A Randomized, Double-blind, Placebo-controlled Phase 2a Study to Evaluate a Range of Dose Levels of an Ad26.RSV.preF-based Vaccine in Adults Aged 60 Years and Older
Phase: PHASE2
Conditions: Healthy
Sponsor: Janssen Vaccines & Prevention B.V.

1
Status: Approved,  Date: 16 March 2020
Janssen Vaccines & Prevention B.V.*
Clinical Protocol
A Randomized, Double-blind, Placebo-controlled Phase 2a Study to Evaluate a Range of 
Dose Levels of an Ad26.RSV.preF-based Vaccine in Adults Aged 60 Years and Older
Protocol VAC18193RSV2005; Phase 2a
VAC18193 (JNJ-64400141/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).
Status:
Approved
Date:
16 March 2020
Prepared by:
Janssen Vaccines & Prevention B.V.
EDMS number:
EDMS-ERI-201635401, 2.0
GCP Compliance: This study will be conducted in compliance with Good Clinical Practice, and applicable regulatory 
requirements.
Confidentiality Statement
The information in this document contains trade secrets and commercial information that are privileged or confidential and 
may not be disclosed unless such disclosure is required by applicable law or regulations. In any event, persons to whom the 
information is disclosed must be informed that the information is privileged or confidential and may not be further disclosed
by them. These restrictions on disclosure will apply equally to all future information supplied to you that is indicated as 
privileged or confidential.
NCT04453202

VAC18193 (JNJ-64400141/JNJ-64213175)
Clinical Protocol VAC18193RSV2005
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Status: Approved,  Date: 16 March 2020
TABLE OF CONTENTS
TABLE OF CONTENTS ............................................................................................................................... 2
LIST OF IN-TEXT TABLES AND FIGURES................................................................................................ 4
1.
PROTOCOL SUMMARY ..................................................................................................................... 5
1.1.
Synopsis........................................................................................................................................... 5
1.2.
Schema .......................................................................................................................................... 12
1.3.
Schedule of Activities..................................................................................................................... 13
1.3.1.
Cohort 1 ...................................................................................................................................... 13
1.3.2.
Cohorts 2 and 3 .......................................................................................................................... 15
2.
INTRODUCTION................................................................................................................................ 17
2.1.
Study Rationale.............................................................................................................................. 17
2.2.
Background .................................................................................................................................... 17
2.2.1.
Ad26.RSV.preF and RSV preF Protein Nonclinical Studies....................................................... 18
2.2.2.
Ad26.RSV.preF and RSV preF Protein Clinical Studies ............................................................ 18
2.3.
Benefit-risk Assessment................................................................................................................. 20
2.3.1.
Known Benefits........................................................................................................................... 20
2.3.2.
Potential Benefits........................................................................................................................ 20
2.3.3.
Known Risks............................................................................................................................... 21
2.3.4.
Potential Risks............................................................................................................................ 21
2.3.5.
Overall Benefit-risk Assessment................................................................................................. 23
3.
OBJECTIVES AND ENDPOINTS ..................................................................................................... 25
4.
STUDY DESIGN ................................................................................................................................ 27
4.1.
Overall Design................................................................................................................................ 27
4.2.
Scientific Rationale for Study Design............................................................................................. 29
4.2.1.
Study-Specific Ethical Design Considerations ........................................................................... 30
4.3.
Justification for Dose Level ............................................................................................................ 30
4.4.
End of Study Definition................................................................................................................... 31
5.
STUDY POPULATION ...................................................................................................................... 31
5.1.
Inclusion Criteria ............................................................................................................................ 31
5.2.
Exclusion Criteria ........................................................................................................................... 32
5.3.
Lifestyle Considerations................................................................................................................. 35
5.4.
Screen Failures .............................................................................................................................. 35
6.
STUDY VACCINE.............................................................................................................................. 35
6.1.
Study Vaccine Administration ........................................................................................................ 35
6.2.
Preparation/Handling/Storage/Accountability ................................................................................ 36
6.3.
Measures to Minimize Bias: Randomization and Blinding............................................................. 37
6.4.
Study Vaccine Compliance ............................................................................................................ 38
6.5.
Concomitant Therapy..................................................................................................................... 39
6.6.
Intervention After the End of the Study.......................................................................................... 39
7.
DISCONTINUATION OF STUDY VACCINATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ............................................................................................... 40
7.1.
Discontinuation of Study Vaccination............................................................................................. 40
7.2.
Contraindications to Study Vaccination ......................................................................................... 40
7.3.
Study Vaccination Pausing Rules .................................................................................................. 40
7.4.
Participant Discontinuation/Withdrawal From the Study................................................................ 42
7.4.1.
Withdrawal From the Use of Research Samples ....................................................................... 43
7.5.
Lost to Follow-up............................................................................................................................ 43
8.
STUDY ASSESSMENTS AND PROCEDURES ............................................................................... 43

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8.1.
Immunogenicity Assessments ....................................................................................................... 45
8.2.
Safety Assessments....................................................................................................................... 46
8.2.1.
Physical Examinations................................................................................................................ 46
8.2.2.
Vital Signs................................................................................................................................... 46
8.2.3.
Clinical Safety Laboratory Assessments .................................................................................... 47
8.3.
AEs and SAEs................................................................................................................................ 48
8.3.1.
Time Period and Frequency for Collecting AE and SAE Information......................................... 48
8.3.2.
Method of Detecting AEs and SAEs........................................................................................... 49
8.3.3.
Follow-up of AEs and SAEs ....................................................................................................... 50
8.3.4.
Regulatory Reporting Requirements for SAEs........................................................................... 50
8.3.5.
Pregnancy................................................................................................................................... 50
8.4.
Treatment of Overdose .................................................................................................................. 50
8.5.
Genetics ......................................................................................................................................... 51
8.6.
Medical Resource Utilization and Health Economics .................................................................... 51
9.
STATISTICAL CONSIDERATIONS.................................................................................................. 51
9.1.
Statistical Hypotheses.................................................................................................................... 51
9.2.
Sample Size Determination ........................................................................................................... 51
9.2.1.
Immunogenicity (Cohort 1) ......................................................................................................... 51
9.2.2.
Safety (Cohorts 1, 2, and 3) ....................................................................................................... 52
9.3.
Populations for Analyses................................................................................................................ 52
9.4.
Statistical Analyses ........................................................................................................................ 52
9.4.1.
Participant Information................................................................................................................ 53
9.4.2.
Immunogenicity Analyses........................................................................................................... 53
9.4.3.
Safety Analyses .......................................................................................................................... 54
9.5.
Planned Analyses .......................................................................................................................... 55
9.6.
Data Monitoring Committee or Other Review Board ..................................................................... 55
10.
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ............................ 56
10.1.
Appendix 1: Abbreviations ............................................................................................................. 56
10.2.
Appendix 2: Toxicity Grading Scale............................................................................................... 57
10.3.
Appendix 3: Adverse Events: Definitions and Procedures for Recording, Evaluating, 
Follow-up, and Reporting............................................................................................................... 61
ADVERSE EVENT DEFINITIONS AND CLASSIFICATIONS.............................................................. 61
ATTRIBUTION DEFINITIONS.............................................................................................................. 62
SEVERITY CRITERIA .......................................................................................................................... 62
SPECIAL REPORTING SITUATIONS ................................................................................................. 62
PROCEDURES .................................................................................................................................... 63
CONTACTING SPONSOR REGARDING SAFETY............................................................................. 64
PQC HANDLING .................................................................................................................................. 64
10.4.
Appendix 4: Regulatory, Ethical, and Study Oversight Considerations......................................... 66
REGULATORY AND ETHICAL CONSIDERATIONS .......................................................................... 66
FINANCIAL DISCLOSURE .................................................................................................................. 69
INFORMED CONSENT PROCESS ..................................................................................................... 69
DATA PROTECTION ........................................................................................................................... 70
LONG-TERM RETENTION OF SAMPLES FOR ADDITIONAL FUTURE RESEARCH...................... 70
COMMITTEES STRUCTURE .............................................................................................................. 71
PUBLICATION POLICY/DISSEMINATION OF CLINICAL STUDY DATA........................................... 71
DATA QUALITY ASSURANCE ............................................................................................................ 72
CASE REPORT FORM COMPLETION ............................................................................................... 72
SOURCE DOCUMENTS ...................................................................................................................... 73
MONITORING ...................................................................................................................................... 73
ON-SITE AUDITS................................................................................................................................. 74
RECORD RETENTION ........................................................................................................................ 74
STUDY AND SITE START AND CLOSURE........................................................................................ 75
10.5.
Appendix 5: Protocol Amendment History ..................................................................................... 76
11.
REFERENCES................................................................................................................................... 77

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INVESTIGATOR AGREEMENT ................................................................................................................. 79
LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1:
Overview of Clinical Studies With Ad26.RSV.preF................................................................... 19
Table 2:
Overview of the Cohorts, Groups, and Targeted Number of Participants................................ 27
Table 3:
Summary of Possible Immunogenicity Assays (Humoral and Cellular) ................................... 45
Table 4:
Protocol-required Clinical Laboratory Assessments................................................................. 47
Table 5:
Upper Limit of the 95% One-sided Confidence Interval if no Cases are Observed for 
Different Sample Sizes ............................................................................................................. 52
Table 6:
Probability of Observing at Least One AE in a Group of the Considered Sample Size 
Given Several True AE Rates................................................................................................... 52
FIGURES
Figure 1:
Schematic Overview of the Study............................................................................................. 12

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Status: Approved,  Date: 16 March 2020
1. PROTOCOL SUMMARY
1.1.
Synopsis
A Randomized, Double-blind, Placebo-controlled Phase 2a Study to Evaluate a Range of Dose 
Levels of an Ad26.RSV.preF-based Vaccine in Adults Aged 60 Years and Older
The respiratory syncytial virus (RSV) vaccine that will be investigated in the current study, the 
Ad26/protein preF RSV vaccine (VAC18193), is a combination of 2 vaccine components, administered as 
a single intramuscular (IM) injection:

Ad26.RSV.preF (JNJ-64400141), a replication-incompetent adenovirus serotype 26 (Ad26) 
containing a DNA transgene that encodes the prefusion conformation-stabilized F protein (preF) 
derived from the RSV A2 strain.

RSV preF protein (JNJ-64213175), a recombinant preF protein derived from the RSV A2 strain.
The aim of this dose-ranging study is to determine the safety and immunogenicity of different dose levels 
of Ad26.RSV.preF in the Ad26/protein preF RSV vaccine to support the refinement of the acceptance 
criteria for drug product release and stability by generating additional information on clinical safety (for 
the upper release limit) and immunogenicity (for the lower release limit).
OBJECTIVES AND ENDPOINTS
Objectives
Endpoints
Cohort 1
Primary

To explore the dose-response relationship of 
humoral 
immune 
responses 
induced 
by 
different dose levels of the Ad26.RSV.preF-
based vaccine

Antibody titers to RSV preF protein using 
preF enzyme-linked immunosorbent assay 
(ELISA) at 14 days after vaccination
Secondary

To explore the dose-response relationship of 
humoral and cellular immune responses 
induced by different dose levels of the
Ad26.RSV.preF-based vaccine

Antibody titers to RSV preF protein using 
preF ELISA at 3 and 6 months after 
vaccination

RSV A2 neutralizing antibody levels at 
14 days and 3 and 6 months after 
vaccination

Interferon 
(IFN)-γ 
enzyme-linked 
immunospot (ELISpot) assay at 14 days 
and 3 and 6 months after vaccination

To assess the safety and reactogenicity of 
different dose levels of the Ad26.RSV.preF-
based vaccine

Serious adverse events (SAEs) from the 
time of vaccination until the end of the 
study

Solicited local and systemic adverse events 
(AEs) from the time of vaccination until 
7 days after vaccination

Unsolicited 
AEs 
from 
the 
time 
of 
vaccination until 28 days after vaccination

VAC18193 (JNJ-64400141/JNJ-64213175)
Clinical Protocol VAC18193RSV2005
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Status: Approved,  Date: 16 March 2020
Objectives
Endpoints
Cohort 1
Exploratory

To explore additional vaccine-elicited immune 
responses
Assays that may be used include, but are not 
limited to:

Post-F protein binding antibodies (ELISA)

Antigen-specific T-cell immune responses

RSV cross-neutralization of B and/or other 
A strain(s)

Anti-F 
protein 
antibody
specificity 
characterization

Analysis of immunoglobulin (Ig)A and/or 
IgG antibodies binding to RSV F protein in 
prefusion and/or postfusion form in nasal 
samples

Analysis of neutralizing antibodies to Ad26
Objectives
Endpoints
Cohorts 2 and 3
Primary

To assess the safety and reactogenicity of 
different dose levels of the Ad26.RSV.preF-
based vaccine

Solicited local and systemic AEs from the 
time of vaccination until 7 days after 
vaccination

Unsolicited 
AEs 
from 
the 
time 
of 
vaccination until 28 days after vaccination
Secondary

To assess the humoral and cellular immune 
responses induced by different dose levels of 
the Ad26.RSV.preF-based vaccine

Antibody titers to RSV preF protein using 
preF ELISA at 14 days and 3 and 6 months 
after vaccination

RSV A2 neutralizing antibody levels at 
14 days and 3 and 6 months after 
vaccination

IFN-γ ELISpot assay at 14 days and 3 and 
6 months after vaccination

To assess the safety of different dose levels of 
the Ad26.RSV.preF-based vaccine

SAEs from the time of vaccination until the 
end of the study
Exploratory

To explore additional vaccine-elicited immune 
responses
Assays that may be used include, but are not 
limited to:

Post-F protein binding antibodies (ELISA)

Antigen-specific T-cell immune responses

RSV cross-neutralization of B and/or other 
A strain(s)

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Status: Approved,  Date: 16 March 2020
Hypothesis
No formal statistical testing of safety or immunogenicity data is planned; data will be analyzed 
descriptively.
OVERALL DESIGN
This is a randomized, double-blind, placebo-controlled, multicenter, interventional Phase 2a study in male 
and female adults aged ≥60 years who are in stable health, to explore the dose-response relationship, 
safety, and immunogenicity of a range of dose levels of the Ad26.RSV.preF-based vaccine. Participants 
will be randomly assigned to different dose levels of Ad26.RSV.preF in the Ad26/protein preF RSV 
vaccine or to placebo in 3 cohorts. The study vaccine will be administered as a single IM injection.
Cohort 
Group
N
Day 1 (Vaccination)
1 (dose-down)
1
50
Ad26.RSV.preF 1×1011 vp + RSV preF protein 150 μg
2
50
Ad26.RSV.preF 3.3×1010 vp + RSV preF protein 150 μg
3
50
Ad26.RSV.preF 1.1×1010 vp + RSV preF protein 150 μg
4
50
Ad26.RSV.preF 3.7×109 vp + RSV preF protein 150 μg
5
25
Placebo
2 (dose-up)
6
50
Ad26.RSV.preF 1×1011 vp + RSV preF protein 150 μg
7
50
Ad26.RSV.preF 1.3×1011 vp + RSV preF protein 150 μg
8
25
Placebo
3 (dose-up)
9
25
Ad26.RSV.preF 1×1011 vp + RSV preF protein 150 μg
10
50
Ad26.RSV.preF 1.6×1011 vp + RSV preF protein 150 μg
11
25
Placebo
N = number of participants; vp = viral particles.
The study duration will be approximately 6 months per participant. The end of the study is defined as the 
last participant’s last visit. 
An internal Data Review Committee (DRC) will be commissioned for this study, and pre-specified study 
vaccination pausing rules will be applied to ensure safety of the participants.
In the dose-down cohort (Cohort 1), a target of approximately 225 participants will be randomized in
parallel in a 2:2:2:2:1 ratio to 5 groups. In the dose-up Cohort 2, a target of approximately 
125 participants will be randomized in parallel in a 2:2:1 ratio to 3 groups. In the dose-up Cohort 3, a 
target of approximately 100 participants will be randomized in parallel in a 1:2:1 ratio to 3 groups.
Cohorts 1 and 2 may be enrolled in parallel, whereas Cohorts 2 and 3 will be enrolled in a staggered 
manner. A study site will not simultaneously enroll participants in more than one cohort.
Initially, a sentinel group of 5 participants will be enrolled in Cohort 2 in a 2:2:1 ratio to Groups 6 to 8, 
respectively, before enrolling additional participants (Step 1). A blinded 24-hour postvaccination safety 
review will be performed by the principal investigator(s) (PI[s]) and sponsor team members (ie, at least 
the study responsible physician/study responsible scientist). In the absence of any clinical safety concerns, 
an additional 15 participants will be enrolled in a 2:2:1 ratio (Step 2). After review of the 7-day (Day 8)
postvaccination safety data of these 20 participants by the DRC, the remaining participants in the cohort 

Anti-F 
protein 
antibody
specificity 
characterization

Analysis of IgA and/or IgG antibodies 
binding to RSV F protein in prefusion 
and/or postfusion form in nasal samples

Analysis of neutralizing antibodies to Ad26

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will be randomized in a 2:2:1 ratio (Step 3). When all participants in Cohort 2 have completed the Day 8 
postvaccination visit or discontinued earlier, all available safety data up to at least 7 days after vaccination
of all participants in the cohort will be reviewed by the DRC. Based on this review, the sponsor may
decide to not initiate enrollment of Cohort 3.
The enrollment of Cohort 3 will be conducted similarly to Cohort 2. Steps 1 and 2 will be performed with 
a sentinel group of 4 participants and with 12 participants, respectively, both enrolled in a 1:2:1 ratio. 
After review of the 7-day (Day 8) postvaccination safety data of these 16 participants by the DRC, the 
remaining participants in the cohort will be randomized in a 1:2:1 ratio.
After vaccination with study vaccine on Day 1, participants will remain under observation at the study 
site for a minimum of 30 minutes for presence of any acute reactions and solicited events, or longer if 
deemed necessary by the investigator. Any unsolicited and solicited local (injection site) or systemic AEs 
will be documented by the study-site personnel following this observation period. Each participant will 
record solicited local and systemic AEs and body temperature in the participant diary, beginning on the 
evening of the vaccination day and daily for 7 days after vaccination.
Nasosorption samples using synthetic absorptive matrix (SAM) strips, blood samples to assess humoral 
and cellular immune responses, and clinical safety laboratory blood samples (Cohorts 2 and 3 only) will 
be collected. Participant safety throughout the study will further be evaluated via physical examinations 
and vital signs.
NUMBER OF PARTICIPANTS
A target of approximately 450 participants will be randomly assigned to different dose levels of 
Ad26.RSV.preF in the Ad26/protein preF RSV vaccine or to placebo in 3 cohorts. In Cohort 1, a target of 
approximately 225 participants will be randomized, whereas in Cohorts 2 and 3, a target of 125 and 
100 participants will be randomized, respectively.
VACCINATION GROUPS AND DURATION
The study duration will be approximately 6 months per participant. Participants in Cohort 1 will be 
screened on Day 1 (prevaccination), whereas participants in Cohorts 2 and 3 will be screened within 
28 days before study vaccine administration to analyze clinical safety laboratory parameters before 
vaccination. The study further comprises study vaccination (active or placebo) on Day 1 and a 6-month 
safety and immunogenicity follow-up period.
If a participant meets any of the contraindications to vaccination at the scheduled time for study 
vaccination on Day 1, enrollment at a later date is permitted at the discretion of the PI and after discussion 
with the sponsor.
Study Vaccine Administration
On Day 1, participants will receive a single IM injection of study vaccine (ie, the Ad26/protein preF RSV 
vaccine or placebo) in the deltoid muscle. The injection will occur at the study site. The Ad26/protein 
preF RSV vaccine is composed of Ad26.RSV.preF (JNJ-64400141) and RSV preF protein 
(JNJ-64213175). Ad26.RSV.preF will be administered at a dose level ranging from 3.7×109 viral particles 
(vp) to 1.6×1011 vp, and RSV preF protein at a constant dose level of 150 µg. Due to the different dose 
levels of Ad26.RSV.preF, the injection volumes of the study vaccine may differ between the cohorts. 
Ad26.RSV.preF and RSV preF protein will be supplied as solutions in separate single-use vials. Placebo 
will consist of 0.9% saline.
IMMUNOGENICITY EVALUATIONS
Venous blood samples of approximately 10 and 50 mL will be collected for the determination of humoral 
and cellular immune responses, respectively. Nasosorption samples using SAM strips will be collected for 

