic events to be reported to the sponsor as
potential AESIs is provided below. Further guidance may become available on thrombotic events
of interest.
 
MedDRA preferred terms (PTs) for large vessel thrombosis and embolism
 
Aortic embolus, aortic thrombosis, aseptic cavernous sinus thrombosis, brain stem
embolism, brain stem thrombosis, carotid arterial embolus, carotid artery thrombosis,
cavernous sinus thrombosis, cerebral artery thrombosis, cerebral venous sinus
thrombosis, cerebral venous thrombosis, superior sagittal sinus thrombosis, transverse
sinus thrombosis, mesenteric artery embolism, mesenteric artery thrombosis, mesenteric
vein thrombosis, splenic artery thrombosis, splenic embolism, splenic thrombosis,
thrombosis mesenteric vessel, visceral venous thrombosis, hepatic artery embolism,
hepatic artery thrombosis, hepatic vein embolism, hepatic vein thrombosis, portal vein
embolism, portal vein thrombosis, portosplenomesenteric venous thrombosis, splenic
vein thrombosis, spontaneous heparin-induced thrombocytopenia syndrome, femoral
artery embolism, iliac artery embolism, jugular vein embolism, jugular vein thrombosis,
subclavian artery embolism, subclavian vein thrombosis, obstetrical pulmonary
embolism, pulmonary artery thrombosis, pulmonary thrombosis, pulmonary venous
thrombosis, renal artery thrombosis, renal embolism, renal vein embolism, renal vein
thrombosis, brachiocephalic vein thrombosis, vena cava embolism, vena cava
thrombosis, truncus coeliacus thrombosis
 
MedDRA PTs for more common thrombotic events
 
Axillary vein thrombosis, deep vein thrombosis, pulmonary embolism, MedDRA PTs for
acute myocardial infarction*, MedDRA PTs for stroke*
Source: Shimabukuro T. CDC COVID-19 Vaccine Task Force. Thrombosis with thrombocytopenia syndrome (TTS)
following Janssen COVID-19 vaccine. Advisory Committee on Immunization Practices (ACIP). April 23, 2021.
https://www.cdc.gov/vaccines/acip/meetings/slides-2021-04-23.html.
*Vaccine Adverse Event Reporting System (VAERS) Standard Operating Procedures for COVID-19 (as of 29 January
2021) https://www.cdc.gov/vaccinesafety/pdf/VAERS-v2-SOP.pdf
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
140
Status: Approved, Date: 11 October 2022
10.15. Appendix 15: Protocol Amendment History
The Protocol Amendment Summary of Changes Table for the current amendment is located
directly before the Table of Contents (TOC).
Amendment 4 (8 April 2022)
Overall Rationale for the Amendment:
The available immunogenicity data generated in ongoing clinical studies with the Ad26/protein preF RSV
vaccine suggest that immune responses after a single vaccination are durable beyond one year, and that a
revaccination at Month 12 is likely not necessary for efficacy. Therefore, the second dose at Month 12 has
been removed from the protocol. Changes have been made to the planned analyses including the interim
analyses plan. The changes made to this clinical protocol as part of Protocol Amendment 4 are listed below,
including the rationale of each change and a list of all applicable sections.
Section Number
and Name
Description of Change 
Brief Rationale
1.1Synopsis;
Figure 1: 
Schematic Overview
of the Study for all Participants ;
1.3.1Schedule of Activities –
Assessments for All Participants ;
2.1Study Rationale;
3OBJECTIVES AND ENDPOINTS;
4.1Overall Design;
Table 2: Study Design:
VAC18193RSV3001;
5.1Inclusion Criteria;
5.2Exclusion Criteria;
5.5Criteria for Temporarily Delaying
Administration of Study Vaccine;
6.3Measures to Minimize Bias:
Randomization and Blinding;
6.8Concomitant Therapy
8 STUDY ASSESSMENTS AND
PROCEDURES
All references to revaccination
have been removed from the
design and study procedures etc,
including the safety follow-up
(calls, visits)
Immunogenicity data from
ongoing clinical studies with the
Ad26/protein preF RSV vaccine
suggest that the immune
responses after a single
vaccination are durable beyond
one year, and that a
revaccination at Month 12 is
likely not necessary.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
141
Status: Approved, Date: 11 October 2022
Section Number
and Name
Description of Change 
Brief Rationale
7 DISCONTINUATION OF STUDY
VACCINATION AND PARTICIPANT
DISCONTINUATION/WITHDRAWAL
7.1Discontinuation of Study
Vaccination;
8.5.5Pregnancy
Discontinuation of study
vaccination Section 7.1 is not
applicable because participants
will not receive a second
vaccination
A discussion about study
vaccination discontinuation in a
pregnant participant was deleted.
