A Randomized, Double-blind, Phase 2 Study to Evaluate the Immunogenicity, Reactogenicity and Safety of Ad26.COV2.S Administered as Booster Vaccination in Adults 18 Years of Age and Older Who Have Previously Received Primary Vaccination With Ad26.COV2.S or BNT162b2
Phase: PHASE2
Conditions: Coronavirus Disease
Sponsor: Janssen Vaccines & Prevention B.V.

CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
1
Status: Approved,  Date: 20 April 2022
Janssen Vaccines & Prevention B.V.*
Clinical Protocol
Protocol Title
A Randomized, Double-blind, Phase 2 Study to Evaluate the Immunogenicity, Reactogenicity and
Safety of Ad26.COV2.S Administered as Booster Vaccination in Adults 18 Years of Age and Older
Who Have Previously Received Primary Vaccination with Ad26.COV2.S or BNT162b2.
Amplify
Protocol VAC31518COV2008; Phase 2
AMENDMENT 6
VAC31518 (JNJ-78436735 [Ad26.COV2.S])
*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).
Regulatory Agency Identifier Number(s):
IND: 22657
EudraCT NUMBER: not applicable
Status: 
Approved
Date: 
20 April 2022
EDMS number: 
EDMS-RIM-508722, 7.0
GCP Compliance: This study will be conducted in compliance with Good Clinical Practice, and applicable regulatory
requirements.
Confidentiality Statement
The information provided herein contains Company trade secrets, commercial or financial information that the Company
customarily holds close and treats as confidential. The information is being provided under the assurance that the recipient
will maintain the confidentiality of the information under applicable statutes, regulations, rules, protective orders or
otherwise.
NCT04999111

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
2
Status: Approved,  Date: 20 April 2022
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE
DOCUMENT HISTORY
Document 
Date
Amendment 6 
This document
Amendment 5 
17 December 2021
Amendment 4 
30 November 2021
Amendment 3 
08 October 2021
Amendment 2 
22 September 2021
Amendment 1 
16 August 2021
Original Protocol 
30 June 2021
Amendment 6 (This document)
Overall rationale for the Amendment: This amendment is written primarily to clarify the process
for additional interim analyses and final analysis, potential exploratory efficacy analysis, clinical
adjudication of COVID-19disease severity and management of COVID-19 episodes. In addition,
this amendment will allow unblinding for participants rolling over into study
VAC31518COV2015.
Section Number and Name 
Description of Change 
Brief Rationale
1.1 Synopsis 
9.5 Planned Analyses 
Text has been added to 
allow additional interim 
analyses to be conducted 
after the primary analysis. 
To allow additional analysis to be
performed between the primary analysis
and final analysis, allowing earlier
evaluation of booster response durability.
1.3.1 Schedule of Activities:
All Participants
1.3.3 Schedule of Activities
for Participants with COVID-
19-like Signs and Symptoms.
The frequency of the 
COVID-19 
surveillance 
(symptom check), after the
6-month study visit has
been changed to at least
twice a month.
To reduce burden on trial participants and
improve participant retention.
1.1 Synopsis
2.3.3 Benefit-Risk Assessment
of Study Participation
4.1 Overall Design
6.8 Study Pausing Rules
9.5 Planned Analysis
10.3.6 Committee Structure
IDMC review of safety
has been changed from
continual to an ad hoc
basis.
As the safety of Ad26.COV2.S is
established, it is not necessary for all data
to be reviewed by the IDMC  from this
point onwards (post primary analysis).
Emergent safety concerns can be brought
to the IDMC at any time.
1.1 Synopsis
3. Objectives and Endpoints
8.2 Exploratory Efficacy
Analysis
9.3 Populations for Analysis
Sets
9.4.4 Exploratory Endpoints
9.5 Planned Analyses
Text has been added on
exploratory  
efficacy
analyses, if sufficient data
is available.
To allow exploratory analyses of booster
vaccine efficacy  after the primary
analysis (utilizing molecularly confirmed
SARS-CoV-2 infections, N protein
binding antibodies, COVID-19 cases
meeting the US FDA Harmonized
COVID-19 case definition  and cases
meeting criteria for moderate and
moderate/severe disease).

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
3
Status: Approved,  Date: 20 April 2022
1.1 Synopsis 
3. Objectives and Endpoints 
9.4.5 Other Analysis 
Text has been added on 
correlate analysis. 
To determine immunological correlates
of risk and protection, if sufficient data
are available.
1.1 Synopsis 
3. Objectives and Endpoints 
8.1.4 Clinical Severity 
Adjudication Committee 
8.2 Exploratory Efficacy
Analysis
10.3.6 Committee Structure
Text on the ‘Clinical 
Severity 
Adjudication 
Committee’ 
has 
been 
added.
To describe the process of COVID-19
disease severity  evaluation in  study
participants.
1.3.3 Schedule of Activities 
for Participants with COVID- 
19-like Signs and Symptoms. 
8.1.2 Procedures in the Event 
of COVID 19-like Signs and 
Symptoms 
8.3 Safety Assessments
8.4.1 Time Period and
Frequency for Collecting AEs
Text has been added to 
clarify that the end of 
study visit should not be 
postponed for participants 
with an ongoing COVID- 
19 episode. 
The End of Trial (EoT) visit should not
be postponed in the event a participant
has an ongoing COVID-19 illness. The
COVID-19 
Signs 
and 
Symptoms
Schedule of Activities can be stopped at
the time of the EoT visit.
8.5 Virology Assessments
10.2 Appendix 2: Clinical
Laboratory Tests
Wording 
on 
saliva
samples has been changed
from 
‘will 
also 
be
performed’ to ‘may also
be performed’.
Testing of viral load in saliva samples
will be conducted if feasible.
1.1 Synopsis
6.3 Randomization and
Blinding
Edits have been made to
the 
sections 
relating
blinding/unblinding 
and
subsequent 
enrollment
into 
study
VAC31518COV2015.
To 
permit 
rollover 
from 
study
VAC31518COV2008 
into 
Janssen-
sponsored study VAC31518COV2015.
5.2 Exclusion Criteria 
Text 
discouraging
participation in other trials
has been deleted from
criterion #7.
The sponsor would like to allow rollover
of eligible participants from COV2008
into other Janssen sponsored COVID-19
vaccine 
studies 
i.e.
VAC31518COV2015.
6.8 Pausing Rules 
Text on study pause of
COV2007 
has 
been
deleted.
This text is obsolete as the protocol for
COV2007 was not finalized and the study
will not be initiated.
Throughout the protocol 
Minor 
formatting 
and
grammatical changes were
made.
Minor errors were noted.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
4
Status: Approved,  Date: 20 April 2022
TABLE OF CONTENTS
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ............................................................... 2
TABLE OF CONTENTS ............................................................................................................................... 4
LIST OF IN-TEXT TABLES AND FIGURES................................................................................................ 6
1. 
PROTOCOL SUMMARY..................................................................................................................... 7
1.1. 
Synopsis........................................................................................................................................... 7
1.2. 
Schema.......................................................................................................................................... 28
1.3. 
Schedule of Activities..................................................................................................................... 29
1.3.1. 
All Participants............................................................................................................................ 29
1.3.2. 
Participants with a Suspected AESI........................................................................................... 33
1.3.3. 
Participants With COVID-19-like Signs and Symptoms ............................................................. 34
2. 
INTRODUCTION................................................................................................................................ 37
2.1. 
Study Rationale.............................................................................................................................. 37
2.2. 
Background .................................................................................................................................... 38
2.2.1. 
SARS-CoV-2 Virology and COVID-19 Disease Burden............................................................. 38
2.2.2. 
Ad26.COV2.S ............................................................................................................................. 40
2.2.3. 
Ad26-based Vaccines................................................................................................................. 44
2.2.4. 
mRNA-based SARS-CoV-2 Vaccines ........................................................................................ 44
2.3. 
Benefit-Risk Assessment............................................................................................................... 45
2.3.1. 
Risks Related to Study Participation .......................................................................................... 45
2.3.2. 
Benefits of Study Participation.................................................................................................... 49
2.3.3. 
Benefit-Risk Assessment of Study Participation ........................................................................ 49
3. 
OBJECTIVES AND ENDPOINTS ..................................................................................................... 50
4. 
STUDY DESIGN ................................................................................................................................ 63
4.1. 
Overall Design................................................................................................................................ 63
4.2. 
Scientific Rationale for Study Design............................................................................................. 67
4.2.1. 
Study-Specific Ethical Design Considerations ........................................................................... 67
4.3. 
Justification for Dose...................................................................................................................... 68
4.4. 
End of Study Definition................................................................................................................... 68
5. 
STUDY POPULATION ...................................................................................................................... 68
5.1. 
Inclusion Criteria............................................................................................................................ 69
5.2. 
Exclusion Criteria........................................................................................................................... 70
5.3. 
Lifestyle Considerations................................................................................................................. 72
5.4. 
Screen Failures.............................................................................................................................. 72
5.5. 
Criteria for Temporarily Delaying Administration of Study Vaccine ............................................... 73
6. 
STUDY VACCINATION AND CONCOMITANT THERAPY ............................................................. 73
6.1. 
Study Vaccine Administration ........................................................................................................ 73
6.2. 
Preparation/Handling/Storage/Accountability ................................................................................ 74
6.3. 
Measures to Minimize Bias: Randomization and Blinding............................................................. 75
6.4. 
Study Vaccination Compliance ...................................................................................................... 77
6.5. 
Dose Modification........................................................................................................................... 77
6.6. 
Treatment of Overdose .................................................................................................................. 77
6.7. 
Concomitant Therapy..................................................................................................................... 77
6.8. 
Study Pausing Rules...................................................................................................................... 78
7. 
DISCONTINUATION OF STUDY VACCINATION AND PARTICIPANT
DISCONTINUATION/WITHDRAWAL............................................................................................... 79
7.1. 
Discontinuation of Study Vaccination............................................................................................. 79
7.2. 
Participant Discontinuation/Withdrawal From the Study................................................................ 79
7.2.1. 
Withdrawal from the Use of Research Samples......................................................................... 80

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
5
Status: Approved,  Date: 20 April 2022
7.3. 
Lost to Follow-up............................................................................................................................ 80
8. 
STUDY ASSESSMENTS AND PROCEDURES ............................................................................... 81
8.1. 
COVID-19 and Immunogenicity Assessments............................................................................... 84
8.1.1. 
Prespecified Criteria for Suspected COVID-19.......................................................................... 84
8.1.2. 
Procedures in the Event of COVID-19-like Signs and Symptoms.............................................. 85
8.1.3. 
Monitoring for Asymptomatic SARS-CoV-2 Infection ................................................................. 92
8.1.4. 
Clinical Severity Adjudication Committee................................................................................... 92
8.1.5. 
Immunogenicity Assessments .................................................................................................... 92
8.2. 
Exploratory Efficacy Assessments................................................................................................. 94
8.3. 
Safety Assessments....................................................................................................................... 95
8.3.1. 
Physical Examinations................................................................................................................ 96
8.3.2. 
Vital Signs................................................................................................................................... 96
8.3.3. 
Clinical Safety Laboratory Assessments .................................................................................... 97
8.4. 
Adverse Events, Serious Adverse Events, Adverse Events of Special Interest, and Other
Safety Reporting ............................................................................................................................ 97
8.4.1. 
Time Period and Frequency for Collecting Adverse Event, Adverse Event of Special
Interest, and Serious Adverse Event Information....................................................................... 98
8.4.2. 
Method of Detecting Adverse Events, Adverse Events of Special Interest, and Serious
Adverse Events........................................................................................................................... 99
8.4.3. 
Follow-up of Adverse Events, Adverse Events of Special Interest and Serious Adverse
Events....................................................................................................................................... 100
8.4.4. 
Regulatory Reporting Requirements for Serious Adverse Events ........................................... 100
8.4.5. 
Pregnancy................................................................................................................................. 100
8.4.6. 
Disease-Related Events and Disease-Related Outcomes Not Qualifying as Adverse
Events or Serious Adverse Events........................................................................................... 101
8.4.7. 
Adverse Events of Special Interest........................................................................................... 101
8.5. 
Virology Assessments.................................................................................................................. 102
8.6. 
Biomarkers................................................................................................................................... 102
8.7. 
Medical Resource Utilization and Health Economics .................................................................. 102
9. 
STATISTICAL CONSIDERATIONS................................................................................................ 103
9.1. 
Statistical Hypotheses.................................................................................................................. 103
9.2. 
Sample Size Determination ......................................................................................................... 109
9.3. 
Analysis Sets................................................................................................................................ 110
9.4. 
Statistical Analyses ...................................................................................................................... 111
9.4.1. 
General Considerations............................................................................................................ 111
9.4.2. 
Primary Endpoints .................................................................................................................... 111
9.4.3. 
Secondary Endpoint(s)............................................................................................................. 112
9.4.4. 
Exploratory Endpoint(s)............................................................................................................ 115
9.4.5. 
Other Analyses ......................................................................................................................... 115
9.5. 
Planned Analysis.......................................................................................................................... 116
10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS.......................... 119
10.1. 
Appendix 1: Abbreviations and Definitions .................................................................................. 119
10.2. 
Appendix 2: Clinical Laboratory Tests ......................................................................................... 122
10.3. 
Appendix 3: Regulatory, Ethical, and Study Oversight Considerations....................................... 124
10.3.1. 
Regulatory and Ethical Considerations .................................................................................... 124
10.3.2. 
Financial Disclosure.................................................................................................................. 127
10.3.3. 
Informed Consent Process ....................................................................................................... 127
10.3.4. 
Data Protection ......................................................................................................................... 128
10.3.5. 
Long-Term Retention of Samples for Additional Future Research .......................................... 129
10.3.6. 
Committees Structure............................................................................................................... 129
10.3.7. 
Publication Policy/Dissemination of Clinical Study Data.......................................................... 130
10.3.8. 
Data Quality Assurance............................................................................................................ 131
10.3.9. 
Case Report Form Completion................................................................................................. 132
10.3.10. Source Documents ................................................................................................................... 132
10.3.11. Monitoring ................................................................................................................................. 133

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
6
Status: Approved,  Date: 20 April 2022
10.3.12. On-Site Audits........................................................................................................................... 133
10.3.13. Record Retention...................................................................................................................... 134
10.3.14. Study and Site Start and Closure ............................................................................................. 134
10.4. 
Appendix 4: Adverse Events, Serious Adverse Events, Adverse Events of Special
Interest, Product Quality Complaints, and Other Safety Reporting: Definitions and
Procedures for Recording, Evaluating, Follow-up, and Reporting............................................... 136
10.4.1. 
Adverse Event Definitions and Classifications ......................................................................... 136
10.4.2. 
Attribution Definitions................................................................................................................ 137
10.4.3. 
Severity Criteria........................................................................................................................ 137
10.4.4. 
Special Reporting Situations .................................................................................................... 138
10.4.5. 
Procedures ............................................................................................................................... 138
10.4.6. 
Product Quality Complaint Handling......................................................................................... 140
10.4.7. 
Contacting Sponsor Regarding Safety, Including Product Quality........................................... 140
10.5. 
Appendix 5 Symptoms of Infection with Coronavirus-19 (SIC).................................................... 141
10.6. 
Appendix 6: Medical Resource Utilization (MRU) Questionnaire ................................................ 145
10.7. 
Appendix 7: Medically-attended COVID-19 (MA-COV) Form...................................................... 147
10.8. 
Appendix 8: Toxicity Grading Scale............................................................................................. 153
10.9. 
Appendix 9: Summary of Guidance from CDC Website on Underlying Medical Conditions
That Lead or Might Lead to Increased Risk for Severe Illness From COVID-19......................... 158
10.10. Appendix 10: Thrombotic Events to be Reported as AESIs ........................................................ 159
10.11. Appendix 11: TTS AESI Form...................................................................................................... 160
10.12. Appendix 12: Protocol Amendment History................................................................................. 163
11. REFERENCES................................................................................................................................. 170
INVESTIGATOR AGREEMENT............................................................................................................... 174
LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1: 
Schematic Overview of Study Design and Groups................................................................... 64
Table 2: 
Blood Collection Schedule (Whole Blood) for Humoral and Cellular Immunogenicity
Assessments............................................................................................................................. 66
Table 3: 
Blood Collection Schedule (PBMCa) for Cellular Immunogenicity Assessments ..................... 66
Table 4: 
Summary of Humoral Immunogenicity Assays......................................................................... 93
Table 5: 
Summary of Cellular Immunogenicity Assays .......................................................................... 93
Table 6: 
Probability of Observing at Least One Adverse Event Given a True Adverse Event
Incidence................................................................................................................................. 113
FIGURES
Figure 1: Schematic Overview of the Study............................................................................................. 28
Figure 2: Decision Tree for COVID-19 Procedures ................................................................................. 86
Figure 3: Decision Tree-based Hypothesis Testing............................................................................... 105

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
7
Status: Approved,  Date: 20 April 2022
1. 
PROTOCOL SUMMARY
1.1. 
Synopsis
A Randomized, Double-blind, Phase 2 Study to Evaluate the Immunogenicity, Reactogenicity and Safety
of Ad26.COV2.S Administered as Booster Vaccination in Adults 18 Years of Age and Older Who Have
Previously Received Primary Vaccination with Ad26.COV2.S or BNT162b2.
Ad26.COV2.S (also known as VAC31518, JNJ-78436735) is a monovalent vaccine composed of a
recombinant, replication-incompetent adenovirus type 26 (Ad26) vector, constructed to encode the Spike
(S)protein derived from a SARS-CoV-2 clinical isolate (Wuhan 2019, whole genome sequence NC 045512,
further referred to as the original strain), stabilized in its prefusion conformation.
The Pfizer-BioNTech COVID-19 vaccine, BNT162b2, is a lipid nanoparticle-formulated, nucleoside-
modified RNA vaccine encoding a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length
spike protein.
In Cohort 1, participants who previously received Ad26.COV2.S primary vaccination in Janssen-sponsored
study COV3001, will receive a 1-dose booster vaccination regimen with Ad26.COV2.S  (5×1010 vp or
2.5×1010 vp or 1×1010 vp).
In Cohort 2, participants who previously received primary vaccination with the Pfizer BNT162b2 vaccine
will receive a 1-dose booster vaccination with Ad26.COV2.S (5×1010 vp or 2.5×1010 vp or 1×1010 vp).
Information about the disease, correlates of immunity, and safety issues concerning this new pandemic-
causing virus are rapidly evolving. Therefore, it is critical to recognize that the approach outlined in this
document can change as insights and discussions evolve.
OBJECTIVES AND ENDPOINTS
Objectives 
Endpoints
Primary
Primary Objective 1a: To demonstrate the NI 
of the neutralizing antibody response to the 
original strain 14 days after booster vaccination 
with Ad26.COV2.S at the 5×1010 vp dose level, 
administered ≥6 months after single-dose 
primary 
vaccination 
with 
Ad26.COV2.S 
(5×1010vp dose level), compared to the 
neutralizing antibody response to the original
strain 
induced 
by 
single-dose 
primary
vaccination with Ad26.COV2.S at the 5×1010 vp
dose level.
If Primary Objective 1a is met, Primary
Objective 1b will be tested.
 Serological response to vaccination and antibody
titers as measured by virus neutralization assay
(VNA) titers against the original strain, 14 days
after 
Ad26.COV2.S 
booster 
vaccination
(5×1010 vp dose level) after completing 1-dose
primary 
vaccination 
with 
Ad26.COV2.S
(5×1010 vp dose level).
 Serological response to vaccination and antibody
titers (VNA) against the original strain, 28 days
after Ad26.COV2.S (5×1010 vp dose level) single-
dose primary vaccination.
Success criteria for NI:
 
The lower limit of the 100*(1-2*α)% CI on the
difference in responder rate (Ad26.COV2.S
booster - Ad26.COV2.S primary) needs to be
>-10%.
AND
 The lower limit of the 100*(1-2*α)% CI on the
ratio of neutralizing antibody GMTs (GMT
Ad26.COV2.S 
booster/GMT 
Ad26.COV2.S
primary) needs to be >2/3.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
8
Status: Approved,  Date: 20 April 2022
Objectives 
Endpoints
AND
 
An  estimated GMR (GMT Day 15 post-
booster/GMT Day 29 post primary regimen) of
>0.8 is required to conclude NI.
Primary Objective 1b: To demonstrate the NI
of the neutralizing antibody response to the
leading variant of high consequence or
concern* 14 days after booster vaccination with
Ad26.COV2.S at the 5×1010 vp dose level,
administered ≥6 months after single-dose
primary 
vaccination 
with 
Ad26.COV2.S
(5×1010vp dose level), compared to the
neutralizing antibody response to the leading
variant of high consequence or concern*
induced by single-dose primary vaccination
with Ad26.COV2.S at the 5×1010 vp dose level,
if feasible.
If Primary Objective 1b is met, Primary
Objectives 1c and 2a will be tested.
 Serological response to vaccination and antibody
titers as measured by virus neutralization assay
(VNA) titers against the leading variant of high
consequence or concern*, 14 days after
Ad26.COV2.S booster vaccination (5×1010 vp
dose level) after completing 1-dose primary
vaccination with Ad26.COV2.S (5×1010 vp dose
level).
 Serological response to vaccination and antibody
titers (VNA) against the leading variant of high
consequence or concern*, 28 days after
Ad26.COV2.S (5×1010 vp dose level) single-dose
primary vaccination.
Success criteria for NI:
 
The lower limit of the 100*(1-2*α)% CI on the
difference in responder rate (Ad26.COV2.S
booster - Ad26.COV2.S primary) needs to be
>-10%.
AND
 The lower limit of the 100*(1-2*α)% CI on the
ratio of neutralizing antibody GMTs (GMT
Ad26.COV2.S 
booster/GMT 
Ad26.COV2.S
primary) needs to be >2/3.
AND
 
An estimated GMR (GMT Day 15 post-
booster/GMT Day 29 post primary regimen) of
>0.8 is required to conclude NI.
Primary Objective 1c: To demonstrate the NI
of the neutralizing antibody response to the
original strain 14 days after booster vaccination
with Ad26.COV2.S at the 2.5×1010 vp dose
level, administered ≥6 months after single-dose
primary 
vaccination 
with 
Ad26.COV2.S
(5×1010vp dose level), compared to the
neutralizing antibody response to the original
strain 
induced 
by 
single-dose 
primary
vaccination with Ad26.COV2.S at the 5×1010 vp
dose level.
If Primary Objective 1c is met, Primary
Objective 1d will be tested.
 Serological response to vaccination and antibody
titers as measured by virus neutralization assay
(VNA) titers against the original strain, 14 days
after 
Ad26.COV2.S 
booster 
vaccination
(2.5×1010vp dose level) after completing 1-dose
primary 
vaccination 
with 
Ad26.COV2.S
(5×1010 vp dose level).
 Serological response to vaccination and antibody
titers (VNA) against the original strain, 28 days
after Ad26.COV2.S (5×1010 vp dose level) single-
dose primary vaccination.
Success criteria for NI:
 
The lower limit of the 97.5% CI on the difference
in responder rate (Ad26.COV2.S booster -
Ad26.COV2.S primary) needs to be >-10%.
AND

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
9
Status: Approved,  Date: 20 April 2022
Objectives 
Endpoints
 The lower limit of the 97.5% CI on the ratio of
neutralizing 
antibody 
GMTs 
(GMT
Ad26.COV2.S 
booster/GMT 
Ad26.COV2.S
primary) needs to be >2/3.
AND
 
An estimated GMR (GMT Day 15 post-
booster/GMT Day 29 post primary regimen) of
>0.8 is required to conclude NI.
Primary Objective 1d: To demonstrate the NI 
of the neutralizing antibody response to the 
original strain 14 days after booster vaccination 
with Ad26.COV2.S at the 1×1010 vp dose level, 
administered ≥6 months after single-dose 
primary 
vaccination 
with 
Ad26.COV2.S 
(5×1010vp dose level), compared to the 
neutralizing antibody response to the original
strain 
induced 
by 
single-dose 
primary
vaccination with Ad26.COV2.S at the 5×1010 vp
dose level.
 Serological response to vaccination and antibody
titers as measured by virus neutralization assay
(VNA) titers against the original strain, 14 days
after 
Ad26.COV2.S 
booster 
vaccination
(1×1010 vp dose level) after completing 1-dose
primary 
vaccination 
with 
Ad26.COV2.S
(5×1010 vp dose level).
 Serological response to vaccination and antibody
titers (VNA) against the original strain, 28 days
after Ad26.COV2.S (5×1010 vp dose level) single-
dose primary vaccination.
Success criteria for NI:
 
The lower limit of the 97.5% CI on the difference
in responder rate (Ad26.COV2.S booster -
Ad26.COV2.S primary) needs to be >-10%.
AND
 The lower limit of the 97.5% CI on the ratio of
neutralizing 
antibody 
GMTs 
(GMT
Ad26.COV2.S 
booster/GMT 
Ad26.COV2.S
primary) needs to be >2/3.
AND
 
An estimated GMR (GMT Day 15 post-
booster/GMT Day 29 post primary regimen) of
>0.8 is required to conclude NI.
Primary Objective 2a: To demonstrate the NI 
of the neutralizing antibody response to the 
original strain 14 days after booster vaccination 
with Ad26.COV2.S at the 5×1010 vp dose level, 
administered ≥6 months after completing a 2- 
dose 
primary 
vaccination 
with 
Pfizer 
BNT162b2, compared to the neutralizing
antibody response to the original strain induced
by 2-dose primary vaccination with Pfizer
BNT162b2
If Primary Objective 2a is met, Primary 
Objective 2b will be tested. 
 Serological response to vaccination and antibody
titers as measured by virus neutralization assay
(VNA) titers against the original strain, 14  days
after 
Ad26.COV2.S 
booster 
vaccination
(5×1010 vp dose level) after completing 2-dose
primary vaccination with Pfizer BNT162b2
 Serological response to vaccination and antibody
titers (VNA) against the original strain in serum
samples 
of approximately 
300 individuals,
collected 2 weeks to 2 months after completing 2-
dose primary vaccination with Pfizer BNT162b2
(further referred to as Pfizer BNT162b2 external
samples).
Success criteria for NI:
 
The lower limit of the 97.5% CI on the difference
in seropositivity rate (Ad26.COV2.S booster -

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
10
Status: Approved,  Date: 20 April 2022
Objectives 
Endpoints
Pfizer BNT162b2 primary regimen [external
samples]) needs to be >-10%.
AND
 The lower limit of the 97.5% CI on the ratio of
neutralizing 
antibody 
GMTs 
(GMT
Ad26.COV2.S  
booster/GMT 
post 
Pfizer
BNT162b2 primary regimen [external samples])
needs to be >2/3.
AND
 
An estimated GMR (GMT Day 15 post-booster/
post Pfizer BNT162b2 primary regimen [external
samples]) of >0.8 is required to conclude NI.
Primary Objective 2b: To demonstrate the NI 
of neutralizing antibody response to the leading 
variant of high consequence or concern* 14 
days 
after 
booster 
vaccination 
with 
Ad26.COV2.S at the 5×1010 vp dose level, 
administered ≥6 months after completing a 2- 
dose 
primary 
vaccination 
with 
Pfizer 
BNT162b2, compared to the neutralizing
antibody response to the leading variant of high
consequence or concern* induced by 2-dose
primary vaccination with Pfizer BNT162b2, if
feasible
If Primary Objective 2b is met, Primary
Objectives 2c will be tested.
 
Serological response to vaccination and antibody
titers as measured by virus neutralization assay
(VNA) against the leading variant of high
consequence or concern* 14 days after
Ad26.COV2.S booster vaccination (5×1010vp
dose level) after completing 2-dose primary
vaccination with Pfizer BNT162b2
 
Serological response to vaccination and antibody
titers as measured by virus neutralization assay
(VNA) against the leading variant of high
consequence or concern* in Pfizer BNT162b2
external samples
Success criteria for NI:
 
The lower limit of the 97.5% CI on the difference
in seropositivity  rate (Ad26.COV2.S booster -
Pfizer BNT162b2 primary regimen [external
samples]) needs to be >-10%.
AND
 The lower limit of the 97.5% CI on the ratio of
neutralizing 
antibody 
GMTs 
(GMT
Ad26.COV2.S 
booster/GMT 
post 
Pfizer
BNT162b2 primary regimen [external samples])
needs to be >2/3.
AND
 
An estimated GMR (GMT Day 15 post-
booster/GMT post Pfizer BNT162b2 primary
regimen [external samples]) of >0.8 is required to
conclude NI.
Primary Objective 2c: To demonstrate the NI 
of the neutralizing antibody response to the 
original strain 14 days after booster vaccination 
with Ad26.COV2.S at the 2.5×1010 vp dose 
level, administered ≥6 months after completing 
a 2-dose primary vaccination with Pfizer 
BNT162b2, compared to the neutralizing
antibody response to the original strain induced
 Serological response to vaccination and antibody
titers as measured by virus neutralization assay
(VNA) titers against the original strain, 14 days
after 
Ad26.COV2.S 
booster 
vaccination
(2.5×1010vp dose level) after completing 2-dose
primary vaccination with Pfizer BNT162b2.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
11
Status: Approved,  Date: 20 April 2022
Objectives 
Endpoints
by 2-dose primary vaccination with Pfizer 
BNT162b2 
If Primary Objective 2c is met, Primary 
Objective 2d will be tested. 
 Serological response to vaccination and antibody
titers (VNA) against the original strain, in Pfizer
BNT162b2 external samples.
Success criteria for NI:
 
The lower limit of the 97.5% CI on the difference
in seropositivity rate (Ad26.COV2.S booster-
Pfizer BNT162b2 primary regimen [external
samples]) needs to be >-10%.
AND
 The lower limit of the 97.5% CI on the ratio of
neutralizing 
antibody 
GMTs 
(GMT
Ad26.COV2.S booster/post Pfizer BNT162b2
primary regimen [external samples]) needs to be
>2/3.
AND
 
An estimated GMR (GMT Day 15 post-
booster/GMT post Pfizer BNT162b2 primary
regimen [external samples]) of >0.8 is required to
conclude NI.
Primary Objective 2d: To demonstrate the NI 
of the neutralizing antibody response to the 
original strain 14 days after booster vaccination 
with Ad26.COV2.S at the 1×1010 vp dose level, 
administered ≥6 months after completing a 2- 
dose 
primary 
vaccination 
with 
Pfizer 
BNT162b2, compared to neutralizing antibody
response to the original strain induced by 2-dose
primary vaccination with Pfizer BNT162b2
 Serological response to vaccination and antibody
titers as measured by virus neutralization assay
(VNA) titers against the original strain, 14 days
after 
Ad26.COV2.S 
booster 
vaccination
(1×1010 vp dose level) after completing 2-dose
primary vaccination with Pfizer BNT162b2.
 Serological response to vaccination and antibody
titers (VNA) against the original strain, in Pfizer
BNT162b2 external samples .
Success criteria for NI:
 
The lower limit of the 97.5% CI on the difference
in seropositivity rate (Ad26.COV2.S booster-
Pfizer BNT162b2 primary regimen [external
samples]) needs to be >-10%.
AND
 The lower limit of the 97.5% CI on the ratio of
neutralizing 
antibody 
GMTs 
(GMT
Ad26.COV2.S 
booster/GMT 
post 
Pfizer
BNT162b2 primary regimen [external samples])
needs to be >2/3.
AND
 
An estimated GMR (GMT Day 15 post-
booster/GMT post Pfizer BNT162b2 primary
regimen [external samples]) of >0.8 is required to
conclude NI.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
12
Status: Approved,  Date: 20 April 2022
Objectives 
Endpoints
Secondary
To assess the safety and reactogenicity of 
Ad26.COV2.S administered at the 5×1010 vp, 
2.5×1010 vp and 1×1010 vp dose levels
administered as booster vaccinations in adults.
 
Solicited local and systemic adverse events
(AEs) for 7 days after booster vaccination.
 
Unsolicited AEs for 28 days after booster
vaccination.
 
Serious adverse events (SAEs) and adverse
events of special interest (AESIs) throughout the
study (from booster vaccination until end of the
study).
To assess the neutralizing and binding antibody
response to the original strain, leading variant of
high consequence or concern* and other
relevant variants of concern, induced by booster
vaccination with Ad26.COV2.S at the 5×1010
vp, 2.5×1010 vp and 1×1010 vp dose levels, in
adults who have previously completed single-
dose primary vaccination with Ad26.COV2.S at
the 5×1010 vp dose level.
 
Serological response to vaccination and antibody
titers, as measured by VNA, against the original
strain, leading variant of high consequence or
concern* AND other relevant variants of concern,
14 days and 28 days after Ad26.COV2.S booster
vaccination.
 
Antibodies binding to SARS-CoV-2 relevant
variants of concern or individual SARS-CoV-2
proteins (eg, S and/or receptor-binding domain
[RBD] proteins from the SARS-CoV-2 variants of
concern) by ELISA and/or MSD.
To assess the neutralizing and binding antibody
response to the original strain, leading variant of
high consequence or concern* and other
relevant variants of concern, induced by booster
vaccination with Ad26.COV2.S at the 5×1010
vp, 2.5×1010 vp and 1×1010 vp dose levels, in
adults who have previously completed primary
vaccination with Pfizer BNT162b.
 
Serological response to vaccination and antibody
titers, as measured by VNA, against the original
strain, leading variant of high consequence or
concern* AND other relevant variants of concern,
14 days and 28 days after Ad26.COV2.S booster
vaccination.
 
Antibodies binding to SARS-CoV-2 relevant
variants of concern or individual SARS-CoV-2
proteins (eg, S and/or receptor-binding domain
[RBD] proteins from the SARS-CoV-2 variants of
concern) by ELISA and/or MSD.
To assess previous or concomitant infection
with SARS-CoV-2 at baseline.
Antibodies binding to the SARS-CoV-2 nucleocapsid
(N) protein at Day 1 (N-serology).
Exploratory
To assess the neutralizing antibody responses
against the original strain, leading variant of
high consequence or concern* and other
relevant variants of concern, following
Ad26.COV2.S 
booster 
vaccination 
in
participants 
that 
previously 
received
Ad26.COV2.S or Pfizer BNT122b2 as primary
vaccination, compared observationally to
antibody responses 14 days post primary
vaccination 
in 
participants 
from 
Study
COV3009 (2-dose schedule of Ad26.COV2.S
spaced by 56 days).
 
Serological response to vaccination and antibody
titers measured by VNA against the original
strain, 14 days and 28 days after Ad26.COV2.S
booster vaccination (5×1010vp dose level), after
completing 
one-dose 
or 2-dose 
primary
vaccination with Ad26.COV2.S or Pfizer
BNT162b2, respectively.
 
Serological response to vaccination and antibody
titers measured by VNA against the leading
variant of high consequence or concern*, 14 days
and 28 days after Ad26.COV2.S booster
vaccination 
(5×1010vp 
dose 
level), 
after
completing 
one-dose 
or 2-dose 
primary

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
13
Status: Approved,  Date: 20 April 2022
Objectives 
Endpoints
vaccination with Ad26.COV2.S or Pfizer
BNT162b2, respectively.
 
Serological response to vaccination and antibody
titers measured by VNA against other relevant
variants of concern, 14 days and 28 days after
Ad26.COV2.S booster vaccination (5×1010vp
dose level), after completing one-dose or 2-dose
primary vaccination with Ad26.COV2.S or
Pfizer BNT162b2, respectively.
 
Serological response to vaccination and antibody
titers measured by VNA against the original
variant, 14 days after completing Ad26.COV2.S
primary vaccination as a 2-dose schedule spaced
by 56 days (5×1010vp dose level), in a subset of
participants from study COV3009.
Observational comparison of neutralizing 
antibody responses against the original strain 
induced by booster vaccination with 5×1010 vp 
vs those receiving 2.5×1010 vp, in adults who 
previously completed single-dose primary 
vaccination with Ad26.COV2.S at the 5×1010 vp
dose level.
 
Serological response to vaccination and antibody
titers, as measured by VNA, against the original
strain 14 days and 28 days after Ad26.COV2.S
booster vaccination (2.5×1010 vp or 5×1010 vp
dose level).
Observational comparison of neutralizing 
antibody responses against the original strain 
induced by booster vaccination with 5×1010 vp 
vs those receiving 1×1010 vp, in adults who 
previously completed single-dose primary 
vaccination with Ad26.COV2.S at the 5×1010 vp
dose level.
 
Serological response to vaccination and antibody
titers, as measured by VNA, against the original
strain 14 days and 28 days after Ad26.COV2.S
booster vaccination (1×1010vp or 5×1010 vp dose
level).
Observational comparison of neutralizing 
antibody responses against the original strain 
induced by booster vaccination with 5×1010 vp 
in adults who previously completed single-dose 
primary vaccination with Ad26.COV2.S at the 
5×1010 vp dose level vs neutralizing antibody 
responses against the original strain induced by 
booster vaccination with 5×1010 vp in adults 
who previously completed single-dose primary
vaccination with Pfizer BNT162b.
 
Serological response to vaccination and antibody
titers, as measured by VNA, against the original
strain 14 days and 28 days after Ad26.COV2.S
booster vaccination (5×1010vp) in participants
primed with the 1-dose Ad26.COV2.S vaccine at
the 5×1010 vp dose level, and after booster
vaccination at the 5×1010 vp dose level in
participants primed with Pfizer BNT162b.
Observational comparison of neutralizing 
antibody responses against the original strain 
induced by booster vaccination with 5×1010 vp 
in adults who previously completed single-dose 
primary vaccination with Ad26.COV2.S at the 
5×1010 vp dose level vs neutralizing antibody 
responses against the original strain induced by 
booster vaccination with 2.5×1010 vp in adults 
who previously completed primary vaccination 
with Pfizer BNT162b.
 
Serological response to vaccination and antibody
titers, as measured by VNA, against the original
strain 14 days and 28 days after Ad26.COV2.S
booster vaccination at the 5×1010vp dose level in
participants 
primed 
with 
the 
1-dose
Ad26.COV2.S vaccine at the 5×1010 vp dose
level, and booster vaccination at the 2.5×1010 vp
dose level in participants primed with Pfizer
BNT162b.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
14
Status: Approved,  Date: 20 April 2022
Objectives 
Endpoints
Observational comparison of neutralizing 
antibody responses against the original strain 
induced by booster vaccination with 5×1010 vp 
in adults who previously completed single-dose 
primary vaccination with Ad26.COV2.S at the 
5×1010 vp dose level vs neutralizing antibody  
responses against the original strain induced by 
booster vaccination with 1×1010 vp in adults 
who previously completed primary vaccination
with Pfizer BNT162b.
Serological response to vaccination and antibody
titers, as measured by VNA, against the original strain
14 days and 28 days after Ad26.COV2.S booster
vaccination at the 5×1010vp dose level in participants
primed with the 1-dose Ad26.COV2.S vaccine at the
5×1010 vp dose level, and booster vaccination at
1×1010 vp dose level in participants primed with Pfizer
BNT162b.
To determine if any of the primary objectives 
that meet a non-inferiority criterion also meet a 
superiority criterion. 
 
Serological response to vaccination and antibody
titers as measured by virus neutralization assay
(VNA) titers against the original strain, 14 days
after 
Ad26.COV2.S 
booster 
vaccination
(5×1010vp OR 2.5×1010 vp OR 1×1010vp dose
level) 
after 
completing 
1-dose 
primary
vaccination with Ad26.COV2.S OR 2-dose
primary vaccination with Pfizer BNT162b2
 
Serological response to vaccination and antibody
titers (VNA) against the original strain, 28 days
after Ad26.COV2.S (5×1010 vp dose level)
single-dose primary vaccination.
To make observational comparisons between
the 
immunologic 
response 
to 
booster
vaccination and the primary vaccination
regimen, in participants primed with the Pfizer
BNT162b regimen (if appropriate serum
samples are available for testing).
 
Serological response to vaccination and antibody
titers as measured by virus neutralization assay
(VNA) titers against the original strain, 14 days
after 
Ad26.COV2.S 
booster 
vaccination
(5×1010vp OR 2.5×1010 vp OR 1×1010vp dose
level) 
after 
completing 
2-dose 
primary
vaccination with Pfizer BNT162b2
 
Serological response to vaccination and antibody
titers (VNA) against the original strain, 28 days
after completing 2-dose primary vaccination with
Pfizer BNT162b2
To evaluate patient-reported outcomes (PROs)
in relation to the presence of SARS-CoV-2
infection and the presence, severity and duration
of COVID-19 signs and symptoms in
participants who receive booster vaccination.
 
Presence, severity and duration of COVID-19
signs and symptoms
 
Confirmation of SARS-CoV-2 infection by
molecular testing
 
Evaluate all PCR and N ELISA confirmed cases
of SARS-CoV-2 infections according to the
charter of the Clinical Severity  Adjudication
Committee.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
15
Status: Approved,  Date: 20 April 2022
Objectives 
Endpoints
To explore the relative vaccine efficacy (rVE) 
of 
Ad26.COV2.S 
heterologous 
booster 
vaccination in the prevention of SARS-CoV-2 
infection (severe/critical, moderate, moderate to
severe/critical, 
mild, 
symptomatic, 
and
asymptomatic infections, that are serologically
and/or molecularly confirmed) compared to 
Ad26.COV2.S homologous booster vaccination 
at the same dose level (5×1010vp, 2.5×1010vp 
and 1×1010vp). 
 
Asymptomatic 
cases 
of COVID-19, 
as
determined by seropositivity  for the SARS-
CoV-2 N protein.
 
SARS-CoV-2 
infections 
as 
detected 
by
molecular testing (RT-PCR or equivalent).
 
COVID-19 cases meeting the US FDA
Harmonized COVID-19 case definition, with
onset at least 14 days post vaccination in
COV2008.
 
COVID-19 cases meeting the criteria for
“moderate, moderate and severe/critically ill”
COVID-19, with onset at least 14 days post
vaccination in COV2008, if sufficient data are
available.
To explore the rVE of different dose levels of
Ad26.COV2.S homologous booster vaccination
in the prevention of SARS-CoV-2 infection
(severe/critical, 
moderate, 
moderate 
to
severe/critical, symptomatic, and asymptomatic
infections, that are serologically and/or
molecularly confirmed) as follows:
 5×1010vp versus 1×1010vp dose level
 2.5×1010vp versus 1×1010vp dose level
 
Asymptomatic 
cases 
of COVID-19, 
as
determined by seropositivity for the SARS-
CoV-2 N protein.
 
SARS-CoV-2 
infections 
as 
detected 
by
molecular testing (RT-PCR or equivalent).
 
COVID-19 cases meeting the US FDA
Harmonized COVID-19 case definition, with
onset at least 14 days post vaccination in
COV2008.
 
COVID-19 cases meeting the criteria for
“moderate, moderate and severe/critically ill”
COVID-19, with onset at least 14 days post
vaccination in COV2008, if sufficient data are
available.
To explore the rVE of different dose levels of
Ad26.COV2.S 
heterologous 
booster
vaccination in the prevention of SARS-CoV-2
infection (severe/critical, moderate, moderate to
severe/critical, symptomatic, and asymptomatic
infections, that are serologically and/or
molecularly confirmed) as follows:
 5×1010vp versus 1×1010vp dose level
 2.5×1010vp versus 1×1010vp dose level
 
Asymptomatic 
cases 
of COVID-19, 
as
determined 
by 
seropositivity 
for 
the
SARS-CoV-2 N protein.
 
SARS-CoV-2 
infections 
as 
detected 
by
molecular testing (RT-PCR or equivalent).
 
COVID-19 cases meeting the US FDA
Harmonized COVID-19 case definition, with
onset at least 14 days post vaccination in
COV2008.
 
COVID-19 cases meeting the criteria for
“moderate, moderate to severe/critical and
severe/critically ill” COVID-19, with onset at
least 14 days post vaccination in COV2008, if
sufficient data are available.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
16
Status: Approved,  Date: 20 April 2022
Objectives 
Endpoints
If feasible, to investigate the effect of post 
booster cellular responses, mRNA profiles, 
neutralizing responses and/or other functional 
antibody responses on the probability of 
experiencing a COVID-19 event, moderate and 
moderate to severe/critically ill COVID-19 
disease, 
or 
asymptomatic 
SARS-CoV-2 
infection. 
 
Serological response to vaccination and antibody
titers as measured by virus neutralization assay
(VNA) titers against the reference strain and/or
SARS-CoV-2 variants, by ELISA/MSD and/or
other functional antibody assays, 14 days, 6
months and 1 year after homologous or
heterologous 
booster 
vaccination 
with
Ad26.COV2.S, if sufficient data are available.
 
Cellular response to vaccination as measured by
flow 
cytometry, 
ELISPOT 
and/or
transcriptomics, 14 days, 6 months and 1 year
after homologous or heterologous booster
vaccination with Ad26.COV2.S, if sufficient data
are available.
 