VAC18193 (JNJ-64400141/JNJ-64213175)
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Status: Approved,  Date: 16 March 2020
immunogenicity assessments including, but not limited to,
determination of antigen-specific 
immunoglobulin (IgG and IgA).
Assay 
Purpose
Primary and secondary endpoints
Pre-F protein binding antibody (ELISA)
Analysis of antibodies binding to RSV F protein in prefusion form
RSV A2 neutralization
Analysis of neutralizing antibodies to the A2 strain
IFN-γ (ELISpot)
T-cell IFN-γ responses to RSV F protein peptides
Exploratory endpoints
Post-F protein binding antibody (ELISA)
Analysis of antibodies binding to RSV F protein in postfusion form
Antigen-specific T-cell immune 
responses
Analysis of T-cell responses to RSV F protein peptide-stimulated 
PBMCs (including, but not limited to, CD4+/CD8+, IL-2, IFN-γ, 
TNF-α, activation markers and memory) using ICS or CyTOF
RSV strain cross-neutralization
Analysis of cross-neutralizing antibodies to B and/or other 
A strain(s)
Antibody specificity and functional 
characterization
Analysis of pre- and post-F antibody specificity by functional 
assays such as ELISA, competition ELISA, and epitope mapping. 
Functional characterization of antibodies including, but not limited 
to, ADCC, ADCP, avidity, immunoglobulin isotype, and functional 
VNAs to other respiratory viruses
Analysis of nasal antibodies to RSV 
including, but not limited to, IgA and 
IgG
Analysis of nasal antibodies binding to RSV F protein in prefusion 
and/or postfusion form in nasal samples
Adenovirus neutralization assay
Analysis of neutralizing antibodies to Ad26
ADCC = antibody-dependent cell-mediated cytotoxicity; ADCP = antibody-dependent cellular phagocytosis; CD = cluster of 
differentiation; CyTOF = cytometry by time of flight; ICS = intracellular cytokine staining; IL = interleukin; PBMC = peripheral 
bone marrow cell; TNF = tumor necrosis factor; VNA = virus neutralization assay.
SAFETY EVALUATIONS
Key safety assessments will include the monitoring of AEs, physical examinations, vital signs, and 
clinical safety laboratory assessments.
AEs and special reporting situations, whether serious or nonserious, that are related to study procedures or 
that are related to noninvestigational sponsor products will be reported from the time a signed and dated
informed consent form (ICF) is obtained until the end of the study/early withdrawal. All other unsolicited 
AEs and special reporting situations, whether serious or nonserious, will be reported from the time of 
vaccination until 28 days after vaccination. All AEs and SAEs leading to discontinuation of the study 
vaccination (regardless of the causal relationship) are to be reported from the moment of vaccination until 
completion of the participant’s last study-related procedure, which may include contact for safety 
follow-up. All other SAEs (regardless of the causal relationship) are to be reported from the time of 
vaccination until the end of the study/early withdrawal.
Any solicited local (injection site) or systemic AEs occurring during the 30-minute postvaccination 
observation period (or longer if deemed necessary by the investigator) will be documented by the 
study-site personnel following this observation period. Solicited AEs collected through a participant diary 
will be recorded from the time of vaccination until 7 days after vaccination.
STATISTICAL METHODS
Sample Size Determination
Immunogenicity (Cohort 1)
The primary objective of Cohort 1 is to explore the dose-response relationship of humoral immune 
responses (as measured by preF ELISA) induced by different dose levels of the Ad26/protein preF RSV 
vaccine.

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Assuming:

10% of exclusions (eg, drop-outs, missing samples, and major protocol deviations impacting 
immunogenicity data)

a standard deviation on the log2 scale of the preF ELISA of 1.3 on Day 15 and 1.1 on Day 183 for all 
dose levels

4 dose levels
The linear model log2 (preF ELISAtimepoint) = GMT preF ELISAAd26/protein preF RSV vaccine (1x10
11 vp /150 µg),timepoint + 
slope × #titration steps provides a standard error for the slope of 0.052 on Day 15 and 0.040 on Day 183
with 50 participants per arm. This is deemed sufficient for this exploratory study.
Safety (Cohorts 1, 2, and 3)
Placebo recipients are included for blinding and safety purposes and will provide additional control 
specimens for immunogenicity assays.
The observation of 0 events (eg, SAEs) is associated with 95% confidence that the true event rate is 
below the rates specified in the below table for the considered number of participants.
Sample Size
N=25
N=50
N=75
UL 95% one-sided CI
11.3%
5.8%
3.9%
CI = confidence interval; N = number of participants; UL = upper limit.
The table below provides the probability of observing at least one AE in a group of the considered sample 
size given several true AE rates.
True AE Rate (%)
Probability of Observing at Least One AE in N Participants (%)
N=25
N=50
N=75
0.5
12
22
31
1
22
39
53
2.5
47
72
85
10
93
99
100
25
100
100
100
50
100
100
100
N = number of participants.
Analysis Sets
Vaccine assignment will follow the as-treated principle.
The Full Analysis Set (FAS) will include all participants who were randomized and received the study
vaccine, regardless of the occurrence of protocol deviations. All safety and participant information 
analyses will be based on the FAS.
The Per-protocol Immunogenicity (PPI) Set will include all participants who were randomized and 
received the study vaccine, and for whom immunogenicity data are available, excluding participants with 
major protocol deviations expecting to impact the immunogenicity outcomes.
The analysis of all immunogenicity endpoints will be based on the PPI set. For key tables, sensitivity 
immunogenicity analyses might also be performed on the FAS.

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Immunogenicity Analyses
No formal statistical testing of immunogenicity data is planned. Immunogenicity data will be analyzed 
descriptively by cohort and group. In addition, for a selection of tables, data may be pooled over cohorts.
To explore the dose-response relationship between preF ELISA and different dose levels of the
Ad26/protein preF RSV vaccine, a linear regression model will be fitted for each timepoint separately, 
using data of the active groups of Cohort 1, with the log-transformed preF ELISA titers at the considered 
timepoint as dependent variable, the number of titration steps as independent variable, and the geometric 
mean titer (GMT) of preF ELISA of the Ad26/protein preF RSV vaccine (1×1011 vp/150 µg) at the 
considered timepoint as a fixed intercept.
The linear model log2 (preF ELISAtimepoint) = GMT preF ELISAAd26/protein preF RSV vaccine (1x10
11 vp/150 ug),timepoint + 
slope × #titration steps will initially be fitted for the active groups of Cohort 1 but may be extended in a 
later stage with data of the active groups of Cohorts 2 and 3. A similar model may be fitted as well for 
other assays.
Depending on the model fit, other models (eg, log-linear models or EMAX models) may be explored as 
well.
Safety Analyses
No formal statistical testing of safety data is planned. Safety data will be analyzed descriptively by cohort 
and group. In addition, for a selection of tables, data of Cohorts 2 and 3 may be pooled. All safety 
analyses will be based on the FAS.

VAC18193 (JNJ-64400141/JNJ-64213175)
Clinical Protocol VAC18193RSV2005
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Status: Approved,  Date: 16 March 2020
1.2.
Schema
Figure 1:
Schematic Overview of the Study
D = Day.
Note that the scale of the timelines is arbitrary for clarity purposes.
In Cohort 2, a blinded 24-hour (Day 2) postvaccination safety review of the sentinel group of 5 participants will be performed by the PI(s) and sponsor team members 
(Step 1). In the absence of any clinical safety concerns, an additional 15 participants will be enrolled (Step 2). After review of the 7-day (Day 8) postvaccination 
safety data of these 20 participants by the DRC, the remaining participants in the cohort will be enrolled (Step 3). Based on the review of all available safety data up 
to at least 7 days after vaccination of all participants in Cohort 2 by the DRC (dashed line), the sponsor may decide to not initiate enrollment of Cohort 3.
The enrollment of Cohort 3 will be conducted similarly to Cohort 2. Steps 1 and 2 will be performed with a sentinel group of 4 participants and with 12 participants, 
respectively. After review of the 7-day (Day 8) postvaccination safety data of these 16 participants by the DRC, the remaining participants in the cohort will be 
enrolled.

VAC18193 (JNJ-64400141/JNJ-64213175)
Clinical Protocol VAC18193RSV2005
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Status: Approved,  Date: 16 March 2020
prevaccination; pre- and postvaccination; if the early exit visit is within 8 days after vaccination; blood samples for immunogenicity will only be taken if the early exit visit is at least 
14 days after the previous immunogenicity blood draw; if the early exit visit is within 7 days after vaccination; if the early exit visit is within 28 days after vaccination; at the discretion of the 
investigator (based on health status of the participant).
a.
Can be electronic (eg, e-mail, text messages) or by phone.
b.
An early exit visit will be conducted for those participants who are unable to continue participation in the study and withdraw from the study before Day 183, but who do not 
withdraw consent. Participants who wish to withdraw consent from participation in the study will be offered an early exit visit (prior to formal withdrawal of consent).
c.
Signing of the ICF should be done before any study-related activity.
d.
Prestudy therapies administered up to 30 days before vaccination must be recorded.
e.
A physical examination (including height and body weight) will be carried out at screening. At all other visits, an abbreviated, symptom-directed physical examination will be 
performed if deemed necessary by the investigator.
f.
Systolic and diastolic blood pressure (supine) and heart and respiratory rate measurements should be preceded by at least 5 minutes of rest in a quiet setting without distractions 
(eg, television, cell phones). Vital signs measurements should be taken before nasal sampling and blood draws, if applicable.
g.
Investigator must check for acute illness or body temperature of ≥38.0°C (≥100.4ºF) at the time of vaccination. In such cases, the participant may be vaccinated up to, and no later 
than, 10 days after the scheduled vaccination, or be withdrawn from vaccination at the discretion of the investigator.
h.
After vaccination, participants will be closely observed for a minimum of 30 minutes to monitor for the development of any acute reactions and solicited events, or longer if deemed 
necessary by the investigator. Any unsolicited and solicited local (injection site) or systemic AEs, and vital signs (heart and respiratory rate, systolic and diastolic blood pressure
[supine], and body temperature) will be documented by the study-site personnel following this observation period.
i.
Participants will be asked to note in the participant diary occurrences of injection site pain/tenderness, erythema, and swelling at the injection site daily. The extent (largest diameter) 
of any erythema and swelling should be measured using the supplied ruler and recorded daily. Body temperature (oral route preferred) should be measured at approximately the same 
time each day, preferably in the evening, using the supplied thermometer. If more than one measurement is made on any given day, the highest body temperature of that day will be 
used in the participant diary.
j.
AEs and special reporting situations related to study procedures or to noninvestigational sponsor products will be reported from the time a signed and dated ICF is obtained until the 
end of the study/early withdrawal. All other AEs (unsolicited) and other special reporting situations will be reported from the time of vaccination until 28 days after vaccination.
All AEs leading to discontinuation of study vaccination (regardless of the causal relationship) are to be reported from the moment of vaccination until completion of the participant’s 
last study-related procedure, which may include contact for safety follow-up.
k.
SAEs related to study procedures or to noninvestigational sponsor products will be reported from the time a signed and dated ICF is obtained until the end of the study/early 
withdrawal. All SAEs leading to discontinuation of study vaccination (regardless of the causal relationship) are to be reported from the moment of vaccination until completion of 
the participant’s last study-related procedure, which may include contact for safety follow-up. All other SAEs (regardless of the causal relationship) are to be reported from the time 
of vaccination until the end of the study/early withdrawal.
l.
Concomitant therapies such as analgesic/antipyretic medications and nonsteroidal anti-inflammatory drugs, corticosteroids, and antihistaminic must be recorded until 28 days after 
vaccination. All other concomitant therapies should also be recorded if administered in conjunction with new or worsening AEs reported per protocol requirements outlined in 
Section 10.3, Appendix 3.
m.
Participants will be contacted at Day 8 to review the information noted in the participant diary. If the participant diary review is missed, the diary information will be reviewed 
during the following visit. The participant diary will be collected at the Day 15 visit.

VAC18193 (JNJ-64400141/JNJ-64213175)
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Status: Approved,  Date: 16 March 2020
a.
Can be electronic (eg, e-mail, text messages) or by phone.
b.
An early exit visit will be conducted for those participants who are unable to continue participation in the study and withdraw from the study before Day 183, but who do not 
withdraw consent. Participants who wish to withdraw consent from participation in the study will be offered an early exit visit (prior to formal withdrawal of consent).
c.
In addition, the first 4 participants in each cohort will be contacted by phone 24 hours after vaccination. In the absence of any clinical safety concerns, the remaining 8 participants of 
the cohort can be enrolled.
d.
Signing of the ICF should be done before any study-related activity.
e.
Prestudy therapies administered up to 30 days before vaccination must be recorded.
f.
A physical examination (including height and body weight) will be carried out at screening. At all other visits, an abbreviated, symptom-directed physical examination will be 
performed if deemed necessary by the investigator.
g.
Systolic and diastolic blood pressure (supine) and heart and respiratory rate measurements should be preceded by at least 5 minutes of rest in a quiet setting without distractions 
(eg, television, cell phones). Vital signs measurements should be taken before nasal sampling and blood draws, if applicable.
h.
To review inclusion criterion 3 and exclusion criteria 2, 8, 9, 10, 11, and 12.
i.
Investigator must check for acute illness or body temperature of ≥38.0°C (≥100.4ºF) at the time of vaccination. In such cases, the participant may be vaccinated up to, and no later 
than, 10 days after the scheduled vaccination, or be withdrawn from vaccination at the discretion of the investigator.
j.
After vaccination, participants will be closely observed for a minimum of 30 minutes to monitor for the development of any acute reactions and solicited events, or longer if deemed 
necessary by the investigator. Any unsolicited and solicited local (injection site) or systemic AEs, and vital signs (heart and respiratory rate, systolic and diastolic blood pressure
[supine], and body temperature) will be documented by the study-site personnel following this observation period.
k.
Participants will be asked to note in the participant diary occurrences of injection site pain/tenderness, erythema, and swelling at the injection site daily. The extent (largest diameter) 
of any erythema and swelling should be measured using the supplied ruler and recorded daily. Body temperature (oral route preferred) should be measured at approximately the same 
time each day, preferably in the evening, using the supplied thermometer. If more than one measurement is made on any given day, the highest body temperature of that day will be 
used in the participant diary.
l.
AEs and special reporting situations related to study procedures or to noninvestigational sponsor products will be reported from the time a signed and dated ICF is obtained until the 
end of the study/early withdrawal. All other AEs (unsolicited) and other special reporting situations will be reported from the time of vaccination until 28 days after vaccination.
All AEs leading to discontinuation of study vaccination (regardless of the causal relationship) are to be reported from the moment of vaccination until completion of the participant’s 
last study-related procedure, which may include contact for safety follow-up.
m.
SAEs related to study procedures or to noninvestigational sponsor products will be reported from the time a signed and dated ICF is obtained until the end of the study/early 
withdrawal. All SAEs leading to discontinuation of study vaccination (regardless of the causal relationship) are to be reported from the moment of vaccination until completion of 
the participant’s last study-related procedure, which may include contact for safety follow-up. All other SAEs (regardless of the causal relationship) are to be reported from the time 
of vaccination until the end of the study/early withdrawal.
n.
Concomitant therapies such as analgesic/antipyretic medications and nonsteroidal anti-inflammatory drugs, corticosteroids, and antihistaminic must be recorded until 28 days after 
vaccination. All other concomitant therapies should also be recorded if administered in conjunction with new or worsening AEs reported per protocol requirements outlined in 
Section 10.3, Appendix 3.

VAC18193 (JNJ-64400141/JNJ-64213175)
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Status: Approved,  Date: 16 March 2020
2. INTRODUCTION
The respiratory syncytial virus (RSV) vaccine that will be investigated in the current study, the 
Ad26/protein preF RSV vaccine (VAC18193), is a combination of 2 vaccine components, 
administered as a single intramuscular (IM) injection:

Ad26.RSV.preF (JNJ-64400141), a replication-incompetent adenovirus serotype 26 (Ad26) 
containing a DNA transgene that encodes the prefusion conformation-stabilized F protein 
(preF) derived from the RSV A2 strain.