Participants will receive only 1
dose of active vaccine/placebo
1.1Synopsis;
2.1Study Rationale;
3OBJECTIVES AND ENDPOINTS;
4.1Overall Design;
8.1ARI Assessments and Procedures;
8.4Safety Assessments;
8.5.1Time Period and Frequency for
Collecting Adverse Event, Serious
Adverse Event, and Adverse Event of
Special Interest Information
The timing of safety assessments
has been revised in several
sections from “end of first RSV
season” or “end of second RSV
season” to time from vaccination.
To align the safety follow-up
process with the removal of the
second vaccination
5.1Inclusion Criteria;
Inclusion criterion 5
Inclusion criterion # 5 was
modified to delete the note
discussing the Month 12
revaccination.
Participants will receive only
1 dose of active
vaccine/placebo.
5.2Exclusion Criteria;
Exclusion criterion 16
Exclusion criterion #16 was
modified to remove reference to
the full course of vaccination
Participants will receive only
1 dose of active
vaccine/placebo.
5.2Exclusion Criteria;
Exclusion criterion 19
Exclusion criterion #19 was
modified to remove reference to a
subsequent vaccination
Participants will receive only
1 dose of active
vaccine/placebo.
5.2Exclusion Criteria;
Exclusion criterion 20
Exclusion criterion #20 was
modified to remove reference to
“each” vaccination.
Participants will receive only
1 dose of active
vaccine/placebo.
1.1Synopsis;
4.1Overall Design
Sample size was updated to clarify
the number of participants
enrolled in specific Asian
countries/territories under local
protocols
To clarify the number of
participants for which safety
data will be available
1.1Synopsis;
6.3Measures to Minimize Bias:
Randomization and Blinding;
9.4.1Efficacy Analysis;
9.4.2Immunogenicity Analyses;
9.5Planned Analyses
The planned analyses and
randomization sections were
updated to reflect the lack of a
second vaccination.
Revisions to planned analyses,
including the interim analyses
were made.
Statistical analyses were
updated to reflect revision to
objectives/endpoints/hypothesis,
to align with health authority
feedback and program needs.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
142
Status: Approved, Date: 11 October 2022
Section Number
and Name
Description of Change 
Brief Rationale
Figure 3: 
Interim and Primary
Analysis Plan
1.1Synopsis;
1.2Schema;
2.1Study Rationale;
4.1Overall Design;
8.1 ARI Assessments and Procedures;
9STATISTICAL CONSIDERATIONS
The study duration was increased
to 24 months from date of
vaccination (Day 1).
To allow a full 2-year follow-up
of all participants
1.3.2Schedule of Activities –
Assessments for Participants with an
ARI Episode;
4.1Overall Design;
8.1ARI Assessments and Procedures
Information from a protocol
clarification communication
(PCC) was included on the blood
sample collection and Day 3-5
ARI visit.
PCC text:
To reduce the burden on the
participant and to avoid collection
of blood samples (ie, serology
blood sample, whole blood
PAXgene sample and whole blood
sample with PROT1 stabilizer),
not related to an
RSV/hMPV/influenza related
ARI, participants and investigators
can choose the preferred option
during each Day 3-5 visit
between:
1) Collecting blood samples
before the nasal swab samples are
tested or in the setting where a
sputum sample is collected
independent of the RT-PCR
results;
2) Collecting blood samples after
the nasal swab RT-PCR results are
available, according to nasal swab
test results, and for ARIs where
there is no sputum sample
collection. If this is the preferred
option by the participant and
investigator, the participant will
need to wait at the site for the time
needed to test the swab samples
(estimated time: 2 hours). In this
scenario, if the swab samples are
negative for RSV, hMPV and
influenza AND if no sputum
sample can be collected, the blood
samples collection at the ARI Day
To reduce the burden on the
participant during an ARI
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
143
Status: Approved, Date: 11 October 2022
Section Number
and Name
Description of Change 
Brief Rationale
3-5 timepoint can be omitted. If
the swab samples are positive for
RSV, hMPV or influenza OR if a
sputum sample is collected, the
blood samples collection has to be
performed.
Whenever a sputum sample is
collected during the ARI Day 3-5
visit, the blood sample must still
be collected as the RT-PCR test
on the sputum sample will be
performed at the central lab and
not on site.
Also, note that a split ARI Day 3-
5 visit is not allowed.
1.1Synopsis; 
4.1Overall Design;
8.2.4Diagnosis of RSV and Other 
Respiratory Infections; 
Figure 2: 
Schematic Overview
of the ARI Assessments and Procedures
RT-PCR test results related to the
detection of respiratory pathogens
other than RSV, hMPV and
influenza can be communicated to
participants
Clarification that RT-PCR
results related to the detection
of other respiratory pathogens
can be communicated to
participants
1.3.1Schedule of Activities – 
Assessments for All Participants; 
8STUDY ASSESSMENTS AND
PROCEDURES
Total blood volumes have been
reduced because the second
vaccination will not be
administered.