COVID-19 cases meeting the US FDA
Harmonized COVID-19 case definition, with
onset at least 14 days post booster vaccination in
study COV2008, if sufficient data are available.
 
COVID-19 cases meeting the criteria for
“moderate and moderate to severe/critically ill”
COVID-19, with onset at least 14 days post
vaccination in COV2008, if sufficient data are
available.
 
Asymptomatic SARS-CoV-2 infection, with
onset at least 14 days post vaccination in
COV2008, if sufficient data are available.
 
Analysis of gene expression by RNA transcript
profiling and correlation with humoral and
cellular immune responses.
In a subset, to assess the cellular immune
response to the original strain, leading variant of
high consequence or concern* and other
relevant variants of concern, after booster
vaccination with Ad26.COV2.S at the 5×1010
vp, 2.5×1010 vp and 1×1010 vp dose levels, at
baseline (Day 1, pre-booster vaccination) and
14 days, 6 months and 1 year after booster
vaccination in adults.
This objective will be tested only if PBMC
collection is feasible.
T helper (Th) 1 and Th2 immune responses as
assessed by:
 
Flow cytometry after SARS-CoV-2 S protein
peptide 
stimulation 
of peripheral 
blood
mononuclear cells (PBMC) and intracellular
staining (ICS) including CD4+/CD8+, interferon
gamma (IFNγ), interleukin (IL)2, tumor necrosis
factor alpha (TNFα), IL-4, IL-5, IL13, and/or
other Th1/Th2 markers.
AND/OR
 
Dual or single IFNγ and IL-4 enzyme-linked
immunospot (ELISpot) assay after stimulation of
PBMCs with SARS-CoV-2 S protein peptides.
In a subset of participants, to assess the cellular
immune response to the original strain, leading
variant of high consequence or concern* and
other relevant variants of interest, after booster
T helper (Th) 1 and Th2 immune responses as
assessed by:
 
Flow cytometry after SARS-CoV-2 S protein
peptide 
stimulation 
of peripheral 
blood

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
17
Status: Approved,  Date: 20 April 2022
Objectives 
Endpoints
vaccination with Ad26.COV2.S in adults who 
have completed a primary vaccination regimen 
with Ad26.COV2.S or BNT162b2, at baseline 
(Day 1, pre-booster vaccination) and 14 days, 6 
months and 1 year after booster vaccination. 
This objective will be tested only if PBMC 
collection is feasible.
mononuclear cells (PBMC) and intracellular
staining (ICS) including CD4+/CD8+, interferon
gamma (IFNγ), interleukin (IL)2, tumor necrosis
factor alpha (TNFα), IL-4, IL-5, IL13, and/or
other Th1/Th2 markers.
AND/OR
 
Dual or single IFNγ and IL-4 enzyme-linked
immunospot (ELISpot) assay after stimulation of
PBMCs with SARS-CoV-2 S protein peptides.
To further explore the humoral immune
response to Ad26.COV2.S booster vaccination
in adults.
Exploratory analyses may include the following
assays:
 
SARS-CoV-2 neutralization as assessed by
alternative SARS-CoV-2 neutralization assays
(VNA).
 
Adenovirus neutralization.
 
Functional 
and 
molecular 
antibody
characterization including Fc-mediated viral
clearance, avidity, Fc characteristics, Ig subclass
and IgG isotype.
 
Epitope-specificity 
characterization 
of
antibodies.
 
Cytokine profiling: Analysis of cytokines,
chemokines, and other proteins of the innate or
adaptive immune response in the serum or
plasma.
 
Passive transfer: Analysis of immune mediators
correlating with protection against experimental
SARS-CoV-2 challenge in a suitable animal
model.
In a subset, to assess humoral and cellular
responses (if feasible) 28 days following the
second dose of Pfizer BNT162b2 against the
original strain, leading variant of high
consequence or concern* and other relevant
variant strains for comparison to booster
responses in the different regimens and the
primary response to Ad26.COV2.S.
 
Assay panels similar to those tested for the other
groups will be utilized based on availability of
serum and cells. Assessments performed with
different assays to those utilized for other groups
in this study may be utilized.
At one site (BIDMC), in-depth humoral and
cellular immunogenicity assessment may be
performed on participants enrolled at that site
and in a subset of participants enrolled at other
sites.
Exploratory analyses may include the following
assays:
 
SARS-CoV-2 neutralization as assessed by
alternative SARS-CoV-2 neutralization assays
(VNA).
 
Adenovirus neutralization.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
18
Status: Approved,  Date: 20 April 2022
Objectives 
Endpoints
 
Functional 
and 
molecular 
antibody
characterization including Fc-mediated viral
clearance, avidity, Fc characteristics, Ig subclass
and IgG isotype.
 
Epitope-specificity 
characterization 
of
antibodies.
 
Cytokine profiling: Analysis of cytokines,
chemokines, and other proteins of the innate or
adaptive immune response in the serum or
plasma.
 
Passive transfer: Analysis of immune mediators
correlating with protection against experimental
SARS-CoV-2 challenge in a suitable animal
model.
 
Analysis of gene expression by RNA transcript
profiling
To characterize and establish correlations 
between mRNA profiling and immunologic 
responses to the booster vaccinations. 
 
Analysis of gene expression by RNA transcript
profiling and correlation with humoral and
cellular immune responses.
To explore markers of inflammation and 
upregulation of pathways that may be involved 
in the thrombosis with thrombocytopenia 
syndrome 
(TTS) 
rarely  occurring 
after 
vaccination with Ad26.COV2.S. 
 
Descriptive comparison of RNA sequence
profiles 
from 
participants 
receiving
Ad26.COV2.S vaccination to the RNA profiles
of participants receiving other Ad26-based
vaccines.
Explore the relationship between humoral and 
cellular (if feasible) responses in relationship to 
the time between primary and booster 
immunization  
 
In silico modelling of the humoral and cellular
immune responses elicited by Ad26.COV2.S as
primary regimen and by Ad26.COV2.S as
booster, over time.
To assess the vaccine recipient’s risk of 
developing 
thrombotic 
events 
after 
Ad26.COV2.S administration. 
 
Platelet count pre-vaccination at Day 1 (all
participants) and Day 29 post-vaccination (for
participants with a suspected AESI).
 
Based on the clinical evaluation of the suspected
AESI (eg, whether thrombocytopenia is observed
with a thrombotic event), a panel of coagulation-
related tests may be conducted on the stored pre-
vaccination sample (retrospective test), on Day
29 post vaccination, and on the samples obtained
as part of the AESI investigation).
* As defined by the Centers for Disease Control and Prevention (CDC Aug 2021c) at the time of the analysis

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
19
Status: Approved,  Date: 20 April 2022
Hypothesis
No formal statistical testing of safety data is planned. Safety data will be analyzed descriptively by vaccine
group. The neutralizing antibody response 14 days post Ad26.COV2.S booster vs the neutralizing antibody
response 28 days post primary vaccination with Ad26.COV2.S will be used to test the following 7
hypotheses:
Cohort 1 
Cohort 2
1. Non-inferiority 
of neutralizing 
antibody 
response to the original strain 14 days after 
booster vaccination with Ad26.COV2.S at the 
5×1010 vp dose level, ≥6 months after single- 
dose primary vaccination with Ad26.COV2.S 
(5×1010 vp dose level), compared to the 
neutralizing antibody response to the original 
strain 
induced 
by single-dose primary 
vaccination with Ad26.COV2.S at the 
5×1010 vp dose level.
2. Non-inferiority 
of neutralizing 
antibody 
response to the leading variant of high 
consequence or concern* 14 days after booster 
vaccination with Ad26.COV2.S at the 5×1010 
vp dose level, ≥6 months after single-dose 
primary vaccination with Ad26.COV2.S 
(5×1010 vp dose level), compared to the 
neutralizing antibody response to the leading 
variant of high consequence or concern* 
induced by single-dose primary vaccination 
with Ad26.COV2.S at the 5×1010 vp dose level, 
if feasible. 
3. Non-inferiority 
of neutralizing 
antibody 
response to the original strain 14 days after 
booster vaccination with Ad26.COV2.S at the 
2.5×1010 vp dose level, ≥6 months after single- 
dose primary vaccination with Ad26.COV2.S 
(5×1010 vp dose level), compared to the 
neutralizing antibody response to the original 
strain induced by single-dose primary 
vaccination with Ad26.COV2.S at the 5×1010
vp dose level. 
4. 
Non-inferiority of neutralizing antibody 
response to the original strain 14 days after 
booster vaccination with Ad26.COV2.S at the 
1×1010 vp dose level, ≥6 months after single- 
dose primary vaccination with Ad26.COV2.S 
(5×1010 vp dose level), compared to the 
neutralizing antibody response to the original
strain induced by single-dose primary
vaccination with Ad26.COV2.S at the
5×1010 vp dose level.
5. 
Non-inferiority of neutralizing antibody
response to the original strain 14 days after
booster vaccination with Ad26.COV2.S at the
5×1010 vp dose level, ≥6 months after
completing a 2-dose primary vaccination with
Pfizer 
BNT162b2, 
compared 
to 
the
neutralizing antibody response to the original
strain induced by a 2-dose primary
vaccination with Pfizer BNT162b2.
6. 
Non-inferiority of neutralizing antibody
response to the leading variant of high
consequence or concern* 14 days after
booster vaccination with Ad26.COV2.S at the
5×1010 vp dose level, ≥6 months after
completing a 2-dose primary vaccination with
Pfizer 
BNT162b2, 
compared 
to 
the
neutralizing antibody response to the leading
variant of high consequence or concern*
induced by a 2-dose primary vaccination with
Pfizer BNT162b2, if feasible
7. 
Non-inferiority of neutralizing antibody
response to the original strain 14 days after
booster vaccination with Ad26.COV2.S at the
2.5×1010 vp dose level, ≥6 months after
completing a 2-dose primary vaccination with
Pfizer 
BNT162b2, 
compared 
to 
the
neutralizing antibody response to the original
strain induced by a 2-dose primary
vaccination with Pfizer BNT162b2.
8. 
Non-inferiority of neutralizing antibody
response to the original strain 14 days after
booster vaccination with Ad26.COV2.S atthe
1×1010 vp dose level, ≥6 months after
completing a 2-dose primary vaccination with
Pfizer 
BNT162b2, 
compared 
to 
the
neutralizing antibody response to the original
strain induced by a 2-dose primary
vaccination with Pfizer BNT162b2.
* 
As defined by the Centers for Disease Control and Prevention (CDC Aug 2021c) at the time of the analysis

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
20
Status: Approved,  Date: 20 April 2022
OVERALL DESIGN
This randomized, double-blind, parallel, multicenter study will assess the immunogenicity, reactogenicity
and safety of a booster dose of Ad26.COV2.S in adults 18 years of age, who have previously received
primary vaccination with Ad26.COV2.S or BNT162b2.
The primary immunogenicity endpoints are designed to sequentially show non-inferiority of the responses
after boosting with various doses of Ad26.COV2.S in volunteers either primed with Ad26.COV2.S at a
5×1010 vp dose level, or Pfizer BNT162b2, vs the neutralizing antibody responses to the primary 1-dose
regimen of Ad26.COV2.S which has shown efficacy in a prospective randomized Phase 3 efficacy trial.
This study will therefore attempt to show which booster regimens will induce neutralizing antibody
responses non-inferior to those seen with the Janssen 1-dose regimen of Ad26.COV2.S which has
demonstrated efficacy.
In Cohort 1, a target of approximately 770 participants who have received Ad26.COV2.S in study
VAC31518COV3001 (ENSEMBLE)will initially be randomized in a 1:1:1 ratio into 3 groups to receive a
1-dose booster vaccination regimen with Ad26.COV2.S  until the group 3 is fully enrolled. Thereafter,
randomization will continue in a 1:1 ratio in  groups 1 and 2 (see the table below). When at least
330 participants from Groups 1 to 3 in Cohort 1 have been enrolled, have completed the Day 15 visit and
it is estimated that immunogenicity data can be obtained from 110 or more participants in Group 1, an
interim analysis may be conducted whereby, if conducted, the formal non-inferiority testing of Cohort 1 –
Group 1 (Primary objectives 1a and 1b) will be performed on available data from the Cohort 1 –Group 1
participants. The other primary objectives will only be tested at the primary analysis.
In Cohort 2, a target of approximately 770 participants who have received primary vaccination with the
Pfizer BNT162b2 vaccine will initially be randomized in a 1:1:1 ratio into 3 groups to receive a 1-dose
booster vaccination regimen with Ad26.COV2.S until group 6 is fully enrolled. Thereafter, randomization
will continue in a 1:1 ratio in groups 4 and 5 (see table below).
Schematic Overview of Study Design and Groups
Cohort 
Group  
N 
Day 1
Vaccination
Cohort 1 
(Ad26.COV2.S 
primary vaccination)
1 
~ 330 
Ad26.COV2.S at 5×1010 vp
2 
~ 330 
Ad26.COV2.S at 2.5×1010 vp
3 
~ 110 
Ad26.COV2.S at 1×1010 vp
Cohort 2 
(BNT162b2 primary 
vaccination) 
4 
~ 330 
Ad26.COV2.S at 5×1010 vp
5 
~ 330 
Ad26.COV2.S at 2.5×1010 vp
6 
~ 110 
Ad26.COV2.S at 1×1010 vp
In Cohort 2 participants, the study vaccine will first be administered to 6 sentinel participants (2 participants
per group), enrolled at the same study site, to monitor for unexpected severe adverse reactions. The sentinel
participants will be vaccinated at least 1 hour apart and will be closely observed for a minimum of
30 minutes post-vaccination for the development ofacute reactions. Each sentinel participant is scheduled
to come to the site for a study visit on Day 2 (approximately 24 hours post-vaccination) to collect safety
data, which will include solicited AEs (collected through a e-Diary), unsolicited AEs, AESIs, and SAEs.
The collected data will be reviewed in a blinded manner by the principal investigator and the sponsor’s
study responsible physician/scientist. Randomization and vaccination of additional participants will be
halted until the review of sentinel data is completed. In the absence of clinically significant findings from
the review of 24-hour safety data from the sentinel participants, randomization  and vaccination will
continue in Cohort 2.
The study duration from screening until the last follow-up visit will be approximately 1 year per participant.
The study will consist of a 14-day screening phase, vaccination on Day 1, and follow-up visits up to 1 year
after booster vaccination (Target Visit Day 361±21 days).

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
21
Status: Approved,  Date: 20 April 2022
For each group, safety will be assessed by collection of solicited local (at injection site) and systemic AEs,
unsolicited AEs, AESIs, and SAEs. Other safety assessments include clinical laboratory assessments, vital
signs measurements (pulse/heart rate, preferably supine systolic and diastolic blood pressure, respiratory
rate, and body temperature) and physical examinations.
Active surveillance for COVID-19-like signs and symptoms will occur, including a COVID-19 surveillance
(symptom check) through the eCOA. All participants with COVID-19-like signs or symptoms meeting the
prespecified criteria for suspected COVID-19 and all participants with at least 1 positive RT-PCR test for
SARS-CoV-2 within 5 days of symptom onset, should undertake pre-specified COVID-19 procedures.
The Clinical Severity Adjudication Committee (CSAC) has been established and is tasked with reviewing
clinical and study information on cases of COVID-19 that occur in study participants during their time on
the study. The CSAC adjudicates the severity of each episode in line with the processes described in the
CSAC Charter. The CSAC's assessment of severity is considered the definitive classification of severity for
each case. Re-adjudication can occur if new/updated information for a case becomes available. The final
adjudication of a case by the CSAC determines its severity for analysis.
The first ~330 randomized participants in each of the cohorts will be assigned to 1 of 4 blood collection
subsets (Subsets 1, 2, 3 and 4). Blood samples will be collected for immunogenicity assessments as shown
in the tables below. Once the 4 blood collection subsets are enrolled, subsequent participants will not be
assigned to a subset. Participants not assigned to a subset (‘non-subset’ in table below) will have
immunogenicity samples taken at Day 1, Day 15, Day 120, Day 181 and Day 361.
Blood Collection Schedule (Whole Blood) for Humoral and Cellular Immunogenicity Assessments
Cohort 
Group  
Day 
1ab 
Day 
2a,b 
Day 
8ab 
Day 
15ab 
Day 
29a 
Day 
71 
Day 120 
Day 181 
Day
361
1 
1 
All 
Subset 3 
(N ~27) 
Subset 1 
(N ~27) 
All 
Subset 2 
(N ~28) 
Subset 3 
(N ~27) 
Non
Subsetc 
(N ~380)
All 
All
2 
All 
Subset 3 
(N ~27) 
Subset 1 
(N ~27) 
All 
Subset 2 
(N ~28) 
Subset 3 
(N ~27) 
All 
All
3 
All 
Subset 3 
(N ~27) 
Subset 1 
(N ~27) 
All 
Subset 2 
(N ~28) 
Subset 3 
(N ~27)
All 
All
2 
4 
All 
Subset 3 
(N ~27) 
Subset 1 
(N ~27) 
All 
Subset 2 
(N ~28) 
Subset 3 
(N ~27) 
Non
Subsetc 
(N ~380)
All 
All
5 
All 
Subset 3 
(N ~27) 
Subset 1 
(N ~27) 
All 
Subset 2 
(N ~28) 
Subset 3 
(N ~27) 
All 
All
6 
All 
Subset 3 
(N ~27) 
Subset 1 
(N ~27) 
All 
Subset 2 
(N ~28) 
Subset 3 
(N ~27)
All 
All
a. Selected timepoints include samples for PAXgene analysis.
b. Selected time points include samples for cytokine analysis (Subset 1, 2 and 3 only).
c. Day 120 blood draw only for participants not allocated to a subset
Blood Collection Schedule (PBMCa) for Cellular Immunogenicity Assessments
Cohort 
Group  
Day 1 
Day 15 
Day 181 
Day 361
1 
1 
Subset 4 
(N ~28) 
Subset 4 
(N ~28) 
Subset 4 
(N ~28) 
Subset 4
(N ~28)
2 
Subset 4 
(N ~28) 
Subset 4 
(N ~28) 
Subset 4 
(N ~28) 
Subset 4
(N ~28)
3 
Subset 4 
(N ~28) 
Subset 4 
(N ~28) 
Subset 4 
(N ~28) 
Subset 4
(N ~28)
2 
4 
Subset 4 
(N ~28) 
Subset 4 
(N ~28) 
Subset 4 
(N ~28) 
Subset 4
(N ~28)
5 
Subset 4 
(N ~28) 
Subset 4 
(N ~28) 
Subset 4 
(N ~28) 
Subset 4
(N ~28)
6 
Subset 4 
(N ~28) 
Subset 4 
(N ~28) 
Subset 4 
(N ~28) 
Subset 4
(N ~28)
a. Blood collection for PBMC will be performed in a subset of participants in all groups (Subset 4), if PBMC analysis is
feasible.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
22
Status: Approved,  Date: 20 April 2022
From external sources, the sponsor will obtain serum samples of approximately 300 individuals collected
2 weeks to 2 months after completion of the 2-dose primary vaccination with Pfizer BNT162b2. These
samples will be used to assess NI of the seropositivity rate induced by a Ad26.COV2.S booster following
a primary Pfizer BNT162b2 regimen to the seropositivity post a primary Pfizer BNT162b2 regimen.
Safety issues and concerns will be presented to the Independent Data Monitoring Committee (IDMC) , as
appropriate. .
NUMBER OF PARTICIPANTS
Overall, a target ofapproximately 770 adult participants aged 18 years, who have received Ad26.COV2.S
in study COV3001 will be enrolled in the study. In addition, a target of approximately 770 participants who
have completed primary vaccination with the 2-dose Pfizer BNT162b2 regimen will be enrolled.
DOSAGE AND ADMINISTRATION
Ad26.COV2.S will be supplied at a concentration of 1×1011 vp/mL, as suspensions in single-use vials. The
study will assess 3 dose levels of Ad26.COV2.S: 5×1010 vp, 2.5×1010 vp and 1×1010 vp. Details on study
vaccine administration are provided in the Investigational Product Preparation Instructions [IPPI]).
Formulation buffer will be supplied as diluent.
MONITORING FOR ASYMPTOMATIC SARS-COV-2 INFECTION
Analysis of antibodies binding to the SARS-CoV-2 N protein will be measured at Day 1 by non-S-protein
assays (eg, N protein ELISA and/or SARS-CoV-2 immunoglobulin assay that is dependent on the
SARS-CoV-2 N protein).
IMMUNOGENICITY EVALUATIONS
Venous blood samples will be collected for assessment of humoral and cellular immune responses as
detailed in the Schedule of Activities.
From external sources, the sponsor will obtain serum samples of approximately 300 individuals collected
2 weeks to 2 months after completion of the 2-dose primary vaccination with Pfizer BNT162b2. These
samples will be used to assess NI of the seropositivity rate induced by a Ad26.COV2.S booster following
a primary Pfizer BNT162b2 regimen to the seropositivity post a primary Pfizer BNT162b2 regimen.
Immunogenicity assays are summarized in the tables below.
Summary of Humoral Immunogenicity Assays
Assay 
Purpose
Primary/Secondary endpoints
SARS CoV 2 neutralization (VNA) 
Analysis of neutralizing antibodies to the live SARS CoV 2 original strain and leading
variant of high consequence or concern* using a live VNA and/or pseudovirion
expressing S protein neutralization assay
Secondary endpoints
SARS CoV 2 neutralization (VNA)
Analysis of neutralizing antibodies to additional relevant live SARS CoV 2 variants of
concern and/or pseudovirion expressing S protein from SARS CoV 2 variants of
concern
SARS CoV 2 binding antibodies
(ELISA and/or MSD)
Analysis of antibodies binding to SARS CoV 2 or individual SARS CoV 2 proteins
(eg, S and RBD proteins from the SARS CoV 2 original strain, leading variant of high
consequence or concern* and/or other variants of concern)
Exploratory endpoints
SARS CoV 2 neutralization
(neutralization assay)
Analysis of neutralizing antibodies to the vaccine strain (or other strain), as measured
by an alternative neutralization assay (different from the VNA used for the primary
and secondary endpoint)
Adenovirus neutralization
(neutralization assay)
Analysis of neutralizing antibodies to adenovirus

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
23
Status: Approved,  Date: 20 April 2022
Assay 
Purpose
SARS CoV 2 binding antibodies 
Analysis of antibodies binding to SARS CoV 2 or individual SARS CoV2 proteins
(eg, S and RBD proteins from the SARS CoV 2 original strain, leading variant of high
consequence or concern* and/or other relevant variants of concern)measured by an
alternative binding antibody assay (different from the binding antibody assay used in
the secondary endpoints)
Functional and molecular antibody 
characterization 
Analysis of antibody characteristics including Fc mediated viral clearance, avidity, Fc
characteristics, Ig subclass and IgG isotype directed against the original SARS CoV 2
strain, leading variant of high consequence or concern* and/or other variants of
concern
Epitope specificity characterization 
Analysis of site specificity, epitope mapping
Cytokine profiling 
Analysis of cytokines, chemokines, and other proteins of the innate or adaptive
immune response in the serum or plasma
Passive transfer 
Analysis of immune mediators correlating with protection against experimental SARS
CoV 2 challenge in a suitable animal model
ELISA  enzyme linked immunosorbent assay; Ig  immunoglobulin; MSD  Meso Scale Discovery; RBD  receptor binding
domain; S  spike; SARS CoV 2  severe acute respiratory syndrome coronavirus 2; VNA  virus neutralization assay
* As defined by the Centers for Disease Control and Prevention (CDC Aug 2021c) at the time of the analysis
Summary of Cellular Immunogenicity Assays
Assay 
Purpose
Exploratory endpoints
Flow cytometry (ICS) 
Analysis of T cell responses to SARS CoV 2 S protein peptides from the original strain,
leading variant of high consequence or concern* and/or other variants of concern by ICS
including CD4+/CD8+, IFNγ, IL 2, TNFα, IL 4, IL 5, IL 13, and/or other Th1/Th2 markers
(if feasible)
ELISpot 
IFNγ and IL 4 responses to SARS CoV 2 S protein peptides by PBMCs (if feasible), based
on single or dual ELISpot
Gene expression analysis 
Analysis of gene expression by RNA transcript profiling and/or analysis of protein
translates, in cells or whole blood stimulated with SARS CoV 2S protein peptides or in
unstimulated cells or whole blood (ex vivo)
ELISpot  enzyme linked immunospot (assay); ICS  intracellular cytokine staining; IFNγ  interferon gamma; IL
 interleukin;
PBMC  peripheral blood mononuclear cell; S  spike; SARS CoV 2  severe acute respiratory syndrome coronavirus 2;
Th
T helper; TNFα  tumor necrosis factor alpha
* As defined by the Centers for Disease Control and Prevention (CDC Aug 2021c) at the start of sample analysis
SAFETY EVALUATIONS
After booster vaccination, participants will remain under observation at the study site for at least 30 minutes
to monitor for acute reactions and solicited events. Participants will be asked to note in the e-Diary
occurrences of injection site pain/tenderness, erythema and swelling at the study vaccine injection site daily
for 7 days post-vaccination (day of vaccination and for the subsequent 7 days). Participants will be
instructed on how to record daily temperature using a thermometer provided for home use.
Participants should record the temperature in the e-Diary in the evening of the day of vaccination, and then
daily for the next 7 days approximately at the same time each day. Participants will also be instructed on
how to note signs and symptoms in the e-Diary on a daily basis for 7 days post-vaccination (day of
vaccination and for the subsequent 7 days), for the following events: fatigue, headache, nausea, and
myalgia.
Adverse events and special reporting situations, whether serious or non-serious, that are related to study
procedures or that are related to non-investigational sponsor products will be reported from the time a
signed and dated informed consent form (ICF) is obtained until the end of the study/early withdrawal. All
other unsolicited AEs will be reported from the time of vaccination until 28 days post-vaccination. All
AESIs, SAEs, and AEs leading to discontinuation from the study (regardless of the causal relationship) are
to be reported from the moment of vaccination until completion of the participant’s last study-related
procedure.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
24
Status: Approved,  Date: 20 April 2022
Thrombosis with thrombocytopenia syndrome (TTS) is considered to be an AESI (Adverse Event of Special
Interest). Suspected AESIs (thrombotic events and thrombocytopenia [defined as platelet count below
150,000/µLa])will be reported from the moment of vaccination until the end of the study/early withdrawal.
An AESI Adjudication Committee with appropriate expertise will be established to evaluate each suspected
AESI and determine whether it meets the definition of TTS.
Any participants who receive a Covid-19 booster vaccine off study will remain on study (continuing with
all scheduled procedures and follow-up) but will be excluded from the formal hypothesis testing of the
primary objectives.
STATISTICAL METHODS
Sample Size Determination
The following assumptions were made in the sample size determinations:
For the non-inferiority comparisons based on seroresponse rate:
 
Under the null hypothesis, a 90% responder rate on Day 15 post -booster and a 90% responder rate
on Day 29 post primary vaccination
 
Non-inferiority margin of -10% for the difference between 14 days post-booster and 28 days post
primary vaccination responder rate on Day 29
 
Farrington & Manning Likelihood Score Test used in the non-inferiority testing of the difference
between the two responder rates
For the non-inferiority comparisons based on GMT:
 
Log transformed (log10 scale) VNA data are normally distributed
 
A standard deviation (SD) of VNA = 0.56 (log10 scale)
 
Under the null hypothesis, a GMT ratio (Day 15 post-booster/Day 29 post primary regimen) of 1.0
 
Non-inferiority margin = log10(2/3) = -0.176 for the GMT ratio testing
 
No correlation between immune responses 28 days post-dose 1 and 14 days post-booster
In addition, a drop-out rate approximately 10% is assumed.
With the above assumptions, the required sample size to achieve approximately 95% power to demonstrate
non-inferiority, at alpha 0.025 (1-sided), of primary hypothesis 1a is N=297 (N=330 adjusted for the 10%
dropout). With this sample size, the power to demonstrate non-inferiority of response rate is 98% and the
power to demonstrate non-inferiority of the geometric mean ratio (GMR) is 97%, resulting in a combined
power of approximately 95%.
Similarly, the required sample size to achieve 90% power to demonstrate the non-inferiority, at alpha
0.0125 (1-sided), of the remaining primary hypotheses is N=297 (N=330 adjusted for the 10% dropout).
With this sample size, the power to demonstrate non-inferiority of response rate is 95% and the power to
a Updated Proposed Brighton Collaboration process for developing a standard case definition for study of new clinical
syndrome X, as applied to Thrombosis with Thrombocytopenia Syndrome (TTS). 18 May 2021.
https://brightoncollaboration.us/wp-content/uploads/2021/05/TTS-Interim-Case-Definition-v10.16.3-May-23-
2021.pdf.Accessed: 02 September 2021.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
25
Status: Approved,  Date: 20 April 2022
demonstrate non-inferiority of the geometric mean ratio (GMR) is 94%, resulting in a combined power of
approximately 90%.
When at least 330 participants from Groups 1 to 3 in Cohort 1 have been enrolled, have completed the
Day 15 visit and it is estimated that immunogenicity data can be obtained from 110 or more participants in
Group 1, an interim analysis may be conducted whereby, if conducted, the formal non-inferiority testing of
Cohort 1 –Group 1 (Primary Objectives 1a and 1b) will be performed on the available data from the Cohort
–Group 1 participants. If the interim analysis is conducted, an O’Brien-Fleming adjustment will be used
whereby the type I error for the non-inferiority test at the interim analysis is 0.0003 (one-sided) and at the
final analysis 0.0249. Because an O’Brien-Fleming adjustment is used, the total sample size is not increased
for this interim analysis.
Populations for Analysis Sets
For purposes of analysis, the following populations are defined:
FAS: The full analysis set will include all participants with a documented study vaccine administration
(Ad26.COV2.S). Analyses of safety and reactogenicity will be performed on the FAS.
PPI: The per protocol immunogenicity population will include all vaccinated participants for whom
post-baseline immunogenicity data are available excluding participants with major protocol deviations
expected to impact the immunogenicity outcomes. In addition, samples obtained after natural SARS-CoV-2
infection (if applicable) will be excluded from the analysis.
NI: The NI analysis set will include all PPI participants who are SARS-COV-2 seronegative at baseline
(based on the serological test for SARS CoV-2-specific nucleocapsid antibodies [N serology]). The NI
hypothesis tests, as well as descriptive analysis of secondary endpoints for other VOCs, will be performed
on the NI analysis set.
PPE: The per protocol for efficacy analysis set will include all vaccinated participants who are SARS-
CoV-2 seronegative at baseline and who have no major protocol deviations expected to impact the efficacy
outcomes.
Pfizer BNT162b2 external samples: serum samples from external sources of approximately 300
individuals collected 2 weeks to 2 months after completion of the 2-dose primary vaccination with Pfizer
BNT162b2. These samples will be used for NI assessments for Cohort 2.
Primary Endpoints
Immunogenicity Endpoints
For NI assessments of primary objectives 1a and 1b (evaluated at the interim or primary analysis), the
Ad26.COV2.S booster vaccine at the 5×1010vp dose level against the original strain (objective 1a) and
leading variant of concern (objective 1b) at 14 days post booster as compared to the Ad26.COV2.S vaccine
against the original strain (objective 1a) and leading variant of concern (objective 1b) at 28 days post-
vaccination, two NI hypothesis tests will be performed:
1. 
Statistical NI of responder rate, with a margin of -10%: the difference in responder rate between
post booster minus post prime will be estimated, with a 100*(1-2*α)% CI. Non-inferiority for
responder rate will be demonstrated if the 2-sided 100*(1-2*α)% CI lies entirely above -10%.
2. 
Statistical NI of GMTs, with a margin of 1.5-fold: the ratio of the GMTs (post booster GMT
divided by post prime GMT, i.e; the Geometric Mean Ratio [GMR]) will be estimated, with
the corresponding 100*(1-2*α)%  CI. Non-inferiority will be demonstrated if the 2-sided
100*(1-2*α)% CI of the estimated GMT ratio lies entirely above 2/3.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
26
Status: Approved,  Date: 20 April 2022
3. 
In addition to the above, an estimated GMR (GMT Day 15 post-booster/GMT Day 29 post
primary regimen) of >0.8 is required to conclude NI.
For objective 1a and 1b, at the interim analysis (if conducted), an O’Brien-Fleming adjustment will be used,
α=0.0003 and a 99.4% CI will be calculated. At the primary analysis, α=0.0249 and a 95.02% CI will be
calculated, if the interim analysis is conducted. Otherwise, α=0.025 and a 95% CI will be calculated.
Similar non-inferiority criteria will be used for the remaining primary objectives 1c, 1d, 2a, 2b, 2c and 2d
(evaluated only at the primary analysis), except that 97.5% CI will be used for both the responder rate and
GMT hypothesis testing. A hierarchical testing strategy will be applied.
For primary objectives 1a, 1b, 1c and 1d, formal NI testing will be conducted as a “within-subjects”
analysis, in which participants’ VNA data are considered matched pairs across the two time points. The NI
analysis on responder rate will be based on the Agresti-Min (Agresti 2005) method to estimate the
difference in proportions and its CI. This method was chosen because of its well-behaved coverage
probability (CP) properties compared to other methods for the analysis of matched pairs data (Reed 2009).
Coverage probability is generally used to evaluate (1 –α) CIs where α is the Type I error rate. The NI
analysis on the GMR will use a paired t-test to estimate the difference in means and its CI on log10
transformed data. The estimated difference and its CI will be back transformed to yield the GMT ratio
(GMR) and its CI.
As a sensitivity analysis, 28 days post-dose 1 VNA data may be pooled across the three study arms and
compared to the 14 days post booster VNA data in the study arm of interest. This sensitivity analysis will
use appropriate statistical models, such as linear mixed models for the GMR and Generalized Estimating
Equations (GEE) models for the difference in responder rates.
For primary objectives 2a, 2b, 2c and 2d relating to Cohort 2, formal NI testing will be conducted by
comparing VNA data from external samples, collected 2 weeks to 2 months after completing a 2-dose
primary vaccination with Pfizer BNT162b2, compared to the 14 days post booster VNA data in the study
arm of interest (groups 4, 5 or 6).
Secondary Endpoints
No formal statistical testing of safety data is planned. Safety data will be analyzed descriptively by vaccine
group. All safety analyses will be made on the FAS. The immunogenicity analyses will be performed on
the PPI and FAS population.
Descriptive statistics (geometric mean and CIs, or median and interquartile range Q1-Q3, as appropriate)
will be calculated for continuous immunologic parameters. Several definitions of serological response will
be applied as applicable (GMC [S-ELISA], GMT [VNA]). Graphical representations of immunologic
parameters will be made as applicable. Frequency tabulations will be calculated for discrete (qualitative)
immunologic parameters, as applicable.
In addition, the ratio between neutralizing and binding antibodies as determined by VNA and S-ELISA,
respectively, will be calculated together with CIs.
Planned Analysis
When at least 330 participants from Groups 1 to 3 in Cohort 1 have been enrolled, have completed the Day
15 visit and it is estimated that immunogenicity data can be obtained from 110 or more participants in
Group 1, an interim analysis may be conducted whereby, if conducted, the formal non-inferiority testing of
Cohort 1 –Group 1 (Primary Objectives 1a and 1b) will be performed on the available data from the Cohort
1 –Group 1 participants. The other primary objectives will only be tested at the primary analysis.
The primary analysis of safety and immunogenicity in Cohort 1 or Cohort 2 will be performed when all
evaluable participants in the respective cohort have completed the visit that takes place 28 days after study

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
27
Status: Approved,  Date: 20 April 2022
vaccination or discontinued earlier. The analysis will include immunogenicity data (VNA, N-serology, and
S-ELISA and/or MSD [if available at the time of analysis]) for all evaluable participants through Day 15
and all available safety data. The sponsor will be unblinded at the time of this primary analysis, with the
exception of specific sponsor personnel (see below). If the primary analysis of Cohort 1 is performed before
the primary analysis of Cohort 2, then the sponsor will be unblinded only for Cohort 1 at the time of the
Cohort 1 primary analysis, and unblinded for only Cohort 2 at the time of the primary analysis of Cohort 2.
For the primary analysis, and for any analyses after the primary analysis on the same cohort(s), unblinded
data at the participant level will be available to sponsor personnel including statistical programming,
statistics, clinical and clinical immunology personnel involved in the analysis, and the sponsor committee
involved in making future decisions for the program. Sponsor personnel directly involved in data collection,
data management, and safety monitoring will not have access to unblinded data at the participant level until
the study end. Sites and study participants will not have access to unblinded data at the participant level
until the end of study, with two exceptions. Firstly, the investigator may, in an emergency, determine the
identity of the intervention. Secondly, the sponsor may unblind the study at selected sites after all
participants still on study at those sites have reached the 6-month post booster timepoint, to generate a list
of participants who may be eligible for enrollment into the sponsor-supported VAC31518COV2015 study.
Group level data may be shared with investigators or other blinded clinical staff, as needed, but every effort
will be made to preserve the blinding to the individual participant allocation until the end of study.
The final analysis in Cohort 1 or Cohort 2 will be performed when all included participants in the respective
cohort have completed their last visit or discontinued earlier
There are no planned formal assessments of efficacy in this study. However, data on molecularly confirmed
SARS-CoV-2 infections, N protein binding antibodies and COVID-19-like signs and symptoms will be
reported after the primary analysis, and relative efficacy may be estimated as permitted by the available
data.
After the Primary Analysis, additional Interim Analyses may be performed by the sponsor as required.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
28
Status: Approved,  Date: 20 April 2022
1.2. 
Schema
Figure 1: 
Schematic Overview of the Study
D= Day, N= number of participants in each vaccine group, NI = non-inferiority

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
29
Status: Approved,  Date: 20 April 2022
1.3. 
Schedule of Activities
1.3.1. 
All Participants
Phase 
Screeninga 
Follow-upb
Clinic Visit # 
1 
2 
3w
4u 
5 
6v 
7w 
7Abb
8 
9aa
10
Exitx
Visit Timing 
Vac
Vac 
+1d  
Vac 
+ 7 d  
Vac 
+ 14 d  
Vac 
+ 28 d  
Vac 
+ 70 d  
Vac 
+ 119 d 
Vac 
+ 180 d  
Vac 
+ 270 
Vac
+ 360 d
Visit Day ±Window  
-14 to 1 
1 
2 
8±2c 
15 -3/+7 
29 -3/+10 
71±14 
120±14 
181±21 
271±21aa  
361±21
Visit Type 
Screening 
Vaccine 
Safety  
Safety 
and 
immuno 
Safety 
and 
Immuno 
Safety and 
immuno/Safety
phone call
Safety and
immuno
Safety and
immuno
Safety and
immuno
Safety
phone
callaa  
Safety
and
immuno
Early
Exit
Written informed consentd 

Inclusion/exclusion criteria 
 
1
Demographics 

Medical history/prestudy meds 

Physical examinatione 

Vital signsfincl. body temperature 
 
2 

Subset 3 
 
Subset 1 
 
All 
 
Subset 2 
 
Subset 3 
 
No Subset 
 
All 
 

All

Pregnancy test (for participants of
child bearing potential only)

 
 
 
 
 
 
 
 
 
Randomization 
1
Prevaccination checkg 
1
Clinical laboratory blood sample 
(whole blood)i 
 
1

All
Serological test for SARS‑CoV 2
specific nucleocapsid antibodies 
(based on N serology) 
1  
 
 
 
All 
 
Subset 2 
 
Subset 3 
 

No Subset
 
All 
 

All

All
Humoral immunity (serum), blood 
draw  
1 
All 
 
 
Subset 1 
 
All 
 
Subset 2 
 
Subset 3 
 
No Subset 
 
All  
 

All
3
Cellular immunity (PBMC), blood 
draw  
j 
1 
Subset 4 
 
Subset 4 
 
 
 
Subset 4 
 

Subset 4
Blood draw for exploratory
researchz 
1  
 
 
 
 
 


 
 

3
RNA Sequencing (whole blood, 
PAXgene® tubes) 
1 All
 
Subset 3 
 
Subset 1 
 
All 

Subset 2
 
 
 
 
 
Cytokines, blood draw
1
Subset
1,2&3

Subset 3

Subset 1 

Subset 2
 
 
 
 
 
 
Nasal sample collection for SARS
CoV 2 testingk
1
 
 
 
 
 
 
 