RSV preF protein (JNJ-64213175), a recombinant preF protein derived from the RSV A2 
strain.
For the most comprehensive nonclinical and clinical information regarding the Ad26/protein 
preF RSV vaccine, refer to the latest versions of the Investigator’s Brochures (IBs) for
Ad26.RSV.preF and RSV preF protein.8,9
The term "study vaccine" used throughout the protocol refers to the Ad26/protein preF RSV 
vaccine or placebo.
The term "sponsor" used throughout this document refers to the entities listed in the Contact 
Information page(s), which will be provided as a separate document.
2.1.
Study Rationale
The aim of this dose-ranging study is to determine the safety and immunogenicity of different 
dose levels of Ad26.RSV.preF in the Ad26/protein preF RSV vaccine to support the refinement 
of the acceptance criteria for drug product release and stability by generating additional 
information on clinical safety (for the upper release limit) and immunogenicity (for the lower 
release limit).
2.2.
Background
RSV is an important cause of serious respiratory infections in adults aged ≥60 years, 
immunocompromised
individuals, and those with underlying chronic cardiopulmonary 
conditions.5 Exact numbers on the burden of RSV disease in adults aged ≥60 years are limited.
In long-term care facilities, RSV is estimated to infect 5% to 10% of the residents per year with 
significant rates of pneumonia (10%-20%) and death (2%-5%) as a consequence.6 In the United 
States, approximately 177,000 hospital admissions and approximately 10,000 to 14,000 deaths 
per year are due to severe RSV infections in adults aged ≥65 years.5 These data support the 
importance of developing a safe and effective vaccine for certain adult populations, such as older 
adults. Currently, there are no vaccines or specific treatments available for RSV.
Several studies have suggested that decreased protection against RSV in older adults could be 
attributed to an age-related decline in interferon (IFN)-γ production by peripheral blood 
mononuclear cells, a reduced ratio of cluster of differentiation (CD)8+ to CD4+ T cells, and 
reduced numbers of circulating RSV-specific CD8+ memory T cells.4,12,13 High levels of serum 

VAC18193 (JNJ-64400141/JNJ-64213175)
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Status: Approved,  Date: 16 March 2020
neutralizing antibody are associated with less severe infections in older adults.19
The Ad26.RSV.preF vaccine component being evaluated in this protocol is based on the AdVac®
platform which has been shown to promote a strong antibody response as well as cellular
responses.2,3,10,15
2.2.1.
Ad26.RSV.preF and RSV preF Protein Nonclinical Studies
Ad26.RSV.preF and RSV preF protein were immunogenic when IM administered as single 
components in various RSV-naïve or pre-exposed animal models. In RSV-naïve and pre-exposed 
mice, the combination of RSV preF protein with a suboptimal dose of Ad26.RSV.preF, either 
together in a 1-dose immunization or in a heterologous 2-dose schedule, gave higher virus 
neutralizing titers (VNTs) than immunization with Ad26.RSV.preF alone. In RSV pre-exposed 
nonhuman primates (NHPs), the combination of the human dose of both Ad26.RSV.preF and 
RSV preF protein induced high VNTs. Due to the high VNT response induced by the high dose 
of Ad26.RSV.preF alone, there was no significant difference observed with the VNT induced by 
the combination of RSV preF protein and Ad26.RSV.preF. In both RSV pre-exposed mice and 
NHPs, Ad26.RSV.preF induced Th1-skewed cellular responses, in combination with RSV preF 
protein and alone, as suggested by IFN-γ enzyme-linked immunospot (ELISpot) assays and
intracellular cytokine staining (ICS). In contrast, RSV preF protein alone induced only low 
cellular responses. In RSV pre-exposed NHPs, immunization with the combination of 
Ad26.RSV.preF and RSV preF protein boosted pre-existing neutralizing antibody responses
against a panel of different RSV A and B strains, including recent clinical isolates. VNTs against 
RSV A strains were monitored for 55 weeks in NHPs after a single injection and maintained 
above pre-exposure levels.
In the naïve cotton rat efficacy model, a 1-dose immunization with Ad26.RSV.preF and a 2-dose
immunization regimen with alum-adjuvanted RSV preF protein induced VNTs and gave full 
lower and upper respiratory tract protection in 100% of animals after RSV A2 intranasal 
challenge. Due to the high efficacy of Ad26.RSV.preF alone in the naïve cotton rat model even 
at lowest doses that elicited an immune response, the value of the addition of RSV preF protein 
for protection of lower respiratory tract could not be evaluated. However, upper respiratory tract 
protection was significantly improved by addition of the preF protein to suboptimal doses of 
Ad26.RSV.preF.
2.2.2.
Ad26.RSV.preF and RSV preF Protein Clinical Studies
At the time of protocol writing, 2
Phase 1 studies
(VAC18193RSV1003
and 
VAC18193RSV1005) and 2 Phase 2a studies (VAC18193RSV2002 and VAC18193RSV2003) 
with Ad26.RSV.preF have been completed. Three Phase 1/2a studies (VAC18193RSV1004, 
VAC18194RSV2001, and VAC18194RSV2002) and one Phase 2b study (VAC18193RSV2001) 
are ongoing (Table 1).

VAC18193 (JNJ-64400141/JNJ-64213175)
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Status: Approved,  Date: 16 March 2020
Table 1:
Overview of Clinical Studies With Ad26.RSV.preF
Study Identifier
Study Status
Clinical 
Phase
Vaccine
N
Study Population
Senior Program
VAC18193RSV1003
Completed
1
Ad26.RSV.preF 
72
Adult participants aged 60 years and older in 
stable health
VAC18193RSV1005
Completed*
1
Ad26.RSV.preF 
24
Adult participants aged 18 years and older in 
stable health (including 3 participants aged 
>65 years)
VAC18193RSV2002
Completed
2a
Ad26.RSV.preF
63
Healthy adult participants aged 18 to 50 years
VAC18193RSV2003
Completed
2a
Ad26.RSV.preF
180
Adult participants aged 60 years and older in 
stable health
VAC18193RSV1004
Ongoing
1/2a
Ad26.RSV.preF/
RSV preF protein 
667
Adult participants aged 60 years and older in 
stable health
VAC18193RSV2001
Ongoing
2b
Ad26.RSV.preF/
RSV preF protein 
5,800
Adult participants aged 65 years and older with 
and without comorbidities 
Junior Program
VAC18194RSV2001
Ongoing
1/2a
Ad26.RSV.preF 
12 adults
36 toddlers
Healthy adult participants aged 18 to 50 years 
and healthy RSV-seropositive toddlers aged 
12 to 24 months
VAC18194RSV2002
Ongoing
1/2a
Ad26.RSV.preF 
48 toddlers
Healthy RSV-seronegative toddlers aged 
12 to 24 months
* Clinical study report writing in progress.
Clinical studies are ordered to align with the order in the clinical development plan.
N = actual number of participants (for completed studies) or planned number of participants (for ongoing studies).
Study VAC18193RSV1003 is a completed single-center, randomized, placebo-controlled, 
double-blind, first-in-human Phase 1 study for the Ad26.RSV.preF vaccine, and demonstrated 
that Ad26.RSV.preF was safe and well tolerated at 2 doses (5×1010 viral particles [vp] and 
1×1011 vp) and can elicit durable (up to 2 years) humoral and cellular immune responses against 
RSV. The data suggested a trend towards higher humoral responses after vaccination with the 
higher dose level of Ad26.RSV.preF compared with the lower dose level.
After the safety, tolerability, and immunogenicity profile of Ad26.RSV.preF was first established 
in study VAC18193RSV1003, study VAC18193RSV2002,
a completed single-center, 
randomized, placebo-controlled, double-blind exploratory Phase 2a human challenge study, was 
conducted in participants aged 18 to 50 years to evaluate the prophylactic efficacy of a single 
immunization of Ad26.RSV.preF against RSV infection in a virus challenge model. There was a 
statistically significant reduction in the viral load as measured by the area under the curve
(VL-AUC) in the Ad26.RSV.preF group compared with placebo, and Ad26.RSV.preF 
vaccination was associated with lower peak viral loads (by quantitative reverse transcriptase 
polymerase chain reaction), lower VL-AUC (by quantitative culture), and a substantial reduction 
in the median area under the curve of the total clinical symptom score. Immunization with 
Ad26.RSV.preF substantially reduced the proportion of participants infected by RSV after 
challenge. Symptoms of RSV infection and RSV viral load by quantitative culture were 
markedly reduced in Ad26.RSV.preF vaccinated participants with breakthrough RSV infection 
compared with placebo. Vaccination with Ad26.RSV.preF induced favorable humoral immune 
responses compared with placebo as measured prior to RSV challenge.

VAC18193 (JNJ-64400141/JNJ-64213175)
Clinical Protocol VAC18193RSV2005
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Status: Approved,  Date: 16 March 2020
With the availability of clinical trial material (CTM) for RSV preF protein and taking the results 
of the VAC18193RSV1003 and VAC18193RSV2002 studies into account, the following clinical 
studies with Ad26.RSV.preF and RSV preF protein were initiated and are ongoing:
Study VAC18193RSV1004 is a multicenter, randomized, double-blind, placebo-controlled
Phase 1/2a regimen selection study in 667 participants aged ≥60 years in stable health to evaluate
the safety and immunogenicity of Ad26.RSV.preF alone, of combinations of Ad26.RSV.preF 
and RSV preF protein, and of separate administration of Ad26.RSV.preF and RSV preF protein.
A significant increase in humoral immune responses including virus neutralization assays 
(VNAs) and preF antibody titers was observed in the groups combining Ad26.RSV.preF and
RSV preF protein compared with Ad26.RSV.preF alone. No relevant differences between the 
combination groups and Ad26.RSV.preF alone were noted for cellular immune responses 
measured at the time of primary analysis. All regimens had acceptable safety and reactogenicity
profiles, which were similar across groups. Available safety data support that this vaccine is safe 
and has an acceptable reactogenicity profile.
Study VAC18193RSV2001 is a multicenter, randomized, double-blind, placebo-controlled
Phase 2b proof-of-concept study in approximately 5,800 participants aged ≥65 years with and 
without comorbidities to confirm the potential for efficacy of the Ad26/protein preF RSV
vaccine and to assess 3 case definitions of RSV-mediated lower respiratory tract disease.
2.3.
Benefit-risk Assessment
Below, the known and potential benefits and risks of VAC18193 (JNJ-64400141/JNJ-64213175)
are discussed. More detailed information about the known and expected benefits and risks of the 
Ad26/protein preF RSV vaccine may be found in the IBs for Ad26.RSV.preF8 and RSV preF 
protein9.
2.3.1.
Known Benefits
The clinical benefits of the Ad26/protein preF RSV vaccine have yet to be established.
2.3.2.
Potential Benefits
The Ad26/protein preF RSV vaccine is under development for prophylaxis of RSV, however,
vaccine efficacy has not yet been evaluated. Based on preliminary immunogenicity data, there 
could be a potential benefit from RSV vaccination in terms of immune response: vaccination 
could raise an immune response which might confer additional protection against a future RSV 
infection (Section 2.2.2). The individual benefit from vaccination for the participants at the 
current development stage is not known.
Participants may benefit from clinical testing and physical examination; others may benefit from 
the knowledge that they may aid in the development of an RSV vaccine.

VAC18193 (JNJ-64400141/JNJ-64213175)
Clinical Protocol VAC18193RSV2005
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Status: Approved,  Date: 16 March 2020
2.3.3.
Known Risks
All vaccines have the potential to cause adverse experiences. To date, limited clinical data with 
the Ad26/protein preF RSV vaccine showed an acceptable safety and reactogenicity profile
(Section 2.2.2).
2.3.4.
Potential Risks
The following potential risks for the Ad26/protein preF RSV vaccine will be monitored during 
the study:
Risks Related to Vaccination
In general, IM injection may cause local itching, warmth, pain, tenderness, erythema/redness, 
induration/swelling, arm discomfort, or bruising of the skin at vaccine injection sites. 
Participants may exhibit general signs and symptoms associated with administration of a 
vaccine, or vaccination with placebo, including fever, chills, rash, myalgia, nausea/vomiting, 
headache, dizziness, arthralgia, general itching, and fatigue. These side effects will be monitored 
but 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 injury from falling. If syncope 
develops, participants should be observed until the 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 allergy 
or history of anaphylaxis or other serious adverse reactions to vaccines or vaccine components 
(including any of the constituents of the study vaccine) will be excluded from the study. Study 
sites should have medical treatment available in case of severe allergic reactions following 
vaccine administration.
Risks Related to Adenoviral-vectored Vaccines
Safety data available from 23 clinical studies in 3,694 adults vaccinated with Ad26-vectored 
vaccine candidates, in which Ad26 with different inserts has been evaluated at dose levels 
ranging from 1×109 to 1×1011 vp, indicate that no safety concerns would be anticipated from 
vaccination with Ad26.RSV.preF at dose levels up to and including 1×1011 vp.1
Postvaccination reactogenicity after administration of Ad26-based vaccines have consisted of 
mild to moderate adverse events (AEs), including local injection site reactions (most frequently 
injection site pain), and malaise, fatigue, headache, and myalgia. A trend towards an increase in 
the incidence of injection site pain and arthralgia, chills, fatigue, headache, malaise, myalgia, and 
nausea with an increase in Ad26 dose level was observed. There was no clear trend in the 
frequency of unsolicited AEs with increasing the Ad26 dose level. Transient decreases in 
neutrophil counts have been associated with adenovirus-based vaccines, and decrease in 
hemoglobin from baseline was the most frequent laboratory abnormality.1

VAC18193 (JNJ-64400141/JNJ-64213175)
Clinical Protocol VAC18193RSV2005
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Status: Approved,  Date: 16 March 2020
Risks Related to RSV preF Protein
RSV preF protein is being evaluated in the ongoing studies VAC18193RSV1004 and 
VAC18193RSV2001. To date, limited clinical data have shown an acceptable safety and 
reactogenicity profile.
Risks from Collection of Nasosorption Samples
Nasosorption sampling is more comfortable and less invasive than using a conventional swab
(which may cause nose bleeds).
Risks from Blood Draws
As with all clinical studies requiring blood sampling, there are risks associated with venipuncture 
and multiple blood sample collection. Blood drawing may cause pain, tenderness, bruising, 
bleeding, dizziness, vaso-vagal response, syncope, and, rarely, infection at the site where the 
blood is taken. The total blood volume to be collected is considered to be an acceptable amount of 
blood over this time period from the population in this study (Section 4.2.1). Participants with 
contraindications to IM injections and blood draws (eg, bleeding disorders) will be excluded.
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.
Concomitant Vaccination
Concomitant vaccination might have an influence on both the safety profile and immunogenicity 
of Ad26.RSV.preF and/or RSV preF protein. Likewise, Ad26.RSV.preF and/or RSV preF protein
might have an influence on both the safety profile and immunogenicity of any concomitant 
vaccination. As a result, licensed live attenuated vaccines should be given at least 28 days before 
or after vaccination. Other licensed (not live) vaccines (eg, influenza, tetanus, hepatitis A, 
hepatitis B, rabies) should be given at least 14 days before or after 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.
Reproductive Risks and Pregnancy
The effect of Ad26.RSV.preF and RSV preF protein on a fetus or nursing baby is unknown. 
Female 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. Women who have had hysterectomies are also eligible for the study. Because the 
effect on sperm is unknown, male participants must inform the study-site personnel if their 
partner becomes pregnant during the study. Follow-up information regarding the outcome of the 
pregnancy and any postnatal sequelae in the infant will be required.

VAC18193 (JNJ-64400141/JNJ-64213175)
Clinical Protocol VAC18193RSV2005
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Status: Approved,  Date: 16 March 2020
Unknown Risks 
There may be other risks that are not known. If any significant new risks are identified, the 
principal investigator (PI) and participants will be informed.
2.3.5.
Overall Benefit-risk Assessment
Based on the available data and proposed safety measures, the overall benefit-risk assessment for 
this clinical study is considered acceptable for the following reasons:

The dose level of 1×1011 vp for Ad26.RSV.preF and 150 µg for RSV preF protein 
(administered in all 3 cohorts) was selected from the primary analysis of Cohort 2 in study 
VAC18193RSV1004
and 
is 
currently 
under 
further 
evaluation 
in 
studies
VAC18193RSV1004 and VAC18193RSV2001 (Section 4.1). Available safety data of study
VAC18193RSV1004 support that this vaccine is safe and has an acceptable reactogenicity
profile at a dose level up to 1×1011 vp (Section 2.2.2). As no data are available for higher 
dose levels, adequate safety measures will be taken to minimize the risk to participants (see 
below).

Only participants who meet all inclusion criteria (Section 5.1) and none of the exclusion 
criteria (Section 5.2) will be allowed to participate in this study. The selection criteria 
include adequate provisions to minimize the risk and protect the well-being of participants in 
the study.

Safety (including the recording of AEs, physical examinations, vital signs, and clinical 
safety laboratory assessments) 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 (Section 1.3).

After vaccination, participants will remain at the study site for a minimum of 
30 minutes, or longer if deemed necessary by the investigator, and will be closely 
observed by study-site personnel. Necessary emergency equipment and medications 
must be available at the study site to treat severe allergic reactions. Participants will use 
a participant diary to document solicited local and systemic symptoms. Details are 
provided in Sections 8.2 and 8.3.

The investigator or the designee will document unsolicited AEs as indicated in
Section 8.3.1.

After vaccination, participants will enter a 6-month safety and immunogenicity 
follow-up period. All AEs, serious adverse events (SAEs), and clinically significant 
laboratory abnormalities (including those persisting at the end of the study/early 
withdrawal) will be followed by the investigator until clinical resolution or until a 
clinically stable endpoint is reached, or until the participant has been deemed lost to 
follow-up after demonstration of due diligence of follow-up efforts. An early exit visit 
will be conducted for those participants who are unable to continue participation in the 
study and withdraw from the study before Day 183, but who do not withdraw consent.
Participants who wish to withdraw consent from participation in the study will be 
offered an early exit visit (prior to formal withdrawal of consent) (Section 7.4).

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
Several safety measures are included in this protocol to minimize the potential risk to 
participants, including the following:

An internal Data Review Committee (DRC) will be commissioned for this study 
(Section 9.6). In addition to the planned review of postvaccination safety data of 
participants in Cohorts 2 and 3, the DRC will be consulted if at least one of the study 
vaccination pausing rules has been met and/or if the participant’s safety may be 
threatened.

There are prespecified rules that would result in pausing of further vaccination of 
participants if predefined conditions occur, preventing exposure of new participants to 
study vaccine until the DRC reviews all available safety data and subsequent 
communication between the sponsor and the PI(s) takes place (Section 7.3). When a
first DRC meeting has been triggered by the occurrence of a given study vaccination 
pausing rule, the DRC will convene thereafter for each additional participant meeting 
that pausing rule. Possible actions upon review include, but are not limited to, study 
suspension, study adaptation, or discontinuation of further vaccination.

In Cohort 2, a sentinel group of 5 participants will be enrolled before enrolling 
additional participants (Step 1) (Section 4.1). In the absence of any clinical safety 
concerns upon a blinded 24-hour postvaccination safety review, an additional 
15 participants will be enrolled (Step 2). After review of the 7-day (Day 8) 
postvaccination safety data of these 20 participants by the DRC, the remaining 
participants will be enrolled (Step 3).

The enrollment of Cohort 3 will be conducted similarly to Cohort 2. Steps 1 and 2 will 
be performed with a sentinel group of 4 participants and with 12 participants, 
respectively, both enrolled in a 1:2:1 ratio. After review of the 7-day (Day 8) 
postvaccination safety data of these 16 participants by the DRC, the remaining 
participants in the cohort will be randomized in a 1:2:1 ratio.

Cohorts 2 and 3 will be enrolled in a staggered manner (Section 4.1). Based on the 
review of all available safety data up to at least 7 days after vaccination of all 
participants in Cohort 2 by the DRC, the sponsor may decide to not initiate enrollment 
of Cohort 3.

Contraindications to vaccination are included in Section 7.2.
Taking into account the measures taken to minimize risk to participants of this study, the 
potential risks identified in association with the Ad26/protein preF RSV vaccine are justified by 
the anticipated benefits that may be obtained.