Blood draws associated with the
second vaccination will not be
collected.
2.3.1Risks of Study Participation 
The risks related to Ad26/protein
preF RSV vaccine have been
updated
Based on ongoing clinical trial
data, the risks to the active
vaccine have been updated.
Throughout protocol 
Wording revisions to references
and procedures related to a second
vaccination and to references
related to RSV season.
Minor typographical corrections.
Clarification
Throughout protocol 
Language was updated from
“should” to “must” in applicable
sections to reflect updated
template language
Update to protocol template
language
Amendment 3 (10 November 2021)
Overall Rationale for the Amendment: This amendment is made to align the protocol following
comments from CBER that all cases meeting the programmed case definition of RT-PCR confirmed RSV
lower respiratory tract disease (LRTD) should be reviewed by the Clinical Event Adjudication Committee
(CEC). Additionally, to increase the probability of having a primary analysis at the end of the first RSV
season, an interim analysis by the IDMC has been added if the number of observed RSV cases is ≥24 to
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
144
Status: Approved, Date: 11 October 2022
<62. If the interim analysis by the IDMC has positive results, then the study will be unblinded and the
primary analysis will be performed by the sponsor. The changes made to this clinical protocol as part of
Protocol Amendment 3 are listed below, including the rationale of each change and a list of all applicable
sections.
Section Number 
and Name
Description of Change 
Brief Rationale
1.1 Synopsis; 4.1 Overall Design;
8.2.1 Case Definition for RT-PCR-
confirmed RSV-mediated LRTD;
9.4.1.4 Exploratory Endpoints; 9.6.2
Clinical Event Adjudication
Committee (new section); 10.2.6.2
Clinical Event Adjudication
Committee (new section)
The Clinical Event Adjudication
Committee (CEC) will review all
available data of all RSV-mediated
acute respiratory infections (ARIs)
and will confirm if the RT-PCR-
confirmed RSV-mediated LRTD
definition criteria were met. Further
for all RT-PCR-confirmed RSV
LRTD cases the CEC will assess their
severity (mild, moderate or severe).
To use the outcome of the
adjudication performed by the
CEC on each protocol-defined
RSV-positive ARI for primary
and secondary endpoints related
to LRTD and to have an
independent expert clinical
assessment on the severity of
each RSV-positive LRTD case
for the exploratory related
endpoint.
1.1 Synopsis; 2.1 Study Rationale; 3
OBJECTIVES AND ENDPOINTS;
9.1 Statistical Hypotheses; 9.4.1.1
Primary Endpoint; 9.4.1.2
Secondary Efficacy Endpoints;
9.4.1.3 Testing Strategy for Primary
and Confirmatory Secondary
Endpoints; 9.4.1.4 Exploratory
Endpoints; 9.5.1 Analysis Plan for
the Interim and Primary Analyses;
9.6.1 Independent Data Monitoring
Committee; 10.2.6.1 Independent
Data Monitoring Committee
An interim analysis (IA) at the end of
the RSV season was added. An IA
will be performed by the IDMC if the
number of primary endpoint events
observed is ≥24 and <62. If the
interim analysis by the IDMC has
positive results, then the study will be
unblinded and the primary analysis
will be performed by the sponsor. If
≥62 primary endpoint events are
observed, then the primary analysis
(PA) will be performed by the
sponsor. The testing strategy was
updated accordingly. There will be at
most one IA by the IDMC.
To increase the probability of
having a primary analysis at the
end of the first NH RSV season,
in the event of an atypical RSV
season.
6.3 Measures to Minimize Bias:
Randomization and Blinding; 9.5.2
Year 2 Analysis (new section); 9.5.3
End-of-Study Analysis
For a NH + SH study, a Year 2
analysis is added prior to the final
analysis. If the PA occurs prior to or at
the end of the second NH RSV season,
the Year 2 analysis will be performed
at the end of the second NH RSV
season. The second SH RSV season
will be considered supportive. If the
PA occurs only at the end of the
second SH RSV season, then the Year
2 analysis will coincide with the final
analysis.
To increase the likelihood to
have key confirmatory
secondary endpoints available at
the end of the second NH RSV
season.
1.1 Synopsis; 3 OBJECTIVES
AND ENDPOINTS; 9.4.1.4
Exploratory Endpoints
An objective was added to explore the
relative VE against RT-PCR
confirmed RSV-mediated LRTD
during the second RSV season and
over the whole study between the
group with active vaccination at Day 1
and Day 365 and the group with active
vaccination at Day 1.