Vaccination 

30 minute post vaccination
observationl 


VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
31
Status: Approved,  Date: 20 April 2022
f. 
Pulse/heart rate, systolic and diastolic blood pressure, respiratory rate, and body temperature. Blood pressure measurements should be taken in the supine position
(preferably) and preceded by at least 5 minutes of rest. Vital signs measurements are recommended before blood sampling. Body temperatures will be measured
preferably via the oral route.
g. 
Investigator must check for acute illness or body temperature ≥38.0°C/100.4°F at the time of vaccination. If any of these events occur at the scheduled time for
vaccination, the vaccination can be rescheduled as long as this is in agreement with the allowed window. If the vaccination visit cannot be rescheduled within the
allowed window or the contraindications to vaccination persist, the sponsor should be contacted for further guidance. The investigator should also check if any
other reasons have been met and would prevent study vaccination.
h. 
eCOA set up and training to be provided for Cohort 2 participants. eCOA set up and training will have been conducted for all COV3001 participants. If required,
retraining will be provided for Cohort 1 COV2008 participants. All COV2008 participants will complete the eCOA using an application on their own eDevice
(smartphone or tablet) if their device is compatible with the application or using the web portal. All eCOA assessments should be conducted/completed before any
tests, procedures, or other consultations to prevent influencing participant responses. If a participant is unable to complete the eCOA, a study staff member or the
participant’s caregiver can collect information on the participant’s behalf as detailed in Section 8.1.2.
i. 
Whole blood samples will be used for a platelet count (as part of a complete blood count if applicable) in a local laboratory or substitute for local laboratory,
depending on local feasibility towards turnaround time of sample processing. Results are to be reported in the eCRF. Serum and plasma samples will be derived
from the whole blood sample and stored for potential future coagulation-related testing in a central laboratory if the participant experiences a suspected AESI (see
Appendix 2).
j. 
Collection of blood samples for PBMC analysis will be performed in a subset of participants in all groups (Subset 4), if PBMC analysis is feasible.
k. 
Nasal swabs to be batch tested centrally (result is NOT required for randomization).
l. 
Participants will be closely observed for a minimum of 30 minutes post-vaccination. Any solicited local (at injection site) and systemic AEs, unsolicited AEs,
AESIs, SAEs, concomitant medications, and vital signs will be documented by study-site personnel following this observation period and participants will be
allowed to leave the study site after it is documented that the 30-minutes post-vaccination observation period is complete.
m. AEs and special reporting situations that are related to study procedures or that are related to non-investigational sponsor products will be reported from the time a
signed and dated ICF is obtained until the end of the study/early withdrawal. All other unsolicited AEs and special reporting situations will be reported from the
time of vaccination until 28 days post-vaccination.
n. 
All SAEs related to study procedures or non-investigational sponsor products will be reported for all participants from the time a signed and dated ICF is obtained
until the end of the study/early withdrawal. All other SAEs are to be reported for all participants from the moment of vaccination until completion of the
participant’s last study-related procedure. AEs leading to study discontinuation are to be reported from the moment of vaccination until completion of the
participant’s last study-related procedure. Suspected AESIs are to be reported from the moment of vaccination until completion of the participant’s last study-
related procedure (see Section 8.4.1).
o. 
Cohort 1 participants will have received COVID-19-like Symptom surveillance booklet, nasal swab kit and saliva sample training for COV3001. If required,
replacement kits and/or retraining will be provided prior to booster vaccination. Booklet, nasal swab kit and training to be provided to Cohort 2 participants.
p. 
The SIC questionnaire asks the participant if he/she had any of the prespecified signs or symptoms (see Appendix 5)during the past 24 hours (including highest
temperature in the last 24 hours), and (when applicable) to rate the severity. If a participant develops COVID-19-like signs and symptoms, refer to Section 1.3.3
and Section 8.1.2.
q. 
Concomitant therapies such as analgesic/antipyretic medications and non-steroidal anti-inflammatory drugs, corticosteroids, antihistamines, and vaccinations must
be recorded from the moment of vaccination until 28 days after administration of study vaccine. All other concomitant therapies should also be recorded if
administered in conjunction with a confirmed COVID-19 case or with new or worsening AEs reported per protocol requirements outlined in Section 8.4.1.
r. 
The e-Diary, a ruler and thermometer to be distributed to Cohort 2 participants. Materials will have been distributed to Cohort 1 participants for COV3001,
replacement materials and/or retraining will be provided if required.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
32
Status: Approved,  Date: 20 April 2022
s. 
Pulse oximeters to be provided to Cohort 2 participants at their baseline visit to measure blood oxygen saturation and pulse rate during a COVID-19 episode (see
Section 1.3.3). All Cohort 1 participants will have been provided a pulse oximeter at their baseline COV3001 visit, any misplaced/malfunctioning oximeters will
be replaced prior to booster vaccination on study COV2008.
t. 
If an event is still ongoing 7 days after the vaccination, the participant should continue to collect information in the diary until resolution.
u. 
Visit for participants in immunogenicity subset 1 only.
v. 
Visit for participants in immunogenicity subset 2 only and a phone call will be made to the participants not in immunogenicity subset 2 to confirm the collection of
unsolicited AEs.
w. Visit for participants in immunogenicity subset 3 only. Window for Visit 3 is 24 hours post vaccination for sentinel participants and 24 to 72 hours post vaccination
for non-sentinel participants.
x. 
For those participants who are unable to continue participation in the study up to Visit 7, but for whom consent is not withdrawn, who are not lost to follow-up, or
who have not died, an early exit visit will be conducted as soon as possible. Participants who wish to withdraw consent from participation in the study will be
offered an optional visit for safety follow-up. This includes the safety assessments of the early exit visit (no blood sampling for immunogenicity).
y. 
MA-COV form to be provided to Cohort 2 participants at the vaccination visit. The MA-COV form (Appendix 7) will have been provided to all Cohort 1
participants at the COV3001vaccination visit. If needed, a new form should be provided prior to booster vaccination on study COV2008. The MA-COV form
should be completed by the medical care provider or the study site personnel during medical visits for COVID-19 or COVID-19 complications.
z. 
Only applicable to participants enrolled at the BIDMC site.
aa. The site staff will phone the participants to ensure retention and to check on the occurrence of SAEs, AESIs or MAAEs.
bb. Only for participants not assigned to a blood drawing subset, and participants enrolled at BIDMC.
AE = adverse event; AESI = adverse event of special interest; COVID-19 = coronavirus disease-2019; d = day(s); eCOA= electronic clinical outcome assessment; eCRF
= electronic case report form, ICF = informed consent form; PBMC = peripheral blood mononuclear cell; SAE = serious adverse event; SARS‑CoV-2 = severe acute
respiratory syndrome coronavirus‑2; SIC = Symptoms of Infection with Coronavirus-1; vac = vaccination.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
33
Status: Approved,  Date: 20 April 2022
1.3.2. 
Participants with a Suspected AESI
The medical management of thrombotic events with thrombocytopenia is different from the management of isolated thromboembolic diseases. Study site
personnel and/or treating physicians should follow available guidelines for treatment of thrombotic thrombocytopenia (eg, from the American Society of
Hematology 2021; British Society of Haematology - Expert Haematology Panel 2021, and the CDC 2021d). The use of heparin may be harmful and
alternative treatments may be needed. Consultation with a hematologist is strongly recommended. Management of the participant should not be delayed
by decision-making of the AESI Adjudication Committee. In the event of a suspected thrombotic event, thrombocytopenia, or TTS, laboratory assessments
(to be performed locally) are required to facilitate diagnosis and determine treatment options, including but not limited to platelet count and anti-PF4 tests.
Additional blood samples should be collected for central laboratory testing as detailed below. However, results of central laboratory testing may not be
available to guide immediate treatment decisions.
a. Day 1 refers to first awareness of the event, which might be later than the date of onset. Every effort should be made to report as much information as possible about
the event to the sponsor in a reasonable timeframe. The investigator should contact the sponsor for input on the feasibility of collecting blood samples, including the
need for additional samples based on the nature of the event.
b. Day 29 is to be calculated relative to the actual day of onset of the event. If the event is not resolved on Day 29, subsequent follow-up assessments can be performed
at unscheduled visits as needed until resolution of the event. If the event is reported to the investigator more than 28 days after the onset of the event, the AESI Day 29
visit becomes redundant and does not need to be performed.
c. Suspected AESIs must be reported to the sponsor within 24 hours of awareness, irrespective of seriousness (ie, serious and non-serious AEs) or causality assessment,
using the SAE form (see Section 8.4.7).
d. Whole blood samples will be used for a platelet count (as part of a complete blood count, if applicable) in a local laboratory or substitute for local laboratory, depending
on local feasibility towards turnaround time of sample processing. Results are to be reported in the eCRF. Serum and plasma samples will be derived from the whole
blood sample for coagulation-related testing in a central laboratory (see Appendix 2). For the follow-up visit, the volume of blood to be collected may vary depending
on the clinical evaluation of the case.
e. Medical information on local case management will be collected. Upon becoming aware of the suspected AESI, study site personnel should provide information on
an ongoing basis. See Section 8.4.7 and Appendix 11 for further details.
f. Refer to Section 6.7 for collection and recording of concomitant therapies associated with a suspected AESI.
AE =adverse event; AESI = adverse event of special interest; CDC = Centers for Disease Control and Prevention; PF4 = platelet factor 4; TTS = thrombosis with
thrombocytopenia syndrome
Timing relative to onset of suspected AESI
AESI 
Day 1a 
AESI
Day 29b 
Visit window  
±7 d
Site to report AESIc 

Clinical lab blood sample (whole blood)d 
 

TTS AESI forme 
- - - - Continuous- - - - -
Concomitant therapiesf 
 


VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
35
Status: Approved,  Date: 20 April 2022
c. Participants should be encouraged by the site to collect nasal swabs and saliva samples as indicated in the Schedule of Activities. Ifthe participant is unable or
unwilling to collect all samples as requested, the participant should still complete the other COVID-19 assessments, including the visit at COVID-19 Day 29.
d. As soon as it is confirmed that both nasal swabs (collected on COVID-19 Day 1-2 and COVID-19 Day 3-5) are negative for SARS-CoV-2, the participant will not
undertake any further COVID-19 procedures and will fall back to the default Schedule of Activities, until the end of the study/early withdrawal.
e. Participants should undertake the COVID-19 procedures until 14 days after symptom onset (COVID-19 Day 15) or until resolution of the COVID-19 episode,
whichever comes last. Resolution of a COVID-19 episode is defined as having 2 consecutive SARS-CoV-2 negative nasal swabs and 2 consecutive days with no
COVID-19-related signs or symptoms. Once past COVID-19 Day 15, participants should stop the collection of nasal swabs and saliva samples as soon as
2 consecutive nasal samples are SARS-CoV-2 negative, but (if still symptomatic at that time) should continue completing the ePROs (including SIC, body
temperature, and pulse oximetry) in the eCOA until 2 consecutive days with no COVID-19-related signs or symptoms (Section 8.1.1).
f. 
Only applicable for participants that have at least 1 SARS-CoV-2 positive nasal swab collected on COVID-19 Day 1-2 or Day 3-5. COVID-19 Day 29 visit should
still be performed even if the nasal swabs results are still pending.
g. The visit on COVID-19 Day 29 can be combined with a regular study visit if within the applicable visit windows.
h. The COVID-19 Day 1-2 nasal swab can be collected at the study site (or hospital or other location, if needed), if preferred by the participant.
i. 
All COVID-19 Day 3-5 and Day 29 assessments may be performed by a trained HCP at the participant’s home, if allowed per local and/or institutional regulations.
j. 
If a participant has a positive test result for SARS-CoV-2 infection and/or depending on the medical status of the participant, the participant may be requested to
remain at home and not visit the study site. If necessary, study-site personnel or a trained HCP will visit the participant at home (or at the hospital or other location,
if needed), if allowed by local regulations. Under these circumstances, the participant will be contacted by the site at least once per week and the participant’s
medical care provider will be notified.
k. In case of COVID-19 like symptoms, based on the information collected through the SIC, the site will reach out to the participant at the latest on COVID-19 Day 2
(the day after the day of symptom onset) to assess whether the reported signs and symptoms qualify as a suspected COVID-19 episode using prespecified criteria
(Section 8.1.1). As several of the prespecified criteria for suspected COVID-19 overlap with vaccine-related reactogenicity, investigators’ clinical judgement is
required to exclude vaccine-related events. In case the participant would actively reach out to the site already on COVID-19 Day 1, the site should already make a
first assessment on COVID-19 Day 1 to check whether the reported signs and symptoms qualify as a suspected COVID-19 episode using prespecified criteria
(Section 8.1.1).
l. 
In case of COVID-19 like symptoms, the site will interview the participant to assess whether the reported signs and symptoms still qualify as a suspected COVID-
19 episode using prespecified criteria (Section 8.1.1).
m. A nasal swab should be collected from the participant at home (using available material for home swabs provided by the study staff) as soon as the prespecified
criteria for suspected COVID-19 are met and, in case of COVID-19 like symptoms, preferably on the day of symptom onset or the day thereafter (COVID-19 Day
1-2). The sample collected on COVID-19 Day 1-2 should be transferred to the study site, as arranged by the study site, as soon as possible after collection,
preferably within 24 hours. Nasal swabs should also be collected once every 2 days until 14 days after symptoms onset (COVID-19 Day 15) or until resolution of
the COVID-19 episode, whichever comes last. These samples should be transferred to the study site, as arranged by the study site, within 3 days after collection.
Details are provided in the laboratory manual. If the participant requires assistance, a trained HCP can help the participant to collect the nasal swabs.
If 2 consecutive nasal swabs negative for SARS-CoV-2 are not available due to operational reasons (eg, delays in results availability), participants may cease collection
of nasal swabs and saliva samples after COVID-19 Day 29, provided they have 2 consecutive days with no COVID-19-related signs and symptoms. In these cases,
participants may be asked to resume sample collection if nasal sample results—once available—do not present with 2 consecutive negative swabs for SARS-CoV-2.
n. The nasal swab should be collected and pulse oximetry should be started as soon as possible after it has been confirmed that the prespecified criteria for suspected
COVID-19 (Section 8.1.1) are met.
o. All nasal swabs will also be tested by a local laboratory for case management.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
36
Status: Approved,  Date: 20 April 2022
p. Saliva samples should be collected from the participant (using recipients provided by the study staff). The samples should be transferred to the study site, as
arranged by the study site, within 3 days after collection. Details are provided in the laboratory manual. If the participant requires assistance, a trained HCP can help
the participant to collect the saliva samples.
q. Blood sample for humoral immunity also includes sample for sero-confirmation of SARS-CoV-2 infection (antibody).
r. Blood sample for exploration of biomarkers correlating with SARS-CoV-2 infection and COVID-19 severity.
s. Participants should complete the (suspected) COVID-19 surveillance (symptom check). In case of COVID-19 like signs and symptoms, participants should be
encouraged by the site to complete the SIC (Appendix 5) daily, preferably in the evening around the same time each day, starting on the first day they experience
symptoms. Sites should remind the participant to complete the SIC, unless special circumstances occur such as hospitalization or ventilation, in which case the
reason for not completing the SIC should be recorded by site staff in the clinical database If signs and symptoms are still ongoing on COVID-19 Day 3-5,
collection of SIC will be continued until AT LEAST 14 days after onset UNLESS both COVID-19 Day 1-2 and COVID-19 Day 3-5 are both negative. If either of
the swabs is positive or the result is unknown AND the participant is beyond 14 days after onset of symptoms, the SIC can be stopped after 2 days without signs and
symptoms.
If a participant is unable to complete the eCOA, a study staff member or the participant’s caregiver can collect information on the participant’s behalf as detailed in
Section 8.1.2.
Participant should measure body temperature daily (oral route preferred, or in accordance with the local standard of care) and record the highest temperature in the
last 24 hours.
t. 
If the participant does not have symptoms at that time, he/she will only need to complete the (suspected) COVID-19 surveillance (symptom check).
u. Includes measurement of supine (preferably) systolic and diastolic blood pressure, heart rate, and respiratory rate [after at least 5 minutes rest] and body
temperature. It is recommended that vital signs are measured before collection of nasal swabs and blood draws.
v. In case of COVID-19 like symptoms, the participant will be asked to measure blood oxygen saturation and pulse rate at home 3 times a day (preferably in the
morning, at lunch time, and in the evening). The results will be recorded by the participant in the eCOA.
w. Data collected as part of the MRU will be recorded in the eCRF.
x. The MA-COV form (Appendix 7) will be provided to the participant at the first study visit and should be completed by the medical care provider or the study site
personnel during medical visits for COVID-19 or COVID-19 complications.
Upon closure of the COVID-19 episode and procedures, all participants will fall back to the default Schedule of Activities, until the end of the study/early withdrawal.
If the participant experiences new signs or symptoms suggesting possible COVID-19 at a later point in time, the participant would re-start the COVID-19 procedures
from COVID-19 Day 1 onwards. For participants experiencing COVID-19 episodes close to the end of their study participation: follow COVID episode procedures up
to their EoT visit. For example, if an episode starts -4 days prior to scheduled EoT visit, complete COVID-19 Day 1- 2 and COVID-19 Day 3-5 procedures as much as
possible, and then stop study procedures.
COVID-19 = coronavirus disease-2019; eCOA = electronic clinical outcome assessment; eCRF = electronic case report form; EoT= end of trial, ePRO = electronic
patient-reported outcome; MA-COV = medically-attended COVID-19; MRU = medical resource utilization; SARS-CoV-2 = severe acute respiratory syndrome
coronavirus-2; SIC = Symptoms of Infection with Coronavirus-19.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
37
Status: Approved,  Date: 20 April 2022
2. 
INTRODUCTION
In this study, immune responses against the original SARS-CoV-2 strain and leading variant of
high consequence or concerna (and other variants of concern)induced by booster vaccination with
Ad26.COV2.S ≥6 months after primary vaccination with Ad26.COV2.S or BNT162b2 will be
compared to responses induced by Ad26.COV2.S or Pfizer BNT162b2 primary vaccination
against the original SARS-CoV-2 strain and leading variant of high consequence or concernb (and
other variants of concern).
Ad26.COV2.S Vaccine
Ad26.COV2.S (also known as VAC31518, JNJ-78436735) is a monovalent vaccine composed of
a recombinant, replication-incompetent Ad26 vector, constructed to encode the S protein derived
from a SARS-CoV-2 clinical isolate (Wuhan 2019, whole genome sequence NC_045512),
stabilized in its prefusion conformation.
In response to the public health emergency caused by the global SARS-CoV-2 pandemic, the
Ad26.COV2.S vaccine was authorized for emergency use in the United States (US) on
27 February 2021 and received a conditional Marketing Authorization approval in the European
Union on 11 March 2021. On 12 March 2021, the Ad26.COV2.S vaccine was recommended for
emergency use under the World Health Organization (WHO) Emergency Use Listing Procedure.
For the most comprehensive nonclinical and clinical information regarding Ad26.COV2.S refer to
the latest version of the Investigator's Brochure (IB) (and Addenda, if applicable) for
Ad26.COV2.S.
The term “study vaccine” throughout the protocol, refers to Ad26.COV2.S as defined in Section 6.1.
The term "sponsor" used throughout this document refers to the entities listed in the Contact
Information page(s), which will be provided as a separate document.
Study COV2008 is being conducted under the sponsorship of Janssen (Janssen Vaccines &
Prevention B.V).
2.1. 
Study Rationale
The currently authorized Ad26.COV2.S vaccine directed against the original SARS-CoV-2 strain
was associated with demonstrated clinical protective efficacy against COVID-19 (Sadoff 2021b).
This study will assess the reactogenicity, safety, and immunogenicity of a booster dose of
Ad26.COV2.S in adults ≥18 years of age, who have previously received primary vaccination with
Ad26.COV2.S or the Pfizer mRNA-based vaccine BNT162b2.
a As defined by the Centers for Disease Control and Prevention (CDC Aug 2021c) at the time of the analysis

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
38
Status: Approved,  Date: 20 April 2022
The purpose of the study is to demonstrate that:
 
The humoral neutralizing immune response elicited by booster vaccination with
Ad26.COV2.S in participants who previously received primary vaccination with
Ad26.COV2.S or BNT162B2 is non-inferior (NI) to the response elicited by primary
vaccination with Ad26.COV2.S.
For Cohort 2 study arms, formal NI testing will be conducted by pooling 28 days post-dose 1 VNA
data across groups 1, 2 and 3 (Cohort 1) compared to the 14 days post booster VNA data in the
study arm of interest (groups 4, 5 or 6).
The Ad26.COV2.S booster will be assessed at dose levels of 5×1010 vp, 2.5×1010vp and 1×1010 vp.
Non-inferiority Testing
The neutralizing antibody response observed 14 days after booster vaccination will be the basis
for NI evaluations. The primary purpose of the study is to assess whether individuals who received
vaccination against the originally dominant strain  with Ad26.COV2.S (Cohort 1), or with
BNT162b2 (Cohort 2) can be adequately boosted by the standard dose level (5×1010 vp/dose), or
lower dose levels (2.5×1010vp and 1×1010 vp) of Ad26.COV2.S. Note: Analysis of Cohort 1 data
can be completed prior to analysis of Cohort 2 data.
See Section 4.3 for further information ofdose selection.
Other Evaluations
The study will assess the neutralization ability of the antibodies induced by the vaccine against the
heterologous virus, as well the humoral immune response against other SARS-CoV-2 variants of
concern. This includes, but is not limited to, the B.1.1.7 variant which first emerged in the United
Kingdom [Leung 2021] and variants of the P.1 lineage which first emerged in Brazil [Faria 2021].
The study design and NI assessment are in line with guidance from the Food and Drug
Administration (FDA 2021b) and the European Medicines Agency (EMA 2021) for the evaluation
of a modified vaccine against a variant of SARS-CoV-2 in view of its authorization under
Emergency Use Authorization or conditional Marketing Authorization.
2.2. 
Background
2.2.1. 
SARS-CoV-2 Virology and COVID-19 Disease Burden
SARS-CoV-2 is an enveloped, positive-sense, single-stranded ribonucleic acid (RNA)
Betacoronavirus (Coronaviridae Study Group of the International Committee on Taxonomy of
Viruses 2020; Wu 2020). In late December 2019, investigation of a cluster of pneumonia cases of
unknown origin in Wuhan, China resulted in identification of a novel coronavirus (Chen N 2020;
Li 2020) from the family Coronaviridae (Lu 2020; WHO 2020c). Phylogenetic analysis of the
complete viral genome revealed that the virus, SARS-CoV-2, is part of the subgenus Sarbecovirus
of the genus Betacoronavirus (Lu 2020; Zhou 2020). The virus is distinct from both severe acute

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
39
Status: Approved,  Date: 20 April 2022
respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome
coronavirus (MERS-CoV), although closely related.
SARS-CoV-2 is a highly transmissible and pathogenic coronavirus that has spread rapidly and
globally since its emergence. The WHO declared that the outbreak constituted a public health
emergency of international concern on 30 January 2020 and declared the outbreak to be a pandemic
on 11 March 2020 (WHO 2020a; WHO 2020c). As of 17 April 2021, approximately 140,123,393
global cases of COVID-19 and approximately 3,002,736 COVID-19-related deaths have been
reported worldwide. Within the United States alone, as of 17 April 2021, approximately
31,584,046 cases of COVID-19 and approximately 566,406 COVID-19-related deaths COVID-19
have been reported since the start of the outbreak (Johns Hopkins CSSE 2021). Within the
European Union (EU)/European Economic Area (EEA) countries, as of 11 February 2021, a total
of 20,478,718 cases of COVID-19 and 495,672 COVID-19-related deaths were reported
(ECDC 2021).
During the COVID-19 pandemic, several new SARS-CoV-2 variants of concern emerged in the
United Kingdom (B.1.1.7 lineage), in Brazil (P.1 lineage), in the Republic of South Africa
(B.1.351 lineage), and in India (B.1.617 lineage) and new variants of interest (eg, B.1.427/B.1.429
lineage in California) continue to emerge, which may spread globally. The emergence of SARS
CoV-2 variants with multiple mutations in the S protein have raised concerns because of their
increased transmission rates, more severe disease (increased hospitalizations or deaths), and
because of the possibility that current COVID-19 vaccines authorized under Emergency Use
Authorization (EUA) or otherwise in clinical development will provide reduced protection against
these variants (CDC 2021c; Rambaut 2020; Tegally 2020). For example, data suggest that the
B.1.351 variant is not neutralized by some monoclonal antibodies directed to the SARS CoV-2 S
protein and is resistant to neutralization by plasma from individuals previously infected with
‘Wuhan-like’ SARS-CoV-2 (Wibmer 2021). Although, data obtained to date suggest that the
impact on neutralization by convalescent and post-vaccination sera is minimal to moderate
(CDC 2021c).
A wide range of symptoms have been reported in association with SARS-CoV-2 infection.
Symptoms usually appear 2 to 14 days (most commonly around 5 days) following exposure, with
dyspnea and pneumonia typically developing within 8 days from onset of symptoms. Clinical
manifestations of disease range from mild symptoms to severe illness or death usually associated
with acute respiratory distress syndrome (ARDS) and respiratory failure. Multiple organ failure
has also been reported in some COVID-19 cases (CDC 2020b; Guan 2020; Linton 2020; US San
Diego Health 2020; WHO 2020b). Individuals aged 60 years or older as well as younger adults
with serious comorbidities, such as cardiovascular disease, diabetes, hypertension and underlying
pulmonary disease, are subject to the highest incidence of morbidity and mortality (CDC 2020h;
Garg 2020; Verity 2020), with an increased risk of severe illness related to COVID-19 infection
resulting in hospitalization, admission to the intensive care unit (ICU), intubation or mechanical
ventilation, or death.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
40
Status: Approved,  Date: 20 April 2022
SARS-CoV-2 infection is often asymptomatic or associated with mild to moderate self-limiting
symptoms such as fever, dry cough, myalgia, and fatigue (Huang C 2020; Chen G 2020). However,
a subset of patients, especially younger adults, with severe SARS-CoV-2 infection develop a
clinically severe hyperinflammatory state known as cytokine storm (CS) that is associated with
elevated levels of the cytokines IL-6, and to a lesser extent IL-10 and TNF-, as well as severe
T cell lymphopenia and coagulopathy  for which pulmonary involvement such as ARDS is a
principal feature, resulting in a requirement for mechanical ventilation, and often death
(Copaescu 2020)..A multisystem inflammatory syndrome (MIS) that appears distinct from the
adult CS and exhibiting features similar to atypical Kawasaki disease, has also been observed in a
subgroup of previously healthy children following acute SARS-CoV-2 infection (CDC 2020g;
Riphagen 2020).
Histopathological changes in patients with COVID-19 occur mainly in the lungs, with evidence of
bilateral diffused alveolar damage. SARS-CoV-2 binds to the angiotensin-converting enzyme 2
(ACE2) receptor expressed on epithelial cells in the upper respiratory tract and alveolar epithelial
cells in the lungs, eliciting a powerful cytokine mediated immune response that results in ARDS
and respiratory failure, the main cause of death in patients with COVID-19 (Hu 2021).
Lymphocytes expressing the ACE2 receptor may also be directly infected by the SARS-CoV-2
virus following sequestration at sites of infections such as the lung (Huang I 2020). Mild
thrombocytopenia has been detected in 58-95% of severe cases of COVD-19, with severe
thrombocytopenia only rarely reported. A meta-analysis of 7,613 COVID-19 patients revealed that
patients with severe disease had lower platelet counts, often associated with increased mortality
(Wool 2021).
To date, there are no proven effective therapies for COVID-19 or antivirals against SARS-CoV-2,
although preliminary data suggests that some treatments may confer benefits to certain
subpopulations of patients. A number of clinical studies to evaluate potential therapies for
COVID-19 are currently ongoing. Vaccination remains the most effective method for a long-term
strategy for prevention and control of COVID-19 in the foreseeable future. The SARS-CoV-2 virus
that is responsible for COVID-19 is highly contagious and poses a severe threat to global health.
SARS-CoV-2 has been shown to be highly pathogenic. The emergence of new variants with
increased transmissibility that have the potential to cause more severe disease is a major concern.
2.2.2. 
Ad26.COV2.S
Nonclinical Pharmacology
Nonclinical pharmacology of Ad26.COV2.S was evaluated in murine, rabbit, Syrian hamster, and
non-human primate (NHP) animal models for immunogenicity, including assessment of
immunological parameters relevant to the theoretical risk of vaccine-associated enhanced
respiratory disease (VAERD). In addition, vaccine efficacy of Ad26.COV2.S including lung
histopathology assessment was evaluated in Syrian hamsters and NHPs. Details are provided in
the IB (IB Edition 4 Ad26.COV2.S 2021 and its addenda).

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
41
Status: Approved,  Date: 20 April 2022
Nonclinical Safety
Biodistribution
To assess distribution, persistence, and clearance of the Ad26 viral vector platform, intramuscular
(IM) biodistribution studies have been conducted in rabbits using an Ad26-based human
immunodeficiency virus (HIV) vaccine, Ad26.ENVA.01 (Ad26 vector encoding the Clade A
envelope protein of HIV type 1), and an Ad26-based respiratory syncytial virus (RSV) vaccine,
Ad26.RSV.preF (Ad26 vector encoding the prefusion conformation-stabilized F protein [pre-F] of
RSV A2 strain). No pharmacokinetic or biodistribution studies have been conducted with the
initial vaccine Ad26.COV2.S or the modified vaccine A26.COV2-S.02 specifically. The
biodistribution studies showed a pattern of limited distribution of the Ad26 vector; Ad26 vector
DNA was primarily detected at the site of injection, draining lymph nodes and (to a lesser extent)
the spleen. Clearance (ie, reflected by a downward trend in number of positive tissues and vector
copies over time, to levels close to, or below, the respective detection limits) of the Ad26 vector
from the tissues was observed, indicating that the vector does not replicate and/or persist in the
tissues. Both Ad26 vectors showed a comparable biodistribution profile despite carrying different
antigen transgenes.
As biodistribution is considered dependent on the viral vector platform and not on the transgene
insert, the biodistribution results obtained with Ad26.ENVA.01 and Ad26.RSV.preF are
considered sufficient to inform on the biodistribution profile of Ad26.COV2.S when administered
via the same (ie, IM) route.
Toxicology
In a GLP-compliant repeat-dose toxicity and local tolerance study in rabbits (TOX14382),
Ad26.COV2.S was well tolerated when administered on 3 occasions over 4 weeks (ie, every
2 weeks) at 1×1011 virus particles (vp)/dose. The observed changes were related to a normal,
anticipated (local and systemic) immunologic response to vaccination, and consisted clinically of
(rare) transient local injection site dermal reactions, with transient minimal hyperthermia and
minimal body weight loss or lower body weight gain after injection. This was associated with a
transient (acute phase/immune) response in clinical pathology parameters, characterized by
increases in plasma proteins and white blood cell counts. Microscopic pathology findings of
minimal to slight inflammation and hemorrhage were observed at the injection sites, along with
increased lymphoid cellularity of germinal centers in popliteal and iliac lymph nodes and the
spleen, which is consistent with an immune response to the vaccine administration. Overall, the
findings were considered non-adverse and were partially or completely reversible after a 3-week
treatment-free period. Details are provided in the IB (IB Edition 4 Ad26.COV2.S 2021).
Reproductive and Developmental Toxicology
There was no harmful effect of Ad26.COV2.S with respect to female reproductive toxicity and
fertility as assessed in a GLP combined EF‑PPND toxicity study in the rabbit (TOX14389), in
which Ad26.COV2.S was administered on 3 occasions (ie, 7 days prior to mating, followed by one
vaccination during early gestation [GD6] and one vaccination during late gestation [GD20]) at
1×1011 vp/dose. No adverse effects were observed on reproductive performance, fertility, ovarian

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
42
Status: Approved,  Date: 20 April 2022
and uterine examinations, or parturition. In addition, there was no adverse effect of vaccination on
fetal body weights, external, visceral and skeletal evaluations, or on postnatal development of the
offspring. The parental females as well as their fetuses and offspring exhibited SARS-CoV-2 S
protein-specific antibody titers, indicating that maternal antibodies were transferred to the fetuses
during gestation. Further details are provided in the IB (IB Edition 4 Ad26.COV2.S 2021).
Clinical Studies
At the time of protocol writing, Phase 1/2a (COV1001, COV1002) and Phase 2a (COV2001)
clinical studies to assess the safety, reactogenicity, and immunogenicity of Ad26.COV2.S, as well
as Phase 3 (COV3001, COV3009) clinical studies to assess the efficacy of Ad26.COV2.S in the
prevention of molecularly confirmed moderate to severe/critical COVID-19 in adults are ongoing
and data from interim analyses from these studies, except COV3009, are available.
Efficacy
A single dose of Ad26.COV2.S at 5×1010 vp protects against COVID-19 in adults ≥18 years of
age, including adults ≥60 years of age. Based on the primary efficacy analysis of the pivotal
Phase 3 study COV3001, including 19,630 participants who received Ad26.COV2.S and
19,691 participants who received placebo, vaccine efficacy (adjusted 95% confidence interval
[CI]) for the co-primary endpoints against molecularly confirmed moderate to severe/critical
COVID-19 in participants who were seronegative at time of vaccination was 66.9% (59.03; 73.40)
when considering cases from at least 14 days after vaccination and 66.1% (55.01; 74.80) when
considering cases from at least 28 days after vaccination. Ad26.COV2.S has been shown to be
effective against all symptomatic COVID-19, highly effective in the prevention of severe/critical
COVID-19 (particularly in prevention of hospitalization and death, across all countries and all
ages), and effective against newly emerging strains, such as the 20H/501Y.V2 strain.
Safety
The most extensive safety information of the single-dose regimen of Ad26.COV2.S at 5×1010 vp
is available from ≥43,000 participants, 18 years of age and above, including adults 60 years of age
and above, enrolled in the ongoing pivotal Phase 3 study COV3001. A 2-dose vaccine regimen of
Ad26.COV2.S at 5×1010 vp is currently under evaluation in the ongoing Phase 3 study COV3009.
Supportive safety information (adverse events [AEs], clinical laboratory abnormalities, vital signs,
and physical examination findings) is available from the interim analysis of the Phase 1 and 2
studies COV1001, COV1002, and COV2001. In COV2001, Ad26.COV2.S is being evaluated at
a range of doses and intervals (1.25×1010 vp, 2.5×1010 vp, 5×1010 vp, and 1×1011 vp) in adolescents
12 to 17 years of age, adults 18 to 55 years of age and 65 years of age.
Ad26.COV2.S has an acceptable safety and reactogenicity profile when administered as a single-
dose or as a 2-dose regimen in adults 18 years of age, including adults 60 years of age. No
significant safety issues were identified. In general, a lower reactogenicity profile was observed in
older adults compared to younger adults.
Overall, up to 22 January 2021, no safety concerns were identified after vaccination with
Ad26.COV2.S as a single-dose or 2-dose vaccine regimen at dose levels up to 1×1011 vp. There

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
43
Status: Approved,  Date: 20 April 2022
was a trend towards a decrease in the frequency of solicited local and systemic AEs
(reactogenicity) with a decreasing dose level of Ad26.COV2.S (from 1×1011 vp to 2.5×1010 vp).
Reactogenicity was demonstrated to be transient and most solicited AEs, including pyrexia,
generally resolved in 1 to 2 days post-vaccination. In the ongoing Phase 3 study COV3001, out of
over 43,000 participants, 19deaths were reported, 3 in the Ad26.COV2.S group and 16 in the
placebo group, all of which were considered unrelated to the study vaccine by the investigator. No
AEs with a fatal outcome have been reported in the supportive Phase 1 and Phase 2 studies
COV1001, COV1002 and COV2001. In the COV3001 study, at the time of the primary analysis,
0.4% participants in the Ad26.COV2.S group and 0.6% participants in the placebo group reported
1 or more serious adverse events (SAEs). Ten (<0.1%) participants reported SAEs that were
considered to be related to the study vaccine: 7 SAEs were reported in 7 participants in the
Ad26.COV2.S group: Grade 4: Guillain-Barré syndrome and pericarditis (one of each); Grade 3:
radiculitis brachial, post-vaccination syndrome, and Type IV hypersensitivity (one of each);
Grade 2: facial paralysis (Bell’s Palsy - 2 cases reported); 3 SAEs were reported in 2 participants
in the placebo group: Grade 4: deep vein thrombosis (DVT) (one participant); Grade 3: Epstein-
Barr virus infection and atrial flutter (both were reported in the same participant). No participants
in either vaccine group (Ad26.COV2.S or placebo) were withdrawn from the study due to AEs.
Across studies COV1001, and COV1002, COV2001, 2 participants reported SAEs which were
considered to be related to the study vaccine (both occurred in study COV1001): Grade 3 pyrexia
and Grade 2 multiple sclerosis. Early discontinuations of vaccination or the study due to (S)AEs
were infrequent in all groups.
Since then, 6 cases of severe allergic reactions were reported in study COV3012 (Sisonke
[Together]), an open-label, single-arm Phase 3b vaccine implementation study sponsored by the
South African Medical Research Council and conducted in collaboration with Janssen, which is
currently ongoing in the Republic of South Africa. One case met the Brighton Collaboration case
definition of anaphylaxis with level 2 of diagnosis certainty (Rüggeberg 2007). The review of the
cases of severe allergic reactions reported from this study identified a plausible causal relationship
between the administration of the Ad26.COV2.S vaccine and the occurrence of severe allergic
reactions including anaphylaxis.
Cases of thrombotic events with thrombocytopenia have very rarely been observed in individuals
who received Ad26.COV2.S. At the time of primary analysis of study COV3001 (Data lock point
22 January 2021), one case of cerebral venous sinus thrombosis (CVST) with thrombocytopenia
had been reported which triggered a temporary pause in vaccinations across Ad26.COV2.S clinical
studies. One additional case of DVT with thrombocytopenia was since reported in study
COV3001. As of 17 April 2021, 6 spontaneous reports of CVST with thrombocytopenia and
1 spontaneous report of DVT with thrombocytopenia have been reported from the US in the
context of the routine vaccination programs, one of which had a fatal outcome. At that time, more
than 7.9 million people had received Ad26.COV2.S in the US.
Immunogenicity
Across studies COV1001, COV1002 and COV2001, a single dose of Ad26.COV2.S was shown
to elicit SARS-CoV-2 neutralizing antibodies in both the 18 to 55 years age group and in adults

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
44
Status: Approved,  Date: 20 April 2022
65 years of age. In studies COV1001 and COV3001, SARS-CoV-2 S protein binding antibodies
were elicited in the vast majority of 18 to 55 years age group and in adults 65 years of age.
In study COV1001, Ad26.COV2.S induced CD4+ T cell responses with a Th1 dominant
phenotype and CD8+ T cell responses in 18-55 and above 65 years of age participants.
Refer to the latest IB for more details on the ongoing clinical studies with Ad26.COV2.S.
2.2.3. 
Ad26-based Vaccines
Safety of Ad26-vectored vaccines has been evaluated in adults in clinical studies by the sponsor.
Replication-incompetent Ad26 is being used as a vector in the development of vaccines against
diseases such as malaria, RSV, HIV, Zika virus, filovirus, and HPV, and has been used in the now
licensed Ebola virus vaccine (Zabdeno/Ad26.ZEBOV) and for emergency use licensed COVID-19
vaccine (Ad26.COV2.S).
As of 17 April 2021, Ad26-based vaccines developed by the sponsor have been administered to
more than 8 million participants. The majority of these participants are enrolled in an ongoing
immunization campaign in the United States (COVID-19 Vaccine Program Campaign) (more than
7.9 million) and an ongoing Ebola vaccine study in the Democratic Republic of the Congo and an
ongoing immunization campaign in Rwanda (UMURINZI Ebola Vaccine Program campaign)
(more than 156,000 to be updated with cut-off 17 April).
Overall, the Ad26-based vaccines were well tolerated irrespective of the antigen transgene, without
significant safety issues. Recently, rare disorders including blood clots in combination with low
platelets have been observed after vaccination with Ad26-based COVID-19 vaccines, including
the Ad26.COV2.S vaccine (refer to Section 2.3.1 for more details).
2.2.4. 
mRNA-based SARS-CoV-2 Vaccines
The Pfizer-BioNTech COVID-19 vaccine, BNT162b2, is a lipid nanoparticle-formulated,
nucleoside-modified RNA vaccine encoding a prefusion stabilized, membrane-anchored
SARS-CoV-2 full-length spike protein (Polack 2020).
The vaccine was evaluated in study NCT04368728 in which a total of 21,720 participants received
injections with BNT162b2 and 21,728 with placebo. A two-dose regimen of BNT162b2 conferred
95% protection against COVID-19 in participants aged ≥16 years. Safety over a median of 2
months was similar to other viral vaccines, with short-term, mild-to-moderate injection site pain,
fatigue, and headache. The incidence of SAEs was low and was similar across the vaccine and
placebo groups (Polack 2020).
The BNT162b2 vaccine is currently available in the U.S. under an Emergency Use Authorization
(EUA) granted by the FDA on December 11, 2020.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
45
Status: Approved,  Date: 20 April 2022
2.3. 
Benefit-Risk Assessment
More detailed information about the known and expected benefits and risks of Ad26.COV2.S may
be found in the most recent version of the IB and addenda.
2.3.1. 
Risks Related to Study Participation
The following potential risks for Ad26.COV2.S will be monitored during the study and are
specified in the protocol:
Risks Related to Ad26.COV2.S
At the time of initial protocol writing, efficacy, immunogenicity and safety data were available
from the ongoing clinical studies COV1001, COV1002, COV2001, COV3001, and COV3009 (see
Section 2.2 for details).
Sites should advise participants that side effects include fever as well as injection site pain,
headache, fatigue, myalgia, and nausea per the current ICF; however, the occurrence of fever
appears to be more common in younger adults and can be severe.
Based on recent data (see Section 2.2.2 for details), anaphylaxis is considered an important
identified risk for Ad26.COV2.S. Individuals should be observed by a healthcare provider after
vaccination per protocol requirements.
Thrombosis in combination with thrombocytopenia (thrombosis with thrombocytopenia syndrome
[TTS]), in some cases accompanied by bleeding, has been observed very rarely following
vaccination with Ad26.COV2.S (see Section 2.2.2 for details). Reports include severe cases of
venous thrombosis at unusual sites such as CVST, splanchnic vein thrombosis, and arterial
thrombosis, in combination with thrombocytopenia. These cases occurred approximately
1-2 weeks following vaccination, mostly in women under 60 years of age. Thrombosis in
combination with thrombocytopenia can be fatal. The exact physiology of TTS is unclear. TTS is
considered an important identified risk for Ad26.COV2.S. Participants should be instructed to seek
immediate medical attention if they develop symptoms such as shortness of breath, chest pain, leg
swelling, persistent abdominal pain, severe or persistent headaches, blurred vision, skin bruising
and/or petechiae beyond the site of vaccination. The medical management of thrombosis with
thrombocytopenia is different from the management of isolated thromboembolic diseases. Study
site personnel and/or treating physicians should follow available guidelines for treatment of
thrombotic thrombocytopenia (eg, from the American Society of Hematology 2021; British Society of
Haematology - Expert Haematology Panel 2021, and the CDC 2021d). The use of heparin may be
harmful and alternative treatments may be needed. Consultation with a hematologist is strongly
recommended. Management of the participant should not be delayed by decision-making of the
AESI Adjudication Committee. Due to the possibility of the occurrence of TTS after vaccination
with Ad26.COV2.S, additional reporting and data collection procedures have been included in the
study for thrombotic events, thrombocytopenia, and TTS (see Section 8.4.7), which may facilitate
diagnosis and clinical management of the event.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
46
Status: Approved,  Date: 20 April 2022
Guillain-Barré syndrome (GBS) has been reported very rarely following vaccination with
Ad26.COV2.S. As a result, it is considered an identified risk. Investigators should be alert to GBS
signs and symptoms to facilitate diagnosis, and to initiate adequate supportive care and treatment.
For the most comprehensive nonclinical and clinical information regarding Ad26.COV2.S, refer
to the most recent version of the IB and addenda.
Risks Related to Ad26.COV2.S Administration after Primary Vaccination with mRNA
Vaccines
To date, no clinical data are available for Ad26.COV2.S vaccination after primary vaccination
with BNT162b2.
Risks Related to Adenoviral-vectored Vaccines
The clinical AdVac® safety database (report version 6.0, dated 20 April 2021, cut-off date
31 December 2019) contains pooled safety data from 32 Janssen-sponsored clinical studies with
Ad26 vaccine candidates: Ad26.ZEBOV (Ebola; 10 studies), Ad26.ENVA.01, Ad26.Mos.HIV
and Ad26.Mos4.HIV (HIV; 8 studies), Ad26.CS.01 (malaria; 1 study), Ad26.RSV.FA2 and
Ad26.RSV.preF (RSV; 10 studies), and Ad26.Filo (filovirus; 1 study), Ad26.ZIKV.001
(Zikavirus; 1 study), and Ad26.HPV16 and Ad26.HPV18 (human papillomavirus [HPV]; 1 study).
In these studies, 8,152 adult participants received at least 1 vaccination with an Ad26-based
vaccine. The AdVac® safety database report includes data only from studies for which the database
had been locked for either the interim, primary, or final analysis for which the sponsor has been
fully unblinded at the cut-off date of this report. Overall, the Ad26-based vaccines were well
tolerated, without significant safety issues identified.
The majority of solicited local and systemic AEs were of mild or moderate severity and usually
started within 1 to 2 days after vaccination. Most of the events resolved within 1 to 3 days.
In adults, the most frequently reported solicited local AE was injection site pain (57.0% of Ad26
participants, compared with 19.2% of placebo participants). All other solicited local AEs were
experienced by less than 25% of adult participants. Severe injection site pain was experienced by
1.0% of adult Ad26 participants and 0.1% of adult placebo recipients.
There was a trend toward an increase in the frequency of some local AEs with an increase in Ad26
dose, ie, injection site pain (18.7% of participants at the 0.8×1010 vp dose level, 38.7% of
participants at the 2×1010 vp dose level, 52.0% of participants at the 5×1010 vp dose level, and
77.1% of participants at the 1×1011 vp dose level), and to a lesser extent injection site swelling
(6.7%, 2.7%, 9.3%, and 17.6%, respectively). Injection site warmth was not collected at the
0.8×1010 vp and the 2×1010 vp dose level. The frequency of injection site warmth at the 5×1010 vp
and the 1×1011 vp dose level was 19.5% and 26.7%, respectively. This trend needs to be interpreted
with caution since the participants in the lower dose groups (0.8×1010 vp and 2×1010 vp dose level)
were all from a single study (VAC52150EBL3002), and the majority of the participants in the
highest dose group (1×1011 vp dose level) were also from a single study (VAC18193RSV2003).