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3. OBJECTIVES AND ENDPOINTS
Objectives
Endpoints
Cohort 1
Primary

To explore the dose-response relationship of 
humoral 
immune 
responses 
induced 
by 
different dose levels of the Ad26.RSV.preF-
based vaccine

Antibody titers to RSV preF protein using 
preF enzyme-linked immunosorbent assay 
(ELISA) at 14 days after vaccination
Secondary

To explore the dose-response relationship of 
humoral and cellular immune responses 
induced by different dose levels of the
Ad26.RSV.preF-based vaccine

Antibody titers to RSV preF protein using 
preF ELISA at 3 and 6 months after 
vaccination

RSV A2 neutralizing antibody levels at 
14 days and 3 and 6 months after 
vaccination

IFN-γ ELISpot assay at 14 days and 3 and 
6 months after vaccination

To assess the safety and reactogenicity of 
different dose levels of the Ad26.RSV.preF-
based vaccine

SAEs from the time of vaccination until the 
end of the study

Solicited local and systemic AEs from the 
time of vaccination until 7 days after 
vaccination

Unsolicited 
AEs 
from 
the 
time 
of 
vaccination until 28 days after vaccination
Exploratory

To explore additional vaccine-elicited immune 
responses
Assays that may be used include, but are not 
limited to:

Post-F protein binding antibodies (ELISA)

Antigen-specific T-cell immune responses

RSV cross-neutralization of B and/or other 
A strain(s)

Anti-F 
protein 
antibody
specificity 
characterization

Analysis of immunoglobulin (Ig)A and/or 
IgG antibodies binding to RSV F protein in 
prefusion and/or postfusion form in nasal 
samples

Analysis of neutralizing antibodies to Ad26

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Refer to Section 8 for evaluations related to endpoints.
HYPOTHESIS
No formal statistical testing of safety or immunogenicity data is planned; data will be analyzed 
descriptively.
Objectives
Endpoints
Cohorts 2 and 3
Primary

To assess the safety and reactogenicity of 
different dose levels of the Ad26.RSV.preF-
based vaccine

Solicited local and systemic AEs from the 
time of vaccination until 7 days after 
vaccination

Unsolicited 
AEs 
from 
the 
time 
of 
vaccination until 28 days after vaccination
Secondary

To assess the humoral and cellular immune 
responses induced by different dose levels of 
the Ad26.RSV.preF-based vaccine

Antibody titers to RSV preF protein using 
preF ELISA at 14 days and 3 and 6 months 
after vaccination

RSV A2 neutralizing antibody levels at 
14 days and 3 and 6 months after 
vaccination

IFN-γ ELISpot assay at 14 days and 3 and 
6 months after vaccination

To assess the safety of different dose levels of 
the Ad26.RSV.preF-based vaccine

SAEs from the time of vaccination until the 
end of the study
Exploratory

To explore additional vaccine-elicited immune 
responses
Assays that may be used include, but are not 
limited to:

Post-F protein binding antibodies (ELISA)

Antigen-specific T-cell immune responses

RSV cross-neutralization of B and/or other 
A strain(s)

Anti-F 
protein 
antibody
specificity 
characterization

Analysis of IgA and/or IgG antibodies 
binding to RSV F protein in prefusion 
and/or postfusion form in nasal samples

Analysis of neutralizing antibodies to Ad26

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4. STUDY DESIGN
4.1.
Overall Design
This is a randomized, double-blind, placebo-controlled, multicenter, interventional Phase 2a
study in male and female adults aged ≥60 years who are in stable health, to explore the 
dose-response relationship, safety, and immunogenicity of a range of dose levels of the
Ad26.RSV.preF-based vaccine. A target of approximately 450 participants will be randomly 
assigned to different dose levels of Ad26.RSV.preF in the Ad26/protein preF RSV vaccine or to 
placebo in 3 cohorts (Table 2). The study vaccine will be administered as a single IM injection.
Table 2:
Overview of the Cohorts, Groups, and Targeted Number of Participants
Cohort 
Group
N
Day 1 (Vaccination)
1 (dose-down)
1
50
Ad26.RSV.preF 1×1011 vp + RSV preF protein 150 μg
2
50
Ad26.RSV.preF 3.3×1010 vp + RSV preF protein 150 μg
3
50
Ad26.RSV.preF 1.1×1010 vp + RSV preF protein 150 μg
4
50
Ad26.RSV.preF 3.7×109 vp + RSV preF protein 150 μg
5
25
Placebo 
2 (dose-up)
6
50
Ad26.RSV.preF 1×1011 vp + RSV preF protein 150 μg
7
50
Ad26.RSV.preF 1.3×1011 vp + RSV preF protein 150 μg
8
25
Placebo
3 (dose-up)
9
25
Ad26.RSV.preF 1×1011 vp + RSV preF protein 150 μg
10
50
Ad26.RSV.preF 1.6×1011 vp + RSV preF protein 150 μg
11
25
Placebo
N = number of participants.
The study duration will be approximately 6 months per participant. Participants in Cohort 1 will 
be screened on Day 1 (prevaccination), whereas participants in Cohorts 2 and 3 will be screened 
within 28 days before study vaccine administration to analyze clinical safety laboratory 
parameters before vaccination. (Section 1.3). The study further comprises study vaccination 
(active or placebo) on Day 1 and a 6-month safety and immunogenicity follow-up period. 
The end of the study is defined as the last participant’s last visit (Section 4.4).
In the dose-down cohort (Cohort 1), a target of approximately 225 participants will be 
randomized in parallel in a 2:2:2:2:1 ratio to 5 groups (Table 2). Participants in Groups 1 to 4 
will receive different dose levels of Ad26.RSV.preF (ranging from 1×1011 vp to 3.7×109 vp) and 
a constant dose level of RSV preF protein (150 µg) (Section 4.3). Participants in Group 5 will 
receive placebo.
In the dose-up Cohort 2, a target of approximately 125 participants will be randomized in parallel
in a 2:2:1 ratio to 3 groups (Table 2). Participants in Groups 6 and 8 will receive 1×1011 vp 
Ad26.RSV.preF/150 µg RSV preF protein and placebo, respectively, while participants in 
Group 7 will receive 1.3×1011 vp Ad26.RSV.preF/150 µg RSV preF protein.
In the dose-up Cohort 3, a target of approximately 100 participants will be randomized in parallel 
in a 1:2:1 ratio to 3 groups. Participants in Groups 9 and 11 will receive 1×1011 vp 

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Ad26.RSV.preF/150 µg RSV preF protein and placebo, respectively, while participants in 
Group 10 will receive 1.6×1011 vp Ad26.RSV.preF/150 µg RSV preF protein (Section 4.3).
Cohorts 1 and 2 may be enrolled in parallel, whereas Cohorts 2 and 3 will be enrolled in a 
staggered manner (Figure 1). A study site will not simultaneously enroll participants in more 
than one cohort. Cohort enrollment to each study site will be controlled via the interactive web 
response system (IWRS).
Initially, a sentinel group of 5 participants will be enrolled in Cohort 2 in a 2:2:1 ratio to 
Groups 6 to 8, respectively, before enrolling additional participants (Step 1). A blinded 24-hour 
postvaccination safety review will be performed by the PI(s) and sponsor team members (ie, at 
least the study responsible physician [SRP]/study responsible scientist [SRS]). In the absence of 
any clinical safety concerns, an additional 15 participants will be enrolled in a 2:2:1 ratio 
(Step 2). After review of the 7-day (Day 8) postvaccination safety data of these 20 participants
by the DRC, the remaining participants in the cohort will be randomized in a 2:2:1 ratio (Step 3).
When all participants in Cohort 2 have completed the Day 8 postvaccination visit or discontinued 
earlier, all available safety data up to at least 7 days after vaccination of all participants in the
cohort will be reviewed by the DRC. Based on this review, the sponsor may decide to not initiate 
enrollment of Cohort 3.
The enrollment of Cohort 3 will be conducted similarly to Cohort 2. Steps 1 and 2 will be 
performed with a sentinel group of 4 participants and with 12 participants, respectively, both 
enrolled in a 1:2:1 ratio. After review of the 7-day (Day 8) postvaccination safety data of these 
16 participants by the DRC, the remaining participants in the cohort will be randomized in a 
1:2:1 ratio.
The planned primary and final analyses of all cohorts are detailed in Section 9.5. The primary 
analyses of Cohorts 2 and 3 will be combined.
After vaccination with study vaccine on Day 1, participants will remain under observation at the 
study site for a minimum of 30 minutes for presence of any acute reactions and solicited events, 
or longer if deemed necessary by the investigator. Any unsolicited and solicited local (injection 
site) or systemic AEs will be documented by the study-site personnel following this observation 
period. Participants will be given a thermometer, ruler, and a daily assessment (participant) diary 
with instructions for the proper recording of events. Each participant will record solicited local
and systemic AEs and body temperature in the participant diary, beginning on the evening of the 
vaccination day and daily for 7 days after vaccination. Body temperature should be taken at 
approximately the same time each day. Study-site personnel will collect and review participant 
diary information and confirm the entries at the next visit.
The reporting periods of AEs, SAEs, and special reporting situations are detailed in Section 8.3. 
Reporting periods for concomitant therapy are outlined in Section 6.5.
Nasosorption samples using synthetic absorptive matrix (SAM) strips will be collected on Day 1 
(prevaccination) and at 14 days and 3 and 6 months after vaccination (Section 8.1). Blood 

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samples to assess humoral and cellular immune responses will be collected on Day 1 
(prevaccination) and at 14 days and 3 and 6 months after vaccination (Section 8.1). Clinical 
safety laboratory blood samples (Cohorts 2 and 3 only) will be collected at the screening visit, on 
Day 1 (prevaccination), and at 7 days after vaccination (or at the early exit visit if this visit is 
within 8 days after vaccination and the participant discontinues the study without withdrawing 
consent) (Section 8.2.3). Participant safety throughout the study will further be evaluated via 
physical examinations and vital signs (Sections 8.2.1 and 8.2.2, respectively).
If a participant meets any of the contraindications to vaccination at the scheduled time for study 
vaccination on Day 1, enrollment at a later date is permitted at the discretion of the PI and after 
discussion with the sponsor (Section 7.2). Prior to vaccination on Day 1, a recheck of a selection 
of inclusion and exclusion criteria will be performed for participants in Cohorts 2 and 3 only. 
Participants who fail this recheck may be enrolled at a later date at the discretion of the PI and 
after discussion with the sponsor. Criteria for participant discontinuation/withdrawal from the 
study, together with the respective actions that must be undertaken, are described in Section 7.
An internal DRC will be commissioned for this study. Refer to Section 9.6 for details.
A diagram of the study design is provided in Section 1.2.
4.2.
Scientific Rationale for Study Design
Blinding, Control, Vaccination 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 vaccine. Randomization will be used to 
minimize bias in the assignment of participants to groups, to increase the likelihood that known 
and unknown participant attributes (eg, demographic and baseline characteristics) are evenly 
balanced across groups, and to enhance the validity of statistical comparisons across groups. 
Blinded vaccine will be used to reduce potential bias during data collection and evaluation of 
clinical endpoints.
Vaccine Component Selection
The rationale behind the selection of Ad26.RSV.preF and RSV preF protein is described in 
Section 2.2.
Dose Level Selection
The rationale behind the dose level selection for Ad26.RSV.preF and RSV preF protein is 
described in Section 4.3.
Staggered Cohort Enrollment and Stepwise Approach
This is the first time that healthy participants will be vaccinated with Ad26.RSV.preF at a dose 
level of 1.3×1011 vp or 1.6×1011 vp. Therefore, Cohorts 2 and 3 will be enrolled in a staggered 
manner to allow a review of all available safety data up to at least 7 days after vaccination of all 
participants in Cohort 2 by the DRC before enrolling participants in Cohort 3. Based on this 

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review, the sponsor may decide to not initiate enrollment of Cohort 3. In addition, participants in 
Cohorts 2 and 3 will be enrolled in a stepwise approach.
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 in stable 
health who will receive no direct benefit from participation in the study, except for financial 
compensation for the time and inconveniences that may arise from participation in the study. 
Refer to 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
United States Department of Health and Human Services Office for Human Research Protections
and Food and Drug Administration (FDA) guidelines.17,18
4.3.
Justification for Dose Level
The dose level of 1×1011 vp for Ad26.RSV.preF and 150 µg for RSV preF protein (administered 
in all 3 cohorts) was selected
from the primary analysis of Cohort 2 in study 
VAC18193RSV1004 and is currently under further evaluation in studies VAC18193RSV1004
and VAC18193RSV2001 (Section 2.2.2).
The lower dose levels for Ad26.RSV.preF in Cohort 1 of the current study were selected based 
on the assumption that half-log intervals in dose response are biologically meaningful for 
vaccines.
There are currently no safety data available of Ad26.RSV.preF at a dose level above 1×1011 vp. 
Two higher dose levels of Ad26.RSV.preF (ie, 1.3×1011 vp [Cohort 2] and 1.6×1011 vp 
[Cohort 3]) will therefore be assessed in this study. An increase of 0.3×1011 vp per dose level 
could lead to a potential increase of target fill concentration of approximately 15%.
In all cohorts, the dose level of RSV preF protein will be kept constant (150 µg). This dose level 
has been tested in other (ongoing) clinical studies (Section 2.2.2).

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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 study. The final data 
from the study site will be sent to the sponsor after completion of the final participant visit at that 
study site, in the timeframe specified in the clinical trial agreement.
Based on the review of all available safety data up to at least 7 days after vaccination of all 
participants in Cohort 2 by the DRC, the sponsor may decide to not initiate enrollment of 
Cohort 3.
Study Completion Definition
A participant will be considered to have completed the study if he or she has completed 
assessments at the Day 183 visit.
5. STUDY POPULATION
Screening for eligible participants will be performed prevaccination on Day 1 (Cohort 1) or 
within 28 days before study vaccine administration (Cohorts 2 and 3). Refer to Section 5.4 for 
conditions under which the repeat of any screening procedures are allowed.
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 representative and resolve any issues before enrolling a participant in the study. Waivers 
are not allowed.
Investigators should ensure that all study enrollment criteria have been met at screening. If a 
participant’s clinical status changes (including any available laboratory results or receipt of 
additional medical records) after screening but before the time of vaccination such that he or she 
no longer meets all eligibility criteria, then the participant should be excluded from participation 
in the study.
For a discussion of the statistical considerations of participant selection, refer to Section 9.2.
5.1.
Inclusion Criteria
Each potential participant must satisfy all of the following criteria to be enrolled in the study:
1.
Sign an informed consent form (ICF) indicating that he or she understands the purpose, 
procedures, and potential risks and benefits of the study, is willing to participate in the 
study and attend all scheduled visits, and is willing and able to comply with all study 
procedures and adhere to the lifestyle restrictions specified in this protocol.
2.
Male or female, aged ≥60 years on the day of signing the ICF.
3.
In the investigator’s clinical judgment, participants must be either in good or stable 
health. Participants may have underlying illnesses such as hypertension, type 2 diabetes 

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mellitus, hyperlipoproteinemia, or hypothyroidism, as long as their signs and symptoms 
are stable and medically controlled in the judgment of the investigator. Participants will 
be included on the basis of medical history and of physical examination and vital signs 
performed at screening (all cohorts), and of physical examination and/or vital signs 
performed prevaccination on Day 1 (Cohorts 2 and 3).
Note: Retesting of abnormal vital sign values that may lead to exclusion, or due to 
equipment malfunction, is allowed once without prior approval from the sponsor.
4.
A woman must be postmenopausal (defined as no menses for 12 months without an 
alternative medical cause) and not intending to conceive by any methods.
Note: Women who have had hysterectomies are also eligible for the study.
5.
Agree to not donate blood from the time of vaccination until 3 months after vaccination.
6.
Have a body mass index (BMI) <40 kg/m².
7.
Be willing to provide verifiable identification and have means to be contacted and to 
contact the investigator during the study.
For participants in Cohorts 2 and 3 only:
10.
Be healthy on the basis of clinical laboratory tests performed at screening. If the results 
of the laboratory screening tests are outside the central laboratory normal reference 
ranges and additionally within the limits of toxicity Grade 2 according to the United 
States FDA toxicity tables (ie, for tests in the FDA table) (Section 10.2, Appendix 2), 
the participant may be included only if the investigator judges the abnormalities or 
deviations from normal to be not clinically significant and appropriate and reasonable 
for the population under study. This determination must be recorded in the participant’s 
source documents and initialed by the investigator.
Note: Screening laboratory tests are to be done within 28 days before vaccination. If the 
results of the laboratory screening tests are outside the central laboratory normal 
reference ranges and deemed clinically significant by the investigator, repeat of 
screening laboratory tests will be permitted once using an unscheduled visit during the 
screening period to assess eligibility.
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 contraindication to IM injections and blood draws (eg, bleeding disorders).
2.
Has a clinically significant acute illness (this does not include minor illnesses such as 
diarrhea or mild upper respiratory tract infection) or body temperature of ≥38.0ºC 

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(≥100.4ºF) within 24 hours prior to the planned administration of study vaccine.
Note: Enrollment at a later date is permitted. For participants in Cohorts 2 and 3, 
clinical safety laboratory assessments should be repeated if vaccination is postponed 
and the time between clinical safety laboratory assessments and vaccination exceeds 
28 days.
3.
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 history of malignancy within 5 years, which is considered 
cured with minimal risk of recurrence per investigator’s judgement, can be 
enrolled.
4.
Known allergy or history of anaphylaxis or other serious adverse reactions to vaccines 
or vaccine components (including any of the constituents of the study vaccine).8,9
5.
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 or 2 diabetes mellitus) that is stable and inactive without the 
use of systemic immunomodulators and glucocorticoids may be enrolled at the 
discretion of the investigator.
b. Chronic (>10 days) or recurrent use of systemic corticosteroids within 6 months 
before administration of study vaccine.
Note: Ocular, topical, or inhaled steroids are allowed.
c. Administration of antineoplastic and immunomodulating agents (eg, cancer 
chemotherapeutic agents or systemic corticosteroids) or radiotherapy within 
6 months before administration of study vaccine.
6.
History of acute polyneuropathy (eg, Guillain-Barré syndrome) or chronic idiopathic 
demyelinating polyneuropathy.
7.
History of chronic urticaria (recurrent hives), eczema, or atopic dermatitis.
8.
Received hematopoietic stem cell transplant in medical history, treatment with 
immunoglobulins in the 2 months, immunoglobulins specific to RSV, human 
metapneumovirus, or parainfluenza viruses in the 12 months, apheresis therapies in the 
4 months, or blood products in the 6 months before the planned administration of the
study vaccine or has any plans to receive such treatment during the study.