To comply with regulatory
authority recommendations.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
145
Status: Approved, Date: 11 October 2022
Section Number
and Name
Description of Change 
Brief Rationale
2.1 Study Rationale; 6.3 Measures
to Minimize Bias: Randomization
and Blinding; 9.2.2
Immunogenicity; 9.2.3 Safety
Removal of reference to NH only
scenario.
The study will be recruited in the
NH + SH.
1.3.1 Schedule of Activities –
Assessments for All Participants;
9.5.1 Analysis Plan for the Interim
and Primary Analyses, Footnote to
Figure 3
The end of RSV season dates were
shifted by 2 weeks earlier.
There are indications of shifting
seasonality.
1.1 Synopsis; 1.3.2 Schedule of
Activities –Assessments for
Participants with an ARI Episode;
4.1 Overall Design; 8 STUDY
ASSESSMENTS AND
PROCEDURES; 8.1 ARI
Assessments and Procedures
Additional instructions were provided
with regard to ARI Day 3-5 sample
collection in case of first positivity for
SARS-CoV-2 infection during ARI
Day 1-2 and subsequent self-isolation.
For these cases, 2 swab kits will be
provided to the participant.
Because of local regulations,
participants whose standard-of-
care testing is positive for
SARS-CoV-2 at ARI Day 1-2
will not come to the site for the
ARI Day 3-5 visit. Therefore,
additional kit material is
provided to self-collect the ARI
Day 3-5 swab.
1.1 Synopsis; 8.1 ARI Assessments
and Procedures; 8.2 Efficacy
Assessments; 8.2.4 Diagnosis of
RSV and Other Respiratory
Infections
Clarification on central testing, in case
BioFire Filmarray Respiratory panel
unavailability in the country or at the
site.
Due to logistic reasons, it may
be that the BioFire Filmarray
Respiratory panel will not be
available in some countries or
sites. This change introduces the
possibility to perform these tests
centrally, in this circumstance.
2.3.1 Risks of Study Participation;
8.5.5 Pregnancy
In case of pregnancy, postnatal
sequelae in the infant will not be
followed-up.
Note: Follow up info regarding the
outcome of the pregnancy of the study
participant themselves or of the
partner of the participant will be
requested (upon consent).
According to the current Janssen
SOP ‘Receipt, Follow-up, and
Reporting of Janssen Medicinal
Product Individual Case Safety
Reports’, follow-up of postnatal
sequelae in the infant is not a
requirement.
The sponsor protocol template is
planned to be modified to reflect
this change.
5.1 Inclusion Criteria, Criterion #5 
Footnote for Inclusion Criterion 5 was
updated to allow participants with
values for vital signs measurements
≤Grade 3 (other than temperature) to
be enrolled in the study, if the values
are deemed not clinically significant
by the investigator.
To clarify that participants with
a Grade 3 vital sign abnormality
at screening may also be eligible
for the study.
5.2 Exclusion Criteria, Criterion 
#11 
Footnote for Exclusion Criterion 11
was updated to allow participants who
participate in the observational phase
of interventional studies to be enrolled
in the study, if approved by the
sponsor or its delegate.
To clarify that participants who
participate in the observational
phase of an interventional study
at screening may also be eligible
for the study.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
146
Status: Approved, Date: 11 October 2022
Section Number
and Name
Description of Change 
Brief Rationale
1.3.1 Schedule of Activities –
Assessments for All Participants
Update of the relevant medical history
to be reported including thrombotic
events and/or thrombocytopenia.
To facilitate the assessment of
adverse events of special interest
(AESIs) reported during the
study.
8.5.1 Time Period and Frequency
for Collecting Adverse Event,
Serious Adverse Event, and
Adverse Event of Special Interest
Information; 8.5.6.1 Thrombosis
with Thrombocytopenia Syndrome
To remove the word “Symptomatic”
from “Symptomatic
Thrombocytopenia”.
The definition of
thrombocytopenia was
broadened to include all cases of
thrombocytopenia the
investigators observe (including
participant’s routine blood test
or blood test performed
concomitantly to any AE/SAE/
hospitalization, or any other) in
the period of 6 months after
vaccination; these should be
reported as AESIs.
1.3.1 Schedule of Activities – 
Assessments for All Participants – 
footnote z; 8.5.6.1 Thrombosis with 
Thrombocytopenia Syndrome 
Additional language referring to
laboratory diagnostic tests for the
assessment of potential AESIs is
added.
To facilitate and simplify the
local site management of
potential AESIs.
5 STUDY POPULATION; 1.3.1 
Schedule of Activities – 
Assessments for All Participants 
To clarify that in case of a split visit,
efforts should be made that the visits
occur preferably within 3 to 5 days but
no later than 14 days apart.
To ensure that the health
conditions of the potential
participant are unchanged during
the split visit window.
1.3.1 Schedule of Activities – 
Assessments for All Participants; 8 
STUDY ASSESSMENTS AND 
PROCEDURES –Visit Windows. 