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
47
Status: Approved,  Date: 20 April 2022
The most frequently reported solicited systemic AEs (ie, reported in more than 30% of
participants) for adult Ad26 participants were malaise (53.8%), fatigue (47.1%), headache
(42.6%), and myalgia (37.6%), all of which were more frequent for Ad26 participants compared
with placebo (36.4%, 25.8%, 23.6%, and 14.6% of placebo participants, respectively). Most of
these events were considered related to the study vaccine. Pyrexia (9.2%) and vaccine-related
pyrexia (8.4%) were also reported more frequently after administration of an Ad26-based vaccine
compared with placebo (2.5% and 2.0%, respectively).
The majority of solicited systemic AEs were of mild or moderate severity. For adults, 6.3% of
Ad26 participants and 1.6% of placebo participants reported severe solicited systemic AEs, mostly
malaise, fatigue, chills, headache, and myalgia. Other severe solicited systemic AEs were reported
in less than 1.5% of adult Ad26 participants.
The most frequently reported unsolicited AE in adult Ad26 participants was upper respiratory tract
infection (4.5% vs. 5.2% in adult placebo participants). The most frequently reported unsolicited
AEs considered related to the vaccine were neutropenia (0.7% of adult Ad26 participants vs. 0.3%
of adult placebo participants) and dizziness (0.6% vs. 0.1%, respectively).
General 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. Participants may exhibit general signs
and symptoms associated with IM injection of a vaccine and/or 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. Instructions regarding use of
antipyretic medication can be found in Section 6.7.
Syncope can occur in association with administration of injectable vaccines. Syncope can be
accompanied by falls. Procedures should be in place to avoid falling injury. If syncope develops,
participants should be observed until the symptoms resolve. 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 (see above risks related to Ad26.COV2.S). Severe reactions are
rare. Participants with a known allergy, or history of anaphylaxis or other serious adverse reactions
to vaccines or their excipients (including specifically the excipients of the study vaccine) will be
excluded from the study.
After vaccination, participants will remain at the study site for at least 30 minutes and will be
closely observed by study staff. Necessary emergency equipment and medications must be
available in the clinic to treat severe allergic reactions.
Pregnancy and Birth Control
The effect of the study vaccine on a fetus or on a nursing baby is unknown.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
48
Status: Approved,  Date: 20 April 2022
Given the limited number of incident pregnancies in the clinical studies with Ad26-based vaccines
in the AdVac® safety database report (HIV vaccine: 20 pregnancies in participants and 10 in
partners of participants; Ebola vaccine: 32 pregnancies in participants and 13 in partners of
participants), it is not possible at present to draw firm conclusions on the safety of the vaccines
when administered around the time of conception or prior to the initiation of the pregnancies. There
is currently no concerning pattern of AEs in the pregnancies initiated around the time of
vaccination or after exposure to the Ad26-based vaccines in the Janssen vaccines clinical
development programs.
Participants who are pregnant and breastfeeding are allowed to participate in the study.
Risks from Blood Draws
Blood draws may cause pain, tenderness, bruising, bleeding, dizziness, vasovagal response,
syncope, and rarely, infection at the site where the blood is taken.
Theoretical Risk of Vaccine-associated Enhanced Respiratory Disease
Vaccine-associated enhanced disease (VAED) has been linked to a Th2-polarized immune
response and inadequate induction of neutralizing antibody responses and it was characterized by
enhanced lung histopathology in nonclinical challenge models of other coronaviruses or RSV
(Agrawal 2016; Bolles 2011; Deming 2006; Honda-okubo 2015; Houser 2017). There is, therefore,
a theoretical risk of VAED) including vaccine-associated enhanced respiratory disease (VAERD),
for SARS-CoV-2 vaccines. The potential of Ad26.COV2.S to predispose for VAERD and VAED
has been evaluated in nonclinical challenge models established by the sponsor and partners.
Ad26.COV2.S immunized Syrian hamsters and NHP showed absence of enhanced lung pathology
and clinical signs of disease compared with controls after SARS-CoV-2 inoculation, even under
conditions ofsuboptimal immunity allowing breakthrough infection. Together with induction of
neutralizing antibodies and a Th1 dominant immune response after Ad26.COV2.S dosing these
data suggest that the theoretical risk of VAERD and VAED for Ad26.COV2.S is low (He 2021;
van der Lubbe 2021). In both species, no signs of enhanced respiratory tract pathology were
observed in animals dosed with Ad26.COV2.S compared with challenge control groups.
VAERD has so far not been reported in any of the clinical studies, including interim data reported
from Phase 2/3 clinical trials of mRNA-based vaccines and an adenovector-based vaccine,
expressing SARS-CoV-2 S protein as antigen (Baden 2020b; Polack 2020; Voysey 2021).
Similarly, no cases of VAERD have been reported in any of the ongoing clinical studies conducted
to date by the sponsor, including the Phase 1, Phase 2a and Phase 3 studies. The Ad26 vaccine
vector platform has been assessed in several nonclinical and clinical studies so far, and uniformly
induced potent humoral and cellular immune responses with a clear Th1 bias (Barouch 2018;
Salisch 2019; van der Fits 2020; Widjojoatmodjo 2015). The Ad26.COV2.S vaccine candidate,
which encodes the SARS-CoV-2 S protein, has been shown to induce S-protein binding antibodies
and virus neutralizing antibodies in mice, rabbits, hamsters and NHP. Ad26.COV2.S was shown
to induce a Th1 skewed immune response in mice and in NHP including aged NHP.
Immunogenicity data from Study COV1001 demonstrated that a single vaccination with
Ad26.COV2.S induces robust neutralizing and binding antibody, CD4+ T cell responses with a

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
49
Status: Approved,  Date: 20 April 2022
Th1-dominant phenotype, and CD8+ T cell responses (Anywaine 2019; Barouch 2013;
Barouch 2018; Sadoff 2021a).
Participants in the present study will be informed of the theoretical risk of disease enhancement in
the informed consent form (ICF).
Unknown Risks
There may be other risks that are not known. If any significant new risks are identified, the
investigators and participants will be informed.
2.3.2. 
Benefits of Study Participation
Participants may benefit from clinical testing and physical examination.
The efficacy, immunogenicity and safety data to date support a favorable benefit-risk profile for
Ad26.COV2.S in the proposed indication, ie, active immunization to prevent COVID-19 caused
by SARS-CoV-2 in adults ≥18 years of age (see Section 2.2). The overall evaluation of the benefit
and risk balance for individual participants receiving Ad26.COV2.S in clinical studies and
vaccination campaigns is ongoing.
2.3.3. 
Benefit-Risk Assessment of Study Participation
Based on the available data and proposed safety measures, the overall benefit-risk assessment for
this clinical study is considered acceptable for the following reasons:
 
A single dose of Ad26.COV2.S protects against moderate to severe/critical COVID-19 as
early as 14 days after vaccination as demonstrated in adults ≥18 years of age, including adults
≥60 years of age.
 
Only participants who meet all inclusion criteria and none of the exclusion criteria
(specified in Section 5) 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 will be closely monitored throughout the study:
 
In general, safety evaluations will be performed at scheduled visits during the study, as
indicated in the Schedule of Activities.
 
After vaccination, participants will remain at the study site for at least 30 minutes and
will be closely observed by study staff. Necessary emergency equipment and medications
must be available in the clinic to treat severe allergic reactions. Participants will use an
e-Diary to document solicited signs and symptoms. Details are provided in Section 8.3.
 
The investigator or the designee will document unsolicited AEs and SAEs as indicated in
Section 8.3, Section 8.4, and Appendix 4.
 
TTS is considered to be an adverse event of special interest (AESI) (Section 8.4.7.1).
Suspected AESIs (thrombotic events and thrombocytopenia [defined as platelet count
below 150,000/µL (Brighton Collaboration 2021)]) must be reported to the sponsor

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
50
Status: Approved,  Date: 20 April 2022
within 24 hours of awareness. Suspected AESIs will be followed up as described in the
Schedule of Activities in Section 1.3.2.
 
Any clinically significant abnormalities (including those persisting at the end of the
study/early withdrawal) will be followed by the investigator until resolution or until
clinically stable.
 
An Independent Data Monitoring Committee (IDMC) for this compound has been assembled
by the sponsor. The safety of this vaccine has been, and is being, reviewed by the IDMC under
several study protocols. Post primary analysis, safety data from the study does not require
routine presentation to the IDMC. Nevertheless, the IDMC will review safety data from this
study on an ad hoc basis should any safety issues or concerns arise. The IDMC's
responsibilities, authorities, and procedures are documented in the IDMC Charter.Several
safety measures are included in this protocol to minimize the potential risk to participants,
including the following:
 
In each group  in Cohort 2, 2 sentinel participants will be evaluated for safety before
extending enrollment. The sentinel participants will be vaccinated at least 1 hour apart.
Sentinel participants will come in for a study visit on Day 2 (approximately 24 hours
post-vaccination) to collect safety data. The blinded 24-hourpost-vaccination safety data
in these sentinel participants will be reviewed by the principal investigator (PI) and
sponsor’s study responsible physician (SRP)/study responsible scientist (SRS).
Randomization and vaccination of additional Cohort 2 participants will be halted until
this 24-hour sentinel safety evaluation is completed. Refer to Section 4.1 for further
details.
 
Clinical laboratory assessments (see Appendix 2) will be performed as indicated in the
Schedule of Activities.
 
There are pre-specified pausing rules for all participants (see Section 6.8), that if met
would result in pausing of further vaccinations, preventing exposure of new participants
to study vaccine until the IDMC reviews all safety data.
 
Reasons for Participant Discontinuation/Withdrawal are included in Section 7.
 
Contraindications to vaccination are included in Section 5.5.
3. 
OBJECTIVES AND ENDPOINTS
Objectives 
Endpoints
Primary
Primary Objective 1a:To demonstrate the 
NI of the neutralizing antibody response to 
the original strain 14 days after booster 
vaccination with Ad26.COV2.S at the 
5×1010 vp dose level, administered ≥6 
months 
after 
single-dose 
primary 
vaccination with Ad26.COV2.S (5×1010 vp 
dose level), compared to the neutralizing
antibody response to the original strain
 Serological response to vaccination and
antibody titers as measured by virus
neutralization assay (VNA) titers against the
original strain, 14 days after Ad26.COV2.S
booster vaccination (5×1010vp dose level)
after completing 1-dose primary vaccination
with Ad26.COV2.S (5×1010vp dose level).

Serological
response
to
vaccination and
antibody titers (VNA) against the original

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
51
Status: Approved,  Date: 20 April 2022
Objectives 
Endpoints
induced by single-dose primary vaccination 
with Ad26.COV2.S at the 5×1010 vp dose 
level.
If Primary Objective 1a is met, Primary 
Objective 1b will be tested. 
strain, 28 days after Ad26.COV2.S (5×1010 vp
dose level) single-dose primary vaccination.
Success criteria for NI:
 The lower limit of the 100*(1-2*α)% CI on
the 
difference 
in 
responder 
rate
(Ad26.COV2.S booster - Ad26.COV2.S
primary) needs to be >-10%.
AND
 The lower limit of the 100*(1-2*α)% CI on
the ratio of neutralizing antibody GMTs
(GMT 
Ad26.COV2.S 
booster/GMT
Ad26.COV2.S primary) needs to be >2/3.
AND
 An estimated GMR (GMT Day 15 post-
booster/GMT Day 29 post primary regimen)
of >0.8 is required to conclude NI.
Primary Objective 1b:To demonstrate the 
NI of the neutralizing antibody response to 
the leading variant of high consequence or 
concern* 14 days after booster vaccination 
with Ad26.COV2.S at the 5×1010 vp dose 
level, administered ≥6 months after single- 
dose 
primary 
vaccination 
with 
Ad26.COV2.S (5×1010vp dose level), 
compared to the neutralizing antibody
response to the leading variant of high
consequence or concern* induced by single-
dose 
primary 
vaccination 
with
Ad26.COV2.S at the 5×1010 vp dose level,
if feasible.
If Primary Objective 1b is met, Primary
Objectives 1c and 2a will be tested.
 Serological response to vaccination and
antibody titers as measured by virus
neutralization assay (VNA) titers against the
leading variant of high consequence or
concern*, 14 days after Ad26.COV2.S
booster vaccination (5×1010vp dose level)
after completing 1-dose primary vaccination
with Ad26.COV2.S (5×1010vp dose level).
 Serological response to vaccination and
antibody titers (VNA) against the leading
variant of high consequence or concern*, 28
days after Ad26.COV2.S (5×1010 vp dose
level) single-dose primary vaccination.
Success criteria for NI:
 The lower limit of the 100*(1-2*α)% CI on
the 
difference 
in 
responder 
rate
(Ad26.COV2.S booster - Ad26.COV2.S
primary) needs to be >-10%.
AND
 The lower limit of the 100*(1-2*α)% CI on
the ratio of neutralizing antibody GMTs
(GMT 
Ad26.COV2.S 
booster/GMT
Ad26.COV2.S primary) needs to be >2/3.
AND
 An estimated GMR (GMT Day 15 post-
booster/GMT Day 29 post primary regimen)
of >0.8 is required to conclude NI.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
52
Status: Approved,  Date: 20 April 2022
Objectives 
Endpoints
Primary Objective 1c: To demonstrate the 
NI of the neutralizing antibody response to 
the original strain 14 days after booster 
vaccination with Ad26.COV2.S at the 
2.5×1010 vp dose level, administered ≥6 
months 
after 
single-dose 
primary 
vaccination with Ad26.COV2.S (5×1010 vp 
dose level), compared to the neutralizing
antibody response to the original strain
induced by single-dose primary vaccination
with Ad26.COV2.S at the 5×1010 vp dose
level.
If Primary Objective 1c is met, Primary
Objective 1d will be tested.
 Serological response to vaccination and
antibody titers as measured by virus
neutralization assay (VNA) titers against the
original strain, 14 days after Ad26.COV2.S
booster vaccination (2.5×1010 vp dose level)
after completing 1-dose primary vaccination
with Ad26.COV2.S (5×1010vp dose level).

Serological response to vaccination and
antibody titers (VNA) against the original
strain, 28 days after Ad26.COV2.S (5×1010vp
dose level) single-dose primary vaccination.
Success criteria for NI:
 The lower limit of the 97.5% CI on the
difference in responder rate (Ad26.COV2.S
booster - Ad26.COV2.S primary) needs to be
>-10%.
AND
 The lower limit of the 97.5% CI on the ratio
of neutralizing antibody GMTs (GMT
Ad26.COV2.S booster/GMT Ad26.COV2.S
primary) needs to be >2/3.
AND
 An estimated GMR (GMT Day 15 post-
booster/GMT Day 29 post primary regimen)
of >0.8 is required to conclude NI.
Primary Objective 1d:To demonstrate the
NI of the neutralizing antibody response to
the original strain 14 days after booster
vaccination with Ad26.COV2.S at the
1×1010 vp dose level, administered ≥6
months 
after 
single-dose 
primary
vaccination with Ad26.COV2.S (5×1010 vp
dose level), compared to the neutralizing
antibody response to the original strain
induced by single-dose primary vaccination
with Ad26.COV2.S at the 5×1010 vp dose
level.
 Serological response to vaccination and
antibody titers as measured by virus
neutralization assay (VNA) titers against the
original strain, 14 days after Ad26.COV2.S
booster vaccination (1×1010vp dose level)
after completing 1-dose primary vaccination
with Ad26.COV2.S (5×1010vp dose level).
 Serological response to vaccination and
antibody  titers (VNA) against the original
strain, 28 days after Ad26.COV2.S (5×1010 vp
dose level) single-dose primary vaccination.
Success criteria for NI:
 The lower limit of the 97.5% CI on the
difference in responder rate (Ad26.COV2.S
booster - Ad26.COV2.S primary) needs to be
>-10%.
AND

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
53
Status: Approved,  Date: 20 April 2022
Objectives 
Endpoints
 The lower limit of the 97.5% CI on the ratio
of neutralizing antibody GMTs (GMT
Ad26.COV2.S booster/GMT Ad26.COV2.S
primary) needs to be >2/3.
AND
 An estimated GMR (GMT Day 15 post-
booster/GMT Day 29 post primary regimen)
of >0.8 is required to conclude NI.
Primary Objective 2a:To demonstrate the 
NI of the neutralizing antibody response to 
the original strain 14 days after booster 
vaccination with Ad26.COV2.S at the 
5×1010 vp dose level, administered ≥6 
months after completing a 2-dose primary 
vaccination 
with 
Pfizer 
BNT162b2, 
compared to the neutralizing antibody
response to the original strain induced by 2-
dose primary vaccination with Pfizer
BNT162b2
If Primary Objective 2a is met, Primary 
Objective 2b will be tested. 
 Serological response to vaccination and
antibody titers as measured by virus
neutralization assay (VNA) titers against the
original strain, 14 days after Ad26.COV2.S
booster vaccination (5×1010vp dose level)
after completing 2-dose primary vaccination
with Pfizer BNT162b2
 Serological response to vaccination and
antibody titers (VNA) against the original
strain in serum samples of approximately
300 individuals, collected 2 weeks to 2
months after completing 2-dose primary
vaccination with Pfizer BNT162b2 (further
referred to as Pfizer BNT162b2 external
samples).
Success criteria for NI:
 The lower limit of the 97.5% CI on the
difference 
in 
seropositivity 
rate
(Ad26.COV2.S booster - Pfizer BNT162b2
primary regimen [external samples]) needs to
be > -10%.
AND
 The lower limit of the 97.5% CI on the ratio
of neutralizing antibody GMTs (GMT
Ad26.COV2.S booster/GMT post Pfizer
BNT162b2 
primary 
regimen 
[external
samples]) needs to be >2/3.
AND
 An estimated GMR (GMT Day 15 post-
booster/ post Pfizer BNT162b2 primary
regimen [external samples]) of >0.8 is
required to conclude NI.
Primary Objective 2b:To demonstrate the 
NI of neutralizing antibody response to the 
leading variant of high consequence or 
concern* 14 days after booster vaccination 
 Serological response to vaccination and
antibody titers as measured by virus
neutralization assay (VNA) against the
leading variant of high consequence or

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
54
Status: Approved,  Date: 20 April 2022
Objectives 
Endpoints
with Ad26.COV2.S at the 5×1010 vp dose 
level, administered ≥6 months after 
completing a 2-dose primary vaccination 
with Pfizer BNT162b2, compared to the 
neutralizing antibody response to the
leading variant of high consequence or
concern* induced by 2-dose primary
vaccination with Pfizer BNT162b2, if
feasible
If Primary Objective 2b is met, Primary 
Objectives 2c will be tested.
concern* 14 days after Ad26.COV2.S booster
vaccination (5×1010 vp dose level) after
completing 2-dose primary vaccination with
Pfizer BNT162b2
 Serological response to vaccination and
antibody titers as measured by virus
neutralization assay (VNA) against the
leading variant of high consequence or
concern* in Pfizer BNT162b2 external
samples
Success criteria for NI:
 The lower limit of the 97.5% CI on the
difference 
in 
seropositivity 
rate
(Ad26.COV2.S booster - Pfizer BNT162b2
primary regimen [external samples]) needs to
be > -10%.
AND
 The lower limit of the 97.5% CI on the ratio
of neutralizing antibody GMTs (GMT
Ad26.COV2.S booster/GMT post Pfizer
BNT162b2 
primary 
regimen 
[external
samples]) needs to be >2/3.
AND
 An estimated GMR (GMT Day 15 post-
booster/GMT post Pfizer BNT162b2 primary
regimen [external samples]) of >0.8 is
required to conclude NI.
Primary Objective 2c: To demonstrate the
NI of the neutralizing antibody response to
the original strain 14 days after booster
vaccination with Ad26.COV2.S at the
2.5×1010 vp dose level, administered ≥6
months after completing a 2-dose primary
vaccination 
with 
Pfizer 
BNT162b2,
compared to the neutralizing antibody
response to the original strain induced by 2-
dose primary vaccination with Pfizer
BNT162b2
If Primary Objective 2c is met, Primary
Objective 2d will be tested.
 Serological response to vaccination and
antibody titers as measured by virus
neutralization assay (VNA) titers against the
original strain, 14 days after Ad26.COV2.S
booster vaccination (2.5×1010 vp dose level)
after completing 2-dose primary vaccination
with Pfizer BNT162b2.
 Serological response to vaccination and
antibody titers (VNA) against the original
strain, in Pfizer BNT162b2 external samples.
Success criteria for NI:
 The lower limit of the 97.5% CI on the
difference 
in 
seropositivity 
rate
(Ad26.COV2.S booster- Pfizer BNT162b2

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
55
Status: Approved,  Date: 20 April 2022
Objectives 
Endpoints
primary regimen [external samples]) needs to
be > -10%.
AND
 The lower limit of the 97.5% CI on the ratio
of neutralizing antibody GMTs (GMT
Ad26.COV2.S 
booster/post 
Pfizer
BNT162b2 
primary 
regimen 
[external
samples]) needs to be >2/3.
AND
 An estimated GMR (GMT Day 15 post-
booster/GMT post Pfizer BNT162b2 primary
regimen [external samples]) of >0.8 is
required to conclude NI.
Primary Objective 2d:To demonstrate the
NI of the neutralizing antibody response to
the original strain 14 days after booster
vaccination with Ad26.COV2.S at the
1×1010 vp dose level, administered ≥6
months after completing a 2-dose primary
vaccination 
with 
Pfizer 
BNT162b2,
compared to neutralizing antibody response
to the original strain induced by 2-dose
primary vaccination with Pfizer BNT162b2
 Serological response to vaccination and
antibody titers as measured by virus
neutralization assay (VNA) titers against the
original strain, 14 days after Ad26.COV2.S
booster vaccination (1×1010vp dose level)
after completing 2-dose primary vaccination
with Pfizer BNT162b2.
 Serological response to vaccination and
antibody titers (VNA) against the original
strain, in Pfizer BNT162b2 external samples .
Success criteria for NI:
 The lower limit of the 97.5% CI on the
difference 
in 
seropositivity 
rate
(Ad26.COV2.S booster- Pfizer BNT162b2
primary regimen [external samples]) needs to
be > -10%.
AND
 The lower limit of the 97.5% CI on the ratio
of neutralizing antibody GMTs (GMT
Ad26.COV2.S booster/GMT post Pfizer
BNT162b2 
primary 
regimen 
[external
samples]) needs to be >2/3.
AND
 An estimated GMR (GMT Day 15 post-
booster/GMT post Pfizer BNT162b2 primary
regimen [external samples]) of >0.8 is
required to conclude NI.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
56
Status: Approved,  Date: 20 April 2022
Objectives 
Endpoints
Secondary
To assess the safety and reactogenicity of 
Ad26.COV2.S administered at the 5×1010 
vp, 2.5×1010 vp and 1×1010 vp dose levels
administered as booster vaccinations in
adults.
 
Solicited local and systemic adverse events
(AEs) for 7 days after booster vaccination.

Unsolicited AEs for 28 days after booster
vaccination.
 
Serious adverse events (SAEs) and adverse
events of special interest (AESIs) throughout
the study (from booster vaccination until end
of the study).
To assess the neutralizing and binding
antibody response to the original strain,
leading variant of high consequence or
concern* and other relevant variants of
concern, induced by booster vaccination
with Ad26.COV2.S at the 5×1010 vp,
2.5×1010 vp and 1×1010 vp dose levels, in
adults who have previously completed
single-dose primary vaccination with
Ad26.COV2.S at the 5×1010 vp dose level.
 Serological response to vaccination and
antibody titers, as measured by VNA, against
the original strain, leading variant of high
consequence or concern* AND other relevant
variants of concern, 14 days and 28 days after
Ad26.COV2.S booster vaccination.
 Antibodies binding to SARS-CoV-2 relevant
variants of concern or individual SARS-CoV-
2 proteins (eg, S and/or receptor-binding
domain [RBD] proteins from the SARS-CoV-
2 variants of concern) by ELISA and/or MSD.
To assess the neutralizing and binding
antibody response to the original strain,
leading variant of high consequence or
concern* and other relevant variants of
concern, induced by booster vaccination
with Ad26.COV2.S at the 5×1010 vp,
2.5×1010 vp and 1×1010 vp dose levels, in
adults who have previously completed
primary vaccination with Pfizer BNT162b.
 Serological response to vaccination and
antibody titers, as measured by VNA, against
the original strain, leading variant of high
consequence or concern* AND other relevant
variants of concern, 14 days and 28 days after
Ad26.COV2.S booster vaccination.
 Antibodies binding to SARS-CoV-2 relevant
variants of concern or individual SARS-CoV-
2 proteins (eg, S and/or receptor-binding
domain [RBD] proteins from the SARS-CoV-
2 variants of concern) by ELISA and/or MSD.
To assess previous or concomitant infection
with SARS-CoV-2 at baseline.
Antibodies 
binding 
to 
the 
SARS-CoV-2
nucleocapsid (N) protein at Day 1 (N-serology).
Exploratory
To assess the neutralizing antibody
responses against the original strain, leading
variant of high consequence or concern*
and other relevant variants of concern,
following 
Ad26.COV2.S 
booster
vaccination in participants that previously
received 
Ad26.COV2.S 
or 
Pfizer
BNT122b2 
as 
primary 
vaccination,
compared observationally to antibody
responses 14 days post primary vaccination
 
Serological response to vaccination and
antibody titers measured by VNA against the
original strain, 14 days and 28 days after
Ad26.COV2.S 
booster 
vaccination
(5×1010vp dose level), after completing one-
dose or 2-dose primary vaccination with
Ad26.COV2.S 
or 
Pfizer 
BNT162b2,
respectively.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
57
Status: Approved,  Date: 20 April 2022
Objectives 
Endpoints
in participants from Study COV3009 (2- 
dose schedule of Ad26.COV2.S spaced by 
56 days). 
 
Serological response to vaccination and
antibody titers measured by VNA against,
leading variant of high consequence or
concern*, 14 days and 28 days after
Ad26.COV2.S 
booster 
vaccination
(5×1010vp dose level), after completing one-
dose or 2-dose primary vaccination with
Ad26.COV2.S 
or 
Pfizer 
BNT162b2,
respectively.
 
Serological response to vaccination and
antibody titers measured by VNA against
other relevant variants of concern, 14 days
and 28 days after Ad26.COV2.S booster
vaccination (5×1010vp dose level), after
completing one-dose or 2-dose primary
vaccination with Ad26.COV2.S or Pfizer
BNT162b2, respectively.
 
Serological response to vaccination and
antibody titers measured by VNA against the
original variant, 14 days after completing
Ad26.COV2.S primary vaccination as a 2-
dose schedule spaced by 56 days (5×1010vp
dose level), in a subset of participants from
study COV3009.
Observational comparison of neutralizing
antibody responses against the original
strain induced by booster vaccination with
5×1010 vp vs those receiving 2.5×1010 vp, in
adults who previously completed single-
dose 
primary 
vaccination 
with
Ad26.COV2.S at the 5×1010 vp dose level.
 
Serological response to vaccination and
antibody titers, as measured by VNA, against
the original strain 14 days and 28 days after
Ad26.COV2.S booster vaccination (2.5×1010
vp or 5×1010 vp dose level).
Observational comparison of neutralizing
antibody responses against the original
strain induced by booster vaccination with
5×1010 vp vs those receiving 1×1010 vp, in
adults who previously completed single-
dose 
primary 
vaccination 
with
Ad26.COV2.S at the 5×1010 vp dose level.
 
Serological response to vaccination and
antibody titers, as measured by VNA, against
the original strain 14 days and 28 days after
Ad26.COV2.S 
booster 
vaccination
(1×1010 vp or 5×1010 vp dose level).
Observational comparison of neutralizing
antibody responses against the original
strain induced by booster vaccination with
5×1010 vp in adults who previously
completed single-dose primary vaccination
with Ad26.COV2.S at the 5×1010 vp dose
level vs neutralizing antibody responses
 
Serological response to vaccination and
antibody titers, as measured by VNA, against
the original strain 14 days and 28 days after
Ad26.COV2.S 
booster 
vaccination
(5×1010 vp) in participants primed with the 1-
dose Ad26.COV2.S vaccine at the 5×1010 vp
dose level, and after booster vaccination at

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
58
Status: Approved,  Date: 20 April 2022
Objectives 
Endpoints
against the original strain induced by 
booster vaccination with 5×1010 vp in adults 
who previously completed single-dose
primary vaccination with Pfizer BNT162b.
the 5×1010 vp dose level in participants
primed with Pfizer BNT162b.
Observational comparison of neutralizing 
antibody responses against the original 
strain induced by booster vaccination with 
5×1010 vp in adults who previously 
completed single-dose primary vaccination 
with Ad26.COV2.S at the 5×1010 vp dose 
level vs neutralizing antibody responses 
against the original strain induced by 
booster vaccination with 2.5×1010 vp in 
adults who previously completed primary
vaccination with Pfizer BNT162b.
 
Serological response to vaccination and
antibody titers, as measured by VNA, against
the original strain 14 days and 28 days after
Ad26.COV2.S booster vaccination at the
5×1010 vp dose level in participants primed
with the 1-dose Ad26.COV2.S vaccine at the
5×1010 vp dose level, and booster vaccination
at the 2.5×1010 vp dose level in participants
primed with Pfizer BNT162b.
Observational comparison of neutralizing 
antibody responses against the original 
strain induced by booster vaccination with 
5×1010 vp in adults who previously 
completed single-dose primary vaccination 
with Ad26.COV2.S at the 5×1010 vp dose 
level vs neutralizing antibody responses 
against the original strain induced by 
booster vaccination with 1×1010 vp in adults 
who 
previously 
completed 
primary
vaccination with Pfizer BNT162b.
Serological response to vaccination and antibody
titers, as measured by VNA, against the original
strain 14 days and 28 days after Ad26.COV2.S
booster vaccination at the 5×1010 vp dose level in
participants 
primed 
with 
the 
1-dose
Ad26.COV2.S vaccine at the 5×1010 vp dose
level, and booster vaccination at 1×1010 vp dose
level in participants primed with Pfizer
BNT162b.
To determine if any of the primary 
objectives that meet a non-inferiority 
criterion also meet a superiority criterion. 
 
Serological response to vaccination and
antibody titers as measured by virus
neutralization assay (VNA) titers against the
original strain, 14 days after Ad26.COV2.S
booster 
vaccination 
(5×1010 vp 
OR
2.5×1010 vp OR 1×1010vp dose level) after
completing 1-dose primary vaccination with
Ad26.COV2.S 
OR 
2-dose 
primary
vaccination with Pfizer BNT162b2
 
Serological response to vaccination and
antibody titers (VNA) against the original
strain, 28 days after Ad26.COV2.S (5×1010
vp 
dose 
level) 
single-dose 
primary
vaccination.
To 
make 
observational 
comparisons 
between the immunologic response to 
booster vaccination and the primary 
vaccination regimen, in participants primed 
with the Pfizer BNT162b regimen (if 
 
Serological response to vaccination and
antibody titers as measured by virus
neutralization assay (VNA) titers against the
original strain, 14 days after Ad26.COV2.S
booster 
vaccination 
(5×1010 vp 
OR
2.5×1010 vp OR 1×1010vp dose level) after

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
59
Status: Approved,  Date: 20 April 2022
Objectives 
Endpoints
appropriate serum samples are available for 
testing). 
completing 2-dose primary vaccination with
Pfizer BNT162b2
 
Serological response to vaccination and
antibody titers (VNA) against the original
strain, 28 days after completing 2-dose
primary vaccination with Pfizer BNT162b2
To evaluate patient-reported outcomes 
(PROs) in relation to the presence of SARS- 
CoV-2 infection and the presence, severity 
and duration of COVID-19 signs and 
symptoms in participants who receive 
booster vaccination. 
 Presence, severity and duration of COVID-19
signs and symptoms
 Confirmation of SARS-CoV-2 infection by
molecular testing
 Evaluate all PCR and N ELISA confirmed
cases of SARS-CoV-2 infections according to
the charter of the Clinical Severity
Adjudication Committee.
To explore the relative vaccine efficacy  
(rVE) of Ad26.COV2.S heterologous 
booster vaccination in the prevention of 
SARS-CoV-2 infection (severe/critical,
moderate, moderate to severe/critical, mild,
symptomatic, and asymptomatic infections,
that are serologically and/or molecularly 
confirmed) compared to Ad26.COV2.S 
homologous booster vaccination at the same 
dose level (5×1010vp, 2.5×1010vp and 
1×1010vp).
 
Asymptomatic cases of COVID-19, as
determined by seropositivity for the SARS-
CoV-2 nucleocapsid (N) protein.
 
SARS-CoV-2 infections as detected by
molecular testing (RT-PCR or equivalent).
 
COVID-19 cases meeting the US FDA
Harmonized COVID-19 case definition, with
onset at least 14 days post vaccination in
COV2008.
 COVID-19 cases meeting the criteria for
“moderate, moderate to severe/critically ill
and severe/critically ill” COVID-19, with
onset at least 14 days post vaccination in
COV2008, if sufficient data are available.
To explore the rVE of different dose levels 
of Ad26.COV2.S homologous booster 
vaccination in the prevention of SARS- 
CoV-2 infection (severe/critical, moderate
to 
severe/critical, 
moderate, 
mild,
symptomatic, and asymptomatic infections,
that are serologically and/or molecularly 
confirmed) as follows: 
 5×1010vp versus 1×1010vp dose 
level 
 2.5×1010vp versus 1×1010vp dose
level
 
Asymptomatic cases of COVID-19, as
determined by seropositivity for the SARS-
CoV-2 N protein.
 
SARS-CoV-2 infections as detected by
molecular testing (RT-PCR or equivalent).
 
COVID-19 cases meeting the US FDA
Harmonized COVID-19 case definition, with
onset at least 14 days post vaccination in
COV2008.
 COVID-19 cases meeting the criteria for
“moderate, moderate to severe/critically ill”
COVID-19, with onset at least 14 days post
vaccination in COV2008, if sufficient data are
available.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
60
Status: Approved,  Date: 20 April 2022
Objectives 
Endpoints
To explore the rVE of different dose levels 
of Ad26.COV2.S heterologous booster 
vaccination in the prevention of SARS- 
CoV-2 infection (severe/critical, moderate
to 
severe/critical, 
moderate, 
mild,
symptomatic, and asymptomatic infections,
that are serologically and/or molecularly 
confirmed) as follows: 
 5×1010vp versus 1×1010vp dose 
level 
 2.5×1010vp versus 1×1010vp dose 
level 
 
Asymptomatic cases of COVID-19, as
determined by seropositivity for the SARS-
CoV-2 N protein.

SARS-CoV-2 infections as detected by
molecular testing (RT-PCR or equivalent).
 
COVID-19 cases meeting the US FDA
Harmonized COVID-19 case definition, with
onset at least 14 days post vaccination in
COV2008.
 COVID-19 cases meeting the criteria for
“moderate and moderate to severe/critically
ill” COVID-19, with  onset at least 14 days
post vaccination in COV2008, if sufficient
data are available.
If feasible, to investigate the effect of post
booster cellular responses, mRNA profiles,
neutralizing 
responses 
and/or 
other
functional antibody responses on the
probability of experiencing a COVID-19
event, 
moderate 
and 
moderate 
to
severe/critically ill COVID-19 disease, or
asymptomatic SARS-CoV-2 infection.
 
Serological response to vaccination and
antibody titers as measured by virus
neutralization assay (VNA) titers against the
reference 
strain 
and/or 
SARS-CoV-2
variants, by ELISA/MSD and/or other
functional antibody assays, 14 days, 6
months and 1 year after homologous or
heterologous booster vaccination with
Ad26.COV2.S, if sufficient data are
available.
 
Cellular response to vaccination as measured
by flow cytometry, ELISPOT and/or
transcriptomics, 14 days, 6 months and 1
year after homologous or heterologous
booster vaccination with Ad26.COV2.S, if
sufficient data are available.
 
COVID-19 cases meeting the US FDA
Harmonized COVID-19 case definition, with
onset at least 14 days post booster
vaccination in study COV2008, if sufficient
data are available.
 
COVID-19 cases meeting the criteria for
“moderate and moderate to severe/critically
ill” COVID-19, with onset at least 14 days
post vaccination in COV2008, if sufficient
data are available.
 
Asymptomatic SARS-CoV-2 infection, with
onset at least 14 days post vaccination in
COV2008, if sufficient data are available.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
61
Status: Approved,  Date: 20 April 2022
Objectives 
Endpoints
 
Analysis of gene expression by RNA
transcript profiling and correlation with
humoral and cellular immune responses.
In a subset, to assess the cellular immune 
response to the original strain, leading 
variant of high consequence or concern*
and other relevant variants of concern, after
booster vaccination with Ad26.COV2.S at
the 5×1010 vp, 2.5×1010 vp and 1×1010 vp
dose levels, at baseline (Day 1, pre-booster
vaccination) and 14 days, 6 months and 1
year after booster vaccination in adults.
This objective will be tested only if PBMC
collection is feasible.
T helper (Th) 1 and Th2 immune responses as
assessed by:
 
Flow cytometry after SARS-CoV-2 S protein
peptide stimulation of peripheral blood
mononuclear cells (PBMC) and intracellular
staining 
(ICS) 
including 
CD4+/CD8+,
interferon gamma (IFNγ), interleukin (IL)2,
tumor necrosis factor alpha (TNFα), IL-4,
IL-5, IL13, and/or other Th1/Th2 markers.
AND/OR
 
Dual or single IFNγ and IL-4 enzyme-linked
immunospot 
(ELISpot) 
assay 
after
stimulation of PBMCs with SARS-CoV-2 S
protein peptides.
In a subset of participants, to assess the 
cellular immune response to the original 
strain, leading variant of high consequence
or concern* and other relevant variants of
interest, after booster vaccination with
Ad26.COV2.S 
in 
adults 
who 
have
completed a primary vaccination regimen
with Ad26.COV2.S or BNT162b2, at
baseline (Day 1, pre-booster vaccination)
and 14 days, 6 months and 1 year after
booster vaccination. 
This objective will be tested only if PBMC 
collection is feasible. 
T helper (Th) 1 and Th2 immune responses as
assessed by:
 
Flow cytometry after SARS-CoV-2 S protein
peptide stimulation of peripheral blood
mononuclear cells (PBMC) and intracellular
staining 
(ICS) 
including 
CD4+/CD8+,
interferon gamma (IFNγ), interleukin (IL)2,
tumor necrosis factor alpha (TNFα), IL-4,
IL-5, IL13, and/or other Th1/Th2 markers.
AND/OR
 
Dual or single IFNγ and IL-4 enzyme-linked
immunospot 
(ELISpot) 
assay 
after
stimulation of PBMCs with SARS-CoV-2 S
protein peptides.
To further explore the humoral immune 
response 
to 
Ad26.COV2.S 
booster 
vaccination in adults.
Exploratory analyses may include the following
assays:
 
SARS-CoV-2 neutralization as assessed by
alternative 
SARS-CoV-2 
neutralization
assays (VNA).
 
Adenovirus neutralization.
 
Functional 
and 
molecular 
antibody
characterization including Fc-mediated viral
clearance, avidity, Fc characteristics, Ig
subclass and IgG isotype.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
62
Status: Approved,  Date: 20 April 2022
Objectives 
Endpoints
 
Epitope-specificity 
characterization 
of
antibodies.
 
Cytokine profiling: Analysis of cytokines,
chemokines, and other proteins of the innate
or adaptive immune response in the serum or
plasma.
 
Passive transfer: Analysis of immune
mediators correlating with protection against
experimental SARS-CoV-2 challenge in a
suitable animal model.
In a subset, to assess humoral and cellular 
responses (if feasible) 28 days following the 
second dose of Pfizer BNT162b2 against 
the original strain, leading variant of high 
consequence or concern* and other relevant 
variant strains for comparison to booster 
responses in the different regimens and the
primary response to Ad26.COV2.S.
 
Assay panels similar to those tested for the
other groups will be utilized based on
availability of serum and cells. Assessments
performed with different assays to those
utilized for other groups in this study may be
utilized.
At one site (BIDMC), in-depth humoral and
cellular immunogenicity assessment may be
performed on participants enrolled at that
site and a subset of participants enrolled at
other sites.
Exploratory analyses may include the following
assays:
 
SARS-CoV-2 neutralization as assessed by
alternative 
SARS-CoV-2 
neutralization
assays (VNA).
 
Adenovirus neutralization.
 
Functional 
and 
molecular 
antibody
characterization including Fc-mediated viral
clearance, avidity, Fc characteristics, Ig
subclass and IgG isotype.
 
Epitope-specificity 
characterization 
of
antibodies.
 
Cytokine profiling: Analysis of cytokines,
chemokines, and other proteins of the innate
or adaptive immune response in the serum or
plasma.
 
Passive transfer: Analysis of immune
mediators correlating with protection against
experimental SARS-CoV-2 challenge in a
suitable animal model.
 
Analysis of gene expression by RNA
transcript profiling

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
63
Status: Approved,  Date: 20 April 2022
Objectives 
Endpoints
To characterize and establish correlations 
between mRNA profiling and immunologic 
responses to the booster vaccinations. 
 
Analysis of gene expression by RNA
transcript profiling and correlation with
humoral and cellular immune responses.
To explore markers of inflammation and 
upregulation of pathways that may be 
involved 
in 
the 
thrombosis 
with 
thrombocytopenia syndrome (TTS) rarely 
occurring 
after 
vaccination 
with 
Ad26.COV2.S.
 
Descriptive comparison of RNA sequence
profiles 
from 
participants 
receiving
Ad26.COV2.S vaccination to the RNA
profiles of participants receiving other Ad26-
based vaccines.
Explore the relationship between humoral 
and cellular (if feasible) responses in 
relationship to the time between primary 
and booster immunization 
 
In silico modelling of the humoral and
cellular immune responses elicited by
Ad26.COV2.S as primary regimen and by
Ad26.COV2.S as booster, over time.
To assess the vaccine recipient’s risk of 
developing 
thrombotic 
events 
after 
Ad26.COV2.S administration. 
 
Platelet count pre-vaccination at Day 1 (all
participants) and Day 29 post-vaccination
(for participants with a suspected AESI).
 