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9.
Received or plans to receive:
a.
Licensed live attenuated vaccines – within 28 days before or after planned 
administration of study vaccine.
b.
Other licensed (not live) vaccines – within 14 days before or after planned 
administration of study vaccine.
10.
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 study vaccine or is currently enrolled or plans to participate in
another investigational study during the course of this study.
Note: Participation in an observational clinical study (ie, without intervention) is 
allowed upon approval of the sponsor.
11.
Has a serious chronic disorder, including severe chronic obstructive pulmonary disease 
or severe congestive heart failure, end-stage renal disease with or without dialysis, 
clinically unstable cardiac disease, Alzheimer’s disease, or has any condition for which, 
in the opinion of the investigator, participation would not be in the best interest of the 
participant (eg, compromise the well-being) or that could prevent, limit, or confound the 
protocol-specified assessments.
12.
Had major surgery (as per the investigator’s judgment) within 4 weeks before 
vaccination, will not have fully recovered from surgery prior to vaccination, or has 
major surgery within 6 months after administration of study vaccine.
Note: Participants with planned surgical procedures to be conducted under local or 
locoregional anesthesia and not judged as major by the investigator may participate.
13.
Is an employee of the investigator or study site, with direct involvement in the proposed 
study or other studies under the direction of that investigator or study site, as well as 
family members of the employees or the investigator, or an employee of the sponsor.
14.
Has hepatitis B or C infection, including history of treated hepatitis C infection (per 
medical history).
15.
Has human immunodeficiency virus type 1 or 2 infection (per medical history).
16.
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.
17.
Cannot communicate reliably with the investigator.
18.
Is unlikely to adhere to the requirements of the study or unlikely to complete the full 
course of observation in the opinion of the investigator.

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19.
Received an active RSV vaccine in a previous RSV vaccine study or an Ad26-vectored 
vaccine at any time prior to randomization.
20.
Taken any disallowed therapies as noted in Section 6.5 before vaccination.
5.3.
Lifestyle Considerations
Potential participants must be willing and able to adhere to the following lifestyle restrictions 
during the course of the study to be eligible for participation:
1.
Refer to Section 6.5 for details regarding prohibited and restricted therapy during the 
study.
2.
Agree to follow all requirements that must be met during the study as noted in the 
inclusion and exclusion criteria (Sections 5.1 and 5.2, respectively).
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.
Individuals who do not meet all eligibility criteria (screen failure) but at some point in the future 
are expected to meet the eligibility criteria may be rescreened on one occasion only. Rescreened 
participants will be assigned a new participant number, undergo the informed consent process, 
and then restart a new screening phase.
6. STUDY VACCINE
6.1.
Study Vaccine Administration
On Day 1, participants will receive a single IM injection of study vaccine (ie, the Ad26/protein 
preF RSV vaccine or placebo) in the deltoid muscle. The injection will occur at the study site
according to the overview shown in Table 2. The Ad26/protein preF RSV vaccine is composed 
of Ad26.RSV.preF (JNJ-64400141) and RSV preF protein (JNJ-64213175) (Section 2).
Ad26.RSV.preF will be administered at a dose level ranging from 3.7×109 vp to 1.6×1011 vp, and 
RSV preF protein at a constant dose level of 150 µg (Table 2). Refer to Section 4.3 for 
justification of the dose levels. Due to the different dose levels of Ad26.RSV.preF, the injection 
volumes of the study vaccine may differ between the cohorts. Ad26.RSV.preF and RSV preF 

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protein will be supplied as solutions in separate single-use vials. Placebo will consist of 0.9% 
saline. The use of concomitant therapy stated in Section 6.5 should be respected. Study 
vaccination pausing rules are listed in Section 7.3.
Study vaccine administration must be captured in the source documents and the electronic case 
report form (eCRF).
Ad26.RSV.preF and RSV preF protein will be manufactured and provided under the 
responsibility of the sponsor. Ad26.RSV.preF will be supplied as a frozen liquid to be thawed 
prior to use. Labels will contain information to meet the applicable regulatory requirements. 
Note that RSV preF protein CTM will be labelled as “RSV-F Vaccine”. Refer to the IBs for 
Ad26.RSV.preF8 and RSV preF protein9 for details of the components and a list of excipients.
For a definition of study vaccine overdose, refer to Section 8.4.
6.2.
Preparation/Handling/Storage/Accountability
Preparation/Handling/Storage
Vials must be stored in a secured location under controlled temperature with no access for 
unauthorized personnel. The study refrigerator/freezer must be equipped with a continuous 
temperature monitor and alarm and should be equipped with back-up power systems. If the study 
vaccine components are exposed to temperatures outside the specified temperature range, all 
relevant data will be sent to the sponsor to determine if the affected study vaccine components 
can be used or will be replaced. The affected study vaccine components must be quarantined and 
not used until further instruction from the sponsor is received.
An unblinded study-site pharmacist, or other qualified individual, who will have no other study 
function following vaccination, will prepare the appropriate vials and syringes, labeled with the 
participant’s identification number, and provide the syringes for the study vaccine in a blinded 
manner to the blinded study vaccine administrator who will perform the injection. An unblinded 
study-site pharmacist, or other qualified individual, may also perform the vaccination but will 
have no other study function following vaccination.
Refer to the Investigational Product Preparation Instructions and Study Site Investigational 
Product and Procedures Manual for additional guidance on study vaccine preparation, handling, 
and storage.
Accountability
The investigator is responsible for ensuring that all study vaccine received at the study 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 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 

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environmental conditions. Unused study vaccine must be available for verification by the 
sponsor’s study-site monitor during on-site monitoring visits. The return to the sponsor of unused 
study vaccine will be documented on the vaccine return form. When the study site is an 
authorized destruction unit and study vaccine supplies are destroyed on site, this must also be 
documented on the vaccine return form.
Potentially hazardous materials 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 should be dispensed under the supervision of the investigator or a qualified 
member of the study-site personnel, or by a hospital/clinic pharmacist. Study vaccine will be 
supplied only to 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 study site other than the study sites agreed upon with the 
sponsor.
6.3.
Measures to Minimize Bias: Randomization and Blinding
Study Vaccine Allocation
Procedures for Randomization
Central randomization will be implemented in this study. Within each cohort, participants will be 
randomly assigned to the groups based on a computer-generated randomization schedule 
prepared before the study by or under the supervision of the sponsor. In Cohort 1, the 
randomization ratio is 2:2:2:2:1 to Groups 1 to 5, respectively, in Cohort 2, the randomization 
ratio is 2:2:1 to Groups 6 to 8, respectively, and in Cohort 3, the randomization ratio is 1:2:1 to 
Groups 9 to 11, respectively. The randomization will be balanced by using randomly permuted 
blocks. The IWRS will assign a unique code, which will dictate the group assignment for the 
participant. The requestor must use his or her own user identification and personal identification 
number when contacting the IWRS, and will then give the relevant participant details to uniquely 
identify the participant.
If randomized participants discontinue from the study before the study vaccine is administered, 
additional participants may be recruited to replace these participants at the discretion of the 
sponsor. Any replacement participant will be assigned to the same group as the original 
(discontinued) participant. The replacement participant’s randomization number will equal the 
randomization number of the discontinued participant +1000 (eg, participant 0001 would be 
replaced by participant 1001). These additional participants should also be randomized through 
IWRS. No replacements or additional randomizations will be done for withdrawals after 
vaccination.

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Blinding
The investigator will not be provided with randomization codes until database lock of the final 
analysis of the complete study. The codes will be maintained within the IWRS, which has the 
functionality to allow the investigator to break the blind for an individual participant.
At the sponsor level, unblinding (at the participant level) will occur at the time of the primary 
analysis for each cohort (Section 9.5). From the primary analysis onwards, group level results 
may be shared as needed, however, efforts will be made to preserve the blinding to the individual 
participant allocation.
Data that may potentially unblind the study vaccine assignment (eg, immunogenicity data, study 
vaccine preparation/accountability data, study vaccine allocation) will be handled with special 
care to ensure that the integrity of the blind is maintained and the potential for bias is minimized. 
This can include making special provisions, such as segregating the data in question from view 
by the investigators, clinical team, or others as appropriate until the time of database lock and 
unblinding.
The investigator may in an emergency determine the identity of the study vaccine by contacting 
the IWRS. While the responsibility to break the study vaccine allocation code in emergency 
situations resides solely with the investigator, it is recommended that the investigator contacts
the sponsor if possible to discuss the particular situation, before breaking the blind. Telephone 
contact with the sponsor will be available 24 hours per day, 7 days 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.
The pharmacist or qualified individual with primary responsibility for study vaccine preparation 
and dispensing will be unblinded to study vaccine allocation (Section 6.2).
Participants who have had their study vaccine assignment unblinded should continue to return 
for scheduled evaluations.
6.4.
Study Vaccine Compliance
Study vaccine will be IM administered by a blinded study vaccine administrator (ie, a trained and 
qualified study nurse, medical doctor, or otherwise qualified healthcare professional) at the study 
site. The unblinded study-site pharmacist, or other qualified individual, may also perform the 
vaccination, but will have no other study function following vaccination. Details of each 
administration will be recorded in the eCRF (including date and time of injection). For blinding 
procedures, see Section 6.3.

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6.5.
Concomitant Therapy
Prestudy therapies administered up to 30 days before vaccination must be recorded in the eCRF 
at screening (all cohorts) and additionally on Day 1 for Cohorts 2 and 3.
Concomitant 
therapies 
such 
as 
analgesic/antipyretic 
medications 
and 
nonsteroidal 
anti-inflammatory drugs, corticosteroids, and antihistaminic must be recorded in the eCRF until 
28 days after vaccination. All other concomitant therapies should also be recorded in the eCRF if 
administered in conjunction with new or worsening AEs reported per protocol requirements 
outlined in Section 10.3, Appendix 3.
Analgesic/antipyretic medications and nonsteroidal anti-inflammatory drugs may be used after 
vaccination only in cases of medical need (eg, fever or pain). Use of these medications as routine 
prophylaxis before vaccination is discouraged.
Information on concomitant use of herbal supplements or vitamins will not be collected.
Use of systemic corticosteroids must be documented during the study. Use of ocular, topical, or 
inhaled steroids during the study is allowed, whereas chronic (>10 days) or recurrent use of 
systemic corticosteroids during the study is prohibited. Antineoplastic and immunomodulating 
agents or radiotherapy are prohibited during the study. If chronic use of systemic corticosteroids 
or antineoplastic or immunomodulating agents becomes medically indicated during the study for 
any participant, the sponsor should be notified.
Vaccination with licensed live attenuated vaccines within 28 days of study vaccination 
(ie, before or after) is prohibited. Other licensed (not live) vaccines (eg, influenza, tetanus, 
hepatitis A, hepatitis B, rabies) should be given at least 14 days before (or at least 14 days after) 
administration of study vaccine in order to avoid potential confusion of adverse reactions and 
potential immune interference. If a vaccine is indicated in a postexposure setting (eg, rabies or 
tetanus), it must take priority over the study vaccine.
Use of any experimental medication (including experimental vaccines other than the study 
vaccine) during the study is not allowed.
The sponsor must be notified in advance (or as soon as possible thereafter) of any instances in 
which prohibited therapies are administered.
6.6.
Intervention After the End of the Study
Participants will be instructed that study vaccine will not be made available to them after they 
have completed/discontinued study vaccination.

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7. DISCONTINUATION OF STUDY VACCINATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1.
Discontinuation of Study Vaccination
A participant’s study vaccination must be discontinued if:

The participant withdraws consent to receive study vaccination.

The investigator believes that for safety reasons or reactogenicity reasons (eg, AE) it is in 
the best interest of the participant to discontinue study vaccination.
Study vaccine assigned to the participant who discontinued study vaccination may not be 
assigned to another participant. Additional participants will be entered to ensure the 
protocol-specified number of participants complete the study.
7.2.
Contraindications to Study Vaccination
The following events assessed by the investigator constitute a temporary contraindication to 
study vaccination:

Acute illness at the planned time of vaccination. This does not include minor illnesses, such 
as diarrhea or mild upper respiratory tract infection.

Fever (body temperature of ≥38.0°C [≥100.4ºF]) at the planned time of vaccination.
If any of these events occur at the planned time of vaccination, the participant may be vaccinated 
up to, and no later than, 10 days after the planned vaccination, or be withdrawn from vaccination 
at the discretion of the investigator.
Note: For participants in Cohorts 2 and 3, clinical safety laboratory assessments should be 
repeated if vaccination is postponed and the time between clinical safety laboratory assessments
and vaccination exceeds 28 days.
7.3.
Study Vaccination Pausing Rules
The PI(s) and sponsor team members (ie, SRP/SRS) will monitor the study vaccination pausing 
rules listed below. If vaccination is considered to raise significant safety concerns (ie, if at least 
one of the study vaccination pausing rules has been met), further vaccination of participants will 
be paused until the DRC review of all available data is carried out and subsequent 
communication between the sponsor and the PI(s) takes place. The DRC will review blinded data 
first but is entitled to and has the right to require submission of unblinded data if deemed 
necessary. When a first DRC meeting has been triggered by the occurrence of a given study 
vaccination pausing rule, the DRC will convene thereafter for each additional participant 
meeting that pausing rule. Possible actions upon review include, but are not limited to, study 
suspension, study adaptation, or discontinuation of further vaccination.

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The following list of study vaccination pausing rules applies for concerned AEs that occur up to 
28 days after vaccination and concerned SAEs:
1.
One or more participants experience an SAE or other potentially life-threatening (Grade 4) 
event that is determined to be related to study vaccine; OR
2.
One or more participants experience anaphylaxis clearly not attributable to other causes than 
vaccination with study vaccine; OR
3.
Two or more participants experience a Grade 3 or 4 unsolicited AE of the same type, 
determined to be related to study vaccine, that persists for 72 hours or longer; OR
4.
Two or more participants experience a Grade 3 or 4 solicited systemic AE of the same type, 
determined to be related to study vaccine, that persists for 72 hours or longer; OR
5.
Two or more participants experience a persistent (upon repeated testing) Grade 3 or 4 
laboratory abnormality related to the same laboratory parameter and considered related to 
study vaccine, that persists for 72 hours or longer; OR
6.
Death of any participant considered related to study vaccine or if the causal relationship to 
study vaccine cannot be excluded.
Note: All cases of death will be sent to the DRC. Upon their review, the DRC will decide 
whether a study pause is required.
For study vaccination pausing rule 5: to assess abnormal laboratory values, the test must be 
repeated at least once, within 48 hours of the study site becoming aware of the abnormal value.
After each DRC review of similar AEs, the DRC will indicate the conditions under which it 
requires further notification and review of the subsequent similar AEs.
To enable prompt response to a situation that could trigger study vaccination pausing rules 3, 4,
or 5, the investigator should update the eCRF with information on any Grade 3 or 4 AE on the 
same day that the AE is reported.
Also, the investigator should notify the sponsor’s medical monitor (AND transmit the SAE form 
electronically to Global Medical Safety Operations, if applicable), immediately and no later than 
24 hours after becoming aware of any related AE of Grade 3 or above AND update the eCRF 
with relevant information on the same day the AE information is collected. A thorough analysis 
of all Grade 3 (or above) cases will be carried out by the sponsor’s medical monitor, irrespective 
of whether the criteria for pausing the study are met. Based on the pausing criteria, the sponsor’s 
medical monitor will then decide whether a study pause is warranted. All study sites will be 
notified immediately in case of a study pause. The sponsor’s medical monitor is responsible for 
the immediate notification of the DRC members and coordination of a DRC meeting in case of a 
study pause.
Vaccinations for the study may be suspended for safety concerns other than those described 
above, or before study vaccination pausing rules are met, if, in the judgment of the DRC, 
participant safety may be threatened.

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Resumption of vaccinations will start only upon receipt by the study site of written 
recommendations by the DRC. The study site(s) will be allowed to resume activities upon receipt 
of a written notification from the sponsor. The communications from the DRC will be forwarded 
by the investigator to the Independent Ethics Committee (IEC)/Institutional Review Board (IRB)
and by the sponsor to the relevant health authorities, according to local standards and regulations.
In addition to the study vaccination pausing rules, the sponsor’s medical monitor or the PI(s) 
(upon consultation with the sponsor’s medical monitor) may initiate a DRC review for any single 
event or combination of events which, in their professional opinion, could jeopardize the safety 
of the participants or the reliability of the data.
7.4.
Participant Discontinuation/Withdrawal From the Study
Each participant has the right to withdraw from the study at any time for any reason without 
affecting the right to treatment by the investigator. The investigator should make an attempt to 
contact participants who did not return for scheduled visits or follow-up. Although the 
participant is not obliged to give reason(s) for withdrawing prematurely, the investigator should 
make a reasonable effort to ascertain the reason(s) while fully respecting the participant’s rights.
A participant will be withdrawn from the study for any of the following reasons:

Lost to follow-up

Withdrawal of consent

Death

Repeated failure to comply with protocol requirements or to cooperate with the study-site 
personnel

Decision by the sponsor or the investigator to stop or cancel the study

Decision by local regulatory authorities or IEC/IRB to stop or cancel the study
Any unnecessary study discontinuation should be avoided. 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 to complete and report the observations as thoroughly as 
possible. Study vaccine assigned to the withdrawn participant may not be assigned to another 
participant. Participants who withdraw will be replaced, as long as the participant has not been 
vaccinated (Section 6.3).
An early exit visit will be conducted for those participants who are unable to continue 
participation in the study and withdraw from the study before Day 183, but who do not withdraw 
consent (Section 1.3). Participants who wish to withdraw consent from participation in the study 
will be offered an early exit visit (prior to formal withdrawal of consent). They have the right to 
refuse.

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If a participant is lost to follow-up, every reasonable effort must be made by the study-site 
personnel to contact the participant and determine the reason(s) for discontinuation/withdrawal. 
The measures taken to follow up must be documented.
7.4.1.
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 Section 10.4, Appendix 4). 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.
7.5.
Lost to Follow-up
A participant will be considered lost to follow-up if he or she 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 study-site personnel must make every 
reasonable effort to regain contact with the participant (where possible, 3 telephone calls, 
e-mails, fax, and, if necessary, a certified letter to the participant’s last known mailing 
address, 
or 
local 
equivalent 
methods), 
and 
to 
determine 
the 
reason 
for 
discontinuation/withdrawal. These contact attempts should be documented in the 
participant’s study file.

Should the participant continue to be unreachable, he or she 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 participants to inform them, their contact information will be transferred to 
another study site.
8. STUDY ASSESSMENTS AND PROCEDURES
Overview
The Schedule of Activities
(Section 1.3)
summarizes the frequency and timing of 
immunogenicity and safety measurements applicable to this study. Unscheduled visits may be 
performed based on the investigator’s clinical judgment and may include further evaluations, as 
needed.