Clarification that efforts should be
made so that revaccination occurs not
earlier than mid-June 2022 for the NH
countries, and not earlier than
November 2022 for the SH countries,
and not later than the expected peak of
the RSV season in both NH and SH
countries, respectively. In addition, for
each participant there should be a
minimum of 6 months between the
first and the second vaccination.
To increase the likelihood that
participants are revaccinated
prior to or around the start of the
season during the second year
given the unpredictability of the
RSV season.
Throughout the protocol 
Minor clarifications, grammatical,
formatting, or spelling changes were
made.
Minor errors were noted.
Amendment 2 (19 July 2021)
Overall Rationale for the Amendment: This protocol has been created to align the information and
guidance for investigators on signs and symptoms and on medical management of thrombosis with
thrombocytopenia syndrome (TTS) events across the VAC18193 program.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
147
Status: Approved, Date: 11 October 2022
Section Number
and Name
Description of Change 
Brief Rationale
1.1 Synopsis
1.3.1 Schedule of Activities –
Assessments for All Participants
4.1 Overall Design
6.7 Overdose
6.8 Concomitant Therapy
7.1 Discontinuation of Study
Vaccination
8.4 Safety Assessments
8.5.6 Adverse Events of Special
Interest
9.2.3 Safety
10.1 Appendix 1: Abbreviations
10.14 Appendix 14: Thrombotic
Events to be Reported as Potential
AESIs
11 REFERENCES
1.1 Synopsis
1.3.1 Schedule of Activities –
Assessments for All Participants
2.2 Background
2.3.3 Benefit-Risk Assessment of
Study Participation
5.2 Exclusion Criteria
8.4 Safety Assessments
8.5 Adverse Events, Serious
Adverse Events, Adverse Events
of Special Interest, and Other
Safety Reporting
8.5.1 Time Period and Frequency
for Collecting Adverse Event,
Serious Adverse Event, and
Adverse Event of Special Interest
Information
8.5.2 Method of Detecting
Adverse Events, Serious Adverse
Events, and Adverse Events of
Special Interest
8.5.3 Follow-up of Adverse
Events, Serious Adverse Events,
and Adverse Events of Special
Interest
8.5.6 Adverse Events of Special
Interest
8.5.6.1 Thrombosis with
Thrombocytopenia Syndrome
10.1 Appendix 1: Abbreviations
10.2.6 Committees Structure
10.3 Appendix 3: Adverse Events,
Serious Adverse Events, Adverse
Event of Special Interest, Product
Quality Complaints, and Other
Safety Reporting: Definitions and
To rename the immediately reportable
events (IREs) to (potential) adverse
events of special interest (AESIs) and
to update the case definition including
potential cases and symptomatic
thrombocytopenia.
To align the wording on
information and guidance for
investigators on signs and
symptoms and on medical
management of TTS across the
RSV vaccine (VAC18193)
program.
To add AdVac safety wording and to
update and wording on information and
guidance for investigators on signs and
symptoms and on medical management
of thrombosis with thrombocytopenia
syndrome (TTS).
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
148
Status: Approved, Date: 11 October 2022
Section Number
and Name
Description of Change 
Brief Rationale
Procedures for Recording,
Evaluating, Follow-up, and
Reporting
10.3.5 Procedures
10.14 Appendix 14
11 REFERENCES
1.1 Synopsis
1.3.2 Schedule of Activities –
Assessments for Participants with
an ARI Episode
4.1 Overall Design
8.1 ARI Assessments and
Procedures
8.2 Efficacy Assessments
8.2.4 Diagnosis of RSV and Other
Respiratory Infections
8.6 Medical Resource Utilization
and Health Economics
To change the BioFire Filmarray
RP2.1-EZ panel to the BioFire
Filmarray Respiratory panel.
To generalize the type of BioFire
Filmarray that is used to test for
RSV, hMPV, and influenza.
1.1 Synopsis
1.3.2 Schedule of Activities –
Assessments for Participants with
an ARI Episode
4.1 Overall Design
8.1 ARI Assessments and
Procedures
9.4.1.1 Primary Endpoint
To change “Participants with a RT-
PCR-confirmed…” to “Participants
with an ARI and a RT-PCR positive
for…”
To clarify the testing of
participants who have an ARI and
have a RT-PCR that is positive
for RSV, hMPV or influenza.
1.1 Synopsis
3 OBJECTIVES AND
ENDPOINTS
9.4.1.4 Exploratory Endpoints
Minor changes to the planned analyses. 
To align with the statistical
Analysis plan (SAP).
1.1 Synopsis
1.3.2 Schedule of Activities –
Assessments for Participants with
an ARI Episode
4.1 Overall Design
8.2.4 Diagnosis of RSV and Other
Respiratory Infections
To update footnote b in the Schedule of
Activities –assessments for
participants with an ARI Episode and
to provide more guidance on the
disclosure of RT-PCR results to the
participants in the study.