Based on the clinical evaluation of the
suspected 
AESI 
(eg, 
whether
thrombocytopenia is observed with a
thrombotic event), a panel of coagulation-
related tests may be conducted on the stored
pre-vaccination sample (retrospective test),
on Day 29 post vaccination, and on the
samples obtained as part of the AESI
investigation).
* As defined by the Centers for Disease Control and Prevention (CDC Aug 2021c) at the time of the analysis
Refer to Section 8, Study Assessments and Procedures for evaluations related to endpoints.
HYPOTHESIS
No formal statistical testing of safety data is planned. Safety data will be analyzed descriptively
by vaccine group. See Section 9.1 for details of immunogenicity hypothesis testing.
4. 
STUDY DESIGN
4.1. 
Overall Design
This randomized, double-blind, parallel, multicenter study will assess the reactogenicity, safety
and immunogenicity of a booster dose of Ad26.COV2.S in adults ≥18  years of age, who have
previously received primary vaccination with Ad26.COV2.S or BNT162b2.
The primary immunogenicity endpoints are designed to sequentially show non-inferiority of the
responses after boosting with various doses of Ad26.COV2.S in volunteers either primed with
Ad26.COV2.S at a 5×1010 vp dose level, or Pfizer BNT162b2, vs the neutralizing antibody

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
64
Status: Approved,  Date: 20 April 2022
responses to the primary 1-dose regimen of Ad26.COV2.S which has shown efficacy in a
prospective randomized Phase 3 efficacy trial. This study will therefore attempt to show which
booster regimens will induce neutralizing antibody responses non-inferior to those seen with the
Janssen 1-dose regimen of Ad26.COV2.S which has demonstrated efficacy.
In Cohort 1 a target ofapproximately 770 participants who have received Ad26.COV2.S in study
COV3001 will initially be randomized in a 1:1:1 ratio into 3 groups to receive a 1-dose booster
vaccination regimen with Ad26.COV2.S until the group 3 is fully enrolled. Thereafter,
randomization will continue in a 1:1 ratio in groups 1 and 2 as shown in Table 1. When at least
330 participants from Groups 1 to 3 in Cohort 1 have been enrolled, have completed the Day 15
visit and it is estimated that immunogenicity data can be obtained from 110 or more participants
in Group 1, an interim analysis may be conducted whereby, if conducted, the formal non-inferiority
testing of Cohort 1 Group 1 (Primary Objectives 1a and 1b) will be performed on the available
data from the Cohort 1 Group 1 participants. The other primary objectives will only be tested at
the primary analysis.
In Cohort 2 a target of approximately 770 participants who have received primary vaccination with
the Pfizer BNT162b2 vaccine will initially be randomized in a 1:1:1 ratio into 3 groups to receive
a 1-dose booster vaccination regimen with Ad26.COV2.S until the group 6 is fully enrolled.
Thereafter, randomization will continue in a 1:1 ratio in groups 4 and 5 as shown in Table 1.
Table 1: 
Schematic Overview of Study Design and Groups
Cohort 
Group  
N 
Day 1
Vaccination
Cohort 1 
(Ad26.COV2.S 
primary 
vaccination)
1 
~ 330 
Ad26.COV2.S at 5×1010 vp
2 
~ 330 
Ad26.COV2.S at 2.5×1010 vp
3 
~ 110 
Ad26.COV2.S at 1×1010 vp
Cohort 2 
(BNT162b2 
primary 
vaccination)
4 
~ 330 
Ad26.COV2.S at 5×1010 vp
5 
~ 330 
Ad26.COV2.S at 2.5×1010 vp
6 
~ 110 
Ad26.COV2.S at 1×1010 vp
In Cohort 2, the study vaccine will first be administered to 6 sentinel participants (2 participants
per group), enrolled at the same study site, to monitor for unexpected severe adverse reactions.
The sentinel participants will be vaccinated at least 1 hour apart and closely observed for a
minimum of 30 minutes post-vaccination for the development of acute reactions. Each sentinel
participant is scheduled to come to the site for a study visit on Day 2 (approximately 24 hours
post-vaccination) to collect safety data, which will include solicited AEs (collected through e-
Diary) and unsolicited AEs, AESIs, and SAEs. The collected data will be reviewed in a blinded
manner by the PI and the sponsor’s SRP/SRS. Randomization and vaccination of additional
participants will be halted until the review of sentinel data is completed. In the absence of clinically
significant findings from the review of 24-hour safety data from the sentinel participants,
randomization and vaccination will continue.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
65
Status: Approved,  Date: 20 April 2022
Active surveillance for COVID-19-like signs and symptoms will occur, including a COVID-19
surveillance (symptom check) through the eCOA. All participants with COVID-19-like signs or
symptoms meeting the prespecified criteria for suspected COVID-19 (see Section 8.1.1) and all
participants with at least 1 positive RT-PCR test for SARS-CoV-2 within 5 days of symptom onset,
should undertake pre-specified COVID-19 procedures (see Section 8.1.2).
Study Duration
The study duration from screening until the last follow-up visit will be approximately 1 year per
participant. The study will consist of a 14-day screening phase, booster vaccination on Day 1, and
follow-up visits up to 1 year after booster vaccination (Target Visit Day 361±21 days).
If a participant is unable to complete the study, but has not withdrawn consent, an early exit visit
will be conducted. The end of study is considered as the last visit for the last participant in the
study.
Study Procedures
For each group, safety will be assessed by collection of solicited local (at injection site) and
systemic AEs, unsolicited AEs, AESIs, and SAEs. Other safety assessments include clinical
laboratory assessments, vital signs measurements (pulse/heart rate, preferably supine systolic and
diastolic blood pressure, respiratory rate, and body temperature) and physical examinations at the
time points indicated in Section 1.3.
After booster vaccination, participants will remain under observation at the study site for at least
30 minutes for presence of any acute reactions and solicited events. Any solicited local or systemic
AEs, unsolicited AEs, AESIs, SAEs, concomitant medications, and vital signs will be documented
by study site personnel following this observation period. In addition, participants will record
solicited signs and symptoms in an e-Diary for 7 days post-vaccination.
The occurrence of asymptomatic SARS-CoV-2 infection will be assessed by a non-S-protein assay
(eg, nucleocapsid [N] protein ELISA and/or SARS-CoV-2 immunoglobulin assay that is
dependent on the SARS-CoV-2 N protein) (see Section 8.1.1).
The reporting periods of AEs, AESIs, SAEs, and special reporting situations are detailed in
Section 8.4. Reporting periods for concomitant therapy are outlined in Section 6.7.
A final safety and immunogenicity follow-up visit is foreseen 1 year after vaccination for all
participants.
The first ~330 randomized participants in each of the cohorts will be assigned to 1 of 4 blood
collection subsets (Subsets 1, 2, 3 and 4). Blood samples will be collected for immunogenicity
assessments at selected timepoints as indicated in Table 2,
Table 3 and Section 1.3. Once the 4 blood collection subsets are enrolled, subsequent participants
will not be assigned to a subset. Participants not assigned to a subset (‘non-subset’ in Table 2)will
have immunogenicity samples taken at Day 1, Day 15, Day 120, Day 181 and Day 361.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
66
Status: Approved,  Date: 20 April 2022
Table 2: 
Blood Collection Schedule (Whole Blood) for Humoral and Cellular Immunogenicity
Assessments
Cohort 
Group  
Day 
1ab 
Day 
2b 
Day 
8ab 
Day 
15ab 
Day 
29a 
Day 
71 
Day 120 
Day 181 
Day
361
1 
1 
All 
Subset 3 
(N ~27) 
Subset 1 
(N ~27) 
All 
Subset 2 
(N ~28) 
Subset 3 
(N ~27) 
Non-
Subsetc 
(N=~380)
All 
All
2 
All 
Subset 3 
(N ~27) 
Subset 1 
(N ~27) 
All 
Subset 2 
(N ~28) 
Subset 3 
(N ~27)
All 
All
3 
All 
Subset 3 
(N ~27) 
Subset 1 
(N ~27) 
All 
Subset 2 
(N ~28) 
Subset 3
(N ~27)
All 
All
2 
4 
All 
Subset 3 
(N ~27) 
Subset 1 
(N ~27) 
All 
Subset 2 
(N ~28) 
Subset 3 
(N ~27) 
Non-
Subsetc 
(N=~380)
All 
All
5 
All 
Subset 3 
(N ~27) 
Subset 1 
(N ~27) 
All 
Subset 2 
(N ~28) 
Subset 3 
(N ~27) 
All 
All
6 
All 
Subset 3 
(N ~27) 
Subset 1 
(N ~27) 
All 
Subset 2 
(N ~28) 
Subset 3 
(N ~27)
All 
All
a. Selected timepoints include samples for PAXgene analysis.
b. Selected time points include samples for cytokine analysis (Subset 1, 2 and 3 only).
c. Day 120 blood draw for participants not allocated to a subset
Table 3: 
Blood Collection Schedule (PBMCa) for Cellular Immunogenicity Assessments
Group  
Day 1 
Day 15 
Day 181 
Day 361
1 
1 
Subset 4 
(N ~28) 
Subset 4 
(N ~28) 
Subset 4 
(N ~28) 
Subset 4
(N ~28)
2 
Subset 4 
(N ~28) 
Subset 4 
(N ~28) 
Subset 4 
(N ~28) 
Subset 4
(N ~28)
3 
Subset 4 
(N ~28) 
Subset 4 
(N ~28) 
Subset 4 
(N ~28) 
Subset 4
(N ~28)
2 
4 
Subset 4 
(N ~28) 
Subset 4 
(N ~28) 
Subset 4 
(N ~28) 
Subset 4
(N ~28)
5 
Subset 4 
(N ~28) 
Subset 4 
(N ~28) 
Subset 4 
(N ~28) 
Subset 4
(N ~28)
6 
Subset 4 
(N ~28) 
Subset 4 
(N ~28) 
Subset 4 
(N ~28) 
Subset 4
(N ~28)
a. Blood collection for PBMC will be performed in a subset of participants in all groups (Subset 4), if PBMC analysis is
feasible.
From external sources, the sponsor will obtain serum samples of approximately 300 individuals
collected 2 weeks to 2 months after completion of the 2-dose primary vaccination with Pfizer
BNT162b2. These samples will be used to assess NI of the seropositivity rate induced by a
Ad26.COV2.S booster following a primary Pfizer BNT162b2 regimen to the seropositivity post a
primary Pfizer BNT162b2 regimen.
Further details about the immunogenicity assessments are provided in Section 8.1.5.
An IDMC has been commissioned for the Ad26.COV2.S program. Any significant safety
information will be shared with the IDMC. After the primary analysis, data will be shared with the
IDMC on an ad hoc basis, if there is a safety issue or concern. (see Section 6.8).
The planned primary and final analyses are detailed in Section 9.5. A diagram of the study design
is provided in Section 1.2.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
67
Status: Approved,  Date: 20 April 2022
4.2. 
Scientific Rationale for Study Design
Dose Level Selection
The 5×1010 vp dose level was assessed for Ad26.COV2.S in study COV1001 and demonstrated
robust immunogenicity together with acceptable safety and reactogenicity  (see Section 4.3 for
more details).
The study will assess 3 dose levels of Ad26.COV2.S booster vaccination: 5×1010 vp, 2.5×1010 vp
and 1×1010 vp .
Blinding, Control, Study Phase/Periods, Intervention Groups
Randomization will be used to minimize bias in the assignment of participants to vaccine groups,
to increase the likelihood that known and unknown participant attributes (eg, demographic and
baseline characteristics) are evenly balanced across vaccine groups, and to enhance the validity of
statistical comparisons across vaccine groups. Blinded study vaccine will be used to reduce
potential bias during data collection and evaluation ofclinical endpoints.
Blinding will be guaranteed by the preparation of the study vaccine by an unblinded pharmacist or
by other qualified study site personnel with primary responsibility for study vaccine preparation
and dispensing, and by the administration of vaccine in a masked syringe by a blinded study
vaccine administrator. Participants in each Cohort will be randomly assigned to 1 of 3 groups,
based on a computer-generated randomization schedule prepared before the study by, or under the
supervision of, the sponsor.
Biomarker Collection
For participants with a positive test result for SARS-CoV-2 infection, biomarker analysis
(PAXgene, RNA-seq) will be performed for evaluation of COVID-19 cases and to explore
potentially informative biomarkers, eg, those associated with severe COVID-19.
4.2.1. 
Study-Specific Ethical Design Considerations
Potential participants will be fully informed of the risks and requirements of the study and, during
the study, participants will be given any new information that may affect their decision to continue
participation. They will be told that their consent to participate in the study is voluntary and may
be withdrawn at any time with no reason given and without penalty or loss of benefits to which
they would otherwise be entitled. Only participants who are fully able to understand the risks,
benefits, and potential AEs of the study, and provide their consent voluntarily will be enrolled.
The primary ethical concern is that this study will be performed in adult participants who will
receive no benefit from participation in the study, except for receiving vaccination against
SARS-CoV-2 and compensation for their time and for the inconveniences that may arise from
participation in the study. See Section 2.3 for details on potential and known benefits and risks,
and for the safety measures taken to minimize risk to participants.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
68
Status: Approved,  Date: 20 April 2022
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 US Department of
Health and Human Services Office for Human Research Protections, and US FDA guidelines of
550 mL in any 8-week period (US FDA 1998; US DHHS 1998), and as well as the European
Commission guidelines of 500 mL per donation and 3 L per consecutive 12 month period
(EC 1998).
4.3. 
Justification for Dose
The 5×1010 vp dose level of Ad26.COV2.S was evaluated in study COV1001 (see also Section 2).
However, recent data from study COV2001 suggest that a lower dose may be sufficient as a late
booster. A lower booster dose has potential advantages, including a lower inflammatory immune
response and lower incidence of resultant AEs. Therefore, 2.5×1010 vp and 1×1010 vp dose levels
will also be assessed. Evaluation of the 2.5×1010 vp and 1×1010 vp dose levels will generate end-
of-shelf-life data for the 5×1010 vp and 2.5×1010 vp dose levels, respectively.
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 (or designee) after completion of the final participant visit
at that study site, in the time frame specified in the Clinical Trial Agreement.
Study Completion Definition
A participant will be considered to have completed the study if the participant has completed
assessments at the 1-year follow-up visit post-booster vaccination.
5. 
STUDY POPULATION
Cohort 1: Study sites will be provided with a list of COV3001 participants who received
Ad26.COV2.S at that site and who are potentially suitable for roll-over into COV2008. Listed
participants will be those currently enrolled in COV3001 (ie, have not discontinued early), on whom
Day 1 and Day 29 stored serum samples are available, and without major COV3001 protocol
deviations that impacted immunogenicity. In addition, suitable participants will have had their
Day 29(post primary vaccination)blood sample collected within the permitted visit window.
Cohort 2: Participants who received the 2-dose regimen of BNT162b2, either while on Pfizer study
NCT04368728, or post authorization, are potentially eligible for COV2008 enrollment. All former
Pfizer trial participants MUST be no longer participating in study NCT04368728, but judged by the
investigator to be potentially compliant in study COV2008.
Screening suitable participants for enrollment into COV2008 will be performed within 14 days
before administration of the study vaccine. Refer to Section 5.4 for conditions under which the repeat
of any screening procedures are allowed.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
69
Status: Approved,  Date: 20 April 2022
The inclusion and exclusion criteria for enrolling participants into study COV2008 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.
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. 
Criterion modified per Amendment 3:
1.1 Cohort 1: Participant received Ad26.COV2.S in COV3001. The interval between the
Ad26.COV2.S primary vaccination should, preferably, be , ≥6 months prior to study
vaccination on COV2008, however a window of maximum -20 days is allowed.
Note: participants who received Ad26.COV2.S at the unblinding visit in study COV3001
will not be eligible for inclusion in this study.
Cohort 2:Participant completed primary vaccination with a 2-dose regimen of BNT162b2
vaccine (Pfizer). The last dose of BTN162b2 should, preferably, be ≥6 months prior to
study vaccination on COV2008, however a window of a maximum of-20 days is allowed.
2. 
Participant must provide consent indicating that he or she understands the purpose,
procedures and potential risks and benefits of the study, and is willing to participate in the
study.
3. 
Participant is willing and able to adhere to the prohibitions and restrictions specified in
this protocol.
4. 
Participant is 18 years of age on the day of signing the ICF.
5. 
In the investigator’s clinical judgment, participant may have a stable and well-controlled
medical condition including comorbidities associated with an increased risk of
progression to severe COVID-19 (CDC 2021a) (see Appendix 9)(including stable/well
controlled HIV infection)*. If participants are on medication for a medical condition
(including comorbidities associated with an increased risk of progression to severe
COVID-19), the medication dose cannot have been increased within 12 weeks preceding
vaccination and must be expected to remain stable for the duration of the study.
Participants will be included on the basis of relevant medical history and BMI
measurement at screening.
* 
Stable/well-controlled HIV infection includes:
a. Documented CD4 cell count ≥300 cells/µL within 6 months prior to screening.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
70
Status: Approved,  Date: 20 April 2022
b. Documented HIV viral load <50 copies/mL within 6 months prior to screening.
c. Participant must be on a stable anti-retroviral treatment (ART) for 6 months
(unless the change is due to tolerability, in which case the regimen can be for only
the previous 3 months; changes in formulation are allowed; nationwide guidelines
that require transition from one ART regimen to another are allowed) and the
participant must be willing to continue his/her ART throughout the study as
directed by his/her local physician.
Note: Participants with ongoing and progressive comorbidities associated with
HIV infection will be excluded but comorbidities associated with HIV infection
that have been clinically stable for the past 6 months are not an exclusion
criterion.
Laboratory methods for confirming a diagnosis of HIV infection are: Any evidence
(historic or current) from medical records, such as ELISA with confirmation with
Western Blot or real time reverse-transcriptase polymerase chain reaction (RT-
PCR), or of a detectable viral load (country-specific regulatory approved tests).
A laboratory result within 6 months of screening does not need to be repeated.
If a potential participant does not have HIV viral load and CD4 cell count data in
his/her medical records from the last 6 months, they will be instructed to go to
their local health care provider and obtain the necessary data for potential entry
into the study.
8. 
Participant agrees to not donate bone marrow, blood, and blood products from the study
vaccine administration until 3 months after receiving the study vaccine.
9. 
Participant must be willing to provide verifiable identification, has means to be contacted
and to contact the investigator during the study.
10. 
Participant must be able to read, understand, and complete questionnaires in the eCOA
(ie, the COVID-19 signs and symptoms surveillance question, the e-Diary, and the
electronic patient-reported outcomes (ePROs) [see Appendix 1 for definition of terms])a.
5.2. 
Exclusion Criteria
Any potential participant who meets any of the following criteria will be excluded from
participating in the study:
1. Participant has a clinically significant acute illness (this does not include minor illnesses such
as diarrhea or mild upper respiratory tract infection) or temperature ≥38.0ºC (100.4°F) within
24 hours prior to the planned study vaccination; randomization at a later date is permitted at
the discretion of the investigator. Please notify the sponsor (or medical monitor) of this
decision.
a Participants with visual impairment are eligible for study participation and may have caregiver assistance in
completing the eCOA questionnaires.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
71
Status: Approved,  Date: 20 April 2022
2. Participant has a known or suspected allergy or history of anaphylaxis or other serious adverse
reactions to vaccines or their excipients (including specifically the excipients of the study
vaccine; refer to the IB (IB Edition 4 Ad26.COV2.S 2021 and its addenda).
3. Participant has abnormal function of the immune system resulting from:
a. Clinical conditions (eg, autoimmune disease or potential immune mediated disease or
known or suspected immunodeficiency, or participant on hemodialysis) expected to
have an impact on the immune response of the study vaccine. Participants with clinical
conditions stable under non-immunomodulator treatment (eg, autoimmune thyroiditis,
autoimmune inflammatory rheumatic disease such as rheumatoid arthritis) may be
enrolled at the discretion of the investigator. Non-immunomodulator treatment is
allowed as well as steroids at a non-immunosuppressive dose or route of administration.
b. Chronic or recurrent use of systemic corticosteroids within 6 months before
administration of study vaccine and during the study. A substantially
immunosuppressive steroid dose is considered to be ≥2 weeks of daily receipt of 20 mg
of prednisone or equivalent.
Note: Ocular, topical, or inhaled steroids are allowed.
c. Administration of antineoplastic and immunomodulating agents or radiotherapy within
6 months before administration of study vaccine and during the study.
4. Participant received treatment with immunoglobulins (Ig) in the 3 months or exogenous blood
products (autologous blood transfusions are not exclusionary) in the 4 months before the
planned administration of the study vaccine or has any plans to receive such treatment during
the study.
Note: Specific monoclonal antibodies, not directed against SARS-CoV-2, are allowed.
5. Participant 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.
6. Participant has a known history of confirmed SARS-CoV-2 infection.
7. Criterion Modified per Amendment 6
7.1 
Participant received an investigational drug (including investigational drugs for
prophylaxis of COVID-19) within 30 days or used an invasive investigational medical device
within 30 days, received investigational Ig or monoclonal antibodies within 3 months, or received
convalescent serum for COVID-19 treatment within 4 months, or received an investigational
vaccine (excluding Ad26.COV2.S or BNT162b2) within 6 months before the planned
administration of the study vaccine or is currently enrolled or plans to participate in another
investigational study during the course of this study. See also Section 6.7.
Note: Participation in an observational clinical study is allowed at the investigator’s
discretion; please notify the sponsor (or medical monitor) of this decision.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
72
Status: Approved,  Date: 20 April 2022
8. Participant has a history of an underlying clinically significant acute or chronic medical
condition or physical examination findings for which, in the opinion of the investigator,
participation would not be in the best interest of the participant (eg, compromise the
well-being) or that could prevent, limit, or confound the protocol-specified assessments.
9. Participant has a history of heparin-induced thrombocytopenia or thrombosis in combination
with thrombocytopenia.
10. Participant has a contraindication to IM injections and blood draws eg, bleeding disorders.
11. Participant has, or has had, major psychiatric illness which in the investigator’s opinion would
compromise the participant’s safety or compliance with the study procedures.
12. Participant cannot communicate reliably with the investigator.
13. Participant who, in the opinion of the investigator, is unlikely to adhere to the requirements of
the study, or is unlikely to complete the full course of vaccination and observation.
14. Participant has a history of acute polyneuropathy (eg. Guillain-Barré syndrome).
15. Employee of the investigator or study site who has direct involvement in the proposed study.
16. History of capillary leak syndrome.
NOTE: Investigators should ensure that all study enrollment criteria have been met prior to
vaccination. If a participant's clinical status changes (including any available laboratory results or
receipt of additional medical records) after screening but before the study vaccine is given such
that the participant no longer meets all eligibility criteria, then the participant should be excluded
from participation in the study.
5.3. 
Lifestyle Considerations
Potential participants must be willing and able to adhere to the following lifestyle restrictions
during the study to be eligible for participation:
1. 
Refer to Section 6.7 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.
3. 
Agree to follow requirements for the electronic completion of the COVID-19 signs and
symptoms surveillance question in the eCOA.
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.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
73
Status: Approved,  Date: 20 April 2022
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 the criteria for participation in this study (screen failure) may be
rescreened once. Participants who are rescreened will be assigned a new participant number,
undergo the ICF process, and then restart a new screening phase.
5.5. 
Criteria for Temporarily Delaying Administration of Study Vaccine
The following events constitute a temporary contraindication to study vaccination:
 
Clinically significant acute illness at the time of vaccination. This does not include minor
illnesses, such as diarrhea or mild upper respiratory tract infection.
 
Fever (body temperature ≥38.0°C/100.4°F) within 24 hours prior to the planned time of
vaccination.
If any of these events occur at the scheduled time for vaccination, randomization at a later date
within the screening window is permitted at the discretion of the investigator and after consultation
with the sponsor. If randomization cannot occur within the screening window, rescreening is
required. Vaccination can be rescheduled, as long as this is in agreement with the allowed
windows. If the vaccination visit cannot be rescheduled within the allowed window or the
contraindications to vaccination persist, the sponsor should be contacted for further guidance.
6. 
STUDY VACCINATION AND CONCOMITANT THERAPY
6.1. 
Study Vaccine Administration
Ad26.COV2.S will be supplied at a concentration of 1×1011 vp/mL, as suspensions in single-use
vials. The Ad26.COV2.S vaccine will be dosed at 5×1010 vp, 2.5×1010 vp and 1×1010 vp.
Formulation buffer (diluent) will be supplied as 15 mM citrate, 5% (w/w) hydroxypropyl-β-
cyclodextrin, 0.4% (w/w) ethanol, 0.03% (w/w) polysorbate 80, 75 mM NaCl, pH 6.2. Formulation
buffer is withdrawn from one vial and added to a vial of vaccine to achieve the required vp
concentrations for different dose levels (full details in IPPI). Then 0.5 mL is withdrawn from the
vial for injection.
Participants will be vaccinated with the study vaccine on Day 1:
Study vaccines will be administered by IM injection into the deltoid muscle, preferably of the
non-dominant arm. If an injection cannot be given in the deltoids due to a medical or other
contraindication (for example, tattooed upper arms rendering it difficult to assess site
reactogenicity), use alternative locations such as the hip, thigh or buttocks (to be avoided in
overweight participants). In all circumstances, IM injections in other locations than the upper arm
are not considered protocol deviations.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
74
Status: Approved,  Date: 20 April 2022
Study vaccine administration must be captured in the source documents and the electronic case
report form (eCRF).
Study vaccines will be manufactured and provided under the responsibility of the sponsor. Refer
to the IB for a list of excipients (IB Edition 4 Ad26.COV2.S 2021 and its addenda).
Refer to the study site investigational product and procedures manual (SIPPM) and the
Investigational Product Preparation Instructions (IPPI) for additional guidance on study vaccine
administration.
6.2. 
Preparation/Handling/Storage/Accountability
Preparation/Handling/Storage
All study vaccine must be stored in a secured location with no access for unauthorized personnel
and at controlled temperatures as indicated on the clinical labels. If study vaccine is exposed to
temperatures outside the specified temperature range, all relevant data will be sent to the sponsor
to determine if the affected supplies can be used or will be replaced. The affected study vaccine
must be quarantined and not used until further instruction from the sponsor is received.
Refer to the SIPPM and the IPPI for additional guidance on study vaccine preparation, handling,
and storage.
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 vaccine administrator (a trained and qualified study nurse, medical doctor,
or otherwise qualified health care professional [HCP])who will perform the injection.
Accountability
The investigator is responsible for ensuring that all study vaccines received at the site are
inventoried and accounted for throughout the study. The study vaccines administered to the
participant must be documented on the vaccine accountability form. All study vaccines will be
stored and disposed of according to the sponsor's instructions. Study  site personnel must not
combine contents of the study vaccine containers.
Study vaccines must be handled in strict accordance with the protocol and the container label, and
must be stored at the study site in a limited-access area or in a locked cabinet under appropriate
environmental conditions. Unused study vaccines must be available for verification by the
sponsor's study site monitor during on-site monitoring visits. The return to the sponsor of unused
study vaccines will be documented on the vaccine accountability 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 accountability form.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
75
Status: Approved,  Date: 20 April 2022
Potentially hazardous materials containing hazardous liquids, such as needles and syringes, should
be disposed of immediately in a safe manner and therefore will not be retained for vaccine
accountability purposes.
Study vaccines should be dispensed under the supervision of the investigator or a qualified member
of the studysite personnel, or by a hospital/clinic pharmacist. Study vaccines will be supplied only
to participants participating in the study. Returned study vaccines must not be dispensed again,
even to the same participant. Study vaccines may not be relabeled or reassigned for use by other
participants. The investigator agrees neither to dispense the study vaccines from, nor store it at,
any site other than the study sites agreed upon with the sponsor. Further guidance and information
for the final disposition of unused study vaccines are provided in the SIPPM.
6.3. 
Measures to Minimize Bias: Randomization and Blinding
Vaccine Allocation
Procedures for Randomization
Central randomization will be implemented in this study. Cohort 1 participants will be randomly
assigned to 1 of3 Ad26.COV2.S vaccine groups (5×1010 vp [Group 1], 2.5×1010 vp [Group 2] and
1×1010 vp [Group 3]).
Cohort 2 participants will be randomly assigned to 1 of3 Ad26.COV2.S vaccine groups (5×1010
vp [Group 4] 2.5×1010 vp [Group 5] and 1×1010 vp [Group 6] see Section 4.1).
Randomization will be based on a computer-generated randomization schedule prepared before
the study by, or under the supervision of, the sponsor. The randomization will be balanced by using
randomly permuted blocks. The interactive web response system (IWRS) will assign a unique
intervention code, which will dictate the intervention assignment and matching study intervention
kit 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, due to the urgency of study initiation during the ongoing pandemic, the IWRS is not yet
available at the planned time of randomization of the first participant, randomization may be
started based on a paper randomization list until the IWRS is live.
The study will be stratified for age using 2 age strata: 18-59 and ≥60 years of age.
Blinding
The investigator will not be provided with randomization codes. IWRS codes will be maintained
within the IWRS, which has the functionality to allow the investigator to break the blind for an
individual participant.
Data that may potentially unblind the vaccine assignment (ie, immunogenicity data, study vaccine
accountability data, study vaccine allocation, biomarker or other specific laboratory data) will be

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
76
Status: Approved,  Date: 20 April 2022
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.
Under normal circumstances, the blind should not be broken until the database is finalized, with
two exceptions. First, the investigator may, in an emergency, determine the identity of the
intervention by contacting the IWRS. While the responsibility to break the intervention code in
emergency situations resides solely with the investigator, it is recommended that the investigator
contacts the sponsor or its designee if possible, to discuss the particular situation, before breaking
the blind. Telephone contact with the sponsor or its designee will be available 24 hours per day,
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 and in the source
document.
At selected study sites, the sponsor may unblind participants who are potentially eligible to roll
over into sponsor-supported study VAC31518COV2015. This unblinding of selected participants
may occur after all participants at the selected site have completed their 6-month study visit
procedures.
When possible, participants who have had their vaccine assignment unblinded should continue to
return for scheduled evaluations unless they have been selected and enrolled into
VAC31518COV2015, in which case the participants will discontinue the Schedule of Activities
for the current study and begin the Schedule of Activities for VAC31518COV2015. In this event,
participants will have an early exit visit for COV2008 prior to enrolling in VAC31518COV2015.
In general, randomization codes will be disclosed fully only if the study is completed and the
clinical database is closed. However, if a primary analysis is specified, the randomization codes
and, if required, the translation of randomization codes into intervention and control groups will
be disclosed to those authorized and only for those participants included in the primary analysis.
If randomized participants are withdrawn from vaccination 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. If randomized participants are withdrawn after the study vaccine is
administered, they will not be replaced.
In the event that randomization is started based on a paper randomization list, sealed randomization
codes will be provided for each participant containing coded details of study vaccine allocation.
All randomization codes, whether opened or sealed, will be collected after the end of the
participant's participation in the study. If emergency unblinding is required, the investigator may
determine the identity of the study vaccine by opening the sealed code. The date, time, and reason
for the unblinding must be documented in the appropriate section of the eCRF, and in the source
document.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
77
Status: Approved,  Date: 20 April 2022
6.4. 
Study Vaccination Compliance
Study vaccines will be administered IM by blinded qualified study site personnel at the study site.
The date and time of study vaccine administration and the location used will be recorded in the
eCRF.
6.5. 
Dose Modification
Dose modification is not applicable in this study.
6.6. 
Treatment of Overdose
For this study, any dose ofAd26.COV2.S greater than the highest dose tested in this study will be
considered an overdose. The sponsor does not recommend specific treatment for an overdose.
In the event of an overdose, the investigator or treating physician should:
 
Contact the Medical Monitor immediately.
 
Closely monitor the participant for AEs/AESIs/SAEs (ie, the participant will remain at the
study site for at least 1 hour and will be closely monitored for allergic or other reaction by
study staff. Follow-up telephone calls 12 hours and 24 hours post-dose will be made).
 
Document the quantity of the excess dose in the eCRF.
 
Report as a special reporting situation (see Appendix 10.4.4).
6.7. 
Concomitant Therapy
Prestudy specific therapies such as analgesic/antipyretic medications and non-steroidal
anti-inflammatory drugs, corticosteroids, antihistamines, and vaccinations administered up to
30 days before study vaccination must be recorded at screening.
Concomitant therapies such as analgesic/antipyretic medications and non-steroidal
anti-inflammatory drugs, corticosteroids, antihistamines, and vaccinations must be recorded until
28 days after administration of study vaccine. All other concomitant therapies should also be
recorded if administered in conjunction with a confirmed COVID-19 case or new or worsening
AEs reported per protocol requirements outlined in Section 8.4.1.
For all participants, concomitant therapies associated with an SAE or suspected AESI meeting the
criteria outlined in Sections 10.4.1 and 8.4.7, respectively, will be collected and recorded in the
eCRF from the moment of vaccination through the end of the study.
For all participants, concomitant therapies associated with unsolicited AEs will be collected and
recorded in the eCRF from the time of vaccination through 28 days after vaccination. Concomitant
therapies associated with solicited AEs will be collected by the participants and recorded in the
eCRF from the time of vaccination through 7 days after vaccination.
Use of any experimental medication (including experimental vaccines other than the study
vaccines) during the study is not allowed. Any participant who has received an anti-COVID-19

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
78
Status: Approved,  Date: 20 April 2022
vaccine (other than the study vaccine or Pfizer BNT162b2) or treatment will not receive study
vaccination. Participants may not receive an investigational drug (including investigational drugs
for prophylaxis of COVID-19) or use an invasive investigational medical device within 30 days
or receive an investigational Ig or monoclonal antibodies within 3 months, or receive convalescent
serum for COVID-19 treatment within 4 months or receive an investigational vaccine (including
investigational Adenoviral-vectored vaccines other than Ad26.COV2.S) within 6 months before
the planned administration of study vaccine. Cohort 2 participants will be required to provide the
dates they received primary vaccination with BNT162b2. Investigators are required to enter this
information in the eCRF.
Licensed live attenuated vaccines should be given at least 28 days before or at least 28 days after
a study vaccination. Other licensed (not live) vaccines (eg, 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. The
use of any coronavirus vaccine (licensed/authorized or investigational) other than Ad26.COV2.S
and BNT162b2, is disallowed at any time prior to vaccination and during the study. If a vaccine is
indicated in a post-exposure setting (eg, rabies or tetanus), it must take priority over the study
vaccine.
Antipyretics are recommended post-vaccination for symptom relief as needed. Prophylactic
antipyretic use is not encouraged; however, in some instances, it could be considered for
participants with special circumstances and/or comorbidities.
Chronic or recurrent use of systemic corticosteroidsa, at immunosuppressive dose and
administration of antineoplastic and immunomodulating agents or radiotherapy is prohibited
during the study and within 6 months before the planned administration of the study vaccine. If
any of these agents are indicated in a disease setting, these must take priority over the study
vaccine. Refer to Section 5.2 for further details of prohibited therapy.
The sponsor must be notified in advance (or as soon as possible thereafter) of any instances in
which prohibited therapies are administered. Depending on the time of the occurrence, any
participant who receives a prohibited concomitant medication will not be included in the
immunogenicity analyses.
6.8. 
Study Pausing Rules
The sponsor (including designated sponsor teams) and/or Sponsor Committee as well as the
investigator(s) will monitor safety in a blinded manner. Adverse events that may lead to the study
vaccination pausing rules are described below and will be assessed by the designated sponsor
team/committee to confirm that the study pause is warranted.
The occurrence of any of the following events will lead to a pause in further study vaccination:
aNote: Ocular, topical or inhaled steroids are allowed.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
79
Status: Approved,  Date: 20 April 2022
1. Death of a participant, considered related to study vaccine or if the causal relationship to
the study vaccine cannot be excluded; OR
2. One or more participants experience an SAE (solicited or unsolicited) that is determined
to be related to study vaccine; OR
3. One or more participants experience anaphylaxis or generalized urticaria, clearly not
attributable to other causes than vaccination with study vaccine
To enable prompt response to a situation that could trigger pausing rules, the investigator should
notify the sponsor’s medical monitor or designee (AND email the SAE form to Global Medical
Safety Operations, if applicable), immediately and no later than 24 hours after becoming aware of
any related SAE AND update the eCRF with relevant information on the same day the SAE
information is collected (see also Section 8.4). Based on the pausing criteria, the sponsor’s medical
monitor or designee then decides whether a study pause is warranted and informs the IDMC of the
decision. All sites will be notified immediately in case of a study pause. The sponsor’s medical
monitor or designee is responsible for the immediate notification of IDMC  members and
coordination of a IDMC meeting in case of a study pause.
In the case of a study pause, the IDMC will initially review blinded data, but can request unblinded
data, and will make recommendations regarding the continuation of the study to the sponsor study
team. Resumption of vaccinations will start only upon receipt of written recommendations by the
IDMC. The clinical site(s) will be allowed to resume activities uponreceipt of a written notification
from the sponsor. The formal recommendation from the IDMC  will be forwarded by the
investigator to the IRB and by the sponsor to the relevant health authorities, according to local
standards and regulations.
Vaccinations for an individual participant may be suspended for safety concerns other than those
described in the pausing criteria, at the discretion of the investigator if he/she feels the participant’s
safety may be threatened. The sponsor’s medical monitor or designee or the investigator(s) (upon
consultation with the sponsor’s medical monitor or designee) may initiate IDMC review for any
single event or combination of multiple events which, in their professional opinion, could
jeopardize the safety of the participants or the reliability of the data.
Vaccinations for the study may be suspended for safety concerns other than those described above,
or before pausing rules are met, if, in the judgment of the IDMC, participant safety may be
threatened.
7. 
DISCONTINUATION OF STUDY VACCINATION AND PARTICIPANT
DISCONTINUATION/WITHDRAWAL
7.1. 
Discontinuation of Study Vaccination
Not applicable.
7.2. 
Participant Discontinuation/Withdrawal From the Study
A participant will be withdrawn from the study for any of the following reasons:

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
80
Status: Approved,  Date: 20 April 2022
 
Lost to follow-up
 
Withdrawal of consent
 
Death
 
Repeated failure to comply with protocol requirements
When a participant withdraws before study  completion, the reason for withdrawal is to be
documented in the eCRF and in the source document. If the reason for withdrawal from the study
is withdrawal ofconsent, lost to follow-up, or death, then no additional assessments are allowed.
Any participants who receive a COVID-19 booster vaccine off study will remain on study
(continuing with all scheduled procedures and follow-up) but will be excluded from the formal
hypothesis testing of the primary objectives. Investigators are required to enter the off-study
booster information in the eCRF.
Withdrawal of Consent
A participant declining to return for scheduled visits does not necessarily constitute withdrawal of
consent. Alternate follow-up mechanisms that the participant agreed to when signing the consent
form apply as local regulations permit.
7.2.1. 
Withdrawal from the Use of Research Samples
Withdrawal from the Use of Samples in Future Research
The participant may withdraw consent for use of samples for research (refer to Long-Term
Retention of Samples for Additional Future Research in Section 10.3.5. In such a case, samples
will be destroyed after they are no longer needed for the clinical study. Details of the sample
retention for research are presented in the main ICF.
7.3. 
Lost to Follow-up
To reduce the chances of a participant being deemed lost to follow-up, prior to randomization
attempts should be made to obtain contact information from each participant, eg, home, work, and
mobile telephone numbers and email addresses for both the participant as well as appropriate
family members.
A participant will be considered lost to follow-up if the participant repeatedly fails to return for
scheduled visits and is unable to be contacted by the study site. A participant cannot be deemed
lost to follow-up until all reasonable efforts made by the study  site personnel to contact the
participant are deemed futile. The following actions must be taken if a participant fails to return to
the study site for a required study visit:
 
The study site personnel must attempt to contact the participant to reschedule the missed visit
as soon as possible, to counsel the participant on the importance of maintaining the assigned
visit schedule, to ascertain whether the participant wishes to or should continue in the study.
 
Before a participant is deemed lost to follow-up, the investigator or designee must make every
reasonable effort to regain contact with the participant (where possible, 3 telephone calls,

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
81
Status: Approved,  Date: 20 April 2022
emails, fax, and, if necessary, a certified letter to the participant’s last known mailing address,
or local equivalent methods). Locator agencies may also be used as local regulations permit.
These contact attempts should be documented in the participant’s medical records.
 
Should the participant continue to be unreachable, they will be considered to have withdrawn
from the study.
Should a study site close, eg, for operational, financial, or other reasons, and the investigator cannot
reach the participant to inform them, their contact information will be transferred to another study
site.
8. 
STUDY ASSESSMENTS AND PROCEDURES
Overview
The Schedule of Activities summarizes the frequency and timing ofall measurements applicable
to this study.
All participants will have access to an eCOA digital tool. This eCOA will be used to collect
COVID-19 signs and symptoms surveillance info for all participants, ePRO (Symptoms of
infection with Coronavirus-19 [SIC], including body temperature, and pulse oximetry results) for
all participants at baseline and in case of COVID-19-like signs and symptoms, and e-Diary data
on 7-day reactogenicity (solicited signs and symptoms, including body temperature). All eCOA
assessments should be conducted/completed before any tests, procedures, or other consultations to
prevent influencing participant responses. Refer to the PRO completion guidelines for instructions
on the administration of ePROs.
If multiple assessments are scheduled for the same timepoint, it is recommended that procedures
be performed in the following sequence: vital signs before blood draws. If needed, assessments
may be performed at another day within the applicable visit window. Actual dates and times of
assessments will be recorded in the source document and in the eCRF.
All participants will be provided a thermometer to measure body temperature. Participants will be
provided a ruler (to measure local injection site reactions) and a participant e-Diary in the eCOA
digital tool to record body temperature and solicited local (at injection site) and systemic signs and
symptoms. The e-Diary includes instructions on how to capture the data and grading scales to
assess severity of the signs and symptoms post-vaccination (reactogenicity). The study staff is
responsible for providing appropriate training to the participant to avoid missing or incorrect data.
The e-Diary will be reviewed by the study personnel at visits indicated in the Schedule of
Activities. If the e-Diary review is missed, the diary will be reviewed during the following visit.
All participants will also be provided with a kit to collect nasal swabs samples and receptacles to
collect saliva (see Section 8.1.2).
Over the course of the study, a total approximate blood volume up to a maximum of 180 mL will
be collected in participants not included in any of the subsets. A total approximate blood volume
up to a maximum of 405 mL will be collected in a subset of participants (Subset 4), which will

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
82
Status: Approved,  Date: 20 April 2022
include safety and cellular immunogenicity assessments on PBMC (if feasible). For the
participants included in subsets 1, 2, and 3, a total blood volume of approximately 195 mL will be
collected for safety and immunogenicity assessments without PBMC. For participants enrolled at
the BIDMC site, up to an additional 50 mL of blood per blood draw  will be collected for
experimental research amounting to an additional total approximate blood volume of 300 mL. For
participants with a suspected AESI, additional samples up to approximately 30 mL of blood will
be collected. Additional blood samples (up to 35 mL) will be collected from participants that
experience COVID-19-like signs and symptoms meeting prespecified criteria for suspected
COVID-19. The total blood volume to be collected is within the US Department of Health and
Human Services Office for Human Research Protections, and US Food and Drug Administration
(FDA) guidelines of 550 mL in any 8-week period. Refer to the Schedule of Activities for the
timings of blood samples over the course of the study, and in the event of a suspected COVID-19
episode. Repeat or unscheduled samples may be taken for safety reasons or for technical issues
with the samples.
Study visits, other than screening and visits at which study vaccination is scheduled, may take
place at a remote lab service or the participant’s home if there are travel restrictions in case of an
ongoing pandemic.
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 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.
Visit Windows
Visit windows are provided in the Schedule of Activities in Section 1.3. The participant should be
encouraged to come on the exact day planned and resort to use the visit window only when
absolutely necessary.
The timings of the post-vaccination visits will be determined relative to the actual day of the
corresponding vaccination.
Screening
Screening will be performed within 14 days prior to study vaccination or on the day of vaccination.
If screening is performed on the day of vaccination, Visit 1 and Visit 2 will coincide on Day 1 and
the predose assessment does not need to be performed. Screening must be completed and all
eligibility criteria must be fulfilled prior to randomization and vaccination.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
83
Status: Approved,  Date: 20 April 2022
Screening may be conducted in part via a sponsor- and IRB-pre-approved non-study-specific
screening consent process, but only if the relevant pre-screening tests are identical to the per
protocol screening tests and are within 2 weeks prior to vaccination. However, no study-specific
procedures, other than these pre-approved pre-screening assessments, will be performed until the
participant has signed the study-specific ICF. The study-specific ICF date will be entered into the
eCRF. The non-study-specific ICF will be considered source data.
Study-Specific Materials
The investigator will be supplied with the following:
 
IB for Ad26.COV2.S
 
Package Insert for Ad26.COV2.S
 
Thermometer
 
Ruler (to measure diameter of any erythema and swelling)
 
A pulse oximeter
 
Pharmacy manual (IPPI)/SIPPM
 
Laboratory manual
 
IWRS manual
 
eCRF completion guidelines
 
Sample ICF
 
Nasal swab kits, saliva recipients, and participant instructions
 
eCOA platform access and participant instructions. Participants may use their own eDevice
using an application if their device (smartphone or tablet) is compatible, or a web portal.
Provisioned devices will be available on a limited basis.
 
Lab kits/blood collection tubes and aliquoting materials
 
PBMC binders
 
ePRO completion instructions
 
Participant diaries
 
Contact information page(s)

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
84
Status: Approved,  Date: 20 April 2022
8.1. 
COVID-19and Immunogenicity Assessments
8.1.1. 
Prespecified Criteria for Suspected COVID-19
The criteria for suspected COVID-19 (ie, the triggers to proceed with home-collection of the nasal
swabs on COVID-19 Day 1-2 and to proceed with the COVID-19 Day 3-5 visit) are prespecified
as follows:
 A positive RT-PCR result for SARS-CoV-2, through a private or public laboratory
independent of the study, whether symptomatic or asymptomatic
OR
 New onset or worsening of any 1 of these symptoms, which lasts for at least 24 hours,
not otherwise explained:
o 
Headache
o 
Malaise (appetite loss, generally unwell, fatigue, physical weakness)
o 
Myalgia (muscle pain)
o 
Chest congestion
o 
Cough
o 
Runny nose
o 
Shortness of breath or difficulty breathing (resting or on exertion)
o 
Sore throat
o 
Wheezing
o 
Eye irritation or discharge
o 
Chills
o 
Fever (≥38.0°C or ≥100.4°F)
o 
Pulse oximetry value ≤95%, which is a decrease from baseline
o 
Heart rate ≥90 beats/minute at rest, which is an increase from baseline
o 
Gastrointestinal symptoms (diarrhea, vomiting, nausea, abdominal pain)
o 
Neurologic symptoms (numbness, difficulty forming or understanding speech)
o 
Red or bruised looking toes
o 
Skin rash
o 
Taste loss or new/changing sense of smell
o 
Symptoms of blood clots: pain/cramping, swelling or redness in your legs/calves
o 
Confusion

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
85
Status: Approved,  Date: 20 April 2022
o 
Bluish lips or face
o 
Clinical suspicion/judgment by investigator of symptoms suggestive for COVID19
As several of the prespecified criteria for suspected COVID-19 overlap with vaccine-related
reactogenicity, investigators' clinical judgment is required to exclude vaccine-related events when
assessing suspected COVID-19.
8.1.2. 
Procedures in the Event of COVID-19-like Signs and Symptoms
Procedures to be performed in the event a participant experiences signs or symptoms suggesting
possible COVID-19 are detailed in the Schedule of Activities in Section 1.3.3. A high-level
schematic overview is presented in Figure 2.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
87
Status: Approved,  Date: 20 April 2022
For all medical visits for COVID-19 or COVID-19 complications, including those resulting in
hospitalization, a standard list of questions will be provided (MA-COV form [Appendix 7]), with
the aim to collect additional information on any other diagnostics (eg, chest X-rays, spirometry,
pulmonary function tests) or interventions during the clinical course of COVID-19. The MA-COV
form will be provided to the participant at the vaccination visit and should be completed by the
medical care provider or the study site personnel during medical visits for COVID-19 or
COVID-19 complications.
Note: if for any reason a site visit per the procedures described below is not feasible, a member of
the study staff can visit the participant at home (or at the hospital or other location, if needed), if
allowed by local regulations.
Day 1-2 procedures in case of signs and symptoms
If a participant (or their designated caregiver) records in the eCOA or informs the site that he/she
experienced any signs or symptoms suggesting possible COVID-19, this will be considered
COVID-19 Day 1 (day of onset of signs and symptoms). The participant will be asked to complete
the ePROs (ie, the SIC [Appendix 5], including body temperature) in the eCOA.
Notes:
 
The SIC questionnaire asks the participant if he/she had any of the prespecified signs or
symptoms (see Appendix 5) during the past 24 hours, and (when applicable) to rate the
severity. The SIC questionnaire takes approximately 5 minutes to complete.
 
The participant should record the highest temperature in the last 24 hours in the SIC.
 
The participant should record at least 1 of the 3 pulse oximetry readings in the last
24 hours in the eCOA.
 
If a participant is unable to complete the SIC in the eCOA, a study staff member can
collect information on the participant’s symptoms and body temperature, by contacting
the participant by telephone (or visit the participant at home), reading the questions aloud
to the participant and entering the participant’s responses on the participant’s behalf.
More details are provided in eCOA Study Manual.
 