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In addition, a participant diary to record body temperature and solicited injection site and 
systemic signs and symptoms will be provided to the participants on the day of study vaccination 
(Day 1). The participant diary includes instructions on how to capture the data and grading scales 
to assess severity of the signs and symptoms. The study-site personnel will be responsible for 
providing appropriate training to the participant to avoid missing or incorrect data. 
The participant diary will be reviewed by the study-site personnel at the Day 8 visit. If the 
participant diary review is missed, the participant diary will be reviewed during the following 
visit. Thermometers will be given to all participants on the day of study vaccination (Day 1) and 
should be returned to the study site at the end of the study/early withdrawal. Participants will 
also be provided with a ruler on the day of study vaccination (Day 1) to measure local injection 
site reactions.
If multiple assessments are scheduled for the same timepoint, it is recommended that procedures 
be performed in the following sequence: vital signs, nasal 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 document and in the eCRF.
The total blood volume to be collected from each participant will be approximately 240 mL 
(Cohort 1) or 260 mL (Cohorts 2 and 3).
Repeat or unscheduled samples may be taken for safety reasons or for technical issues with the 
samples.
Sample Collection and Handling
The actual dates and times of sample collection must be recorded in the eCRF or laboratory 
requisition form.
Refer to the Schedule of Activities (Section 1.3) for the timing and frequency of all sample 
collections.
Instructions for the collection, handling, storage, and shipment of samples are found in the 
laboratory manual that will be provided. Collection, handling, storage, and shipment of 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:

IB for Ad26.RSV.preF8

IB for RSV preF protein9

Study Site Investigational Product and Procedures Manual

Laboratory manual

Investigational Product Preparation Instructions

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
Participant diary and instructions for use

Rulers (to measure diameter of any erythema and induration/swelling)

Thermometers

Laboratory kits

Contact Information page(s)

Study protocol

IWRS Manual 

Electronic data capture (eDC) Manual/eCRF completion guidelines

Any other manual, as applicable

Wallet card

Sample ICF
8.1.
Immunogenicity Assessments
Venous blood samples of approximately 10 and 50 mL will be collected for the determination of 
humoral and cellular immune responses, respectively (Table 3), at the timepoints indicated in the 
Schedule of Activities (Section 1.3). Nasosorption samples using SAM strips will be collected at 
the timepoints indicated in the Schedule of Activities (Section 1.3), and will be used for 
immunogenicity assessments including, but not limited to, determination of antigen-specific 
immunoglobulin (IgG and IgA) (Table 3).
Sample collection and processing will be performed by the study-site personnel according to 
current versions of approved standard operating procedures.
Table 3:
Summary of Possible Immunogenicity Assays (Humoral and Cellular)
Assay 
Purpose
Primary and secondary endpoints
Pre-F protein binding antibody (ELISA)
Analysis of antibodies binding to RSV F protein in prefusion form
RSV A2 neutralization
Analysis of neutralizing antibodies to the A2 strain
IFN-γ (ELISpot)
T-cell IFN-γ responses to RSV F protein peptides
Exploratory endpoints
Post-F protein binding antibody (ELISA)
Analysis of antibodies binding to RSV F protein in postfusion form
Antigen-specific T-cell immune responses
Analysis of T-cell responses to RSV F protein peptide-stimulated 
PBMCs (including, but not limited to, CD4+/CD8+, IL-2, IFN-γ, 
TNF-α, activation markers and memory) using ICS or CyTOF
RSV strain cross-neutralization
Analysis of cross-neutralizing antibodies to B and/or other 
A strain(s)
Antibody specificity and functional 
characterization
Analysis of pre- and post-F antibody specificity by functional 
assays such as ELISA, competition ELISA, and epitope mapping. 
Functional characterization of antibodies including, but not limited 
to, ADCC, ADCP, avidity, immunoglobulin isotype, and functional 
VNAs to other respiratory viruses

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Analysis of nasal antibodies to RSV 
including, but not limited to, IgA and IgG
Analysis of nasal antibodies binding to RSV F protein in prefusion 
and/or postfusion form in nasal samples
Adenovirus neutralization assay
Analysis of neutralizing antibodies to Ad26
ADCC 
= 
antibody-dependent 
cell-mediated 
cytotoxicity; 
ADCP 
= 
antibody-dependent 
cellular 
phagocytosis; 
CyTOF = cytometry by time of flight; IL = interleukin; PBMC = peripheral bone marrow cell; TNF = tumor necrosis factor.
Immunogenicity samples will be prioritized as outlined in the laboratory manual.
8.2.
Safety Assessments
Safety will be evaluated throughout the study from signing of the ICF until the last study-related 
activity, or until the participant has been deemed lost to follow-up after demonstration of due 
diligence of follow-up efforts.
Key safety assessments will include the monitoring of AEs, physical examinations, vital signs, 
and clinical safety laboratory assessments.
AEs will be reported and followed by the investigator as specified in Section 8.3 and 
Section 10.3, Appendix 3.
Any clinically significant abnormalities (including those persisting at the end of the study/early 
withdrawal) will be followed by the investigator until clinical resolution (return to baseline) or 
until a clinically stable condition is reached, or until the participant has been deemed lost to 
follow-up after demonstration of due diligence of follow-up efforts.
Details regarding the DRC are provided in Section 9.6.
The study will include the following evaluations of safety and reactogenicity according to the 
timepoints provided in the Schedule of Activities (Section 1.3).
8.2.1.
Physical Examinations
A physical examination (including height and body weight) will be carried out at screening 
(Cohorts 2 and 3) or on Day 1 (prevaccination) (Cohort 1). At all other visits, an abbreviated, 
symptom-directed physical examination will be performed if deemed necessary by the 
investigator based on clinically relevant issues, clinically relevant symptoms, and medical 
history. A symptom-directed physical examination may be repeated if deemed necessary by the 
investigator.
Physical examinations will be performed by the investigator or by a designated medically-trained 
clinician. Any clinically relevant abnormalities or changes in severity observed during the review 
of body systems should be documented in the eCRF.
8.2.2.
Vital Signs
Body temperature (oral route preferred), heart rate (beats per minute), respiratory rate (breaths 
per minute), and systolic and diastolic blood pressure (mmHg) will be assessed.
Blood pressure and heart rate measurements will be assessed, if possible, with a completely 
automated device. Manual techniques will be used only if an automated device is not available.

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Systolic and diastolic blood pressure (supine) and heart and respiratory rate measurements 
should be preceded by at least 5 minutes of rest in a quiet setting without distractions 
(eg, television, cell phones). Vital signs measurements should be taken before nasal sampling 
and blood draws, if applicable.
Confirmatory vital signs measurements can be performed if inconsistent with a prior 
measurement. Any clinically relevant abnormalities or changes in severity should be documented 
in the eCRF.
8.2.3.
Clinical Safety Laboratory Assessments
In Cohorts 2 and 3, blood samples for biochemistry and hematology will be collected as noted in
Table 4 at the timepoints indicated in the Schedule of Activities (Section 1.3). All clinical safety 
laboratory analyses will be performed at the central laboratory.
Table 4:
Protocol-required Clinical Laboratory Assessments
Biochemistry Panel
Hematology Panel
sodium
hemoglobin
potassium
white blood cell count with differential
creatinine
platelet count
blood urea nitrogen 
prothrombin timea
aspartate aminotransferase
activated partial thromboplastin timea
alanine aminotransferase
a. Will be measured at screening only.
Review and Grading of Laboratory Data
The investigator must review the laboratory results, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the eCRF. 
The laboratory reports must be filed with the source documents.
Laboratory values will be initially evaluated by the investigator according to central laboratory 
criteria. Abnormal values outside the central laboratory normal range will be graded according to 
the FDA Guidance document “Toxicity Grading Scale from Healthy Adult and Adolescent 
Volunteers Enrolled in Preventive Vaccine Clinical Trials” (Section 10.2, Appendix 2). 
Laboratory values within central laboratory normal limits will not be FDA graded and will be 
considered as normal.
Reporting Laboratory Abnormalities as AEs
Any clinically significant abnormal laboratory value within 28 days after vaccination that falls 
outside the central laboratory normal range will be captured as an AE. Laboratory values outside 
normal ranges that are not clinically significant in the judgment of the investigator should not be 
recorded as AEs. Any laboratory value falling within the central laboratory normal range will not 
be severity graded or recorded as an AE, regardless of whether the value falls within FDA ranges
for Grade 1 or higher.

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Repeat of Clinically Significant Laboratory Tests
For any clinically significant abnormal laboratory value that has increased in grade over baseline, 
the test must be repeated at the next scheduled visit or sooner based on the investigator’s 
judgment, however Grade 3 or higher abnormalities should be retested within 48 hours.
Screening Procedures (Cohorts 2 and 3 Only)
For entry into the study, each participant must be healthy on the basis of clinical laboratory tests 
performed at screening. Refer to inclusion criterion 10 in Section 5.1 for more details.
8.3.
AEs and SAEs
Timely, accurate, and complete reporting and analysis of safety information from clinical studies 
are crucial for the protection of participants, investigators, and the sponsor, and are mandated by 
regulatory agencies worldwide. The sponsor has established standard operating procedures in 
conformity with regulatory requirements worldwide to ensure appropriate reporting of safety 
information; all clinical studies conducted by the sponsor or its affiliates will be conducted in 
accordance with those procedures.
For further details on AEs and SAEs (Definitions and Classifications; Attribution Definitions; 
Severity Criteria; Special Reporting Situations; Procedures) as well as product quality 
complaints (PQCs), refer to Section 10.3, Appendix 3.
8.3.1.
Time Period and Frequency for Collecting AE and SAE Information
AEs and special reporting situations, whether serious or nonserious, that are related to study 
procedures or that are related to noninvestigational 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 date of vaccination will be collected on the Medical History eCRF page as 
pre-existing conditions.
Any solicited local (injection site) or systemic AEs occurring during the 30-minute 
postvaccination observation period (or longer if deemed necessary by the investigator) will be 
documented by the study-site personnel following this observation period. Solicited AEs 
collected through a participant diary will be recorded from the time of vaccination until 7 days 
after vaccination.
All other unsolicited AEs and special reporting situations, whether serious or nonserious, will be 
reported from the time of vaccination until 28 days after vaccination. All AEs and SAEs leading 
to discontinuation of the study vaccination (regardless of the causal relationship) are to be 
reported from the moment of vaccination until completion of the participant’s last study-related 
procedure, which may include contact for safety follow-up. All other SAEs (regardless of the 
causal relationship) are to be reported from the time of vaccination until the end of the 
study/early withdrawal.

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All SAEs 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. 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).
The sponsor will evaluate any safety information that is spontaneously reported by an 
investigator beyond the time frame specified in the protocol.
8.3.2.
Method of Detecting AEs and SAEs
Care will be taken not to introduce bias when detecting AEs or SAEs. Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about AE
occurrence.
Solicited AEs
Solicited AEs are used to assess the reactogenicity of the study vaccine and are predefined local 
(at the injection site) and systemic events for which the participant is specifically questioned and 
which are noted by participants in their participant diary.
After vaccination with study vaccine on Day 1, participants will remain under observation at the 
study site for a minimum of 30 minutes for presence of any acute reactions and solicited events, 
or longer if deemed necessary by the investigator. In addition, participants will record solicited 
signs and symptoms in the participant diary for 7 days after vaccination. All participants will be 
provided with the participant diary and instructions on how to complete the diary (Section 8). 
The study-site personnel will transcribe the information provided by the participant into the 
relevant sections of the eCRF. After review and verbal discussion of the initial participant diary 
entries with the participant, the investigator will complete his or her own assessment in the 
relevant sections of the eCRF. Once a solicited sign or symptom from the participant diary is 
considered to be of severity Grade 1 or above during the investigator’s assessment, it will be 
recorded as a solicited AE.
Solicited Injection Site AEs
Participants will be asked to note in the participant diary occurrences of injection site 
pain/tenderness at the study vaccine injection site daily for 7 days after vaccination (day of 
vaccination and the subsequent 7 days). The extent (largest diameter) of any erythema and 
swelling at the injection site should be measured (using the ruler supplied) and recorded daily. 
The case definitions for solicited injection site events can be found in Gidudu et al.7 and Kohl et 
al.11
Solicited Systemic AEs
Participants will be instructed on how to record daily body temperature using a thermometer 
provided for home use. Participants should record the body temperature (oral route preferred) in 
the participant diary in the evening of the day of vaccination, and then daily for the next 7 days 

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approximately at the same time each day. If more than one measurement is made on any given 
day, the highest body temperature of that day will be used in the eCRF.
Fever is defined as endogenous elevation of body temperature ≥38.0°C [≥100.4ºF], as recorded 
in at least one measurement.14
Participants will also be instructed on how to note signs and symptoms in the participant diary on 
a daily basis for 7 days after vaccination (day of vaccination and the subsequent 7 days), for the 
following events: fatigue, headache, nausea, and myalgia.
Unsolicited AEs
Unsolicited AEs are all AEs for which the participant is not specifically questioned in the 
participant diary.
8.3.3.
Follow-up of AEs and SAEs
AEs, including pregnancies in partners of male participants, will be followed by the investigator 
as specified in Section 10.3, Appendix 3.
8.3.4.
Regulatory Reporting Requirements for SAEs
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.
8.3.5.
Pregnancy
All initial reports of pregnancy in female 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 the SAE Form.
Follow-up information regarding the outcome of the pregnancy and any postnatal sequelae in the 
infant will be required.
8.4.
Treatment of Overdose
For this study, any dose of
the Ad26/protein preF RSV vaccine
greater than
the 
protocol-specified dose will be considered an overdose. The sponsor does not recommend 
specific intervention for an overdose.

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In the event of an overdose, the investigator or treating physician should:

Contact the medical monitor immediately.

Closely monitor the participant for AE/SAE and laboratory abnormalities until resolution.

Document the quantity of the excess dose in the eCRF.

Report as a special reporting situation.
8.5.
Genetics
Genetics are not evaluated in this study.
8.6.
Medical Resource Utilization and Health Economics
Health Economics/Medical Resource Utilization and Health Economics parameters are not 
evaluated in this study.
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 immunogenicity and safety data is 
outlined below. Specific details will be provided in the statistical analysis plan (SAP).
9.1.
Statistical Hypotheses
No formal statistical testing of safety or immunogenicity data is planned; data will be analyzed 
descriptively.
9.2.
Sample Size Determination
9.2.1.
Immunogenicity (Cohort 1)
The primary objective of Cohort 1 is to explore the dose-response relationship of humoral 
immune responses (as measured by preF ELISA) induced by different dose levels of the 
Ad26/protein preF RSV vaccine.
Assuming:

10% of exclusions (eg, drop-outs, missing samples, and major protocol deviations impacting 
immunogenicity data)

a standard deviation on the log2 scale of the preF ELISA of 1.3 on Day 15 and 1.1 on 
Day 183 for all dose levels

4 dose levels
The linear model log2 (preF ELISAtimepoint) = GMT preF ELISAAd26/protein preF RSV vaccine (1x10
11 vp/150 µg),timepoint + 
slope × #titration steps provides a standard error for the slope of 0.052 on Day 15 and 0.040 on 
Day 183 with 50 participants per arm. This is deemed sufficient for this exploratory study.

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9.2.2.
Safety (Cohorts 1, 2, and 3)
Placebo recipients are included for blinding and safety purposes and will provide additional 
control specimens for immunogenicity assays.
The observation of 0 events (eg, SAEs) is associated with 95% confidence that the true event rate
is below the rates specified in the below table for the considered number of participants.
Table 5:
Upper Limit of the 95% One-sided Confidence Interval if no Cases are Observed for Different 
Sample Sizes
Sample Size
N=25
N=50
N=75
UL 95% one-sided CI
11.3%
5.8%
3.9%
CI = confidence interval; N = number of participants; UL = upper limit.
The table below provides the probability of observing at least one AE in a group of the 
considered sample size given several true AE rates.
Table 6:
Probability of Observing at Least One AE in a Group of the Considered Sample Size Given 
Several True AE Rates
True AE Rate (%)
Probability of Observing at Least One AE in N Participants (%)
N=25
N=50
N=75
0.5
12
22
31
1
22
39
53
2.5
47
72
85
10
93
99
100
25
100
100
100
50
100
100
100
N = number of participants.
9.3.
Populations for Analyses
Vaccine assignment will follow the as-treated principle.
The Full Analysis Set (FAS) will include all participants who were randomized and received the 
study vaccine, regardless of the occurrence of protocol deviations. All safety and participant 
information analyses will be based on the FAS.
The Per-protocol Immunogenicity (PPI) Set will include all participants who were randomized 
and received the study vaccine, and for whom immunogenicity data are available, excluding 
participants with major protocol deviations expecting to impact the immunogenicity outcomes.
The analysis of all immunogenicity endpoints will be based on the PPI set. For key tables, 
sensitivity immunogenicity analyses might also be performed on the FAS.
9.4.
Statistical Analyses
The SAP will be finalized prior to database lock of the primary analysis and 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 key secondary endpoints.

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9.4.1.
Participant Information
For all participants, demographic characteristics (eg, age, height, body weight, BMI, race, and 
gender) and other baseline characteristics will be tabulated and summarized descriptively by 
cohort.
9.4.2.
Immunogenicity Analyses
No formal statistical testing of immunogenicity data is planned. Immunogenicity data will be 
analyzed descriptively by cohort and group. In addition, for a selection of tables, data may be 
pooled over cohorts.
Descriptive statistics (eg, geometric mean and 95% confidence interval [CI] for ELISA and VNA
data; median and quartiles for ELISpot) will be calculated for continuous immunologic 
parameters at all timepoints. For the humoral assays, geometric mean fold rises from baseline 
and corresponding 95% CIs might additionally be calculated. Baseline is considered as the last 
available assessment before vaccination. Graphical representations of immunologic parameters 
will be made as applicable.
Frequency tabulations will be calculated for discrete (qualitative) immunologic parameters as 
applicable.
To explore the dose-response relationship between preF ELISA and different dose levels of the
Ad26/protein preF RSV vaccine, a linear regression model will be fitted for each timepoint 
separately, using data of the active groups of Cohort 1, with the log-transformed preF ELISA 
titers at the considered timepoint as dependent variable, the number of titration steps as 
independent variable, and the geometric mean titer (GMT) of preF ELISA of the Ad26/protein 
preF RSV vaccine (1×1011 vp/150 µg) at the considered timepoint as a fixed intercept.
The linear model log2 (preF ELISAtimepoint) = GMT preF ELISAAd26/protein preF RSV vaccine (1x10
11 vp/150 ug),timepoint + 
slope × #titration steps will initially be fitted for the active groups of Cohort 1 but may be 
extended in a later stage with data of the active groups of Cohorts 2 and 3. A similar model may 
be fitted as well for other assays.
Depending on the model fit, other models (eg, log-linear models or EMAX models) may be 
explored as well.
The incidence of neutralizing antibodies to Ad26 might be summarized for participants who are 
positive for antibodies to Ad26.
Other immunogenicity analyses may be performed to further characterize the immune responses 
that are generated.
The primary analysis set for the immunogenicity analysis is the PPI set. As a sensitivity analysis, 
key tables may also be based on the FAS.