To clarify that the RT-PCR
results for RSV, hMPV, and
influenza are not shared with the
participant.
1.1 Synopsis
1.3.2 Schedule of Activities –
Assessments for Participants with
an ARI Episode
4.1 Overall Design
8.1 ARI Assessments and
Procedures
8.2.4 Diagnosis of RSV and Other
Respiratory Infections
Participants who have a positive
SARS-CoV-2 RT-PCR test as part of
the study procedures should be referred
to their own healthcare provider for a
locally approved diagnostic test
and further management, in
accordance with local/site
specific guidelines.
To clarify the study procedures
for participants who have a
positive SARS-CoV-2 RT-PCR
test.
1.1 Synopsis
8.3 Immunogenicity Assessments
Added further details of assays that
will be used for assessment of RSV
cross-neutralization.
To clarify assays in scope for the
corresponding exploratory
endpoint.
1.1 Synopsis
8.3 Immunogenicity Assessments
Blood samples from all participants for
immunogenicity are collected for the
analysis of correlates of risk of RSV
disease and correlates of protection.
To specify the purpose of the
immunogenicity samples.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
149
Status: Approved, Date: 11 October 2022
Section Number 
and Name
Description of Change 
Brief Rationale
Throughout the protocol 
Minor grammatical, formatting, or 
spelling changes were made.
Minor errors were noted.
Amendment 1 (3 May 2021)
Overall Rationale for the Amendment: Several changes are made to follow recommendations from
regulatory authorities (eg, update of the primary hypothesis of vaccine efficacy against RT-PCR- confirmed
RSV mediated lower respiratory tract disease (LRTD), stratification and minimization factors for the
randomization, secondary endpoints testing strategy).
Section Number 
and Name
Description of Change 
Brief Rationale
1.1 Synopsis;
1.3.2 Schedule of
Activities–Assessments
for Participants with an
ARI Episode;
4.1 Overall Design;
8.1 ARI Assessments and
Procedures;
8.2 Efficacy Assessments
Sputum testing will be performed at the
central laboratory; in those cases (when
sputum is collected and sent to the central
laboratory), the ARI episode will be followed
up independent of the RT-PCR results from
the nasal swabs.
To ensure that all sputum samples
collected during ARI episodes
will be tested in a CLIA-certified
laboratory.
1.1 Synopsis;
1.3.1 Schedule of
Activities –Assessments
for All Participants;
3 OBJECTIVES AND
ENDPOINTS;
4.1 Overall Design;
6.7 Overdose;
6.8 Concomitant Therapy;
7.1 Discontinuation of
Study Vaccination;
8.4 Safety Assessments;
8.5.6 Immediately
Reportable Events;
9.4.3 Safety Analyses;
Appendix 14: Immediately
Reportable Events
The Schedule of Activities and the text were
updated to include wording about collection of
immediately reportable events (IREs).
The reporting of IREs was
implemented to ensure complete
information will be available for
all thrombotic events allowing
evaluation of those events.
1.1 Synopsis;
1.3.1 Schedule of
Activities –Assessments
for All Participants;
8.4 Safety Assessments;
8.5.1 Time Period and
Frequency for Collecting
Adverse Event and Serious
Adverse Event
Information;
9.4.3 Safety Analyses
The Schedule of Activities and the text were
updated to include wording about collection of
all events of COVID-19 infection.
The reporting of any severity
COVID 19 cases was
implemented to ensure complete
information will be available.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
150
Status: Approved, Date: 11 October 2022
Section Number
and Name
Description of Change 
Brief Rationale 
1.1 Synopsis;
1.3.2 Schedule of
Activities–Assessments
for Participants with an
ARI Episode;
4.1 Overall Design;
8.1 ARI Assessments and
Procedures; Appendix 9
Full RiiQ (Appendix 9) collection was
substituted by the RiiQ Symptom Scale and
the RiiQ Impact on DailyActivities Scale
(Appendix 8). Appendix 9 was deleted.
To comply with regulatory
authorities recommendations and
to have a more specific and
simplified PRO collection during
ARI episode.
1.1 Synopsis;
3 OBJECTIVES AND
ENDPOINTS, Secondary
Endpoints
The secondary endpoint comparing the area
under the curve of the change from baseline in
the RiiQ Total Symptom score in participants
with an RT-PCR-confirmed RSV-mediated
ARI over the whole study was moved to be a
non-confirmatory secondary endpoint.
To comply with regulatory
authority recommendations.
1.1 Synopsis;
4.1 Overall Design;
8.1 ARI Assessments and
Procedures
Footnote was added to clarify the process to
confirm a potential ARI episode.
To clarify the process to confirm
a potential ARI episode.