If a participant is unable to complete the SIC in eCOA, the reason for missing the SIC
completion should be recorded in the eCRF.
Based on the information collected through the SIC, the site will reach out to the participant at the
latest on COVID-19 Day 2 (the day after the day of symptom onset) to assess whether the reported
signs and symptoms qualify as a suspected COVID-19 episode using prespecified criteria
(Section 8.1.1). As several of the prespecified criteria for suspected COVID-19 overlap with
vaccine-related reactogenicity, investigators' clinical judgment is required to exclude vaccine-
related events when assessing suspected COVID-19. If the participant would actively reach out to
the site already on COVID-19 Day 1, the site should already make a first assessment on COVID-19
Day 1 to check whether the reported signs and symptoms qualify as a suspected COVID-19
episode using prespecified criteria (Section 8.1.1). As soon as the prespecified criteria for

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
88
Status: Approved,  Date: 20 April 2022
suspected COVID-19 are met (COVID-19 Day 1-2), the participant will be asked to undertake the
COVID-19 procedures. In particular:
 
The participant will be asked to continue to complete the ePROs in the eCOA as specified
above for COVID-19 Day 1:
o 
SIC (including body temperature): every day, preferably in the evening around the
same time each day.
o 
Blood oxygen saturation and pulse rate using a pulse oximeter 3 times a day,
preferably in the morning, at lunch time, and in the evening.
Note: the ePROs do not have to be completed if special circumstances occur, such as
hospitalization or ventilation, in which case the reason for not completing the ePROs
should be recorded by site staff in the eCRF.
 
The participant will be asked to collect a nasal swab at home on COVID-19 Day 1-2, as
soon as possible after it has been confirmed that the prespecified criteria for suspected
COVID-19 are met. If the participant requires assistance, a trained HCP can help the
participant to collect the nasal swab. The study site should arrange transfer of the nasal
swab to the study site as soon as possible after collection, preferably within 24 hours. The
COVID-19 Day 1-2 nasal swab can also be collected at the study site (or hospital or other
location, if needed), if preferred by the participant.
Day 1-2 procedures in case of a positive RT-PCR test outside the study site context
If a participant becomes aware of a positive RT-PCR test for SARS-CoV-2 he/she should contact
the site as soon as possible. The day the participant became aware of the positive RT-PCR test will
be considered COVID-19 Day 1. Regardless of whether the participant is symptomatic or
asymptomatic, they will be asked to:
 
Complete the (suspected) COVID-19 surveillance (symptom check) in the eCOA. In case
of COVID-like signs and symptoms they will need to complete the SIC (Appendix 5)
including body temperature) in the eCOA.
 
The participant will be asked to collect a nasal swab at home on COVID-19 Day 1-2, as
described for the participants with signs and symptoms (see above).
These precautionary measures are to ensure that site staff who come into physical contact with a
participant deemed to be a COVID-19 case undertake the proper safety procedures such as wearing
of personal protective equipment.
Day 3-5 procedures for all participants who have met the prespecified criteria for (suspected)
COVID-19
The participant will be asked to come to the site on COVID-19 Day 3-5 (between 2 and 4 days
after symptom onset/becoming aware of a positive RT-PCR test).
 
If a site visit is not feasible, a member of the study staff or designee could visit the
participant at home (or at the hospital or other location, if needed), if allowed by local
regulations. The study staff or designee visiting participants at home will use personal

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
89
Status: Approved,  Date: 20 April 2022
protective equipment according to local regulations. The COVID-19 Day 3-5 assessments
may also be performed by a trained HCP, if allowed per local regulations.
 
During Part 1 of the COVID-19 Day 3-5 visit, if the participant has experienced
COVID-19 like signs and symptoms, the site will interview the participant to assess
whether the reported signs and symptoms still qualify as a suspected COVID-19 episode
using prespecified criteria (Section 8.1.1). In addition, for all participants with (suspected)
COVID-19, a qualified member of the study site will measure vital signs (body
temperature, blood pressure, heart rate, and respiratory rate) and pulse oximetry. A
targeted physical examination will be performed based on the judgment of the
investigator. A nasal swab will be collected for detection of SARS-CoV-2 by a qualified
member of the study site.
 
If the signs and symptoms still meet the prespecified criteria for suspected COVID-19 on
COVID-19 Day 3-5 or if at least one nasal sample from COVID-19 Day 1-2 or Day 3-5
visits is positive for SARS-CoV-2 (tested by RT-PCR), the following assessments and
procedures are to be performed during Part 2 of the COVID-19 Day 3-5 visit: a blood
sample for exploration of biomarkers that correlate with SARS-CoV-2 infection and
COVID-19 severity will be collected by a qualified member of the study site. A saliva
sample will be taken by the participant during the study visit. The MRU questionnaire
will be completed based on a clinical interview (Appendix 6). The medical history and
description of COVID-19 episode will be collected by interview with the participant.
 
If signs and symptoms are still ongoing on COVID-19 Day 3-5, collection of SIC will
continue as specified in the next section (Closure of the COVID-19 episode) Closure of
the COVID-19 episode
 
If the signs and symptoms no longer meet the prespecified criteria for suspected
COVID-19 on COVID-19 Day 3-5 and no result from nasal swabs collected on Day 1-2
and/or Day 3-5 visits is available, the participant will not undertake any further
COVID-19 procedures. He/she will fall back to the default Schedule of Activities, until
the end of the study/early withdrawal.
Procedures during the 2-day cycles
If a participant has signs and symptoms that still meet the prespecified criteria for suspected
COVID-19 (Section 8.1.1) at COVID-19 Day 3-5 visit or has at least one positive nasal sample for
SARS-CoV-2 at COVID-19 Day 1-2 or COVID-19 Day 3-5 visits, he or she will be asked to
undertake the COVID-19 procedures, in particular:
 
All participants will be asked to collect a nasal swab and a saliva sample at home once
every 2 days (daily alternating between nasal swabs and saliva samples). If the participant
requires assistance, a trained HCP can help the participant to collect the nasal swabs
and/or saliva samples. The study site should arrange transfer of the nasal swabs and saliva
samples to the study site within 3 days after collection. Details are provided in the
laboratory manual.
 
In case of signs and symptoms: The participant will be reminded to further complete the
ePROs in the eCOA as described for COVID Day 1-2:

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
90
Status: Approved,  Date: 20 April 2022
 
In case the nasal swabs collected on Day 1-2 or Day 3-5 visits are tested positive for
SARS-CoV-2 and the participant is asymptomatic: The participant will be reminded to
further complete (suspected) COVID-19 surveillance (symptom check).
 
If, on COVID-19 Day 3-5, the participant stopped the COVID-19 procedures and
returned to default Schedule of Activities, due to lack of signs and symptoms and
unavailability of results from nasal swabs collected on Day 1-2 and/or Day 35 visits, the
participant will be contacted as soon as at least one of these samples is found to be positive
for SARS-CoV-2 presence. The participant will be asked to resume COVID-19
procedures, until 14 days after symptom onset (COVID-19 Day 15) or until resolution
of the COVID-19 episode, whichever comes last.
Notes:
o 
Participants should be encouraged by the site to collect nasal swabs and saliva
samples as indicated in the Schedule of Activities (Section 1.3). If the participant is
unable or unwilling to collect all samples as requested, the participant should still
complete the other COVID19assessments, including the visit at COVID-19 Day 29.
Day 29 procedures
If a participant has at least 1 SARS-CoV-2 positive nasal swab collected on COVID-19 Day 1-2
or Day 3-5, then he or she will be asked to return to the site on COVID-19 Day 29 (±7 days) where
a blood sample will be drawn for sero-confirmation and exploration of biomarkers that correlate
with SARS-CoV-2 infection and COVID-19 severity. A qualified member of the study site will
measure vital signs (body temperature, blood pressure, heart rate, and respiratory rate) and pulse
oximetry. A targeted physical examination will be performed based on the judgment of the
investigator. The MRU questionnaire will be completed based on a clinical interview
(Appendix 6). The medical history and description of COVID-19 episode will be collected by
interview with the participant. If the participant is still symptomatic, he/she will complete the SIC
(Appendix 5) in the eCOA. Asymptomatic participants will complete the (suspected) COVID-19
surveillance (symptom check).
Notes: COVID-19 Day 29 should still be performed even if the nasal swabs results are still
pending. The COVID-19 Day 29 assessments may also be performed by a trained HCP at
the participant’s home, if allowed per local regulations.
This visit can be combined with a regular study visit if within the applicable visit windows.
Closure of the COVID-19 episode
The participant should continue the COVID-19 procedures until any of the following occurs, based
on molecular test results:
 
If both nasal swabs (collected on COVID-19 Day 1-2 and COVID-19 Day 3-5) are
negative for SARS-CoV-2, the participant will not undertake any further COVID-19
procedures and will fall back to the default Schedule of Activities, until the end of the
study/early withdrawal.
 
If the participant has at least 1 SARS-CoV-2 positive nasal swab collected on COVID-19
Day 1-2 or Day 3-5 visits, then the participant will be asked to undertake the COVID-19

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
91
Status: Approved,  Date: 20 April 2022
procedures (2-day cycles) until the EoT visit or 14 days after symptom onset (COVID-
19 Day 15) or until resolution of the COVID-19 episode, whichever comes lasta.
Resolution of the COVID-19 episode is defined as having 2 consecutive SARS-CoV-2
negative nasal swabs and 2 consecutive days with no COVID-19-related signs or
symptoms. Once past COVID-19 Day 15, participants should stop the collection of nasal
swabs and saliva samples as soon as 2 consecutive nasal swabs are SARS-CoV-2
negative, but (if still symptomatic at that time) should continue completing the ePROs
(including SIC, body temperature, and pulse oximetry) in the eCOA until 2 consecutive
days with no COVID-19-related signs or symptoms.
Note: for participants who have signs and symptoms present at baseline (assessed
pre-vaccination), only signs and symptoms that are associated with COVID-19 and that
developed during the COVID-19 episode are to be taken into account.
Note: For participants experiencing COVID-19 episodes close to the end of their study
participation, COVID-19episode procedures will be followed up to their EoT visit e.g. if
an episode starts -4 days prior to a scheduled EoT visit, COVID-19 Day 1- 2 and
COVID-19 Day 3-5 procedures will be followed as much as possible, and then study
procedures will be stopped.
 
If signs and symptoms are still ongoing on COVID-19 Day 3-5, collection of SIC will
be continued until at least 14 days after onset unless both COVID-19 Day 1-2 and
COVID-19 Day 3-5 are both negative. If either of the swabs is positive or the result is
unknown AND the participant is beyond 14 days after onset of symptoms, the SIC can
be stopped after 2 days without signs and symptoms.
 
If 2 consecutive nasal swabs negative for SARS-CoV-2 are not available due to
operational reasons (eg, delays in results availability), participants may cease collection
of nasal swabs and saliva samples after COVID-19 Day 29, provided they have 2
consecutive days with no COVID-19-related signs and symptoms. In these cases,
participants may be asked to resume sample collection if nasal sample results
once
available
do not present with 2 consecutive negative swabs for SARS-CoV-2.
Upon closure of the COVID-19 episode and procedures, all participants will fall back to the default
Schedule of Activities (Section 1.3), until the end of the study/early withdrawal. All confirmed
COVID-19 episodes will be communicated to the respective participant and to other authorities
according to local regulations.
If the participant experiences new signs or symptoms suggesting possible COVID-19 at a later
point in time, the participant would re-start the COVID-19 procedures from COVID-19 Day 1
onwards.
With regards to the ePRO (ie, the SIC, including body temperature):
 
The ePRO instrument will be provided in the local language in accordance with local
guidelines.
a long-term sequelae of COVID-19 will not be followed until their resolution if not resolved within a month.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
92
Status: Approved,  Date: 20 April 2022
 
The ePRO instrument must be available for regulators and for IRB/ERC submissions,
therefore the ePRO instrument or screen shots need to be attached to the protocol or provided
in a companion manual with the instruments that will be submitted with the protocol.
 
The ePRO and AE data will not be reconciled with 1 another.
8.1.3. 
Monitoring for Asymptomatic SARS-CoV-2 Infection
Analysis of antibodies binding to the SARS-CoV-2 N protein will be measured at Day 1 by non-S
protein assays (eg, N protein ELISA and/or SARS-CoV-2 immunoglobulin assay that is dependent
on the SARS-CoV-2 N protein). Participants who are SARS-CoV-2 N protein positive at any time
during the study will be excluded from the immunogenicity analysis from that timepoint onwards
(see Section 9.3).
8.1.4. 
Clinical Severity Adjudication Committee
The Clinical Severity Adjudication Committee will be utilized for adjudication of the severity of
COVID-19 cases taking into account all available relevant information at the time of adjudication.
The Clinical Severity Adjudication Committee's decisions will be considered the definitive
classification of the case. The role of the Committee and adjudication process will be provided in
the committee's charter and more details regarding the impact on the analysis will be provided in
the Statistical Analysis Plan (SAP).
8.1.5. 
Immunogenicity Assessments
Venous blood samples will be collected for assessment of humoral and cellular immune responses.
Time points are detailed in the Schedule of Activities (Section 1.3).
If the participant is unable to complete the study without withdrawing consent, immunogenicity
samples will be taken at the early exit visit, but only if the early exit visit is at least 10 days after
the previous immunology blood draw. See Section 1.3 for further details.
From external sources, the sponsor will obtain serum samples of approximately 300 individuals
collected 2 weeks to 2 months after completion of the 2-dose primary vaccination with Pfizer
BNT162b2. These samples will be used to assess NI of the seropositivity rate induced by a
Ad26.COV2.S booster following a primary Pfizer BNT162b2 regimen to the seropositivity post a
primary Pfizer BNT162b2 regimen.
Humoral and cellular immunogenicity assays may include, but are not limited to, the assays
summarized in Table 4 and Table 5, respectively.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
93
Status: Approved,  Date: 20 April 2022
Table 4: 
Summary of Humoral Immunogenicity Assays
Assay 
Purpose
Primary/Secondary endpoints
SARS-CoV-2 neutralization
(VNA)
Analysis of neutralizing antibodies to the live SARS-CoV-2 original strain
and leading variant of high consequence or concern*, using a live VNA and/or
pseudovirion expressing S protein neutralization assay
Secondary endpoints
SARS-CoV-2 neutralization
(VNA)
Analysis of neutralizing antibodies to additional relevant live SARS-CoV-2
variants of concern and/or pseudovirion expressing S protein from SARS-
CoV-2 variants of concern
SARS-CoV-2 binding 
antibodies (ELISA and/or MSD) 
Analysis of antibodies binding to SARS-CoV-2 or individual SARS-CoV-2
proteins (eg, S and RBD proteins from the SARS-CoV-2 original strain,
leading variant of high consequence or concern* and/or other relevant variants
of concern)
Exploratory endpoints
SARS-CoV-2 neutralization 
(neutralization assay) 
Analysis of neutralizing antibodies to the vaccine strain (or other strain), as
measured by an alternative neutralization assay (different from the VNA used
for the primary and secondary endpoint)
Adenovirus neutralization 
(neutralization assay)
Analysis of neutralizing antibodies to adenovirus
SARS-CoV-2 binding 
antibodies 
Analysis of antibodies binding to SARS-CoV-2 or individual SARS-CoV-2
proteins (eg, S and RBD proteins from the SARS-CoV-2 original strain,
leading variant of high consequence or concern* and/or other relevant variants
of concern) measured by an alternative binding antibody assay (different from
the binding antibody assay used in the secondary endpoints)
Functional and molecular 
antibody characterization 
Analysis of antibody characteristics including Fc-mediated viral clearance,
avidity, Fc characteristics, Ig subclass and IgG isotype directed against the
original SARS-CoV-2 strain, leading variant of high consequence or concern*
and/or other variants of concern
Epitope-specificity 
characterization
Analysis of site-specificity, epitope mapping
Cytokine profiling 
Analysis of cytokines, chemokines, and other proteins of the innate or
adaptive immune response in the serum or plasma
Passive transfer 
Analysis of immune mediators correlating with protection against
experimental SARS-CoV-2 challenge in a suitable animal model
ELISA  enzyme linked immunosorbent assay; Ig  immunoglobulin; MSD  Meso Scale Discovery; RBD  receptor binding
domain; S  spike; SARS CoV 2  severe acute respiratory syndrome coronavirus 2; VNA  virus neutralization assay
* As defined by the Centers for Disease Control and Prevention (CDC Aug 2021c) at the time of the analysis
Table 5: 
Summary of Cellular Immunogenicity Assays
Assay 
Purpose
Exploratory endpoints
Flow cytometry (ICS) 
Analysis of T cell responses to SARS-CoV-2 S protein peptides from the original
strain, leading variant of high consequence or concern* and/or other variants of
concern by ICS including CD4+/CD8+, IFNγ, IL-2, TNFα, IL-4, IL-5, IL-13,
and/or other Th1/Th2 markers (if feasible)
ELISpot 
IFNγ and IL-4 responses to SARS-CoV-2 S protein peptides by PBMCs (if
feasible), based on single or dual ELISpot
Gene expression analysis 
Analysis of gene expression by RNA transcript profiling and/or analysis of
protein translates, in cells or whole blood stimulated with SARS-CoV-2S protein
peptides or in unstimulated cells or whole blood (ex vivo).
ELISpot  enzyme linked immunospot (assay); ICS  intracellular cytokine staining; IFNγ  interferon gamma; IL
 interleukin;
PBMC  peripheral blood mononuclear cell; S  spike; SARS CoV 2  severe acute respiratory syndrome coronavirus 2; Th:
T helper; TNFα  tumor necrosis factor alpha
* As defined by the Centers for Disease Control and Prevention (CDC Aug 2021c) at the time of the analysis

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
94
Status: Approved,  Date: 20 April 2022
8.2. 
Exploratory Efficacy Assessments
Identification and molecular confirmation of SARS-CoV-2 infection and symptomatic COVID-19
will be performed throughout the study as described in Section 8.1.2 and adjudicated as described
in Section 8.1.4. The ePRO to evaluate vaccine efficacy parameters will be the SIC.
Case Definition for Mild COVID-19
 
A SARS-CoV-2 positive RT-PCR or molecular test result from any available respiratory tract
sample (eg, nasal swab sample, sputum sample, throat swab sample, saliva sample) or other
sample;
AND at any time during the course of observationa:
 
One of the following symptoms: fever (≥38.0C or ≥100.4°F), sore throat, malaise (loss of
appetite, generally unwell, fatigue, physical weakness), headache, muscle pain (myalgia),
gastrointestinal symptoms, cough, chest congestion, runny nose, wheezing, skin rash, eye
irritation or discharge, chills, new or changing olfactory or taste disorders, red or bruised
looking feet or toes, or shaking chills or rigors.
A case is considered mild when it meets the above case definition but not the moderate to
severe/critical definition.
Case Definition for Moderate COVID-19
 
A SARS-CoV-2 positive RT-PCR or molecular test result from any available respiratory tract
sample (eg, nasal swab sample, sputum sample, throat swab sample, saliva sample) or other
sample AND at any time during the course of observation:
Any 1 of the following new or worsening signs or
symptoms:
OR
Any 2 of the following new or worsening signs or
symptoms:
 
Respiratory rate ≥20 breaths/minute
 
Abnormal saturation of oxygen (SpO2) but
still >93% on room air at sea level*
 
Clinical or radiologic evidence of pneumonia
 
Radiologic evidence of deep vein thrombosis
(DVT)
 
Shortness of breath or difficulty breathing
 
Fever (≥38.0°C or ≥100.4°F)
 
Heart rate ≥90 beats/minute
 
Shaking chills or rigors
 
Sore throat
 
Cough
 
Malaise as evidenced by 1 or more of the following**:
 
Loss of appetite
 
Generally unwell
 
Fatigue
 
Physical weakness
 
Headache
 
Muscle pain (myalgia)
 
Gastrointestinal symptoms (diarrhea, vomiting, nausea,
abdominal pain)**
 
New or changing olfactory or taste disorders
 
Red or bruised looking feet or toes
* SpO2 criteria will be adjusted according to altitude, per
the investigator judgment.
** Having 2 or more elements of a symptom (eg,
vomiting and diarrhea or fatigue and loss of appetite) is
counted only as 1 symptom for the case definition. To
meet the case definition, a participant would need to
have at least 2 different symptoms.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
95
Status: Approved,  Date: 20 April 2022
Case Definition for Severe/Critical COVID-19
 
A SARS-CoV-2 positive RT-PCR or molecular test result from any available respiratory tract
sample (eg, nasal swab sample, sputum sample, throat swab sample, saliva sample) or other
sample
AND any 1 of the following at any time during the course of observationa:
 
Clinical signs at rest indicative of severe systemic illness (respiratory rate ≥30 breaths/minute,
heart rate ≥125 beats/minute, oxygen saturation (SpO2)≤93% on room air at sea level*, or
partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2)<300 mm Hg)
* SpO2 criteria will be adjusted according to altitude per the investigator judgment.
 
Respiratory failure (defined as needing high-flow oxygen, non-invasive ventilation,
mechanical ventilation, or extracorporeal membrane oxygenation [ECMO])
 
Evidence of shock (defined as systolic blood pressure <90 mm Hg, diastolic blood pressure
<60 mm Hg, or requiring vasopressors)
 
Significant acute renal, hepatic, or neurologic dysfunction
 
Admission to the ICU
 
Death
Case Definition for Asymptomatic COVID-19
Asymptomatic cases of COVID-19, as determined by seropositivity for the SARS-CoV-2 N
protein.
8.3. 
Safety Assessments
Details regarding the IDMC are provided in Committees Structure in Section 10.3.6.
Adverse events will be reported and followed by the investigator as specified in Section 8.4 and
Appendix 4.
Any clinically relevant changes occurring during the study must be recorded on the AE section of
the eCRF.
a 
Participants will be asked to undertake the COVID-19 procedures until 14 days after symptom onset
(COVID-19 Day 15) or until resolution of the COVID-19 episode, whichever comes last (see Section 8.1.2). For
participants experiencing COVID-19 episodes close to the end of their study participation, COVID episode procedures
will be followed up to their EoT visit.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
96
Status: Approved,  Date: 20 April 2022
Any clinically significant abnormalities persisting at the end of the study/early withdrawal will be
followed by the investigator until resolution or until a clinically stable condition is reached.
For participants undergoing COVID-19 episodes near, or at the end of the trial participation, the
End of Trial (EoT visit) should not be delayed in orderto capture full illness episode. Any clinically
significant abnormalities persisting at the end of the study/early withdrawal will be followed by
the investigator until resolution, or until a clinically stable condition is reached (see Section 8.4.1
for further details).
The study will include the following evaluations of safety and reactogenicity according to the time
points provided in the Schedule of Activities (Section 1.3).
8.3.1. 
Physical Examinations
A history-directed physical examination, including height and body weight, will be carried out at
screening. To obtain the actual body weight, participants must be weighed lightly clothed. The
height should be measured without footwear.
At all other visits, an abbreviated, symptom-directed examination might be performed by the
investigator based on any clinically relevant issues or symptoms, and medical history.
Symptom-directed physical examination may be repeated if deemed necessary by the investigator.
A targeted physical examination will be performed during a COVID-19 episode by the investigator
or designated medically trained clinician (or a trained HCP, if allowed per local regulations).
Physical examinations will be performed by the investigator or 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.
8.3.2. 
Vital Signs
Vital signs will be assessed at the timepoints specified in the Schedule of Activities (Section 1.3).
On Day 1, vital signs will be measured before vaccination and after vaccination following the
30 minutes post-vaccination observation period.
Body temperature (oral route preferred, or in accordance with the local standard of care),
pulse/heart rate, respiratory rate, and blood pressure will be assessed.
Participants will utilize an e-Diary to record body temperature measurements post-vaccination.
All participants with COVID-19 signs and symptoms should measure body temperature daily (oral
route preferred, or in accordance with the local standard of care) and record the highest temperature
in the last 24 hours each day in the ePRO in the eCOA, for the duration of follow-up of COVID-19
episodes (as defined in Section 8.1.2).
Vital signs will be measured during a COVID-19 episode by a qualified member of the study site.
This includes measurement of preferably supine systolic and diastolic blood pressure, heart rate,

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
97
Status: Approved,  Date: 20 April 2022
respiratory rate, oxygen saturation, and body temperature. It is recommended that vital signs are
measured before collection of nasal swabs and blood draws.
Blood pressure measurements will be assessed in a supine position (preferably) with a completely
automated device. Manual techniques will be used only if an automated device is not available.
Blood pressure and pulse/heart rate measurements should be preceded by at least 5 minutes of rest
in a quiet setting without distractions (eg, television, cell phones). Vital signs are recommended
before blood sampling.
8.3.3. 
Clinical Safety Laboratory Assessments
Blood samples for clinical laboratory assessments (as detailed in Appendix 2) will be collected as
described in the Schedules of Activities in Section 1.3.
In the case of a thrombotic event or TTS, every effort should be made to collect local
hospital/laboratory test results obtained by the treating physician to allow rapid diagnosis and
treatment. This information should be reported through the AESI form (see Appendix 11)
electronically per instructions in the eCRF completion guidelines. In addition, every effort should
be made to collect blood samples from the participant for a platelet count (local laboratory  or
substitute for local laboratory) and other applicable testing (central laboratory) (see the Schedule
of Activities in Section 1.3.2 and Appendix 2). The Investigator will review the laboratory test
results to assist the investigation of the AESI.
See Section 8.4.7 for details on laboratory test details to be reported for an AE of
thrombocytopenia.
8.4. 
Adverse Events, Serious Adverse Events, Adverse Events of Special
Interest, and Other Safety Reporting
Timely, accurate, and complete reporting and analysis of safety information, including AEs, SAEs,
AESIs and product quality complaints (PQCs), from clinical studies are crucial for the protection
of participants, investigators, and the sponsor, and are mandated by regulatory agencies
worldwide. The sponsor has established Standard Operating Procedures in conformity with
regulatory requirements worldwide to ensure appropriate reporting of safety information; all
clinical studies conducted by the sponsor or its affiliates will be conducted in accordance with
those procedures.
Adverse events will be reported by the participant (or, when appropriate, by a caregiver, surrogate,
or the participant's legally acceptable representative) for the duration of the study.
Further details on AEs, SAEs, AESIs, and PQCs can be found in Appendix 4.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
98
Status: Approved,  Date: 20 April 2022
8.4.1. 
Time Period and Frequency for Collecting Adverse Event, Adverse
Event of Special Interest, and Serious Adverse Event Information
All Adverse Events
Adverse events and special reporting situations, whether serious or non-serious, that are related to
study procedures or that are related to non-investigational sponsor products will be reported from
the time a signed and dated ICF is obtained until the end of the study/early withdrawal.
Clinically relevant medical events not meeting the above criteria and occurring between signing
of ICF and moment of vaccination will be collected on the medical history eCRF page as
pre-existing conditions.
Solicited AEs, collected through an e-Diary, will be recorded from the time of vaccination until 7
days post-vaccination.
All other unsolicited AEs and special reporting situations, whether serious or non-serious, will be
reported from the time of vaccination until 28 days post-vaccination.
All AESIs, SAEs and AEs leading to discontinuation from the study (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. The
sponsor will evaluate any safety information that is spontaneously reported by an investigator
beyond the time frame specified in the protocol.
All AEs will be followed until resolution or until clinically stable.
For participants experiencing a COVID-19episode near the end of study participation: Procedures
outlined in Section 1.3.3 should be followed up to to the EoT visit only. For example, if a
COVID-19episode starts -4 days prior to scheduled EoT visit, the Day 1- Day 2 and Day 3- Day
5 procedures should be followed, as much is possible, and then study procedures should stop. Once
a participant has had their EoT visit, the outcome cannot be reported in  the eCRF, therefore
investigators should record the resolution/outcome of the COVID-19 illness in the appropriate
source documents.
Adverse Events of Special Interest
TTS is considered to be an AESI. Suspected AESIs (thrombotic events and thrombocytopenia
[defined as platelet count below 150,000/µL (Brighton Collaboration 2021)]) will be recorded
from the moment of vaccination until the end of the study/early withdrawal. An AESI Adjudication
Committee with appropriate expertise will be established to evaluate each suspected AESI and
determine whether it is a case of TTS (see Section 8.4.7).
Serious Adverse Events
All SAEs, as well as PQCs, occurring during the study must be reported to the appropriate sponsor
contact person by study site personnel within 24 hours of their knowledge of the event.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
99
Status: Approved,  Date: 20 April 2022
Serious adverse events, including those spontaneously reported to the investigator must be
reported. The sponsor will evaluate any safety information that is spontaneously reported by an
investigator beyond the time frame specified in the protocol.
Information regarding SAEs will be transmitted to the sponsor using the SAE Form and Safety
Report Form of the eCRF, which must be completed and reviewed by a physician from the study
site, and transmitted to the sponsor within 24 hours. The initial and follow-up reports of an SAE
should be transmitted electronically or by facsimile (fax). Telephone reporting should be the
exception and the reporter should be asked to complete the appropriate form(s) first.
8.4.2. 
Method of Detecting Adverse Events, Adverse Events of Special
Interest, and Serious Adverse Events
Care will be taken not to introduce bias when detecting AEs, AESIs, or SAEs. Open-ended and
nonleading verbal questioning of the participant is the preferred method to inquire about AE
occurrence.
Solicited Adverse Events
Solicited AEs are used to assess the reactogenicity of the study vaccine and are predefined local
(at injection site) and systemic events for which the participant is specifically questioned and
which are noted by participants in their e-Diary.
After booster vaccination, participants will remain under observation at the study site for at least
30 minutes for the presence of any acute reactions and solicited events.
In addition, participants will record solicited signs and symptoms in an  e-Diary for 7 days
post-vaccination. All participants will be provided with an  e-Diary and instructions on how to
complete the diary (see Overview in Section 8). Electronic diary information will be transferred
from the e-Diary source to the sponsor. After review and verbal discussion of the initial e-Diary
entries with the participant, the investigator will complete his/her own assessment in the relevant
sections of the eCRF/eCOA. Once a solicited sign or symptom from an e-Diary is considered to
be of severity Grade 1 or above, it will be recorded as a solicited AE.
1) 
Solicited Injection Site (Local) Adverse Events
Participants will be asked to note in the e-Diary occurrences of injection site pain/tenderness,
erythema and swelling at the study vaccine injection site daily for 7 days post-vaccination (day of
vaccination and the subsequent 7 days). The extent (largest diameter) of any erythema and swelling
should be measured (using the ruler supplied) and recorded daily. The case definitions for solicited
injection site events can be found in the references (Gidudu 2012; Kohl 2007).
2) 
Solicited Systemic Adverse Events
Participants will be instructed on how to record daily temperature using a thermometer provided
for home use. Participants should record the temperature in the e-Diary in the evening of the day
of vaccination, and then daily for the next 7 days approximately at the same time each day. If more

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
100
Status: Approved,  Date: 20 April 2022
than one measurement is made on any given day, the highest temperature of that day will be used
in the eCRF.
Fever is defined as endogenous elevation of body temperature ≥38° C, as recorded in at least one
measurement (Marcy 2004).
Participants will also be instructed on how to note signs and symptoms in the e-Diary on a daily
basis for 7 days post-vaccination (day of vaccination and the subsequent 7 days), for the following
events: fatigue, headache, nausea, and myalgia.
Unsolicited Adverse Events
Unsolicited AEs are all AEs for which the participant is not specifically questioned in the
participant e-Diary.
For details about AESIs, refer to Section 8.4.7.
8.4.3. 
Follow-up of Adverse Events, Adverse Events of Special Interest and
Serious Adverse Events
The investigator is obligated to perform or arrange for the conduct of supplemental measurements
and evaluations as medically indicated to elucidate the nature and causality of the AE, AESI, SAE,
or PQC as fully as possible. This may include additional laboratory tests or investigations,
histopathological examinations, or consultation with other health care professionals.
Adverse events, including pregnancy, will be followed by the investigator as specified in
Appendix 4.
8.4.4. 
Regulatory Reporting Requirements for Serious Adverse Events
The sponsor assumes responsibility for appropriate reporting of AEs to the regulatory authorities.
The sponsor will also report to the investigator (and the head of the investigational institute where
required) all suspected unexpected serious adverse reactions (SUSARs). The investigator (or
sponsor where required) must report SUSARs to the appropriate Institutional Review Board (IRB)
that approved the protocol unless otherwise required and documented by the IRB. A SUSAR will
be reported to regulatory authorities unblinded. Participating investigators and IRB will receive a
blinded SUSAR summary, unless otherwise specified.
8.4.5. 
Pregnancy
All initial reports of pregnancy in participants or partners of male participants must be reported to
the sponsor by the study site personnel within 24 hours of their knowledge of the event using the
appropriate pregnancy notification form. Abnormal pregnancy outcomes (eg, spontaneous
abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy) are considered SAEs and
must be reported using an SAE reporting form. Any participant who becomes pregnant during the
study will remain in the study and will continue to undergo all procedures for follow-up and all
safety follow-up as outlined in the protocol for all participants.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
101
Status: Approved,  Date: 20 April 2022
Follow-up information regarding the outcome of the pregnancy and any postnatal sequelae in the
infant will be required.
8.4.6. 
Disease-Related Events and Disease-Related Outcomes Not
Qualifying as Adverse Events or Serious Adverse Events
Serious adverse events caused by molecularly confirmed SARS-CoV-2 infection will be removed
at the analysis level from the (S)AE listings and tables and presented separately.
All events that meet the definition of an SAE will be reported as SAEs, regardless of whether they
are protocol-specific assessments.
8.4.7. 
Adverse Events of Special Interest
Adverse events of special interest (AESIs) are significant AEs that are judged to be of special
interest because of clinical importance, known class effects, or based on nonclinical signals.
Adverse events of special interest will be carefully monitored during the study by the sponsor.
AESIs must be reported to the sponsor within 24 hours of awareness irrespective of seriousness
(ie, serious and non-serious AEs) or causality following the procedure described above for SAEs.
Specific requirements for the AESI are described below.
8.4.7.1. 
Thrombosis with Thrombocytopenia Syndrome
As described in Section 2.3.1, TTS has been observed very rarely following vaccination with
Ad26.COV2.S and is considered to be an AESI in this study. TTS is a syndrome characterized by
a combination of both a thrombotic event and thrombocytopenia (American Society of
Hematology 2021; Brighton Collaboration 2021).
Because this syndrome is rare and not completely understood, all cases of thrombosis and/or
thrombocytopenia will be considered a suspected case of TTS until further adjudication can be
performed. An AESI Adjudication Committee with appropriate expertise will be established to
evaluate each suspected AESI and determine whether it is a case of TTS. The investigator shall be
responsible for reporting any suspected AESI of TTS using the SAE form and the form detailed in
Appendix 11. A suspected TTS case is defined as:
 
Thrombotic events: suspected deep vessel venous or arterial thrombotic events as detailed in
Appendix 10
 
Thrombocytopenia, defined as platelet count below 150,000/µL (Brighton Collaboration
2021)
Symptoms, signs, or conditions suggestive of a thrombotic events should be recorded and reported
as a suspected AESI even if the final or definitive diagnosis has not yet been determined, and
alternative diagnoses have not yet been eliminated or shown to be less likely. Follow-up
information and final diagnoses, if applicable, should be submitted to the sponsor as soon as they
become available.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
102
Status: Approved,  Date: 20 April 2022
In the event of thrombocytopenia, study site personnel should report the absolute value for the
platelet count and the reference range for the laboratory test used.
For either a thrombotic event or thrombocytopenia, testing for anti-PF4 should be performed at
the local laboratory or substitute local laboratory; repeat testing may be requested for confirmation
upon sponsor discretion.
Suspected AESIs will require enhanced data collection and evaluation (see Section 1.3.2). Every
effort should be made to report as much information as possible about the AESI to the sponsor in
a reasonable timeframe.
If an event meets the criteria for an SAE (Section 10.4.1), it should be reported using the same
process as for other SAEs.
The form detailed in Appendix 11 is intended as a guide for assessment of the AESIs to facilitate
diagnosis and determine treatment options. If the investigator is not the treating physician, every
effort should be made to collect the information requested in the form from the treating physician
and enter the available information in the eCRF.
8.5. 
Virology Assessments
Nasal swabs will be used to detect and/or quantify SARS-CoV-2. Exploratory quantification of
the SARS-CoV-2 viral load in saliva samples may also be performed.
Nasal swabs collected during a confirmed COVID-19 episode may also be tested at a central
laboratory for the presence of other respiratory pathogens using a broad respiratory pathogens
panel.
All confirmed COVID-19 episodes will be communicated to the respective participant and to other
authorities according to local regulations.
Participants, with stable/well-controlled HIV infection, will be encouraged to have HIV RNA viral
load and CD4 cell count assessed at least twice a year and to provide these data for inclusion in
the eCRF.
8.6. 
Biomarkers
During a COVID-19 episode, blood will be collected on COVID-19 Day 3-5 and on COVID-19
Day 29 for evaluation of biomarkers (eg, those associated with severe COVID-19).
8.7. 
Medical Resource Utilization and Health Economics
In this study, MRU will be collected by interview with the participant and recorded in the eCRF
by the investigator and study-site personnel on COVID-19 Day 3-5 and COVID-19 Day 29 (for
all participants during a COVID-19 episode; which is defined to be resolved after having
2 consecutive SARS-CoV-2 negative nasal swabs and 2 consecutive days with no COVID-19-
related signs or symptoms; see Section 8.1.2) (Appendix 6). Medical resource utilization data will
also be collected through the MA-COV form (Appendix 7). This form will be provided to the

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
103
Status: Approved,  Date: 20 April 2022
participant at the booster vaccination visit and should be completed by the medical care provider
or the study site personnel during medical visits for COVID-19 or COVID-19 complications.
Protocol-mandated procedures, tests, and encounters are excluded. The data collected will include:
 
Number and duration of medical care encounters, including selected procedures (inpatient and
outpatient)
 
Duration and type of mechanical ventilation and ECMO use
 
Duration of hospitalization (total days length of stay, including duration by wards; eg, ICU)
 
Number and character of diagnostic and therapeutic tests and procedures
 
Outpatient medical encounters and treatments (including physician or emergency room visits,
tests and procedures, and medications)
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 data is planned. Safety data will be analyzed descriptively
by vaccine group.
Hierarchical testing will be applied to the NI hypotheses of neutralizing antibody response to the
original strain after boosting vs the original strain after primary vaccination. The NI tests will be
performed on the NI analysis set and must be demonstrated on both co-primary endpoints: GMR
and seropositivity rates. In addition, an estimated GMR (GMT Day 15 post-booster/GMT post
primary regimen) of>0.8 is required to conclude NI.
If the primary hypothesis 1a, in Cohort 1, is met (either at the interim or primary analysis) the
primary hypothesis 1b, in Cohort 1 will be tested, accordingly (either at the interim or primary
analysis). If the primary hypothesis 1b is met, then the remaining primary hypotheses in Cohort 1
(Ad26.COV2.S primary vaccination) and Cohort 2 (BNT162b2 primary vaccination) will be tested
independently (at the primary analysis) and a Bonferroni correction will be used to correct for the
Type I error.
The neutralizing antibody response 14 days post Ad26.COV2.S booster vs the neutralizing
antibody response 28 days post primary vaccination with Ad26.COV2.S will be used to test the 4
hypotheses related to Cohort 1 (as shown in Figure 3); the neutralizing antibody response 14 days
post Ad26.COV2.S booster vs the neutralizing antibody response 2 weeks to 2 months after
completion of the 2-dose primary vaccination with Pfizer BNT162b2 will be used to test the 4
hypotheses related to Cohort 2 (as shown in Figure 3):

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
104
Status: Approved,  Date: 20 April 2022
Cohort 1 
Cohort 2
1. Non-inferiority of neutralizing antibody 
response to the original strain 14 days after 
booster vaccination with Ad26.COV2.S at 
the 5×1010 vp dose level, ≥6 months after 
single-dose primary vaccination with 
Ad26.COV2.S (5×1010 vp dose level), 
compared to the neutralizing antibody 
response to the original strain induced by  
single-dose primary vaccination with 
Ad26.COV2.S at the 5×1010 vp dose level.
2. Non-inferiority of neutralizing antibody 
response to leading variant of high 
consequence or concern* 14 days after 
booster vaccination with Ad26.COV2.S at 
the 5×1010 vp dose level, ≥6 months after 
single-dose primary vaccination with 
Ad26.COV2.S (5×1010 vp dose level), 
compared to the neutralizing antibody 
response to the leading variant of high 
consequence or concern* induced by 
single-dose primary vaccination with
Ad26.COV2.S at the 5×1010 vp dose level,
if feasible.
3. Non-inferiority of neutralizing antibody 
response to the original strain 14 days after 
booster vaccination with Ad26.COV2.S  at 
the 2.5×1010 vp dose level, ≥6 months after 
single-dose primary vaccination with 
Ad26.COV2.S (5×1010 vp dose level), 
compared to the neutralizing antibody
response to the original strain induced by
single-dose primary vaccination with
Ad26.COV2.S at the 5×1010 vp dose level.
4. Non-inferiority of neutralizing antibody 
response to the original strain 14 days after 
booster vaccination with Ad26.COV2.S at 
the 1×1010 vp dose level, ≥6 months after 
single-dose primary vaccination with 
Ad26.COV2.S (5×1010 vp dose level),
compared to the neutralizing antibody
response to the original strain induced by
single-dose primary vaccination with
Ad26.COV2.S at the 5×1010 vp dose level.
5. Non-inferiority of neutralizing antibody
response to the original strain 14 days after
booster vaccination with Ad26.COV2.S at
the 5×1010 vp dose level, ≥6 months after
completing a 2-dose primary vaccination
with Pfizer BNT162b2, compared to the
neutralizing antibody response to the
original strain induced by 2-dose primary
vaccination with Pfizer BNT162b2.
6. Non-inferiority of neutralizing antibody
response to leading variant of high
consequence or concern* 14 days after
booster vaccination with Ad26.COV2.S at
the 5×1010 vp dose level, ≥6 months after
completing a 2-dose primary vaccination
with Pfizer BNT162b2, compared to the
neutralizing antibody response to the
leading variant of high consequence or
concern* induced by 2-dose primary
vaccination with BNT162b2, if feasible.
7. Non-inferiority of neutralizing antibody
response to the original strain 14 days after
booster vaccination with Ad26.COV2.S at
the 2.5×1010 vp dose level, ≥6 months after
completing a 2-dose primary vaccination
with Pfizer BNT162b2, compared to the
neutralizing antibody response to the
original strain induced by 2-dose primary
vaccination with Pfizer BNT162b2.
8. Non-inferiority of neutralizing antibody
response to the original strain 14 days after
booster vaccination with Ad26.COV2.S at
the 1×1010 vp dose level, ≥6 months after
completing a 2-dose primary vaccination
with Pfizer BNT162b2, compared to the
neutralizing antibody response to the
original strain induced by 2-dose primary
vaccination with Pfizer BNT162b2.
* As defined by the Centers for Disease Control and Prevention (CDC Aug 2021c) at the time of the analysis
Figure 3 depicts a tree-based schema for testing the non-inferiority hypotheses controlling the
FWER at α  0.025 (one-sided)at the interim and primary analyses.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
106
Status: Approved,  Date: 20 April 2022
In addition to a GMR ratio (GMT Day 15 post-booster/GMT post primary regimen) threshold of
>0.8, the following success criteria will be applied to each of the NI tests:
Hypothesis 1a
Success Criterion 1:
The responder rate induced by the Ad26.COV2.S 5×1010 vp against the original strain 14 days post
booster is NI as compared to the responder rate induced by the Ad26.COV2.S 5×1010 vaccine
against the original strain 28 days post prime, using a NI margin of -10%.
Success Criterion 2:
Note: success criterion 2 will only be tested if success criterion 1 was successfully met.
The GMT induced by the Ad26.COV2.S 5×1010 vp against the original strain 14 days post booster
is NI as compared to the GMT induced by the Ad26.COV2.S 5×1010 vp against the original strain
28 days post prime, using a NI margin of 1.5-fold.
Note: If primary hypothesis 1a is met at the interim or primary analysis, then primary hypothesis
1b will be tested accordingly (at the interim or primary analysis).
Hypothesis 1b (if feasible)
Success Criterion 1:
The responder rate induced by the Ad26.COV2.S 5×1010 vp against the leading strain of high
consequence or concerna 14 days post booster is NI as compared to the responder rate induced by
the Ad26.COV2.S 5×1010 vaccine against the leading variant of high consequence or concern* 28
days post prime, using a NI margin of -10%.
Success Criterion 2:
Note: success criterion 2 will only be tested if success criterion 1 was successfully met.
The GMT induced by the Ad26.COV2.S 5×1010 vp against the leading strain of high consequence
or concerng 14 days post booster is NI as compared to the GMT induced by the Ad26.COV2.S
5×1010 vp against the leading variant of high consequence or concern* 28 days post prime, using
a NI margin of 1.5-fold.
Note: If primary hypothesis 1b is met, then primary hypotheses 1c and 2a will be tested (at the
primary analysis).
a As defined by the Centers for Disease Control and Prevention (CDC Aug 2021c) at the time of the analysis