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9.4.3.
Safety Analyses
No formal statistical testing of safety data is planned. Safety data will be analyzed descriptively 
by cohort and group. In addition, for a selection of tables, data of Cohorts 2 and 3 may be 
pooled. All safety analyses will be based on the FAS.
AEs (Solicited and Unsolicited)
Solicited local (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 per group as well as frequencies according to severity and duration will 
be calculated for solicited AEs. In addition, the number and percentages of participants with at 
least one solicited local (at the injection site) or systemic AE will be presented.
The verbatim terms used in the eCRF by the investigator to report AEs will be coded using the 
Medical Dictionary for Regulatory Activities (MedDRA). All reported AEs with onset during the 
active vaccination phase (ie, AEs occurring from the time of vaccination until 28 days after 
vaccination) and all SAEs will be included in the analysis. For each AE, the number and 
percentage of participants who experience at least one occurrence of the given event will be 
summarized by group. Frequency tables of unsolicited AEs, separately for all and study 
vaccine-related, will be presented by system organ class and preferred term.
Summaries, listings, datasets, or participant narratives may be provided, as appropriate, for those 
participants who die, who discontinue study vaccination due to an AE, or who experience a 
severe AE or an SAE.
Summaries and/or listings may be provided separately for AEs with onset outside the above 
defined timeframe (ie, beyond 28 days after vaccination).
Clinical Laboratory Tests (Cohorts 2 and 3 only)
Laboratory abnormalities will be determined according to the FDA toxicity grading tables 
(Section 10.2, Appendix 2) or, for tests for which no grades are available, in accordance with the 
normal ranges of the clinical laboratory. Any laboratory value shown as a "graded" value in the 
FDA table that is within central laboratory normal ranges will not be graded for severity.
Vital Signs
A tabulation of the distribution of body temperatures per half degree intervals will be provided. 
For systolic and diastolic blood pressure and heart and respiratory rate, the percentage of 
participants with values beyond clinically relevant limits will be summarized.
Physical Examination
A listing for physical examination abnormalities will be generated.

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9.5.
Planned Analyses
The following analyses will be performed:

Cohort 1 primary analysis will include 14-day immunogenicity and 28-day safety data of all 
groups in Cohort 1. The sponsor will be unblinded for Cohort 1 at the time of the primary 
analysis of Cohort 1, and the blind will be maintained at the participant and study site level 
up to study end.

Cohorts 2 and 3 primary analysis will include 28-day safety data of all groups in Cohorts 2 
and 3. If 14-day immunogenicity data are available at the time of the primary analysis, these 
will be included as well, otherwise these will be analyzed at a later timepoint. The sponsor 
will be unblinded for Cohorts 2 and 3 at the time of the primary analysis, and the blind will 
be maintained at the participant and study site level up to study end.

Final analysis at the end of the study will include safety and immunogenicity data from all 
cohorts. Data collected up to the time of the last visit for the last participant will be included 
in the analysis. This analysis will be performed on unblinded data.
Note: The final analysis might be done per cohort, depending on the timing.
9.6.
Data Monitoring Committee or Other Review Board
An internal DRC will be established for this study (Section 4.1). The DRC will convene, 
according to their charter, to discuss any safety issues and any situation meeting a specific study 
vaccination pausing rule (Section 7.3). The DRC will consist of sponsor personnel not directly 
involved in the conduct of the study and who have expertise in clinical study conduct and 
vaccines, at least one medical expert in the relevant therapeutic area, at least one statistician; and 
a safety expert. Committee membership responsibilities, authorities, and procedures will be 
documented in its charter. The PI(s) and SRP/SRS will inform the DRC of any AE of concern.
In addition, the DRC will review:

All Cohort 2 safety data collected up to the time the 20th participant in Cohort 2 completed
his/her Day 8 visit (or discontinued earlier).

All Cohort 2 safety data collected up to the time the last participant in Cohort 2 completed
his/her Day 8 visit (or discontinued earlier).

All Cohort 3 safety data collected up to the time the 16th participant in Cohort 3 completed
his/her Day 8 visit (or discontinued earlier).
After these reviews, the DRC will make recommendations regarding the continuation of the 
study. Conclusions of the DRC will be communicated to the investigators, the IEC/IRB, and the 
national regulatory authorities as appropriate. Details will be provided in a separate DRC charter.
If deemed necessary for safety review, the DRC may request randomization codes and review 
unblinded data, if applicable.
Safety data from the planned analyses (Section 9.5) will be shared with the DRC.

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10.
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1.
Appendix 1: Abbreviations
Ad26
adenovirus serotype 26
AE
adverse event
BMI
body mass index
CD
cluster of differentiation
CI
confidence interval
CTM
clinical trial material
DNA
deoxyribonucleic acid
DRC
Data Review Committee
eCRF
electronic case report form(s) 
eDC
electronic data capture
ELISA
enzyme-linked immunosorbent assay
ELISpot
enzyme-linked immunospot
FAS
Full Analysis Set
FDA
Food and Drug Administration
GCP
Good Clinical Practice
GMT
geometric mean titer
IB
Investigator’s Brochure
ICF
informed consent form
ICH
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for 
Human Use
ICS
intracellular cytokine staining
IEC
Independent Ethics Committee
IFN
interferon
Ig
immunoglobulin
IM
intramuscular(ly)
IRB
Institutional Review Board
IWRS
interactive web response system
MedDRA
Medical Dictionary for Regulatory Activities
NHP
nonhuman primate
PI
principal investigator
PPI
Per-protocol Immunogenicity 
PQC
Product Quality Complaint
preF
prefusion conformation-stabilized F protein
RSV
respiratory syncytial virus
SAE
serious adverse event
SAM
synthetic absorptive matrix
SAP
statistical analysis plan
SRP
study responsible physician
SRS
study responsible scientist
SUSAR
suspected unexpected serious adverse reaction
Th
T helper
VL-AUC
viral load as measured by the area under the curve
VNA
virus neutralization assay
VNT
virus neutralizing titer
vp
viral particles
Definitions of Terms
Electronic source
(eSource) system
Contains data traditionally maintained in a hospital or clinic record to document medical 
care or data recorded in an eCRF as determined by the protocol. Data in this system may 
be considered source documentation.

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10.2.
Appendix 2: 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
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

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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
No interference with
activity
Some interference
with activity not 
requiring medical 
intervention
Prevents daily
activity and 
requires medical 
intervention
Hospitalization#
# Revised by the sponsor.

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B: Tables for Laboratory Abnormalities
The laboratory values provided in the tables below serve as guidelines and are dependent upon 
institutional normal parameters. Institutional normal reference ranges should be provided to 
demonstrate that they are appropriate.
Serum *
Mild 
(Grade 1)
Moderate
(Grade 2)
Severe
(Grade 3)
Potentially Life
Threatening
(Grade 4)**
Sodium – Hyponatremia mEq/L
132 – 134
130 – 131
125 – 129
< 125
Sodium – Hypernatremia mEq/L
144 – 145
146 – 147
148 – 150
> 150
Potassium – Hyperkalemia mEq/L
5.1 – 5.2
5.3 – 5.4
5.5 – 5.6
> 5.6
Potassium – Hypokalemia mEq/L
3.5 – 3.6
3.3 – 3.4
3.1 – 3.2
< 3.1
Glucose – Hypoglycemia mg/dL
65 – 69
55 – 64
45 – 54
< 45
Glucose – Hyperglycemia
  Fasting mg/dL 
  Random – mg/dL
100 – 110
110 – 125
111 – 125
126 – 200
>125
>200
Insulin 
requirements or 
hyperosmolar 
coma
Blood Urea Nitrogen
BUN mg/dL
23 – 26
27 – 31
> 31
Requires dialysis
Creatinine – mg/dL
1.5 – 1.7
1.8 – 2.0
2.1 – 2.5
> 2.5 or requires 
dialysis
Calcium – hypocalcemia mg/dL
8.0 – 8.4
7.5 – 7.9
7.0 – 7.4
< 7.0
Calcium – hypercalcemia mg/dL
10.5 – 11.0
11.1 – 11.5
11.6 – 12.0
> 12.0
Magnesium – hypomagnesemia mg/dL
1.3 – 1.5
1.1 – 1.2
0.9 – 1.0
< 0.9
Phosphorous – hypophosphatemia mg/dL 2.3 – 2.5
2.0 – 2.2
1.6 – 1.9
< 1.6
CPK – mg/dL
1.25 – 1.5 x
ULN***
1.6 – 3.0 x ULN 3.1 –10 x ULN
> 10 x ULN
Albumin – Hypoalbuminemia g/dL
2.8 – 3.1
2.5 – 2.7
< 2.5
--
Total Protein – Hypoproteinemia g/dL
5.5 – 6.0
5.0 – 5.4
< 5.0
--
Alkaline phosphate –
increase by factor
1.1 – 2.0 x ULN 2.1 – 3.0 x ULN 3.1 – 10 x ULN
> 10 x ULN
Liver Function Tests –ALT, AST
increase by factor
1.1 – 2.5 x ULN 2.6 – 5.0 x ULN 5.1 – 10 x ULN
> 10 x ULN
Bilirubin – when accompanied
by any increase in Liver Function Test 
increase by factor
1.1 – 1.25 x 
ULN
1.26 – 1.5 x 
ULN
1.51 – 1.75 x 
ULN
> 1.75 x ULN
Bilirubin – when Liver Function Test
is normal; increase by factor
1.1 – 1.5 x ULN 1.6 – 2.0 x ULN 2.0 – 3.0 x ULN
> 3.0 x ULN
Cholesterol
201 – 210
211 – 225
> 226
---
Pancreatic enzymes – amylase, lipase
1.1 – 1.5 x ULN 1.6 – 2.0 x ULN 2.1 – 5.0 x ULN
> 5.0 x ULN
* The laboratory values provided in the tables serve as guidelines and are dependent upon institutional normal 
parameters. Institutional normal reference ranges should be provided to demonstrate that they are appropriate.
** The clinical signs or symptoms associated with laboratory abnormalities might result in characterization of the 
laboratory abnormalities as potentially life-threatening (Grade 4). For example. a low sodium value that falls 
within a Grade 3 parameter (125-129 mE/L) should be recorded as a Grade 4 hyponatremia event if the 
participant had a new seizure associated with the low sodium value.
***ULN is the upper limit of the normal range.

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Hematology *
Mild 
(Grade 1)
Moderate
(Grade 2)
Severe
(Grade 3)
Potentially Life
Threatening
(Grade 4)
Hemoglobin (Female) - gm/dL
11.0 – 12.0
9.5 – 10.9
8.0 – 9.4
< 8.0
Hemoglobin (Female)
change from baseline value - gm/dL
Any decrease – 1.5 1.6 – 2.0
2.1 – 5.0
> 5.0
Hemoglobin (Male) - gm/dL
12.5 – 13.5
10.5 – 12.4
8.5 – 10.4
< 8.5
Hemoglobin (Male)
change from baseline value – gm/dL
Any decrease – 1.5 1.6 – 2.0
2.1 – 5.0
> 5.0
WBC Increase - cell/mm3
10,800 – 15,000
15,001 – 20,000 20,001 – 25, 000
> 25,000
WBC Decrease - cell/mm3
2,500 – 3,500
1,500 – 2,499
1,000 – 1,499
< 1,000
Lymphocytes Decrease - cell/mm3
750 – 1,000
500 – 749
250 – 499
< 250
Neutrophils Decrease - cell/mm3
1,500 – 2,000
1,000 – 1,499
500 – 999
< 500
Eosinophils - cell/mm3
650 – 1500
1501 - 5000
> 5000
Hypereosinophilic
Platelets Decreased - cell/mm3
125,000 – 140,000 100,000 –
124,000
25,000 – 99,000
< 25,000
PT – increase by factor
(prothrombin time)
1.0 – 1.10 x
ULN**
1.11 – 1.20 x 
ULN
1.21 – 1.25 x ULN > 1.25 ULN
PTT – increase by factor
(partial thromboplastin time)
1.0 – 1.2 x ULN
1.21 – 1.4 x 
ULN
1.41 – 1.5 x ULN
> 1.5 x ULN
Fibrinogen increase - mg/dL
400 – 500
501 – 600
> 600
--
Fibrinogen decrease - mg/dL
150 – 200
125 – 149
100 – 124
< 100 or associated
with gross bleeding 
or disseminated 
intravascular 
coagulation (DIC)
*
The laboratory values provided in the tables serve as guidelines and are dependent upon institutional normal 
parameters. Institutional normal reference ranges should be provided to demonstrate that they are appropriate.
** ULN is the upper limit of the normal range.

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10.3.
Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
ADVERSE EVENT DEFINITIONS AND CLASSIFICATIONS
AE
An AE is any untoward medical occurrence in a clinical study participant administered a 
medicinal (investigational or noninvestigational) product. An AE does not necessarily have a 
causal relationship with the study vaccine. An AE can therefore be any unfavorable and 
unintended sign (including an abnormal finding), symptom, or disease temporally associated 
with the use of a medicinal (investigational or noninvestigational) product, whether or not related 
to that medicinal (investigational or noninvestigational) 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 AEs under Section 8.3.1.
SAE
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 should be exercised in deciding whether expedited reporting is 
also appropriate in other situations, such as important medical events that may not be 
immediately life threatening or result in death or hospitalization but may jeopardize the 
participant or may require intervention to prevent one of the other outcomes listed in the 
definition above. These should usually be considered serious.
If a serious and unexpected AE occurs for which there is evidence suggesting a causal 
relationship between the study vaccine and the event (eg, death from anaphylaxis), the event 
must be reported as a SUSAR by the sponsor to health authorities and by the investigator to the 
IEC/IRB according to regulatory and local requirements.

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Unlisted (Unexpected) AE/Reference Safety Information
An AE is considered unlisted if the nature or severity is not consistent with the applicable 
product reference safety information. For the Ad26/protein preF RSV vaccine, the expectedness 
of an AE will be determined by whether or not it is listed in the respective IB.
ATTRIBUTION DEFINITIONS
Causality of AEs should be assessed by the investigator based on the following:
Related: there is a reasonable possibility that the study vaccine contributed to the AE.
Unrelated: there is no suspicion that there is a relationship between the study vaccine and the 
AE; there are other more likely causes and administration of the study vaccine is not suspected to 
have contributed to the AE.
By definition, all solicited AEs at the injection site will be considered related to the study 
vaccine administration.
SEVERITY CRITERIA
All AEs and laboratory data will be coded for severity using a modified version of the FDA 
grading table, based on version of September 200716, included in Section 10.2, Appendix 2.
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
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

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
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 should be recorded in the eCRF. Any special reporting situation that 
meets the criteria of an SAE should be recorded on the SAE page of the eCRF.
PROCEDURES
All AEs
All AEs, regardless of seriousness, severity, or presumed relationship to study vaccine, must be 
recorded using medical terminology in the source document and the eCRF. Whenever possible, 
diagnoses should be given when signs and symptoms are due to a common etiology (eg, cough, 
runny nose, sneezing, sore throat, and head congestion should be reported as "upper respiratory 
infection"). Investigators must record in the eCRF their opinion concerning the relationship of 
the AE to study vaccine. All measures required for AE management must be recorded in the 
source document and reported according to sponsor instructions.
For all studies with an outpatient phase, including open-label studies, the participant must 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 24-hour contact telephone number

Local sponsor’s name and 24-hour contact telephone number (for medical personnel only)

Study site number

Participant number

Any other information that is required to do an emergency breaking of the blind
SAEs
All SAEs that have not resolved by the end of the study, or that have not resolved upon 
discontinuation of the participant’s participation in the study, must be followed until any of the 
following occurs:

The event resolves

The event stabilizes

The event returns to baseline, if a baseline value/status is available

The event can be attributed to agents other than the study vaccine or to factors unrelated to 
study conduct

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
It becomes unlikely that any additional information can be obtained (participant or health 
care practitioner refusal to provide additional information, lost to follow-up after 
demonstration of due diligence with follow-up efforts)
Suspected transmission of an infectious agent by a medicinal product will be reported as an SAE. 
Any event requiring hospitalization (or prolongation of hospitalization) that occurs during the 
course of a participant’s participation in a study must be reported as an SAE, except 
hospitalizations for the following:

Hospitalizations not intended to treat an acute illness or 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 during the entire study period, whether or not the 
event is expected or associated with the study vaccine, is considered an SAE and must be 
reported.
CONTACTING SPONSOR REGARDING SAFETY
The names (and corresponding telephone numbers) of the individuals who should be contacted 
regarding safety issues or questions regarding the study are listed in the Contact Information 
page(s), which will be provided as a separate document.
PQC HANDLING
A PQC is defined as any suspicion of a product defect related to manufacturing, labeling, or 
packaging, ie, any dissatisfaction relative to the identity, quality, durability, or reliability of a 
product, including its labeling or package integrity. A PQC may have an impact on the safety and 
efficacy of the product. Timely, accurate, and complete reporting and analysis of PQC 
information from studies are crucial for the protection of participants, investigators, and the 
sponsor, and are mandated by regulatory agencies worldwide. The sponsor has established 
procedures in conformity with regulatory requirements worldwide to ensure appropriate 
reporting of PQC information; all studies conducted by the sponsor or its affiliates will be 
conducted in accordance with those procedures.
Procedures
All initial PQCs must be reported to the sponsor by the study-site personnel within 24 hours after 
being made aware of the event.
If the defect is combined with an SAE, the study-site personnel must report the PQC to the 
sponsor according to the SAE reporting timelines (Section 8.3.1). A sample of the suspected 
product should be maintained for further investigation if requested by the sponsor.

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Contacting Sponsor Regarding Product Quality
The names (and corresponding telephone numbers) of the individuals who should be contacted 
regarding product quality issues are listed in the Contact Information page(s), which will be 
provided as a separate document.

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10.4.
Appendix 4: Regulatory, Ethical, and Study Oversight Considerations
REGULATORY AND ETHICAL CONSIDERATIONS
Investigator Responsibilities
The investigator is responsible for ensuring that the study is performed in accordance with the 
protocol, current ICH guidelines on Good Clinical Practice (GCP), and applicable regulatory and 
country-specific requirements.
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 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 course of the study, in situations where a departure from the protocol is unavoidable, 
the investigator or other physician in attendance will contact the appropriate sponsor 
representative listed in the Contact Information page(s), which will be provided as a separate 
document. Except in emergency situations, this contact should be made before implementing any 
departure from the protocol. In all cases, contact with the sponsor must be made as soon as 
possible to discuss the situation and agree on an appropriate course of action. The data recorded 
in the eCRF and source documents will reflect any departure from the protocol, and the source 
documents will describe this departure and the circumstances requiring it.
Regulatory Approval/Notification
This protocol and any amendment(s) must be submitted to the appropriate regulatory authorities 
in each respective country, if applicable. A study may not be initiated until all local regulatory 
requirements are met.