1.1 Synopsis;
4.1 Overall Design;
8.1 ARI Assessments and
Procedures
Specified that during an ARI episode, in the 
event of concomitant positivity to RSV (or 
hMPV or influenza) and SARS-Cov-2, the 
participants should keep on filling in the ARI 
questionnaire during the entire ARI episode.
The process to stop answer ARI
related questionnaires in the
eDiary by the participant during
an ARI episode was clarified.
1.1 Synopsis;
4.1 Overall Design;
9.2 Sample Size
Determination
Specified that the sponsor is monitoring the 
RSV incidence across the countries involved. 
If the collected information combined with 
ongoing datascience and modeling activities
indicate that the incidence assumptions can be
increased, the sponsor can decrease the sample
size during the recruitment of the study.
To allow sample size decrease
based on ongoing datascience and
modeling activities.
1.1 Synopsis;
4.2 Scientific Rationale for
Study Design;
8.7 Participant Medical
Information Prior to,
During and After the Study
(Real-world Data)
Wording was updated to clarify that, even 
though consent is optional, real-world data 
should be considered as part of the study data. 
To align all sections of the
protocol with the exploratory
study endpoint “Utilization of
tokenization and matching
procedures for exploratory
analysis of participant’s medical
data prior to, during, and
following participation in the
study (real-world data). Analysis
will be performed to relate real-
world data to vaccine immune
responses, efficacy and duration
of protection, and AEs”.
1.1 Synopsis;
8.1 ARI Assessments and
Procedures
If it is not possible to perform the swab testing 
at the site, the swab sample needs to be tested 
centrally and the ARI episode should be 
followed up until resolution of the ARI 
episode. 
To ensure that all available
samples will be tested and used
for the study-related analyses, the
central laboratory will function as
back-up.
1.1 Synopsis;
8.2.2 Case Definition for
RT-PCR-confirmed RSV-
mediated ARI
The ARI case definition was clarified. 
To comply with regulatory
authority recommendations and to
ensure compliance on data
collection.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
151
Status: Approved, Date: 11 October 2022
Section Number
and Name
Description of Change 
Brief Rationale 
1.1 Synopsis;
8.2.3 Predefined Clinically
Relevant Disease
Associated with RT-PCR-
confirmed RSV-mediated
ARI
Wording was updated to clarify the definition
ofdecreased oxygen saturation.
To avoid inconsistencies due to
the use of oxygen saturation
collected with devices/techniques
characterized by different
specifications/accuracies.
1.1 Synopsis;
8.3 Immunogenicity
Assessments
A sentence was added specifying that the
analysis is to be performed on Immuno Subset
only.
To align Section 8.3 with the
secondary objective “in the
Immuno Subset and in subgroups
of the Immuno Subset (including
but not limited to participants at
increased risk of severe RSV
disease), to evaluate the
immunogenicity of active study
vaccine when compared to
placebo”.
1.1 Synopsis;
3 OBJECTIVES AND
ENDPOINTS;
9.1 Statistical Hypotheses;
9.4.1.1 Primary Endpoint
The null hypothesis of LL ≤20% for RT-PCR-
confirmed RSV-mediated LRTD will be tested
versus the alternative hypothesis of LL >20%.
The success criterion was updated to align
with the updated hypotheses and additionally
requires a point estimate for the vaccine
efficacy (VE) of the primary endpoint >50%.
To comply with regulatory
authority recommendations.
1.1 Synopsis;
9.2 Sample Size
Determination
The sample size assumptions and power were
updated to align with the new primary
hypothesis.
To comply with regulatory
authority recommendations.
1.3.1 Schedule of
Activities –Assessments
for All Participants
Table was updated to report height, weight,
and smoking status.
To collect data to assess the
potential impact of BMI, smoking
status and underling relevant
medical conditions on the ARI
reporting.
Footnote j was updated to also include
reporting of Type 2 diabetes and chronic
kidney diseases (CKD) in Relevant Medical
History.
1.3.1 Schedule of 
Activities –Assessments 
for All Participants; 
8.4.1 Physical 
Examinations
Text was added to specify that at each clinical 
visit an abbreviated, symptom-directed 
physical examination will be performed if
deemed necessary by the investigator.
To ensure a complete safety
follow up of the participant.
2.3.1 Risks of Study 
Participation; 
2.3.2 Benefits of Study 
Participation  
Text was updated. 
The risk section was updated with
currently available data and
focusing on Ad26/protein preF
RSV vaccine.
5.2 Exclusion Criteria 
In the exclusion criterion 4 the words 
“diabetes mellitus” were replaced by the 
words “type 1 diabetes”.
To specify that type 1 diabetes is
not an exclusion criterion.
Per exclusion criterion 4, prior use of chronic 
or recurrent systemic corticosteroids is 
prohibited. 