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
107
Status: Approved,  Date: 20 April 2022
Hypothesis 1c
Success Criterion 1:
The responder rate induced by the Ad26.COV2.S 2.5×1010 vp against the original strain 14 days
post booster is NI as compared to the responder rate induced by the Ad26.COV2.S 5×1010 vaccine
against the original strain 28 days post prime, using a NI margin of -10%.
Success Criterion 2:
Note: success criterion 2 will only be tested if success criterion 1 was successfully met.
The GMT induced by the Ad26.COV2.S 2.5×1010 vp against the original strain 14 days post
boosteris NI as compared to the GMT induced by the Ad26.COV2.S 5×1010 vp against the original
strain 28 days post prime, using a NI margin of 1.5-fold.
Note: If primary hypothesis 1b is met, then primary hypothesis 1c will be tested (at the primary
analysis).
Hypothesis 1d
Success Criterion 1:
The responder rate induced by the Ad26.COV2.S 1×1010 vp against the original strain 14 days post
booster is NI as compared to the responder rate induced by the Ad26.COV2.S 5×1010 vaccine
against the original strain 28 days post prime, using a NI margin of -10%.
Success Criterion 2:
Note: success criterion 2 will only be tested if success criterion 1 was successfully met.
The GMT induced by the Ad26.COV2.S 1×1010 vp against the original strain 14 days post booster
is NI as compared to the GMT induced by the Ad26.COV2.S 5×1010 vp against the original strain
28 days post prime, using a NI margin of 1.5-fold.
Hypothesis 2a
Success Criterion 1:
The seropositivity rate induced by the Ad26.COV2.S 5×1010 vp against the original strain 14 days
post booster after 2-dose Pfizer BNT162b2 primary vaccination is NI as compared to the
seropositivityrate induced by the 2-dose Pfizer BNT162b2 primary vaccination (external samples)
against the original strain, using a NI margin of -10%.
Success Criterion 2:
Note: success criterion 2 will only be tested if success criterion 1 was successfully met.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
108
Status: Approved,  Date: 20 April 2022
The GMT induced by the Ad26.COV2.S 5×1010 vp against the original strain 14 days post booster
after 2-dose Pfizer BNT162b2 primary vaccination is NI as compared to the GMT induced by the
2-dose Pfizer BNT162b2 primary vaccination (external samples) against the original strain, using
a NI margin of 1.5-fold.
Note: If primary hypothesis 2a is met, then primary hypothesis 2b will be tested (at the primary
analysis).
Hypothesis 2b (if feasible)
Success Criterion 1:
The seropositivity rate induced by the Ad26.COV2.S 5×1010 vp against the leading strain of high
consequence or concerna 14 days post booster is NI as compared to the seropositivity rate induced
by the 2-dose Pfizer BNT162b2 primary vaccination (external samples) against the leading strain
of high consequence or concernh, using a NI margin of -10%.
Success Criterion 2:
Note: success criterion 2 will only be tested if success criterion 1 was successfully met.
The GMT induced by the Ad26.COV2.S 5×1010 vp against the leading strain of high consequence
or concerng 14 days post booster is NI as compared to the GMT induced by the 2-dose Pfizer
BNT162b2 primary vaccination(external samples) against the leading variant of high consequence
or concern* 28 days post prime, using a NI margin of 1.5-fold.
Note: If primary hypothesis 2b is met, then primary hypothesis 2c will be tested (at the primary
analysis).
Hypothesis 2c
Success Criterion 1:
The seropositivity rate induced by the Ad26.COV2.S 2.5×1010 vp against the original strain 14
days post booster after 2-dose Pfizer BNT162b2 primary vaccination, is NI as compared to the
seropositivityrate induced by the 2-dose Pfizer BNT162b2 primary vaccination (external samples)
against the original strain, using a NI margin of -10%.
a As defined by the Centers for Disease Control and Prevention (CDC Aug 2021c) at the time of the analysis

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
109
Status: Approved,  Date: 20 April 2022
Success Criterion 2:
Note: success criterion 2 will only be tested if success criterion 1 was successfully met.
The GMT induced by the Ad26.COV2.S 2.5×1010 vp against the original strain 14 days post
boosterafter 2-dose Pfizer BNT162b2 primary vaccination, is NI as compared to the GMT induced
by the 2-dose Pfizer BNT162b2 primary vaccination (external samples) against the original strain,
using a NI margin of 1.5-fold.
Note: If primary hypothesis 2c is met, then primary hypothesis 2d will be tested (at the primary
analysis).
Hypothesis 2d
Success Criterion 1:
The seropositivity rate induced by the Ad26.COV2.S 1×1010 vp against the original strain 14 days
post booster after 2-dose Pfizer BNT162b2 primary vaccination, is NI as compared to the
seropositivityrate induced by the 2-dose Pfizer BNT162b2 primary vaccination (external samples)
against the original strain, using a NI margin of -10%.
Success Criterion 2:
Note: success criterion 2 will only be tested if success criterion 1 was successfully met.
The GMT induced by the Ad26.COV2.S 1×1010 vp against the original strain 14 days post booster
after 2-dose Pfizer BNT162b2 primary vaccination, is NI as compared to the GMT induced by the
2-dose Pfizer BNT162b2 primary vaccination (external samples) against the original strain, using
a NI margin of 1.5-fold.
9.2. 
Sample Size Determination
The number of participants chosen is to provide sufficient power for the NI comparison stated in
Section 9.1. The following assumptions were made in the sample size determinations:
For the non-inferiority comparisons based on seroresponse rate:
 
Under the null hypothesis, a 90% responder rate on Day 15 post -booster and a 90%
responder rate on Day 29 post primary vaccination
 
Non-inferiority margin of -10% for the difference between 14 days post-booster and 28
days post primary vaccination responder rate on Day 29
 
Farrington & Manning Likelihood Score Test used in the non-inferiority testing of the
difference between the two responder rates
For the non-inferiority comparisons based on GMT:
 
Log transformed (log10 scale) VNA data are normally distributed
 
A standard deviation (SD) of VNA  0.56 (log10 scale)

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
110
Status: Approved,  Date: 20 April 2022
 
Under the null hypothesis, a GMT ratio (Day 15 post-booster/Day 29 post primary
regimen) of 1.0
 
Non-inferiority criteria margin  log10(2/3)  -0.176 for the GMT ratio testing
 
No correlation between immune responses 28 days post-dose 1 and 14 days post-booster
In addition, a drop-out rate approximately 10% is assumed.
With the above assumptions, the required sample size to achieve approximately 95% power to
demonstrate non-inferiority, at alpha 0.025 (1-sided), ofprimary hypothesis 1a is N 297 (N 330
adjusted for the 10% dropout). With this sample size, the power to demonstrate non-inferiority of
response rate is 98% and the power to demonstrate non-inferiority of the geometric mean ratio
(GMR) is 97% resulting in a combined power of approximately 95%.
Similarly, the required sample size to achieve 90% power to demonstrate the non-inferiority, at
alpha 0.0125 (1-sided), of the remaining primary hypotheses is N 297 (N 330 adjusted for the
10% dropout). With this sample size, the power to demonstrate non-inferiority of response rate is
95% and the power to demonstrate non-inferiority of the geometric mean ratio (GMR) is 94%,
resulting in a combined power of approximately 90%.
When at least 330 participants from Groups 1 to 3 in Cohort 1 have been enrolled, have completed
the Day 15 visit and it is estimated that immunogenicity data can be obtained from 110 or more
participants in Group 1, an interim analysis may be conducted whereby, if conducted, the formal
non-inferiority testing of Cohort 1 Group 1 (Primary Objectives 1a and 1b) will be performed
on the available data from the Cohort 1 
Group 1 participants. In case the interim analysis is
conducted, an O’Brien-Fleming adjustment will be used whereby the type I error for the non-
inferiority test at the interim analysis is 0.0003 (one-sided) and at the final analysis 0.0249. Since
an O’Brien-Fleming adjustment is used, the total sample size is not increased for this interim
analysis.
The statistical software PASS 15 (version 15.0.5) was used in the sample size calculations. In
addition, Addplan version 6.1.1 was used to determine the alpha spending for the interim analysis.
9.3. 
Analysis Sets
For purposes of analysis, the following populations are defined:
FAS: The full analysis set will include all participants with a documented study vaccine
administration (Ad26.COV2.S). Analyses of safety and reactogenicity will be performed on the
FAS.
PPI: The per protocol immunogenicity population will include all vaccinated participants for
whom post-baseline immunogenicity data are available excluding participants with major protocol
deviations expected to impact the immunogenicity outcomes. In addition, samples obtained after
natural SARS-CoV-2 infection (if applicable) will be excluded from the analysis.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
111
Status: Approved,  Date: 20 April 2022
NI: The NI analysis set will include all PPI participants who are SARS-COV-2 seronegative at
baseline (based on the serological test for SARS CoV-2-specific nucleocapsid antibodies [N
serology]). The NI hypothesis tests, as well as descriptive analysis of secondary endpoints for other
VOCs, will be performed on the NI analysis set.
PPE: The per protocol for efficacy analysis set will include all vaccinated participants who are
SARS-CoV-2 seronegative at baseline and who have no major protocol deviations expected to
impact the efficacy outcomes.
Pfizer BNT162b2 external samples: serum samples from external sources of approximately 300
individuals collected 2 weeks to 2 months after completion of the 2-dose primary vaccination with
Pfizer BNT162b2. These samples will be used for NI assessments for Cohort 2.
9.4. 
Statistical Analyses
The SAP will be finalized prior to the database lock of the interim analysis, if conducted. If the
interim analysis is not conducted, then the SAP will be finalized prior to the database lock of the
primary analysis. The SAP 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.
9.4.1. 
General Considerations
For safety and immunogenicity analyses, results will be analyzed by vaccine group (using the “as
treated principle”, ie, by actually received vaccine).
If a participant has a positive SARS-CoV-2 test within 28 days after vaccination, this participant
will remain in the study but will not be included in the immunogenicity analysis.
9.4.2. 
Primary Endpoints
Immunogenicity Endpoints
For NI assessments of primary objectives 1a and 1b (evaluated at the interim or primary analysis),
the Ad26.COV2.S booster vaccine at the 5×1010 vp dose level against the original strain (objective
1a) and leading variant of concern (objective 1b)as compared to the Ad26.COV2.S vaccine against
the original strain (objective 1a) and leading variant of concern (objective 1b) at 28 days post-
vaccination, two NI hypothesis tests will be performed:
1. Statistical NI of responder rate, with a margin of -10%: the difference in responder rate
between post booster minus post prime will be estimated, with a 100*(1-2*α)%  CI.
Non-inferiority for responder rate will be demonstrated if the 2-sided 100*(1-2*α)% CI
lies entirely above -10%.
2. Statistical NI of GMTs, with a margin of 1.5-fold: the ratio of the GMTs (post booster
GMT divided by post prime GMT, i.e; the Geometric Mean Ratio [GMR]) will be
estimated, with the corresponding 100*(1-2*α)% CI. Non-inferiority will be demonstrated
if the 2-sided 100*(1-2*α)% CI of the estimated GMT ratio lies entirely above 2/3.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
112
Status: Approved,  Date: 20 April 2022
3. In addition to the above, an estimated GMR (GMT Day 15 post-booster/GMT Day 29 post
primary regimen) of >0.8 is required to conclude NI.
For objectives 1a and 1b, at the interim analysis (if conducted), an O’Brien-Fleming adjustment
will be used, α 0.0003 and a 99.4% CI will be calculated. At the primary analysis, α 0.0249 and
a 95.02% CI will be calculated, if the interim analysis is conducted. Otherwise, α 0.025 and a 95%
CI will be calculated.
Similar non-inferiority criteria will be used for the remaining primary objectives 1c, 1d, 2a, 2b, 2c
and 2d (evaluated only at the primary analysis), except that a 97.5% CI will be used for both the
responder rate and GMT hypothesis testing.
A hierarchical testing strategy will be applied as depicted in Figure 3.
For primary objectives 1a, 1b, 1c and 1d, formal NI testing will be conducted as a “within-subjects”
analysis, in which participants’ VNA data are considered matched pairs across the two time points.
The NI analysis on responder rate will be based on Agresti-Min (Agresti 2005) method to estimate
the difference in proportions and its CI. This method was chosen because of its well-behaved CP
properties compared to other methods for the analysis of matched pairs data (Reed 2009). Coverage
probability is generally used to evaluate (1 α) CIs where α is the Type I error rate. The NI analysis
on the GMT ratio (GMR)will use a paired t-test to estimate the difference in means and its CI on
log10 transformed data. The estimated difference and its CI will be back transformed to yield the
GMR and its CI.
As a sensitivity analysis, 28 days post-dose 1 VNA data may be pooled across the three study arms
and compared to the 14 days post booster VNA data in the study arm of interest. This sensitivity
analysis will use appropriate statistical models, such as linear mixed models for the GMR and
Generalized Estimating Equations (GEE) models for the difference in responder rates.
For primary objectives 2a, 2b, 2c and 2d relating to Cohort 2, formal NI testing will be conducted
by comparing VNA data from external samples, collected 2 weeks to 2 months after completing a
2-dose primary vaccination with Pfizer BNT162b2, compared to the 14 days post booster VNA
data in the study arm of interest (groups 4, 5 or 6).
9.4.3. 
Secondary Endpoint(s)
Safety Endpoints
No formal statistical testing of safety data is planned. Safety data will be analyzed descriptively
by vaccine group. All safety analyses will be made on the FAS.
When 330 participants are vaccinated, the observation of 0 reactions would be associated with a
95% confidence that the true rate is less than 0.9%. Table 6 provides the probabilities of observing
at least one AE at given true AE rates.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
113
Status: Approved,  Date: 20 April 2022
Table 6: 
Probability of Observing at Least One Adverse Event Given a True Adverse Event Incidence
Probability of Observing at Least One Adverse Event
True Adverse Event Incidence 
N*=330 
N*=110
0.1% 
28% 
10%
0.5% 
81%  
42%
1%  
96%  
67%
2.5% 
100%  
94%
5%  
100%  
>99%
N: number of participants receiving active vaccine
* N/treatment group: 330 participants in Cohort 1, treatment groups 1 and 2 and Cohort 2, treatment groups 4 and 5; 110
participants in treatment Cohort 1, treatment group 3 and Cohort 2, treatment group 6.
Detailed statistical methodology for analysis of secondary endpoints will be described in the SAP.
Adverse Events
The verbatim terms used in the eCRF by investigators to identify AEs will be coded using the
Medical Dictionary for Regulatory Activities (MedDRA). All reported AEs with onset during the
active vaccination phase (ie, AEs occurring after vaccination up to 28 days post-vaccination),
SAEs and AESIs will be included in the analysis. (S)AEs caused by molecularly confirmed
SARS-CoV-2 infection will be removed at the analysis level from the (S)AE listings and tables
and presented separately. For each AE, the percentage of participants who experience at least
1 occurrence of the given event will be summarized by vaccine group.
Summaries, listings, datasets, or participant narratives may be provided, as appropriate, for those
participants who die, who discontinue intervention due to an AE, or who experience a severe AE,
an AESI, or an SAE.
Solicited local (at injection site) and systemic AEs will be summarized descriptively. The number
and percentages of participants with at least one solicited local (at injection site) or systemic AE
will be presented. The frequencies by vaccine group as well as frequencies according to severity
and duration will be described for solicited AEs. Frequencies of unsolicited AEs, separately for all
and vaccination-related only, will be presented by System Organ Class and preferred term, while
those of solicited AEs will be presented only by preferred term.
Clinical Laboratory Tests
Laboratory data (abnormal or graded, when available) will be listed and/or tabulated by participant
and time point.
Vital Signs
Vital signs including temperature, pulse/heart rate, respiratory rate, and blood pressure (systolic
and diastolic) will be summarized over time, using descriptive statistics and/or graphically. The
percentage of participants with values beyond clinically important limits will be summarized.
Physical Examinations
Physical examination findings will be summarized at baseline. Physical examination abnormal
findings will be listed.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
114
Status: Approved,  Date: 20 April 2022
Immunogenicity Endpoints
Descriptive statistics (geometric mean and CIs, or median and interquartile range Q1-Q3, as
appropriate) will be calculated for continuous immunologic parameters. Several definitions of
serological response will be applied as applicable (GMC [S-ELISA], GMT [VNA]). Graphical
representations of immunologic parameters will be made as applicable. Frequency tabulations will
be calculated for discrete (qualitative) immunologic parameters, as applicable.
In addition, the ratio between neutralizing and binding antibodies as determined by VNA and
S-ELISA, respectively, will be calculated together with CIs.
As described in Section 9.1, the powered primary NI endpoints are based on neutralizing
antibodies to the original strain or to the leading variant of high consequence or concern (as defined
by the Centers for Disease Control and Prevention [CDC Aug 2021c] at the time of the analysis).
Additional descriptive analyses will be conducted on other variants, as available. These descriptive
analyses will be conducted on the NI set and will include assessments that allow interpretation of
the data using NI criteria, but these assessments will not constitute formal hypothesis testing.
For Cohort 1, these assessments will include, but are not limited to:
 
Geometric Mean Titer Ratio (with 95% CI) from 28 days after Ad26.COV2.S (5×1010 vp
dose level) single-dose primary vaccination to 14 days after Ad26.COV2.S booster
vaccination (5×1010 vp dose level) after completing 1-dose primary vaccination with
Ad26.COV2.S (5×1010 vp dose level), using a paired t-test
 
Difference in % responders (with 95% CI) between 28 days after Ad26.COV2.S (5×1010
vp dose level) single-dose primary vaccination and 14 days after Ad26.COV2.S booster
vaccination (5×1010 vp dose level) after completing 1-dose primary vaccination with
Ad26.COV2.S (5×1010 vp dose level), using the Agresti-Min method (Agresti 2005)
Note: as these analyses refer to two time points, only study participants with data at both time
points will contribute to these analyses. Within-subjects analysis methods (paired t-test and
Agresti-Min) will be used.
For Cohort 2, these assessments will include, but are not limited to:
 
Geometric Mean Titer Ratio (with 95% CI) of the neutralizing antibody responses 14
days after Ad26.COV2.S booster vaccination (5×1010vp dose level) after completing 2-
dose primary vaccination with Pfizer BNT162b2 to the neutralizing antibody responses
in serum samples of approximately 300 individuals, collected 2 weeks to 2 months after
completing 2-dose primary vaccination with Pfizer BNT162b2 (also referred to as Pfizer
BNT162b2 external samples), using a t-test
 
Difference in % seropositive participants (with 95% CI) between 14 days after
Ad26.COV2.S booster vaccination (5×1010 vp dose level) after completing 2-dose
primary vaccination with Pfizer BNT162b2 and the Pfizer BNT162b2 external samples,
using the Farrington-Manning test
Note: in contrast to Cohort 1, the use of external samples in Cohort 2 implies that between subjects
analysis methods are to be used in this cohort (t-test and Farrington-Manning test).

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
115
Status: Approved,  Date: 20 April 2022
The immunogenicity analyses will be performed on the PPI population  and the FAS; selected
immunogenicity analyses will be performed on the NI analysis set.
9.4.4. 
Exploratory Endpoint(s)
If feasible, rVE of booster vaccination with Ad26.COV2.S may be estimated at the time of the
final analysis or any interim analysis conducted after the primary analysis, ifthe required data are
available, and a sufficient number of cases are recorded. The following rVE estimates may be
calculated:
 
Within Cohort 1 and Cohort 2 separately: the rVE of Ad26.COV2.S 5×1010 vp compared
to Ad26.COV2.S 1×1010 vp and the rVE of Ad26.COV2.S 2.5×1010 vp compared to
Ad26.COV2.S 1×1010 vp
 
The rVE of Ad26.COV2.S 5×1010 vp in Cohort 2 compared to Cohort 1
 
The rVE of Ad26.COV2.S 2.5×1010 vp in Cohort 2 compared to Cohort 1
 
The rVE Ad26.COV2.S 1×1010 vp in Cohort 2 compared to Cohort 1
The endpoints will be:
 
COVID-19 cases meeting the moderate case definitions
 
COVID-19 cases meeting the moderate to severe/critical case definitions
 
COVID-19 cases meeting the severe/critical case definition
 
COVID-19 cases meeting the US FDA Harmonized COVID-19 case definition
 
Cases meeting the asymptomatic/undetected case definition
 
Case counting will start 14 days post vaccination in COV2008.
The analysis will be based on the Cox proportional hazards model, using the calendar-based time
scale. If feasible, the model may stratify for site or a higher-level geographical region, to account
for potential differences in geographical exposure. In addition, the model(s) may add other relevant
stratification factors such as age group and/or presence/absence of comorbidities.
Furthermore, additional descriptive analyses may be provided. These analyses may include but are
not limited to:
 
The number of symptoms reported by homologous/heterologous vaccination regimen and
by dose level
 
The number and percentage of severe/critically ill cases by homologous/heterologous
vaccination regimen and by dose level
Additional details will be provided in a supplemental SAP.
9.4.5. 
Other Analyses
If feasible, further exploratory analyses may be conducted to investigate the effect of the
immunogenicity responses on the probability of experiencing a COVID-19 event (eg, RNA-seq

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
116
Status: Approved,  Date: 20 April 2022
responses, immunological correlates of protection/risk against SARS-CoV-2 infection if feasible).
These analyses may utilize logistic or probit regression models, in which statistical control for
potential confounders such as age and sex may be included. Additionally, linear regression or other
suitable models may be explored to investigate the effect of the dose level on the mounted immune
responses, while statistically controlling for potential confounders.
Statistical analysis of biomarker responses will be detailed in a separate SAP.
9.5. 
Planned Analysis
Interim Analysis
When at least 330 participants (see Section 4.1) from Groups 1 to 3 in Cohort 1 have been enrolled,
have completed the Day 15 visit, and it is estimated that immunogenicity data can be obtained
from 110 or more participants in Group 1, an interim analysis may be conducted whereby, if
conducted, the formal non-inferiority testing of Cohort 1 Group 1 (Primary Objectives 1a and
1b) will be performed on the available data from the Cohort 1 Group 1 participants.
Scope of the Interim Analysis:
If conducted, the interim analysis will consist of a statistical immunogenicity analysis of Cohort 1
Group 1 participants only. Hypotheses 1a and 1b will be tested, in the hierarchical manner as
outlined in Figure 3: Hypothesis 1b will only be tested if all success criteria of Hypothesis 1a are
met. The other hypotheses (1c, 1d, 2a, 2b, 2c and 2d) will only be tested at the primary analysis.
In addition, limited safety/reactogenicity statistical outputs will be generated in a blinded manner,
for all available participants (Cohort 1 and Cohort 2, all groups). The same outputs will be
generated in an unblinded manner by the independent Statistical Support Group. The unblinded
outputs may also be used to respond to questions or requests from Health Authorities. In this case,
appropriate channels of communication will be used to keep the Sponsor blinded.
Alpha Spending:
If the interim analysis is conducted, an O’Brien-Fleming adjustment will be used whereby the type
I error for the NI test at the interim analysis will be 0.0003 (one-sided). This alpha is calculated
based on an estimated interim analysis sample size of 110 Cohort 1 Group 1 participants (~33%
of the total sample size). If immunogenicity data is available for more than 110 Cohort 1 Group
1 participants at the time of the interim analysis, then the nominal alpha level of the interim analysis
will be kept at 0.0003, but the alpha level at the primary analysis will be recalculated. The
recalculation will be based on the O’Brien-Fleming adjustment and will take into consideration
the alpha spent at the time of the interim analysis and the actual information fraction that was
available at the time.
Procedures to maintain the study blind:

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
117
Status: Approved,  Date: 20 April 2022
If performed, this interim analysis will be conducted by an independent Statistical Support Group.
Only group-level unblinded immunogenicity statistical outputs and blinded safety/reactogenicity
statistical outputs will be available to the Sponsor.
In order to keep the blind at the laboratory, all available Cohort 1 immunogenicity samples, from
all groups, will be shipped and analyzed, if operationally feasible. In case a selection of samples
is needed for operational reasons, the selection will be made in advance by the independent
Statistical Support Group and this selection will include, in addition to the Cohort1 
Group 1
samples, also at least 20 samples of Cohort 1 
Group 2 and at least 20 samples of Cohort 1 
Group 3.
Primary and Final Analyses
The primary and final analyses of Cohort 1 may be performed before the analyses of Cohort 2.
The primary analysis of safety and immunogenicity in Cohort 1 or Cohort 2 will be performed
when all evaluable participants in the respective cohort have completed the visit that takes place
28 days after study vaccination, or discontinued earlier. The analysis will include immunogenicity
data (VNA, N-serology, and S-ELISA and/or MSD [if available at the time of analysis]) for all
evaluable participants through Day 15, and all available safety data. The sponsor will be unblinded
at the time of this primary analysis, with the exception of specific sponsor personnel (see below).
If the primary analysis of Cohort 1 is performed before the primary analysis of Cohort 2, then the
sponsor will be unblinded only for Cohort 1 at the time of the Cohort 1 primary analysis, and
unblinded for only Cohort 2 at the time of the primary analysis of Cohort 2.
For the primary analysis, and for any analyses after the primary analysis on the same cohort(s),
unblinded data at the participant level will be available to sponsor personnel including statistical
programming, statistics, clinical and clinical immunology personnel involved in the analysis, and
the sponsor committee involved in making future decisions for the program. Sponsor personnel
directly involved in data collection, data management, and safety monitoring () will not have
access to unblinded data at the participant level until the study end. Sites and study participants
will not have access to unblinded data at the participant level until the end of study (except for
events such as emergency unblinding). Group level data may be shared with investigators or other
blinded clinical staff, as needed, but every effort will be made to preserve the blinding to the
individual participant allocation until the end of study.
The final analysis in Cohort 1 or Cohort 2 will be performed when all included participants in the
respective cohort have completed their last visit or discontinued earlier.
After the primary analysis, additional interim analyses may be performed by the sponsor as
required.
There is no formal assessment of efficacy in this study. However, data on molecularly confirmed
SARS-CoV-2 infections, SARS-CoV-2 asymptomatic infection (by measurement of nucleocapsid
binding antibodies), moderate, moderate to severe/critical COVID-19 disease, medical

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
118
Status: Approved,  Date: 20 April 2022
intervention/hospitalization and COVID-19-like signs and symptoms will be reported after the
primary analysis, and rVE may be estimated if feasible from the available data (see Section 9.4.4).
The SAP, and supplemental SAP, will describe the planned analyses in greater detail.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
119
Status: Approved,  Date: 20 April 2022
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Abbreviations and Definitions
Ad26 
adenovirus type 26
ACE2 
angiotensin-converting enzyme 2
AdVAC® 
adenoviral vaccine (vector platform)
AE 
adverse event
AESI 
adverse event of special interest
ALT  
alanine aminotransferase
ARDS  
acute respiratory distress syndrome
ART  
anti-retroviral treatment
AST  
aspartate aminotransferase
BIDMC  
Beth Israel Deaconess Medical Center
BMI 
body mass index
BNT162b2 
Pfizer mRNA- based SARS-CoV-2 vaccine
BUN  
Blood Urea Nitrogen
CDC  
Centers for Disease Control and Prevention
CI 
confidence interval
COPD  
chronic obstructive pulmonary disease
COVID-19 
coronavirus disease-2019
CP  
coverage probability
CPK  
creatine phosphokinase
CS  
cytokine storm
CSAC  
Clinical Severity Adjudication Committee
CVST  
cerebral venous sinus thrombosis
DNA  
deoxyribonucleic acid
ECMO  
extracorporeal membrane oxygenation
DVT  
deep vein thrombosis
eCOA  
electronic clinical outcome assessment
eCRF  
electronic case report form
eDC  
electronic data capture
EEA  
European Economic Area
EF-PPND  
embryo-fetal and pre- and postnatal development
EoT  
End of trial
ePRO  
electronic patient-reported outcomes
ELISA  
enzyme-linked immunosorbent assay
ELISpot 
enzyme-linked immunospot
EMA  
European Medicines Agency
EU  
European Union
FAS  
full analysis set
Fc 
crystallizable fragment
FDA  
Food and Drug Administration
FI 
formalin-inactivated
FOIA  
Freedom of Information Act
FWER  
family wise error rate
GCP  
good clinical practice
GMR  
geometric mean ratio
GLP  
good laboratory practice
GMC  
geometric mean concentration
GMT  
geometric mean titer
HA  
Health Authority
HCP  
health care professional
HIT  
heparin-induced thrombocytopenia
HIV  
human immunodeficiency virus
HPV  
human papillomavirus
IB  
investigator's brochure
ICF  
informed consent form

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
120
Status: Approved,  Date: 20 April 2022
ICH  
International Conference on Harmonisation
ICS  
intracellular cytokine staining
ICMJE 
International Committee of Medical Journal Editors
ICU  
intensive care unit
IDMC  
Independent Data Monitoring Committee
IFN-γ 
interferon gamma
Ig 
immunoglobulin
IL 
interleukin
IM  
intramuscular
IND  
Investigational New Drug
IPPI 
Investigational Product Preparation Instructions
IRB  
Institutional Review Board
IWRS  
interactive web response system
MA-COV  
medically-attended COVID-19
MAH  
Marketing Authorization Holders
MedDRA  
Medical Dictionary for Regulatory Activities
MERS(-CoV) 
Middle East respiratory syndrome (coronavirus)
MSD  
Meso Scale Discovery
MIS  
multisystem inflammatory syndrome
MRU  
medical resource utilization
N 
nucleocapsid
NHP  
non-human primate
NI 
non-inferiority
PCR  
polymerase chain reaction
PE 
pulmonary embolism
PI 
principal investigator
PPE 
per protocol efficacy
PPI 
per protocol immunogenicity
PQC  
product quality complaint
PT  
prothombin time
rVE  
relative vaccine efficacy
VNA  
virius neutralization assay
PRO  
patient reported outcomes
RBD  
receptor-binding domain
RNA  
ribonucleic acid
RSV  
respiratory syncytial virus
RT-PCR  
real-time reverse-transcriptase polymerase chain reaction
S 
spike
SAE  
serious adverse event
SAP  
statistical analysis plan
SARS  
severe acute respiratory syndrome
SARS-CoV(-2) 
severe acute respiratory syndrome coronavirus(-2)
SD 
standard deviation
SIC  
Symptoms of Infection with Coronavirus-19
SIPPM  
site investigational product and procedures manual
SRP  
study responsible physician
SRS  
study responsible scientist
SUSAR  
suspected unexpected serious adverse reaction
Th 
T-helper
TNF-α 
tumor necrosis factor alpha
TTS  
thrombosis with thrombocytopenia syndrome
ULN  
upper limit ofthe normal range
UK  
United Kingdom
US  
United States
VAED  
vaccine-associated enhanced disease
VAERD  
vaccine-associated enhanced respiratory disease
VNA  
virus neutralization assay
vp 
virus particle

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
121
Status: Approved,  Date: 20 April 2022
VTE 
venous thromboembolism
WBC  
white blood cell
WHO  
World Health Organization
Definitions of Terms
COVID-19 
COVID-19 is the disease caused by the virus SARS-CoV-2. COVID-19 refers to
SARS-CoV-2 infection with symptoms, and can range from mild to severe disease, the latter
including pneumonia, severe acute respiratory syndrome, multi-organ failure, and death
(US FDA 2020b; US FDA 2021a).
e-COA  
An umbrella term encompassing different types of outcomes assessments, in particular, the
COVID-19 signs and symptoms surveillance question, the ePRO and the e-Diary.
ePRO  
The electronic technology used to collect the patient-reported outcome data. PROs are
reports that come directly from the participant without interpretation by clinician or anyone
else. This includes the SIC questionnaire (Symptoms of Infection with Coronavirus-19) and
the recording of pulse oximetry results.
e-Diary  
The electronic technology used to record solicited signs and symptoms by the participants.
Study Name 
Convention  
In this document, studies are referred to using the short study name (preceding letters and
final digits of the study identifier) only (eg, COV1001).
Electronic source 
system  
Contains data traditionally maintained in a hospital or clinic record to document medical
care or data recorded in a CRF as determined by the protocol. Data in this system may be
considered source documentation.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
122
Status: Approved,  Date: 20 April 2022
10.2. Appendix 2: Clinical Laboratory Tests
The following tests will be performed according to the Section  1.3.1, Section 1.3.2 and
Section 1.3.3:
Protocol-Required Safety Laboratory Assessments
Laboratory 
Assessments
Parameters 
Timepoints
Testing done
centrally
and/or
locally
Whole blood sample for platelet count which
at some sites may be part of a complete
blood count with differential
Pre-booster vaccination and as part of a suspected
AESI investigation if applicable
Testing done
centrally
Serum/plasma samples for coagulation-
related assays such as but not limited to:
 Activated partial thromboplastin time
 Prothrombin time
 International normalized ratio
 Fibrinogen
 D-dimer
 Lupus anticoagulant
 Anti-cardiolipin antibody
 Beta-2 glycoprotein·
 Heparin-induced thrombocytopenia
(HIT)/platelet factor (PF) 4 antibody,
IgG·(HIT assay)
 Platelet activation assay (if HIT/PF4 is
positive)
 Homocysteine
 ADAMTS13 Activity and Inhibitor Profile
Based on the clinical evaluation of the suspected
AESI (eg, whether thrombocytopenia is observed in
conjunction with a thrombotic event), all or some of
these tests may be conducted on the stored pre
vaccination sample (retrospective test) and on the
samples obtained as part of the AESI investigation.
Similar samples from appropriate controls (from
vaccinated participants who did not experience an
AESI) within the study may be used as part of
investigation of AESIs.
Testing done
centrally
Serological test for SARS‑CoV-2-specific
antibodies (based on N serology)
At baseline, Day 15 (all), Day 29 (Subset 2), Day
71 (Subset 3), Day 120 (no subset), Day 181 (all),
Day 361 (all)
Testing done
either locally
or centrally
Nasal swab for virology testing (viral load
testing). Negative baseline test is NOT
required for enrollment and randomization.
 
At baseline (nasal swab collected by
qualified study staffand batch tested
centrally)
 
On COVID-19 Day 1-2 (nasal swab collected
by the participant at home)
 
On COVID-19 Day 3-5 (nasal swab collected
by qualified study staff)
 
Once every 2 days following COVID-19 Day
3-5, until closure of the COVID-19
procedures (nasal sample collected by the
participant at home)

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
123
Status: Approved,  Date: 20 April 2022
Laboratory 
Assessments
Parameters 
Timepoints
Testing done 
centrally  
Saliva 
samples 
for 
virology 
testing 
(molecular confirmation of SARS-CoV-2 
infection and viral load testing), if feasible 
 
On COVID-19 Day 3-5 (saliva sample
collected by the participant at the study site or
at home)
 
Once every 2 days following COVID-19 Day
3-5, until closure of the COVID-19
procedures (saliva sample collected by the
participant at home)

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
124
Status: Approved,  Date: 20 April 2022
10.3. Appendix 3: Regulatory, Ethical, and Study Oversight Considerations
10.3.1. 
Regulatory and Ethical Considerations
Investigator Responsibilities
The investigator is responsible for ensuring that the study is performed in accordance with the
protocol, current International Council for Harmonisation (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 Clarification Communications
If text within a final approved protocol requires clarification (eg, current wording is unclear or
ambiguous) that does not change any aspect of the current study conduct, a protocol clarification
communication (PCC) may be prepared. The PCC Document will be communicated to the
Investigational Site, Site Monitors, Local Trial Managers (LTMs), Clinical Trial Managers
(CTMs), and/or Contract Research Organizations (CROs) who will ensure that the PCC
explanations are followed by the investigators.
The PCC Document may be shared by the sites with Institutional Review Boards (IRBs) per local
regulations.
The PCC Documents must NOT be used in place of protocol amendments, but the content of the
PCC Document must be included in any future protocol amendments.
Protocol Amendments
Neither the investigator nor the sponsor will modify this protocol without a formal amendment by
the sponsor. All protocol amendments must be issued by the sponsor, and signed and dated by the
investigator. Protocol amendments must not be implemented without prior 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 IRB and relevant competent authority. Documentation of amendment
approval by the investigator and IRB must be provided to the sponsor. When the change(s) involve
only logistic or administrative aspects of the study, the IRB (where required) only needs to be
notified.
In situations where a departure from the protocol is unavoidable during the study, 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

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
125
Status: Approved,  Date: 20 April 2022
agree on an appropriate course of action. The data recorded in the electronic case report form
(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.
Required Prestudy Documentation
The following documents must be provided to the sponsor before shipment of study vaccine to the
study site:
 
Protocol and amendment(s), if any, signed and dated by the principal investigator (PI)
 
A copy of the dated and signed (or sealed, where appropriate per local regulations), written
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 IRB, including a current list of the 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 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 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, 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

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
126
Status: Approved,  Date: 20 April 2022
Independent Ethics Committee or Institutional Review Board
Before the start of the study, the investigator (or sponsor where required) will provide the 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)
 
IB (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 IRB)
 
Information regarding funding, name of the sponsor, institutional affiliations, other potential
conflicts of interest, and incentives for participants
 
Any other documents that the IRB requests to fulfill its obligation
This study will be undertaken only after the 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 IRB and the documents
being approved.
During the study the investigator (or sponsor where required) will send the following documents
and updates to the 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 and amendments/addenda
 
Summaries of the status of the study at intervals stipulated in guidelines of the 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

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
127
Status: Approved,  Date: 20 April 2022
 
Report of deaths of participants under the investigator's care
 
Notification if a new investigator is responsible for the study at the site
 
Development Safety Update Report and Line Listings, where applicable
 
Any other requirements of the IRB
For all protocol amendments (excluding the ones that are purely administrative, with no
consequences for participants, data or study conduct), the amendment and applicable ICF revisions
must be submitted promptly to the IRB for review and approval before implementation of the
change(s).
At least once a year, the 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 IRB about the
study completion.
Country Selection
This study will only be conducted in those countries where the intent is to launch or otherwise help
ensure access to the developed product if the need for the product persists, unless explicitly
addressed as a specific ethical consideration in Section 4.2.1.
Other Ethical Considerations
For study-specific ethical design considerations, refer to Section 4.2.1.
10.3.2. 
Financial Disclosure
Investigators and sub  investigators 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 study and
for 1 year after completion of the study.
Refer to Required Prestudy Documentation (above)for details on financial disclosure.
10.3.3. 
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
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

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
128
Status: Approved,  Date: 20 April 2022
consent to participate at any time. They will be informed that choosing not to participate will not
affect the care the participant will receive. Finally, they will be told that the investigator will
maintain a participant identification register for the purposes of long-term follow-up if needed and
that their records may be accessed by health authorities and authorized sponsor personnel without
violating the confidentiality of the participant, to the extent permitted by the applicable law(s) or
regulations. By signing the ICF the participant is authorizing such access. It also denotes that the
participant agrees to allow his or her study physician to recontact the participant for the purpose
of obtaining consent for additional safety evaluations, if needed.
The participant will be given sufficient time to read the ICF and the opportunity to ask questions.
After this explanation and before entry into the study, consent should be appropriately recorded
by means of the participant's personally dated signature. After having obtained the consent, a copy
of the ICF must be given to the participant.
Participants who are rescreened are required to sign a new ICF.
If the participant is unable to read or write, an impartial witness should be present for the entire
informed consent process (which includes reading and explaining all written information) and
should personally date and sign the ICF after the oral consent of the participant is obtained.
10.3.4. 
Data Protection
Privacy of Personal Data
The collection and processing of personal data from participants enrolled in this study will be
limited to those data that are necessary to fulfill the objectives of the study.
These data must be collected and processed with adequate precautions to ensure confidentiality
and compliance with applicable data privacy protection laws and regulations. Appropriate
technical and organizational measures to protect the personal data against unauthorized disclosures
or access, accidental or unlawful destruction, or accidental loss or alteration must be put in place.
Sponsor personnel whose responsibilities require access to personal data agree to keep the identity
of participants confidential.
The informed consent obtained from the 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, 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.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
129
Status: Approved,  Date: 20 April 2022
Exploratory research is not conducted under standards appropriate for the return of data to
participants. In addition, the sponsor cannot make decisions as to the significance of any findings
resulting from exploratory research. Therefore, exploratory research data will not be returned to
participants or investigators, unless required by law or local regulations. Privacy and
confidentiality of data generated in the future on stored samples will be protected by the same
standards applicable to all other clinical data.
10.3.5. 
Long-Term Retention of Samples for Additional Future Research
Samples collected in this study may be stored for up to 15 years (or according to local regulations)
for additional research. Samples will only be used to understand vaccination with Ad26-based
vaccines, including Ad26.COV2.S, to understand SARS-CoV-2 infection, to understand
differential intervention responders, and to develop tests/assays related to Ad26-based vaccines,
includingAd26.COV2.S and SARS-CoV-2 infection. The research may begin at any time during
the study or the post-study storage period.
Stored samples will be coded throughout the sample storage and analysis process and will not be
labeled with personal identifiers. Participants may withdraw their consent for their samples to be
stored for research (refer to Section 7.2.1).
10.3.6. 
Committees Structure
Independent Data Monitoring Committee
An IDMC  consisting of members who are not directly involved in the study conduct, data
management, or statistical analysis, has been established. After the primary analysis, The IDMC
will review data on an ad hoc basis upon request of the sponsor to ensure the continuing safety of
the participants enrolled in this study. The IDMC will review data as indicated in Section 4.1.
When appropriate, the conclusions of the IDMC will be communicated to the investigators, the
IRB, and the national regulatory authorities.
Ad hoc review may be performed further to the occurrence of any AE/AESI/SAE leading to a
study pausing situation as outlined in Section 6.8, or at request of the sponsor’s medical monitor
or designee. The PI(s) and SRP/S will inform the IDMC of any AE of concern.
Upon ad hoc review, the IDMC will review blinded data first but is entitledto request submission
of unblinded data if deemed necessary.
The composition of the IDMC, its responsibilities, authorities and procedures are
documented in the IDMC Charter.AESI Adjudication Committee
An AESI Adjudication Committee with appropriate expertise will be established to evaluate each
suspected AESI and determine whether it is a case of TTS (see Section 8.4.7). A Charter will be
developed to describe the roles and responsibilities of the Committee.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
130
Status: Approved,  Date: 20 April 2022
Clinical Severity Adjudication Committee
The Clinical Severity Adjudication Committee will review all suspected cases of COVID-19,
except for cases already adjudicated as severe, as well as those requiring medical intervention
(such as a composite endpoint of hospitalization, ICU admission, mechanical ventilation, and
ECMO, linked to objective measures such as decreased oxygenation, X-ray or CT findings),
including onset of cases, taking into account all available relevant information at the time of
adjudication. More details will be provided in the charter of the Clinical Severity Adjudication
Committee. Re-adjudication will occur if new information becomes available. The last
adjudication for a given case will determine the status of the case for analysis. The Clinical
Severity Adjudication Committee's assessment will be considered the definitive classification of
the case.
10.3.7. 
Publication Policy/Dissemination of Clinical Study Data
All information, including but not limited to information regarding Ad26.COV2.S or the sponsor's
operations (eg, patent application, formulas, manufacturing processes, basic scientific data, prior
clinical data, formulation information) supplied by the sponsor to the investigator and not
previously published, and any data, including exploratory research data, generated as a result of
this study, are considered confidential and remain the sole property of the sponsor. The investigator
agrees to maintain this information in confidence and use this information only to accomplish this
study and will not use it for other purposes without the sponsor's prior written consent.
The investigator understands that the information developed in the study will be used by the
sponsor in connection with the continued development of Ad26.COV2.S, 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 exploratory
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