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Required Prestudy Documentation
The following documents must be provided to the sponsor before shipment of vaccines to the 
study site:

Protocol and amendment(s), if any, signed and dated by the PI(s).

A copy of the dated and signed (or sealed, where appropriate per local regulations), written 
IEC/IRB approval of the protocol, amendments, ICF, any recruiting materials, and if 
applicable, participant compensation programs. This approval must clearly identify the 
specific protocol by title and number and must be signed (or sealed, where appropriate per 
local regulations) by the chairman or authorized designee.

Name and address of the IEC/IRB, including a current list of the IEC/IRB members and 
their function, with a statement that it is organized and operates according to GCP and the 
applicable laws and regulations. If accompanied by a letter of explanation, or equivalent, 
from the IEC/IRB, a general statement may be substituted for this list. If an investigator or a 
member of the study-site personnel is a member of the IEC/IRB, documentation must be 
obtained to state that this person did not participate in the deliberations or in the 
vote/opinion of the study.

Regulatory authority approval or notification, if applicable.

Signed and dated statement of investigator (eg, Form FDA 1572), if applicable.

Documentation of investigator qualifications (eg, curriculum vitae).

Completed investigator financial disclosure form from the PI(s), where required.

Signed and dated clinical trial agreement, which includes the financial agreement.

Any other documentation required by local regulations.
The following documents must be provided to the sponsor before enrollment of the first 
participant:

Completed investigator financial disclosure forms from all subinvestigators.

Documentation of subinvestigator qualifications (eg, curriculum vitae).

Name and address of any local laboratory conducting tests for the study, and a dated copy of 
current laboratory normal ranges for these tests, if applicable.

Local 
laboratory 
documentation 
demonstrating 
competence 
and 
test 
reliability 
(eg, accreditation/license), if applicable.
IEC or IRB
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)

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
IBs (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 IB(s) and amendments/addenda

Summaries of the status of the study at intervals stipulated in guidelines of the IEC/IRB (at 
least annually)

Reports of AEs that are serious, unlisted/unexpected, and associated with the study vaccine.

New information that may adversely affect the safety of the participants or the conduct of 
the study

Deviations from or changes to the protocol to eliminate immediate hazards to the 
participants

Report of deaths of participants under the investigator's care

Notification if a new investigator is responsible for the study at the study site

Development Safety Update Report and Line Listings, where applicable

Any other requirements of the IEC/IRB

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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.
Other Ethical Considerations
For study-specific ethical design considerations, refer to Section 4.2.1.
FINANCIAL DISCLOSURE
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial 
information in accordance with local regulations to allow the sponsor to submit complete and 
accurate financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interests during the course of 
the study and for one year after completion of the study.
Refer to Required Prestudy Documentation (above) for details on financial disclosure.
INFORMED CONSENT PROCESS
Each participant must give written consent according to local requirements after the nature of the 
study has been fully explained. The ICF(s) must be signed before performance of any 
study-related activity. The ICF(s) that is/are used must be approved by both the sponsor and by 
the reviewing IEC/IRB and be in a language that the participant can read and understand. 
The informed consent should be in accordance with principles that originated in the Declaration 
of Helsinki, current ICH and GCP guidelines, applicable regulatory requirements, and sponsor 
policy.
Before enrollment in the study, the investigator or an authorized member of the study-site 
personnel must explain to potential participants the aims, methods, reasonably anticipated 
benefits, and potential hazards of the study, and any discomfort participation in the study may 
entail. Participants will be informed that their participation is voluntary and that they may 
withdraw consent to participate at any time. They will be informed that choosing not to 
participate will not affect the care the participant will receive. Finally, they will be told that the 
investigator will maintain a participant identification register for the purposes of long-term 
follow-up if needed and that their records may be accessed by health authorities and authorized 
sponsor personnel without violating the confidentiality of the participant, to the extent permitted 
by the applicable law(s) or regulations. By signing the ICF the participant is authorizing such 
access. It also denotes that the participant agrees to allow his or her study physician to recontact 
the participant for the purpose of obtaining consent for additional safety evaluations, if needed.

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The participant will be given sufficient time to read the ICF and the opportunity to ask questions. 
After this explanation and before entry into the study, consent should be appropriately recorded 
by means of the participant’s personally dated signature. After having obtained the consent, a 
copy of the ICF must be given to the participant.
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 participant includes explicit consent for the processing 
of personal data and for the investigator/institution to allow direct access to his or her original 
medical records (source data/documents) for study-related monitoring, audit, IEC/IRB review, 
and regulatory inspection. This consent also addresses the transfer of the data to other entities 
and to other countries.
The participant has the right to request through the investigator access to his or her personal data 
and the right to request rectification of any data that are not correct or complete. Reasonable 
steps will be taken to respond to such a request, taking into consideration the nature of the 
request, the conditions of the study, and the applicable laws and regulations.
LONG-TERM RETENTION OF SAMPLES FOR ADDITIONAL FUTURE RESEARCH
Samples collected in this study may be stored for up to 15 years (or according to local 
regulations) for additional research. Samples will only be used to understand Ad26.RSV.preF 
and RSV preF protein, to understand RSV and other respiratory pathogens, and to develop 
tests/assays related to Ad26.RSV.preF, RSV preF protein, and RSV disease. The research may 
begin at any time during the study or the poststudy storage period. Included are samples from 
participants who were screened but not randomized which may also be used to develop 
tests/assays related to Ad26.RSV.preF, RSV preF protein, and RSV disease.
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 (Section 7.4.1).

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COMMITTEES STRUCTURE
Data Review Committee
A DRC will be established for this study (Section 9.6).
PUBLICATION POLICY/DISSEMINATION OF CLINICAL STUDY DATA
All information, including but not limited to information regarding the 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, 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 the 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 

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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 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.
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 will review eCRF for accuracy and completeness during on-site monitoring visits 
and after transmission to the sponsor; any discrepancies will be resolved with the investigator or 
designee, as appropriate. After upload of the data into the study database they will be verified for 
accuracy and consistency with the data sources.
CASE REPORT FORM COMPLETION
Case report forms are prepared and provided by the sponsor for each participant in electronic 
format. All eCRF entries, corrections, and alterations must be made by the investigator or 
authorized study-site personnel. The investigator must verify that all data entries in the eCRF are 
accurate and correct.
The study data will be transcribed by study-site personnel from the source documents onto an 
eCRF, if applicable. Study-specific data will be transmitted in a secure manner to the sponsor.
Worksheets may be used for the capture of some data to facilitate completion of the eCRF. 
Any such worksheets will become part of the participant’s source documents. Data must be 
entered into the eCRF in English. The eCRF must be completed as soon as possible after a 

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participant visit and the forms should be available for review at the next scheduled monitoring 
visit.
If necessary, queries will be generated in the eDC tool. If corrections to an eCRF are needed 
after the initial entry into the eCRF, this can be done in either of the following ways:

Investigator and study-site personnel can make corrections in the eDC tool at their own 
initiative or as a response to an auto query (generated by the eDC tool).

Sponsor or sponsor delegate can generate a query for resolution by the investigator and 
study-site personnel.
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 immunogenicity parameters as required by 
the protocol; record of all AEs and follow-up of AEs; concomitant medication; vaccine 
receipt/dispensing/return records; study vaccine administration information; and date of study 
completion and reason for early discontinuation of study vaccination or withdrawal from the 
study, if applicable.
The author of an entry in the source documents should be identifiable.
Specific details required as source data for the study and source data collection methods will be 
reviewed with the investigator before the study and will be described in the monitoring 
guidelines (or other equivalent document).
The following participant- and investigator-completed assessments will be recorded and will be 
considered source data: solicited AEs after vaccination and body temperature. The participant 
diary used to collect information regarding solicited signs and symptoms after vaccination will 
be considered source data.
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 the eSource system may be considered source documentation.
MONITORING
The sponsor will use a combination of monitoring techniques (central, remote, or on-site 
monitoring) to monitor this study.
The sponsor will perform on-site monitoring visits as frequently as necessary. The monitor will 
record dates of the visits in a study-site visit log that will be kept at the study site. The first 

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post-initiation visit will be made as soon as possible after enrollment has begun. At these visits, 
the monitor will compare the data entered into the eCRF with the source documents 
(eg, hospital/clinic/physician’s office medical records); 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 study site.
Central monitoring will take place for data identified by the sponsor as requiring central review.
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.
Similar auditing procedures may also be conducted by agents of any regulatory body, either as 
part of a national GCP compliance program or to review the results of this study in support of a 
regulatory submission. The investigator should immediately notify the sponsor if he or she has 
been contacted by a regulatory agency concerning an upcoming inspection.
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.

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Essential documents must be retained until at least 2 years after the last approval of a marketing 
application in an ICH region and until there are no pending or contemplated marketing 
applications in an ICH region or until at least 2 years have elapsed since the formal 
discontinuation of clinical development of the investigational product. These documents will be 
retained for a longer period if required by the applicable regulatory requirements or by an 
agreement with the sponsor. It is the responsibility of the sponsor to inform the 
investigator/institution as to when these documents no longer need to be retained.
If the responsible investigator retires, relocates, or for other reasons withdraws from the 
responsibility of keeping the study records, custody must be transferred to a person who will 
accept the responsibility. The sponsor must be notified in writing of the name and address of the 
new custodian. Under no circumstance shall the investigator relocate or dispose of any study 
documents before having obtained written approval from the sponsor.
If it becomes necessary for the sponsor or the appropriate regulatory authority to review any 
documentation relating to this study, the investigator/institution must permit access to such 
reports.
STUDY AND SITE START AND CLOSURE
First Act of Recruitment
The first study site open is considered the first act of recruitment and it becomes the study start 
date.
Study Termination
The sponsor reserves the right to close the study site or terminate the study at any time for any 
reason at the sole discretion of the sponsor. Study sites will be closed upon study completion. 
A study site is considered closed when all required documents and study supplies have been 
collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to:

Failure of the investigator to comply with the protocol, the requirements of the IEC/IRB or 
local health authorities, the sponsor’s procedures, or GCP guidelines

Inadequate recruitment of participants by the investigator

Discontinuation of further study vaccine development

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10.5.
Appendix 5: Protocol Amendment History
This is an original protocol.

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11.
REFERENCES
1.
Adenoviral Vaccine Safety Database. Version 4.0. Janssen Vaccines & Prevention B.V. (May 2019).
2.
Barouch DH, Liu J, Peter L, et al. Characterization of humoral and cellular immune responses elicited by a 
recombinant adenovirus serotype 26 HIV-1 Env vaccine in healthy adults (IPCAVD 001). J Infect Dis. 
2013;207:248-256.
3.
Barouch DH, Tomaka FL, Wegmann F, et al. Evaluation of a mosaic HIV-1 vaccine in a multicentre, 
randomised, double-blind, placebo-controlled, phase 1/2a clinical trial (APPROACH) and in rhesus monkeys 
(NHP 13-19). Lancet. 2018;392(10143):232-243.
4.
de Bree GJ, Heidema J, van Leeuwen EM, et al. Respiratory syncytial virus-specific CD8+ memory T cell 
responses in elderly persons. J Infect Dis. 2005:191;1710-1718.
5.
Falsey AR, Hennessey PA, Formica MA, Cox C, Walsh EE. Respiratory syncytial virus infection in elderly 
and high-risk adults. N Engl J Med. 2005;352(17):1749-1759.
6.
Falsey AR, Walsh EE. Respiratory syncytial virus infection in adults. Clin Microbiol Rev. 2000;13(3):371-
384.
7.
Gidudu JK, Walco GA, Taddio A, et al./The Brighton Immunization Site Pain Working Group. Immunization
site pain: Case definition and guidelines for collection, analysis, and presentation of immunization safety data. 
Vaccine. 2012;30(30):4558-4577.
8.
Investigator’s Brochure: Ad26.RSV.preF (JNJ-64400141). Edition 10. Janssen Vaccines & Prevention B.V.
(December 2019). 
9.
Investigator’s Brochure: RSV preF protein (JNJ-64213175). Edition 4. Janssen Vaccines & Prevention B.V.
(December 2019).
10.
Janssen Vaccines & Prevention B.V (data on file).
11.
Kohl KS, Walop W, Gidudu J, et al.; Brighton Collaboration Local Reaction Working Group for Swelling at or 
near Injection Site. Swelling at or near injection site: case definition and guidelines for collection, analysis and 
presentation of immunization safety data. Vaccine 2007;25(31);5858-5874.
12.
Lee FE, Walsh EE, Falsey AR, et al. The balance between influenza- and RSV-specific CD4 T cells secreting 
IL-10 or IFNgamma in young and healthy-elderly subjects. Mech Ageing Dev. 2005:126;1223-1229.
13.
Looney RJ, Falsey AR, Walsh E, Campbell D. Effect of aging on cytokine production in response to 
respiratory syncytial virus infection. J Infect Dis. 2002;185:682-685.
14.
Marcy SM, Kohl KS, Dagan R, et al.; Brighton Collaboration Fever Working Group. Fever as an adverse event 
following immunization: case definition and guidelines of data collection, analysis, and presentation. Vaccine 
2004;22:551-556.
15.
Milligan ID, Gibani MM, Sewell R, et al. Safety and immunogenicity of novel adenovirus type 26- and 
modified vaccinia ankara-vectored ebola vaccines: a randomized clinical trial. JAMA. 2016;315:1610-1623.
16.
U.S. Department of Health and Human Services, Food and Drug Administration, Center for Biologics 
Evaluation and Research. September 2007. Guidance for Industry. Toxicity Grading Scale for Healthy Adult 
and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. Available from: 
https://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidan
ces/Vaccines/ucm091977.pdf. Accessed: 17 February 2020.
17.
U.S. Department of Health and Human Services, Food and Drug Administration. March 2018. Conditions for 
IRB Use of Expedited Review. Available from:
https://www fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/GuidancesInformationSheetsandN
otices/ucm118099.htm. Accessed: 14 February 2020.
18.
U.S. Department of Health and Human Services, Office for Human Research Protections. March 2016. OHRP 
Expedited Review Categories (1998). Available from: http://www.hhs.gov/ohrp/regulations-and-
policy/guidance/categories-of-research-expedited-review-procedure-1998/index.html. Accessed: 14 February
2020.

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19.
Walsh EE, Falsey AR. Humoral and mucosal immunity in protection from natural respiratory syncytial virus 
infection in adults. J Infect Dis. 2004;190:373-378.

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

 
 
SIGNATURES 
 
 
 
 
Signed by  
Date  
 
Justification  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
16Mar2020, 16:29:52 PM, UTC
Document Approval
PPD

CONFIDENTIAL – FOIA Exemptions Apply in U.S.
1
Status: Approved,  Date: 11 June 2020
Janssen Vaccines & Prevention B.V.*
Clinical Protocol
COVID-19 Appendix
Protocol Title
A Randomized, Double-blind, Placebo-controlled Phase 2a Study to Evaluate a Range of 
Dose Levels of an Ad26.RSV.preF-based Vaccine in Adults Aged 60 Years and Older
Protocol VAC18193RSV2005; Phase 2a
VAC18193 (JNJ-64400141/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).
Status:
Approved  
Date:
11 June 2020
Prepared by:
Janssen Vaccines & Prevention B.V.
EDMS number:
EDMS-RIM-81100, 1.0
THIS APPENDIX APPLIES TO ALL CURRENT APPROVED VERSIONS OF PROTOCOL
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.
NCT04453202

COVID-19 Appendix
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COVID-19 APPENDIX
GUIDANCE ON STUDY CONDUCT DURING THE COVID-19 PANDEMIC
It is recognized that the Coronavirus Disease 2019 (COVID-19) pandemic may have an impact on 
the conduct of this clinical study due to, for example, self-isolation/quarantine by participants and 
study-site personnel; travel restrictions/limited access to public places, including hospitals; study 
site personnel being reassigned to critical tasks. 
In alignment with recent health authority guidance, the sponsor is providing options for study 
related participant management in the event of disruption to the conduct of the study. This guidance 
does not supersede any local or government requirements or the clinical judgement of the 
investigator to protect the health and well-being of participants and site staff. If, at any time, a 
participant’s safety is considered to be at risk, study intervention will be discontinued, and study 
follow-up will be conducted.
Scheduled visits that cannot be conducted in person at the study site will be performed to the extent 
possible remotely/virtually or delayed until such time that on-site visits can be resumed. At each 
contact, participants will be interviewed to collect safety data. Key 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 via COVID-19 Appendix after consultation with the participant, investigator, and the 
sponsor. Missed assessments/visits will be captured in the clinical trial management system for 
protocol deviations. Discontinuations of study interventions and withdrawal from the study should 
be documented with the prefix “COVID-19-related” in the case report form (CRF). 
The sponsor will continue to monitor the conduct and progress of the clinical study, and any 
changes will be communicated to the sites and to the health authorities according to local guidance.  
If a participant has tested positive for COVID-19, the investigator should contact the sponsor’s 
responsible medical officer to discuss plans for study intervention and follow-up. Modifications 
made to the study conduct as a result of the COVID-19 pandemic should be summarized in the 
clinical study report.

COVID-19 Appendix
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GUIDANCE SPECIFIC TO THIS PROTOCOL:
Screening and Randomization

Enrollment of new participants may continue based on the investigator’s assessment of risks 
versus benefits, depending on the situation at a particular site, and the ability to monitor 
participant safety. 

Baseline visits for participants recently screened for this study should be postponed if the 
current situation does not allow for an orderly conduct of the study.
Site Visits

When site visits are not possible due to local/national guidelines, sites should collect the 
assessments via telephone visits or home-based visits, if the participant allows. The actual 
visit date and the type of visit (ie, telephone or home-based visit) should be captured in the 
eCRF according to the eCRF completion guidelines. Procedures that cannot be performed 
during a home-based visit (eg, clinical assessments, blood samples, nasal samples and 
physical examination), should be excluded. 
Vaccine Administration

When planning for vaccination visits, local/national or institutional guidelines will be 
followed. The study vaccine must be administered by an (unblinded) pharmacist or other 
qualified individual at the study site. If this is not possible, a solution may be considered in 
consultation with the sponsor and taking into consideration participant safety. 
Informed Consent Form

Consenting and re-consenting of participants for the measures taken (including also remote 
consenting by phone or video consultation) will be performed as applicable and according to 
local guidance for informed consent applicable during the COVID-19 pandemic. The process 
is to be documented in the source documents.
Source Data Verification/Monitoring

In case on-site monitoring visits are not be possible, the site monitor may contact the 
investigator to arrange monitoring visits and activities remotely (in accordance with site and 
local requirements). Additional on-site monitoring visits may be needed in the future to catch 
up on source data verification.
Site Audits

During the COVID-19 pandemic and at the impacted sites, study site GCP audits with direct 
impact/engagement from the investigator and study site personnel would not be conducted in 
order to comply with national, local, and/or organizational social distancing restrictions. 
Additional quality assurance activities such as remote audits or focused review of study 
related documents may take place with limited impact/engagement if possible.