Text was updated to reduce the
risk to enroll participants using
systemic corticosteroids
impacting immune response at the
time of enrolment.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
152
Status: Approved, Date: 11 October 2022
Section Number 
and Name
Description of Change 
Brief Rationale
Exclusion criterion 5 was updated and a new 
exclusion criterion 19 was added to cover all 
potential types of SARS-CoV-2 vaccines a 
participant could receive before or during the 
study.
Text was updated to provide
guidance on the enrollment of
participants who received SARS-
CoV-2 vaccines.
A note on monoclonal antibodies use was 
added to exclusion criterion 10. 
Text was updated to clarify the
exclusion criterion related to
monoclonal antibodies
administration.
Exclusion criterion 13 was updated and 
criterion 20 was added to clarify the exclusion 
criteria related to participants who have 
received an Ad26-vectored vaccine. 
Text was updated to o provide
guidance on the enrolment of
participants who received another
Ad26-based vaccine.
Exclusion criterion 14 was deleted. 
The criterion was redundant as
disallowed therapy before
enrollment is already covered by
exclusion criteria 4 and 10.
6.3 Measures to Minimize 
Bias: Randomization and 
Blinding 
The text was updated to consider regions and 
subset as minimization criteria instead of 
stratification factors.
To comply with regulatory
authority recommendations.
6.6 Continued Access to 
Study Vaccine After the 
End of the Study  
New section. 
Section was added to clarify the
access to the vaccine after the end
of the study.
6.8 Concomitant Therapy  
Text was updated. 
Section was updated for
alignment with the amended
exclusion criteria.
1.1 Synopsis; 
4.1 Overall Design; 
8.1 ARI Assessments and 
Procedures;
8.2 Efficacy Assessments;
9.4.1.1 Primary Endpoint
Text was updated specifying that local RT- 
PCR testing will be performed using the 
BioFire® Filmarray RP2.1-EZ panel.
To comply with regulatory
authority recommendations.
Sentence was added to clarify that central RT- 
PCR testing can function as a back-up option 
in case a local RT-PCR test cannot be 
performed.
To avoid missing any important
information on RT- PCR testing
during ARI episode.
8.1 ARI Assessments and 
Procedures 
Specified that if ARI is ongoing at Day 29, 
ARI questionnaires will be triggered until the 
end of the ARI episode. 
The process to stop answer ARI
related questionnaires in the
eDiary by the participant during
an ARI episode was clarified.
8.1.3 Patient Global 
Impression Scores 
Appendix 10: Patient
Global Impression Scales
The response categories for the PGI-S were 
updated. 
To comply with regulatory
authority recommendations.
8.2.4 Diagnosis of RSV 
and Other Respiratory 
Infections 
New section 8.2.4 was added. 
To clarify the distribution and the
purposes of site and central RT-
PCR testing.
8.5.5 Pregnancy  
Text was updated. 
Text was updated to ensure
complete safety follow up of the
participants.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
153
Status: Approved, Date: 11 October 2022
Section Number 
and Name
Description of Change 
Brief Rationale
9.4.1.4 Exploratory 
Endpoints 
The Clinical Evaluation Committee (CEC) 
review will assess, independently and based 
on CRF/eDiary data, the location of the ARI 
(upper or lower respiratory tract infection) and 
the ARI severity. Exploratory endpoints were 
added to explore the efficacy of active study 
vaccine in the prevention of an RT-PCR
confirmed RSV lower respiratory infection as
assessed by the CEC compared to placebo.
To comply with regulatory
authority recommendations, a
CEC review was added to
independently assess the location
of the RSV ARIs and their
severity.
10.2.1 Regulatory and 
Ethical Considerations 
New section on Protocol Clarification 
Communications was added. 
To align with the most recent
Janssen protocol template.
10.2.6 Committees 
Structure 
The sentence “The IDMC will also formally 
monitor the efficacy endpoints at the
timepoints specified in Section 9.5, Planned
Analyses” was deleted.
To align with analysis section.
Throughout the protocol 
The number of RT-PCR-confirmed RSV- 
mediated LRTD events was changed from 50 
to 52.
The number was changed to align
with the updated success criteria.
Throughout the protocol 
Minor grammatical, formatting, or spelling
changes were made. Parenthetical referencing
was applied.
NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
154
Status: Approved, Date: 11 October 2022
11. 
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NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
155
Status: Approved, Date: 11 October 2022
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NCT04908683

VAC18193 (Ad26.RSV.preF [JNJ-64400141]/ RSV preF Protein [JNJ-64213175])
Clinical Protocol VAC18193RSV3001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
156
Status: Approved, Date: 11 October 2022
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 intervention, 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.
NCT04908683
PPD

Signature
User 
Date 
Reason
 
12-Oct-2022
11:08:28
(GMT)
Document Approval
NCT04908683
PPD