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
131
Status: Approved,  Date: 20 April 2022
review at least 60 days before submission for publication or presentation. Expedited reviews will
be arranged for abstracts, poster presentations, or other materials. If requested by the sponsor in
writing, the investigator will withhold such publication for up to an additional 60 days to allow for
filing of a patent application. In the event that issues arise regarding scientific integrity or
regulatory compliance, the sponsor will review these issues with the investigator. The sponsor will
not mandate modifications to scientific content and does not have the right to suppress information.
For multicenter study designs and sub-study approaches, secondary results generally should not
be published before the primary endpoints of a study have been published. Similarly, investigators
will recognize the integrity of a multicenter study by not submitting for publication data derived
from the individual study site until the combined results from the completed study have been
submitted for publication, within 18 months after the study end date, or the sponsor confirms there
will be no multicenter study publication. Authorship of publications resulting from this study will
be based on the guidelines on authorship, such as those described in the ICMJE Recommendations
for the Conduct, Reporting, Editing and Publication of Scholarly Work in Medical Journals, which
state that the named authors must have made a significant contribution to the conception or design
of the work; or the acquisition, analysis, or interpretation of the data for the work; and drafted the
work or revised it critically for important intellectual content; and given final approval of the
version to be published; and agreed to be accountable for all aspects of the work in ensuring that
questions related to the accuracy or integrity of any part of the work are appropriately investigated
and resolved.
Registration of Clinical Studies and Disclosure of Results
The sponsor will register and disclose the existence of and the results of clinical studies as required
by law. The disclosure of the final study results will be performed after the end of study in order
to ensure the statistical analyses are relevant.
10.3.8. 
Data Quality Assurance
Data Quality Assurance/Quality Control
Steps to be taken to ensure the accuracy and reliability of data include the selection of qualified
investigators and appropriate study sites, review of protocol procedures with the investigator and
study site personnel before the study, and periodic monitoring visits by the sponsor. Written
instructions will be provided for collection, handling, storage, and shipment of samples.
Guidelines for eCRF completion will be provided and reviewed with study site personnel before
the start of the study.
The sponsor may review the eCRF for accuracy and completeness during on-site monitoring visits
and after transmission to the sponsor; any discrepancies will be resolved with the investigator or
designee, as appropriate. After upload of the data into the study database they will be verified for
accuracy and consistency with the data sources.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
132
Status: Approved,  Date: 20 April 2022
10.3.9. 
Case Report Form Completion
Case report forms are prepared and provided by the sponsor for each participant in electronic
format. All data relating to the study must be recorded in the eCRF. All eCRF entries, corrections,
and alterations must be made by the investigator or authorized study site personnel. The
investigator must verify that all data entries in the eCRF are accurate and correct.
The study data will be transcribed by study site personnel from the source documents onto an
eCRF, if applicable. Study-specific data will be transmitted in a secure manner to the sponsor.
Worksheets may be used for the capture of some data to facilitate completion of the eCRF. Any
such worksheets will become part of the participant's source documents. Data must be entered into
the eCRF in English. The eCRF must be completed as soon as possible after a participant visit and
the forms should be available for review at the next scheduled monitoring visit.
All participative measurements (eg, questionnaires) will be completed by the same individual who
made the initial baseline determinations whenever possible.
If necessary, queries will be generated in the electronic data capture (eDC) tool. If corrections to
an eCRF are needed after the initial entry into the eCRF, this can be done in either of the following
ways:
 Investigator and study site personnel can make corrections in the eDC tool at their own
initiative or as a response to an auto query (generated by the eDC tool).
 Sponsor or sponsor delegate can generate a query for resolution by the investigator and study
site personnel.
10.3.10. 
Source Documents
At a minimum, source documents consistent in the type and level of detail with that commonly
recorded at the study site as a basis for standard medical care must be available for the following:
participant identification, eligibility, and study identification; study discussion and date of signed
informed consent; dates of visits; results of safety and efficacy parameters as required by the
protocol; record of all AEs and follow-up of AEs; concomitant medication; intervention
receipt/dispensing/return records; study vaccine administration information; and date of study
completion and reason for early discontinuation of study vaccine or withdrawal from the study, if
applicable.
The author of an entry in the source documents should be identifiable. Given that PROs are reports
of a patient’s health condition that come directly from the patient, without interpretation by a
clinician or anyone else, the responses to ePRO measures entered by study participants into source
records cannot be overridden by site staff or investigators.
Participant- and investigator-completed scales and assessments designated by the sponsor (ie, SIC)
will be recorded directly into an eDevice and will be considered source data. The participant’s
e-Diary used to collect information regarding solicited signs and symptoms after vaccination will

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
133
Status: Approved,  Date: 20 April 2022
be considered source data. The documentation of the positive RT-PCR result that serves as a trigger
to start procedures for COVID-19 follow-up, will be considered source data.
Specific details required as source data for the study and source data collection methods will be
reviewed with the investigator before the study and will be described in the monitoring guidelines
(or other equivalent document).
An eSource system may be utilized, which contains data traditionally maintained in a hospital or
clinic record to document medical care (eg, electronic source documents) as well as the clinical
study-specific data fields as determined by the protocol. This data is electronically extracted for
use by the sponsor. If eSource is utilized, references made to the eCRF in the protocol include the
eSource system but information collected through eSource may not be limited to that found in the
eCRF.
10.3.11. 
Monitoring
The sponsor will use a combination of monitoring techniques (central, remote, and/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
post-initiation visit will be made as soon as possible after enrollment has begun. At these visits,
the monitor may  compare the data entered into the eCRF with the source documents
(eg, hospital/clinic/physician’s office medical records). The nature and location of all source
documents will be identified to ensure that all sources of original data required to complete the
eCRF are known to the sponsor and study site personnel and are accessible for verification by the
sponsor study site contact. If electronic records are maintained at the study site, the method of
verification must be discussed with the study site personnel.
Direct access to source documents (medical records) must be allowed for the purpose of verifying
that the recorded data are consistent with the original source data. Findings from this review will
be discussed with the study site personnel. The sponsor expects that, during monitoring visits, the
relevant study site personnel will be available, the source documents will be accessible, and a
suitable environment will be provided for review of study-related documents. The monitor will
meet with the investigator on a regular basis during the study to provide feedback on the study
conduct.
In addition to on-site monitoring visits, remote contacts can occur. It is expected that during these
remote contacts, study site personnel will be available to provide an update on the progress of the
study at the site.
Central monitoring will take place for data identified by the sponsor as requiring central review.
10.3.12. 
On-Site Audits
Representatives of the sponsor's clinical quality assurance department may visit the study site at
any time during or after completion of the study to conduct an audit of the study in compliance

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
134
Status: Approved,  Date: 20 April 2022
with regulatory guidelines and company policy. Remote auditing techniques may also be utilized,
if necessary. These audits will require access to all study records, including source documents, for
inspection. Participant privacy must, however, be respected. The investigator and study site
personnel are responsible for being present and available for consultation during routinely
scheduled study site audit visits conducted by the sponsor or its designees.
Similar auditing procedures may also be conducted by agents of any regulatory body, either as part
of a national GCP compliance program or to review the results of this study in support of a
regulatory submission. The investigator should immediately notify the sponsor if he or she has
been contacted by a regulatory agency concerning an upcoming inspection.
10.3.13. 
Record Retention
In compliance with the ICH/GCP guidelines, the investigator/institution will maintain all eCRF
and all source documents that support the data collected from each participant, as well as all study
documents as specified in ICH/GCP Section 8, Essential Documents for the Conduct of a Clinical
Trial, and all study documents as specified by the applicable regulatory requirement(s). The
investigator/institution will take measures to prevent accidental or premature destruction of these
documents.
Essential documents must be retained until at least 2 years after the last approval of a marketing
application in an ICH region and until there are no pending or contemplated marketing applications
in an ICH region or until at least 2 years have elapsed since the formal discontinuation of clinical
development of the investigational product. These documents will be retained for a longer period
if required by the applicable regulatory requirements or by an agreement with the sponsor. It is the
responsibility of the sponsor to inform the investigator/institution as to when these documents no
longer need to be retained.
If the responsible investigator retires, relocates, or for other reasons withdraws from the
responsibility of keeping the study records, custody must be transferred to a person who will accept
the responsibility. The sponsor must be notified in writing of the name and address of the new
custodian. Under no circumstance shall the investigator relocate or dispose of any study documents
before having obtained written approval from the sponsor.
If it becomes necessary for the sponsor or the appropriate regulatory authority to review any
documentation relating to this study, the investigator/institution must permit access to such reports.
10.3.14. 
Study and Site Start and Closure
First Act of Recruitment
The first site open is considered the first act of recruitment and it becomes the study start date.
Study/Site Termination
The sponsor reserves the right to close the study site or terminate the study at any time for any
reason at the sole discretion of the sponsor. Study sites will be closed upon study completion. A

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
135
Status: Approved,  Date: 20 April 2022
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 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

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
136
Status: Approved,  Date: 20 April 2022
10.4. Appendix 4: Adverse Events, Serious Adverse Events, Adverse Events of
Special Interest, Product Quality Complaints, and Other Safety Reporting:
Definitions and Procedures for Recording, Evaluating, Follow-up, and
Reporting
10.4.1. 
Adverse Event Definitions and Classifications
Adverse Event
An AE is any untoward medical occurrence in a clinical study participant administered a
pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have
a causal relationship with the intervention. An AE can therefore be any unfavorable and unintended
sign (including an abnormal finding), symptom, or disease temporally associated with the use of a
medicinal (investigational or non-investigational) product, whether or not related to that medicinal
(investigational or non-investigational) product (Definition per ICH).
This includes any occurrence that is new in onset or aggravated in severity or frequency from the
baseline condition, or abnormal results of diagnostic procedures, including laboratory test
abnormalities.
Any respiratory tract infection that is not due to SARS-CoV-2 infection will be reported as an AE
if it occurs between the time of any vaccination through the following 28 days. Any respiratory
tract infection recorded as an AE in the eCRF will be excluded from any AE analysis if the
molecular test is subsequently found to be positive for SARS-CoV-2. Respiratory tract infections
arising from SARS-CoV-2 infection will not be reported as (S)AEs in the Clinical Study Report
but will be tabulated separately. In general, any (S)AEs caused by molecularly confirmed
SARS-CoV-2 infection will be removed at the analysis level from the (S)AE listings and tables
and presented separately.
Note: The sponsor collects AEs starting with the signing of the ICF (refer to All Adverse Events
under Section 8.4.1).
Serious Adverse Event
An  SAE based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for
Human Use is any untoward medical occurrence that at any dose:
 
Results in death
 
Is life-threatening
(The participant was at risk of death at the time of the event. It does not refer to an event that
hypothetically might have caused death if it were more severe.)
 
Requires inpatient hospitalization or prolongation of existing hospitalization
 
Results in persistent or significant disability/incapacity
 
Is a congenital anomaly/birth defect
 
Is a suspected transmission of any infectious agent via a medicinal product

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
137
Status: Approved,  Date: 20 April 2022
 
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 serious and unexpected suspected adverse reaction even if it is a component of the study
endpoint (eg, all-cause mortality).
Unlisted (Unexpected) Adverse Event/Reference Safety Information
An AE is considered unlisted if the nature or severity is not consistent with the applicable product
reference safety information. For Ad26.COV2.S, the expectedness of an AE will be determined
by whether or not it is listed in the IB.
10.4.2. 
Attribution Definitions
Assessment of Causality
The causal relationship to study vaccine is determined by the Investigator. The following selection
should be used to assess all AEs.
Related
There is a reasonable causal relationship between study vaccine administration and the AE.
Not Related
There is not a reasonable causal relationship between study vaccine administration and the AE.
The term "reasonable causal relationship" means there is evidence to support a causal relationship.
By definition, all solicited AEs at the injection site (local) will be considered related to the study
vaccine administration.
10.4.3. 
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 2007 (FDA 2007), included in Appendix 8.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
138
Status: Approved,  Date: 20 April 2022
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 emergency room
visit or hospitalization
The severity of solicited signs and symptoms will be graded in the e-Diary by the participant based
on the severity assessment provided in the e-Diary and then verified by the investigator using the
toxicity grading scale in Appendix 8. (Note: severity of the measured events will be derived from
the diameter [for erythema and swelling] and the temperature measurements [for fever]).
10.4.4. 
Special Reporting Situations
Safety events of interest on a sponsor study vaccine in an interventional study that may require
expedited reporting or safety evaluation include, but are not limited to:
 
Overdose of a sponsor study vaccine
 
Suspected abuse/misuse of a sponsor study vaccine
 
Accidental or occupational exposure to a sponsor study vaccine
 
Medication error, intercepted medication error, or potential medication error involving a
Johnson & Johnson medicinal product (with or without patient exposure to the Johnson &
Johnson medicinal product, eg, product name confusion, product label confusion, intercepted
prescribing or dispensing errors)
 
Thrombotic and bleeding events associated with low platelets require immediate reporting the
Marketing authorization holders (MAH).
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.
10.4.5. 
Procedures
All Adverse Events
All AEs, regardless of seriousness, severity, or presumed relationship to study vaccine, must be
recorded using medical terminology in the source document and the eCRF. Whenever possible,
diagnoses should be given when signs and symptoms are due to a common etiology (eg, cough,
runny nose, sneezing, sore throat, and head congestion should be reported as "upper respiratory
infection"). Investigators must record in the eCRF their opinion concerning the relationship of the

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
139
Status: Approved,  Date: 20 April 2022
AE to study therapy. 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 24hour contact telephone number
 
Local sponsor's name and 24-hour contact telephone number (for medical personnel only)
 
Site number
 
Participant number
 
Any other information that is required to do an emergency breaking of the blind
Serious Adverse Events
All SAEs that have not resolved by the end of the study, or that have not resolved upon the
participant's discontinuation from the study, must be followed until any of the following occurs:
 
The event resolves
 
The event stabilizes
 
The event returns to baseline, if a baseline value/status is available
 
The event can be attributed to agents other than the study vaccine or to factors unrelated to
study conduct
 
It becomes unlikely that any additional information can be obtained (participant or health care
practitioner refusal to provide additional information, lost to follow-up after demonstration of
due diligence with follow-up efforts)
Any event requiring hospitalization (or prolongation of hospitalization) that occurs during
participation in the study must be reported as an SAE, except hospitalizations for the following:
 
Hospitalizations not intended to treat an acute illness or AE (eg, social reasons such as pending
placement in long-term care facility)
 
Surgery or procedure planned before entry into the study (must be documented in the eCRF).
Note: Hospitalizations that were planned before the signing of the ICF, and where the
underlying condition for which the hospitalization was planned has not worsened, will not be
considered SAEs. Any AE that results in a prolongation of the originally planned
hospitalization is to be reported as a new SAE.
The cause of death of a participant in a study, whether or not the event is expected or associated
with the study vaccine, is considered an SAE.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
140
Status: Approved,  Date: 20 April 2022
Information regarding SAEs will be transmitted to the sponsor using an SAE reporting form and
safety report form of the eCRF, which must be completed and reviewed by a physician from the
study site, and transmitted in a secure manner to the sponsor within 24 hours. The initial and
follow-up reports of an SAE should be transmitted in a secure manner electronically or by
facsimile (fax). Telephone reporting should be the exception and the reporter should be asked to
complete the appropriate form(s) first.
Adverse Events of Special Interest
AESIs will be carefully monitored during the study by the sponsor. Suspected AESIs must be
reported to the sponsor within 24 hours of awareness irrespective of seriousness (ie, serious and
non-serious AEs) or causality assessment, following the procedure described above for SAEs and
will require enhanced data collection.
10.4.6. 
Product Quality Complaint Handling
Definition
A product quality complaint (PQC) is defined as any suspicion of a product defect related to
manufacturing, labeling, or packaging, ie, any dissatisfaction relative to the identity, quality,
durability, reliability, or performance of a distributed product, including its labeling, drug delivery
system, or package integrity. A PQC may have an impact on the safety and efficacy of the product.
In addition, it includes any technical complaints, defined as any complaint that indicates a potential
quality issue during manufacturing, packaging, release testing, stability monitoring, dose
preparation, storage or distribution of the product or the drug delivery system.
Procedures
All initial PQCs must be reported to the sponsor by the study site personnel within 24 hours after
being made aware of the event.
A sample of the suspected product should be maintained under the correct storage conditions until
a shipment request is received from the sponsor.
10.4.7. 
Contacting Sponsor Regarding Safety, Including Product Quality
The names (and corresponding telephone numbers) of the individuals who should be contacted
regarding safety issues, PQC, or questions regarding the study are listed in the Contact Information
page(s), which will be provided as a separate document.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
141
Status: Approved,  Date: 20 April 2022
10.5. Appendix 5 Symptoms of Infection with Coronavirus-19 (SIC)
The following questions ask about symptoms people with coronavirus-19 infection may
experience. Answer each question carefully by choosing ‘yes’ if you have experienced the
symptom or ‘no’ if you have not experienced the symptom in the last 24 hours. If you
choose ‘yes,’ select the rating that best matches your experience.
In the last 24 hours,
have you
experienced…
Please rate the severity of each symptom you experienced.
Feeling generally
unwell (run down)
Yes   No
    If yes, 
How severe was your feeling (generally unwell or run down) in the last 24 hours?
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10
None 
Worst
possible
Fatigue (tiredness)
Yes   No
    If yes, 
How severe was your fatigue (tiredness) in the last 24 hours?
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10
None 
Worst
possible
Physical weakness
Yes   No
    If yes, 
How severe was your feeling of physical weakness in the last 24 hours?
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10
None 
Worst
possible
Cough
Yes   No
    If yes, 
How severe was your cough in the last 24 hours?
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10
None 
Worst
possible
Shortness of breath
(difficulty
breathing)
Yes   No
    If yes, 
How severe was your shortness of breath (difficulty breathing) in the last 24 hours?
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10
None 
Worst
possible
Sore throat
Yes   No
    If yes, 
How severe was your sore throat in the last 24 hours?
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10
None 
Worst
possible
Nasal congestion
(stuffy nose)
Yes   No
    If yes, 
How severe was your nasal congestion (stuffy nose) in the last 24 hours?
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10
None 
Worst
possible
Wheezing
(whistling sound
while breathing)
Yes    No
    If yes, 
How severe was your wheezing (whistling sound while breathing) in the last 24 hours?
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10
None 
Worst
possible

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
142
Status: Approved,  Date: 20 April 2022
In the last 24 hours,
have you
experienced…
Please rate the severity of each symptom you experienced.
Runny nose
Yes   No
    If yes, 
How severe was your runny nose in the last 24 hours?
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10
None 
Worst
possible
Sneezing
Yes   No
    If yes, 
How severe was your sneezing in the last 24 hours?
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10
None 
Worst
possible
Chest congestion
(mucus in chest)
Yes   No
    If yes, 
How severe was your chest congestion (mucus in chest) in the last 24 hours?
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10
None 
Worst
possible
Chest pain/
pressure/tightness
Yes   No
    If yes, 
How severe was your chest pain/pressure/tightness in the last 24 hours?
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10
None 
Worst
possible
Muscle aches/pains
Yes   No
    If yes, 
How severe were your muscle aches or pains in the last 24 hours?
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10
None 
Worst
possible
Joint aches/pains
Yes   No
    If yes, 
How severe were the aches or pains in your joints in the last 24 hours?
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10
None 
Worst
possible
Headache
Yes   No
    If yes, 
How severe was your headache in the last 24 hours?
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10
None 
Worst
possible
Feeling faint
Yes   No
    If yes, 
How severe was your feeling of faintness in the last 24 hours?
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10
None 
Worst
possible
Problems thinking
clearly/brain fog
Yes   No
    If yes, 
How severe were your problems thinking clearly/brain fog in the last 24 hours?
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10
None 
Worst
possible

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
143
Status: Approved,  Date: 20 April 2022
In the last 24 hours,
have you
experienced…
Please rate the severity of each symptom you experienced.
Chills
Yes   No
    If yes, 
How severe were your chills in the last 24 hours?
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10
None 
Worst
possible
Skin rash
Yes  
No
    If yes, 
How severe was your skin rash in the last 24 hours?
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10
None 
Worst
possible
Eye
irritation/discharge
Yes   No
    If yes, 
How severe was your eye irritation/discharge in the last 24 hours?
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10
None 
Worst
possible
Diarrhea
Yes   No
    If yes, 
How severe was your diarrheain the last 24 hours?
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10
None 
Worst
possible
Vomiting
Yes   No
    If yes, 
How severe was your vomiting in the last 24 hours?
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10
None 
Worst
possible
Nausea
Yes   No
    If yes, 
How severe was your nauseain the last 24 hours?
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10
None 
Worst
possible
Abdominal/
stomach pain
Yes   No
    If yes, 
How severe was your abdominal/stomach pain in the last 24 hours?
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10
None 
Worst possible
Loss of appetite
Yes   No
    If yes, 
How severe was your loss of appetite in the last 24 hours?
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10
None 
Worst
possible

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
144
Status: Approved,  Date: 20 April 2022
What was your highest temperature in the last 24 hours? ____  °C/°F
What method did you use to take your temperature?
oral   armpit    ear   forehead  rectal
In the last 24 hours, have you experienced…
Uncontrollable body shaking/shivering*
Yes   
No
Decreased sense of smell*
Yes   
No
Decreased sense of taste*
Yes   
No
Red or bruised looking feet or toes*
Yes   
No
*Please rate the severity of your symptoms in the last 24 hours?
No Symptoms
Mild
Moderate
Severe

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
145
Status: Approved,  Date: 20 April 2022
10.6. Appendix 6: Medical Resource Utilization (MRU) Questionnaire
Version for Confirmed COVID-19 Cases
Participant ID: 
Date (dd-mmm-yyyy): 
1. Medical consultations
Since onset of the confirmed COVID-19 episode, how many times have you had medical consultations?
No Yes 
Type of contact 
(personal 
consultation/ 
telemedicine) 
If yes, 
specify the 
number of visits 
Specify number of
visits related to
COVID-19 or its
complications
Indicate a
reason for each
visit
General Practitioner
Internal
Medicine/Medical
Outpatient Department
Other Specialist (Please
specify):
Other (eg Physiotherapy,
Pharmacist for a
consultation Please
specify:)
2. Professional home care
Please indicate the need for professional care at home since onset of the confirmed COVID-19 episode
No 
Yes
Type of contact
(personal
consultation/
telemedicine)
If yes,
specify the
number of
visits
Specify number
of visits related to
COVID-19 or its
complications
Indicate a
reason for each
type of
professional
care at home
General Practitioner
Nurse/ Nurse
practitioner
Internal
Medicine/Medical
Outpatient
D partm nt
Specialist (Please
specify):
Other (eg
Physiotherapy,
Pharmacist Please
specify:)
Supplemental oxygen

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
146
Status: Approved,  Date: 20 April 2022
3. Hospital Services
Since onset of the confirmed COVID-19 episode, did you visit the hospital?
Yes: ____
No: ____
No 
Yes
If yes, 
specify number 
of 
visits/admissions 
Specify number
of
visits/admissions
related to
COVID-19 or its
complications
Specify the 
length of each 
stay (days) 
Indicate a
reason for each
hospital visit
Emergency Department*
Short-term hospital visit
(<24 hours admission)
Hospitalization in general
ward#
Hospitalization in
intensive/critical care
Mechanical ventilation use
*Please count Emergency Department visits only if the visit did not result in a hospital admission.
#Please capture type of ward and length of stay in each ward.
4. Institutional care admission(s) other than hospital
Please indicate if there has been any need for admission for care in a long-term facility, since onset of the confirmed
COVID-19 episode.
Yes: ____
No: ____
No 
Yes
If yes,
specify number
of admissions
Specify number
of admissions
related to
COVID-19 or
its
complications
Specify the
length of each
stay (days)
Indicate a
reason for each
institutional
care admission
Long-term facilities
Rehabilitation facility
Supplemental oxygen

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
150
Status: Approved,  Date: 20 April 2022
 
Hyperinflammatory Syndrome
□    Yes     □    No
Severity:   □    Mild 
□    Moderate 
□    Severe
□    Start date: 
        □    End date: 
 
Symptoms or signs of stroke
□    Yes     □    No
Severity:   □    Mild 
□    Moderate 
□    Severe
□    Start date: _____________        □    End date: _____________
 
Numbness, tingling, or weakness face or limbs
□    Yes     □    No
Severity:   □    Mild 
□    Moderate 
□    Severe
□    Start date: _____________        □    End date: _____________
 
Difficulty speaking or forming speech
□    Yes     □    No
Severity:   □    Mild 
□    Moderate 
□    Severe
□    Start date: _____________        □    End date: _____________
 
Difficulty understanding speech
□    Yes     □    No
Severity:   □    Mild 
□    Moderate 
□    Severe
□    Start date: _____________        □    End date: _____________
 
Feelings of confusion
□    Yes     □    No
Severity:   □    Mild 
□    Moderate 
□    Severe
□    Start date: _____________        □    End date: _____________
 
Clinical or radiological evidence of pneumonia
□    Yes     □    No
Severity:   □    Mild 
□    Moderate 
□    Severe
□    Start date: _____________        □    End date: _____________
 
Fever (≥38.0°C or ≥100.4°F)
□    Yes     □    No
Severity:   □    Mild 
□    Moderate 
□    Severe
□    Start date: _____________        □    End date: _____________
 
Shaking chills or rigors
□    Yes     □    No
Severity:   □    Mild 
□    Moderate 
□    Severe
□    Start date: _____________        □    End date: _____________
 
Cough
□    Yes     □    No
Severity:   □    Mild 
□    Moderate 
□    Severe
□    Start date: _____________        □    End date: _____________

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
153
Status: Approved,  Date: 20 April 2022
10.8. Appendix 8: 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)
(US DHHS 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 –155 
> 155 
Hospitalization for
malignant
hypertension#
Hypertension 
(diastolic) - mm Hg 
91 –95 
96 –100 
> 100 
Hospitalization for
malignant
hypertension#
Hypotension 
(systolic) –mm Hg 
85 –89 
80 –84 
< 80 
Hospitalization for
hypotensive shock#
Respiratory Rate – 
breaths per minute
17 –20 
21 –25 
> 25 
Intubation
* Participant should be at rest for all vital sign measurements.
** For oral temperature: no recent hot or cold beverages or smoking.
*** When resting heart rate is between 60 –100 beats per minute. Use clinical judgment when characterizing
bradycardia among some healthy participant populations, for example, conditioned athletes.
# Revised by the sponsor.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
154
Status: Approved,  Date: 20 April 2022
Systemic (General) Mild (Grade 1) 
Moderate (Grade 2) Severe (Grade 3) 
Potentially Life
Threatening
(Grade 4)
Vomiting# 
No interference 
with activity or 1 –2 
episodes/24 hours 
Some interference 
with activity or > 2 
episodes/24 hours 
Prevents daily  
activity, requires 
outpatient IV
hydration
Hospitalization;
Hypotensive shock
Nausea# 
Minimal symptoms; 
causes minimal or no 
interference with 
work, school, or self- 
care activities 
Notable symptoms; 
Requires modification 
in activity or use of 
medications; 
Does NOT result in 
loss of work, school, 
or cancellation of 
social activities
Incapacitating 
symptoms; 
Requires bed rest 
and/or results in loss 
of work, school, or
cancellation of social
activities
Hospitalization;
Inability to perform
basic self-care
functions
Diarrhea# 
2 –3 loose stools or 
< 400 gms/24 hours 
4 –5 stools or 
400 –800 gms/24 
hours 
6 or more watery  
stools or 
> 800 gms/24 hours 
or oral rehydration 
necessary
Hospitalization;
Hypotensive shock
OR IV fluid
replacement indicated
Headache# 
Minimal symptoms;
causes minimal or no
interference with
work, school, or self-
care activities
Notable symptoms; 
Requires modification 
in activity or use of 
medications; 
Does NOT result in 
loss of work, school, 
or cancellation of 
social activities 
Incapacitating
symptoms;
Requires bed rest
and/or results in loss
of work, school, or
cancellation of social
activities;
Use of narcotic pain
reliever
Hospitalization;
Inability to perform
basic self-care
functions
Fatigue# 
Minimal symptoms;
causes minimal or no
interference with
work, school, or self-
care activities
Notable symptoms; 
Requires modification 
in activity or use of 
medications; 
Does NOT result in 
loss of work, school, 
or cancellation of 
social activities 
Incapacitating
symptoms;
Requires bed rest
and/or results in loss
of work, school, or
cancellation of social
activities;
Use of narcotic pain
reliever
Hospitalization;
Inability to perform
basic self-care
functions
Myalgia# 
Minimal symptoms;
causes minimal or no
interference with
work, school, or self-
care activities
Notable symptoms; 
Requires modification 
in activity or use of 
medications; 
Does NOT result in 
loss of work, school, 
or cancellation of 
social activities 
Incapacitating
symptoms;
Requires bed rest
and/or results in loss
of work, school, or
cancellation of social
activities;
Use of narcotic pain
reliever
Hospitalization;
Inability to perform
basic self-care
functions
# Revised by the sponsor.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
155
Status: Approved,  Date: 20 April 2022
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.
B: Tables for Laboratory Abnormalities
Laboratory tests may be performed during routine medical care and assessment of AEs or other
medical events based on the investigator’s judgment.
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
Creatine phosphokinase 
(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

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
156
Status: Approved,  Date: 20 April 2022
Serum * 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life
Threatening
(Grade 4)**
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 mEq/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.
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.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
157
Status: Approved,  Date: 20 April 2022
Urine * 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life-Threatening
(Grade 4)
Protein  
Trace 
1+  
2+ 
Hospitalization or
dialysis
Glucose 
Trace 
1+  
2+ 
Hospitalization for
hyperglycemia
Blood (microscopic) – 
red blood cells per 
high power field (rbc/hpf) 
1 - 10 
11 –50 
> 50 and/or 
gross 
blood 
Hospitalization or
packed red blood cells (PRBC)
transfusion
* 
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.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
158
Status: Approved,  Date: 20 April 2022
10.9. Appendix 9: Summary of Guidance from CDC Websitea on Underlying
Medical Conditions That Lead or Might Lead to Increased Risk for Severe
Illness From COVID-19
Adults of any age with certain underlying medical conditions are at increased risk for severe
illness from COVID-19: Severe illness from COVID-19 is defined as hospitalization, admission
to the ICU, intubation or mechanical ventilation, or death.
Adults of any age with the following conditions can be more likely to become severely ill from
COVID-19b:
 Cancer
 Chronic kidney disease
 Chronic lung diseases, including COPD (chronic obstructive pulmonary disease), asthma
(moderate-to-severe), interstitial lung disease, cystic fibrosis, and pulmonary hypertension
 Dementia or other neurological conditions
 Diabetes (Type 1 and Type 2)
 Down syndrome
 Heart conditions, such as heart failure, coronary artery disease, cardiomyopathies, or
hypertension
 HIV infection
 Immunocompromised state (weakened immune system)
 Liver disease
 Overweight (BMI of >25 kg/m2 but <30 kg/m2), obesity (BMI of 30 kg/m2 but
<40 kg/m2), or severe obesity (BMI ≥40 kg/m2)
 Pregnancy
 Sickle cell disease or thalassemia
 Smoking (current and former)
 Solid organ or blood stem cell transplant
 Stroke or cerebrovascular disease, which affects blood flow to the brain
 Substance use disorder
aSource: https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-
conditions.html?CDC AA refVal=https%3A%2F%2Fwww.cdc.gov%2 Fcoronavirus% 2F2019-ncov%2Fneed-
extra-precautions%2Fgroups-at-higher-risk.html. Updated 29 March 2021. Accessed: 6 April 2021.
b The list of underlying medical conditions is not exhaustive and only includes conditions with sufficient evidence to
draw conclusions.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
159
Status: Approved,  Date: 20 April 2022
10.10. Appendix 10: Thrombotic Events to be Reported as AESIs
At the time of protocol writing, the list of thrombotic events to be reported to the sponsor as AESIs
is provided below. Further guidance may become available on thrombotic events of interest.
 MedDRA PTs for large vessel thrombosis and embolism:
o 
Aortic embolus, aortic thrombosis, aseptic cavernous sinus thrombosis, brain stem
embolism, brain stem thrombosis, carotid arterial embolus, carotid artery thrombosis,
cavernous sinus thrombosis, cerebral artery thrombosis, cerebral venous sinus
thrombosis, cerebral venous thrombosis, superior sagittal sinus thrombosis, transverse
sinus thrombosis, mesenteric artery embolism, mesenteric artery thrombosis, mesenteric
vein thrombosis, splenic artery thrombosis, splenic embolism, splenic thrombosis,
thrombosis mesenteric vessel, visceral venous thrombosis, hepatic artery embolism,
hepatic artery thrombosis, hepatic vein embolism, hepatic vein thrombosis, portal vein
embolism, portal vein thrombosis, portosplenomesenteric venous thrombosis, splenic
vein thrombosis, spontaneous heparin-induced thrombocytopenia syndrome, femoral
artery embolism, iliac artery embolism, jugular vein embolism, jugular vein thrombosis,
subclavian artery embolism, subclavian vein thrombosis, obstetrical pulmonary
embolism, pulmonary artery thrombosis, pulmonary thrombosis, pulmonary venous
thrombosis, renal artery thrombosis, renal embolism, renal vein embolism, renal vein
thrombosis, brachiocephalic vein thrombosis, vena cava embolism, vena cava
thrombosis, truncus coeliacus thrombosis
 MedDRA PTs for more common thrombotic events:
o 
Axillary vein thrombosis, deep vein thrombosis, pulmonary embolism, MedDRA PTs
for acute myocardial infarction*, MedDRA PTs for stroke*
Source: Shimabukuro T. CDC COVID-19 Vaccine Task Force. Thrombosis with thrombocytopenia syndrome (TTS)
following Janssen COVID-19 vaccine. Advisory Committee on Immunization Practices (ACIP). April 23, 2021.
https://www.cdc.gov/vaccines/acip/meetings/slides-2021-04-23.html.
*Vaccine Adverse Event Reporting System (VAERS) Standard Operating Procedures for COVID-19 (as of
29 January 2021) https://www.cdc.gov/vaccinesafety/pdf/VAERS-v2-SOP.pdf

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
160
Status: Approved,  Date: 20 April 2022
10.11. Appendix 11: TTS AESI Form
The form below represents the type of information that may be collected in case of a suspected
AESI in order to help adjudicate whether the event is a case of TTS. Additional data may be
requested by the sponsor for investigation of the event.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
161
Status: Approved,  Date: 20 April 2022

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
162
Status: Approved,  Date: 20 April 2022

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
163
Status: Approved,  Date: 20 April 2022
10.12. Appendix 12: Protocol Amendment History
The Protocol Amendment Summary of Changes Table for the current amendment is located
directly before the Table of Contents (TOC).
Amendment 5 (17 Decemeber 2021)
Overall Rationale for the Amendment: This amendment is written primarily to clarify
procedures in the Schedule of Activities. All changes are listed below, including the rationale for
each change and a list of all applicable sections.
Section number 
and Name
Description of Change 
Brief Rationale
1.3 Schedule of Activities 
Text added to Schedule of Activities
to denote ‘no subset’ for N-serology
and humoral immunity samples at
study visit 7A.
To clarify that these samples are
collected from the ‘no subset’
participants only.
1.3 Schedule of Activities 
Correction of visit timing of
Visit 7A.
Visit timing should read ‘Vac
+119 d’.
1.3 Schedule of Activities 
Vital sign measurements added at
Visit 10 for ‘All’ participants.
Vital sign measurements should be
scheduled for Visit 10.
1.1 Synopsis 
9.5 Planned Analysis 
‘Study Responsible Physician/Study
Responsible Scientist’ removed from
text on data collection, data
management, and safety monitoring.
SRS will no longer be directly
involved in data collection, data
management and safety
monitoring. SRS will be unblinded
to allow review of primary
analysis.
Throughout the protocol 
Minor formatting changes were
made.
Minor errors were noted

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
164
Status: Approved,  Date: 20 April 2022
Amendment 4 (30 November 2021)
Overall Rationale for the Amendment: This amendment is written to add a blood draw for humoral
immunogenicity at the 4-month (Day 120) timepoint, to allow assessment of the trend for duration of the
immune response (i.e; kinetic curve). This and other changes are listed below, including the rationale for
each change and a list of all applicable sections.
Section number 
and Name
Description of Change 
Brief Rationale
1.1 Synopsis
1.3 Schedule of Activities
4.1 Overall Design
8. STUDY
ASSESSMENTS AND
PROCEDURES
10.2 APPENDIX 2
A Day 120 blood draw has been added
(for humoral immunity assessments) for
participants not assigned to any subset.
To allow assessment of the durability
of the immune response at 4 months
post-boost, to in order to evaluate the
kinetics of antibody responses
overtime.
1.3 Schedule of Activities
8. STUDY
ASSESSMENTS AND
PROCEDURES
Exploratory blood draws at Day 28 and
Day 120 have been added for participants
at BIDMC.
To allow assessment of in-depth
exploratory immunogenicity
endpoints at additional timepoints.
6.7 Concomitant
Medications
Added requirement for Cohort 2
participants to provide dates of primary
vaccination with BNT162b2.
To clarify that collection of primary
BNT162b2 vaccination dates is
necessary for the proper conduct of
the analysis.
7.2 Participant 
Discontinuation/Withdrawal 
Added text to state that participants
receiving a Covid-19 booster vaccine off
study will be excluded from all formal
hypothesis testing (primary objectives).
Off study booster vaccinations will
make participants unevaluable in the
protocol defined primary endpoints.
Title Page 
Study name ‘Amplify’ added to Title
page
Study name should have been
included on title page.
Throughout the protocol 
Minor grammatical, formatting changes
and clarifications were made.
Minor errors were noted

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
165
Status: Approved,  Date: 20 April 2022
Amendment 3 (08 October 2021)
Overall Rationale for the Amendment: This amendment is written to make the planned interim analyses
for Cohort 1 optional as study enrollment progress indicates that the timing of interim analysis and primary
analysis will be too close in time to make the interim analysis of significant added value to the study and to
add a Day 29 phone call for all participants to ensure robust reporting of the unsolicited AEs.
These and other changes made to the clinical protocol of study VAC31518COV2008 are listed below,
including the rationale for each change and a list of all applicable sections.
Section number 
and Name
Description of Change 
Brief Rationale
1.1 Synopsis 
4.1 Overall Design  
9.1 Statistical Hypotheses
9.2 Sample Size
Determination
9.4 Statistical Analyses
9.4.2 Primary Endpoints
9.5 Planned Analysis
Text was updated to make the planned interim 
analysis for Cohort 1 optional.
See overall rationale above
1.3.1 All Participants 
Added a Day 29 phone call for all participants. To ensure robust reporting of the
unsolicited AEs in the study.
1.1 Synopsis 
9.5 Planned Analysis 
For the primary analysis, text for the 
immunogenicity data was updated to include 
"S-ELISA and/or MSD, if available at the
time of analysis".
To align with the secondary
endpoints.
1.1 Synopsis 
9.5 Planned Analysis 
Text was added to clarify the unblinding of 
data at the time of primary analysis with
respect to each cohort.
Clarification
1.1 Synopsis 
1.3.1 All Participants 
1.3.3 Participants With 
COVID-19-like Signs and
Symptoms
4.1 Overall Design
8.2.2 Vital Signs
Text was updated to clarify that the preferred 
position for collection of blood pressure
measurements is supine.
Clarification
Throughout the protocol 
Minor grammatical, or formatting changes 
were made and minor clarifications, including
alignment across sections, were added.
Minor errors were noted
Amendment 2 (22 September 2021)
Overall Rationale for the Amendment: This amendment is written to address Health Authority (HA)
feedback, including, the addition of formal non-inferiority (NI) hypothesis testing for the leading severe
acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of high consequence or concern, as
defined by the Centers for Disease Control and Prevention(CDC Aug 2021c), the adjustment of the primary
objectives for Cohort 2, which will now compare post-boost neutralizing antibodies with neutralizing
antibodies post Pfizer primary vaccine series, the addition of another success criterion for the NI
assessments, requiring a geometric mean ratio (GMR; geometric mean titer [GMT] Day 15 post
booster/GMT post primary regimen) >0.8 in order to conclude NI, and the extension of the follow-up phase
from 6 months to 1 year. In addition, an interim analysis is implemented in this study to formally test
Primary Objectives 1a and 1b and the time windows for Visits 5 and 6 have been adjusted.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
166
Status: Approved,  Date: 20 April 2022
Section number
and Name
Description of Change 
Brief Rationale
1.1 Synopsis
4.1 Overall Design
9.1 Statistical Hypotheses
9.2 Sample Size
Determination
9.4 Statistical Analyses
9.4.2 Primary Endpoints
9.5 Planned Analysis
When at least 330 participants from Groups 1
to 3 in Cohort 1 have been enrolled, have
completed the Day 15 visit and it is estimated
that immunogenicity data can be obtained
from 110 or more participants in Group 1, an
interim analysis will be conducted whereby
formal non-inferiority testing of Cohort 1 –
Group 1 (Primary Objectives 1a and 1b) will
be performed on the available data from the
Cohort 1 –Group 1 participants.
To demonstrate NI of the
immunogenicity post booster
vaccination versus post
Ad26.COV2.S primary regimen.
1.1 Synopsis
2 INTRODUCTION
3 OBJECTIVES AND
ENDPOINTS
8.1.5 Immunogenicity
Assessments
9.1 Statistical Hypotheses
9.4.2 Primary Endpoints
11 REFERENCES
The study endpoints have been revised to
include formal hypothesis testing (primary
objective/endpoint) for the effectiveness of the
Ad26.COV2.S booster vaccination at
5x1010 vp following a primary regimen of a
single dose of Ad26.COV2.S at 5x1010 vp or a
2-dose Pfizer BNT162b2 regimen against
leading SARS-CoV-2 variant of high
consequence or concern, as defined by the
CDC (CDC, Aug2021c) in the US at the time
of the analysis. Additional relevant variants
may be analyzed as secondary objective.
HA request to include study
endpoints, with formal hypothesis
testing, evaluating effectiveness
against circulating variants that
are relevant based on US
epidemiology data.
1.1 Synopsis
1.2 Schema
2 INTRODUCTION
3 OBJECTIVES AND
ENDPOINTS
8.1.5 Immunogenicity
Assessments
9.1 Statistical Hypotheses
9.3 Analysis Sets
9.4.2 Primary Endpoints
Primary objectives for Cohort 2 have been
revised. For the NI assessments neutralizing
antibodies post booster will now be compared
to neutralizing antibody response post the
Pfizer primary vaccination instead of the
neutralizing antibody response post a single
Ad26.COV2.S (5x1010 vp) dose. Serum
samples from approximately 300 individuals
who received the Pfizer primary vaccine series
will be obtained from Biobank or other
external studies to perform this analysis.
HA request to include assessment
of immune responses after a
booster dose of Ad26.COV2.S in
participants who received the
primary Pfizer vaccine series
compared to the responses after
the primary Pfizer vaccine series
to ensure that post booster
responses are at least the response
observed post primary
vaccination with the Pfizer
vaccine.
1.1 Synopsis 
3 OBJECTIVES AND  
ENDPOINTS  
9.1 Statistical Hypotheses 
9.4.2 Primary Endpoints 
An additional pre-specified success criterion
for NI hypothesis testing was added. In
addition to statistical NI of responder rate and
statistical NI of GMTs, an estimated GMR
(GMT Day 15 post booster/GMT post primary
regimen) of >0.8 is required to conclude NI.
HA recommendation
1.3 Schedule of Activities 
The visit window of Visits 5 (Day 15) and 6
(Day 29) were adjusted ±3 days to -3/+7 days
for Visit 5 and -3/+10 days for Visit 6.
Learnings from the ongoing
COV2008 study have indicated
that it is challenging for
participants to have the Visits 5
and 6 within the specified time
window. Therefore, the windows
for these visits were extended. In
view of the immunogenicity
results observed in Ad26.COV2.S
studies, including
VAC31518COV1001 and
VAC31518COV2001 studies, a
broader visit window for Visits 5
and 6 should not impact the
immunogenicity assessment.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
167
Status: Approved,  Date: 20 April 2022
Section number 
and Name
Description of Change 
Brief Rationale
1.1 Synopsis 
1.3.1 All Participants 
3 OBJECTIVES AND  
ENDPOINTS
4.1 Overall Design
4.4 End of Study
Definition
8 STUDY
ASSESSMENTS AND
PROCEDURES
The follow-up in the study for safety and 
immunogenicity has been extended to 
12 months post booster. 
To collect extended safety data
and to collect data on durability of
immune response
5.1 Inclusion Criteria 
A time window of maximum -20 days was 
added to the allowed time interval of ≥ 6
months between the primary vaccine regimen
and Ad26.COV2.S booster.
To facilitate recruitment
1.3.2 Participants with a 
Suspected AESI 
It is clarified that if an AESI is reported to the 
investigator more than 28 days after the onset
of the event, the Day AESI 29 visit (28 days
post the onset of the event) becomes obsolete
and does not need to be performed.
Clarification
1.1 Synopsis 
9.4.2 Primary Endpoints 
11 REFERENCES  
It is clarified that for the NI analysis on 
responder rate the Agresti-Min method is
chosen to estimate the difference in
proportions and its CI because of its well-
behaved coverage probability (CP)properties
compared to other methods for the analysis of
matched pairs data (Reed 2009). Coverage
probability is generally used to evaluate (1 –
α) confidence intervals where α is the Type I
error rate.
Clarification
10.2 Appendix 2: Clinical 
Laboratory Tests 
It has been added that, as part of investigation 
of any AESI, samples from appropriate
controls (from vaccinated participants who did
not experience an AESI) within the study may
be used for coagulation-related assays.
Clarification
2.3.1 Risks Related to 
Study Participation  
Text has been added regarding the increased 
risk of Guillain-Barre Syndrome (GBS) 
following use of the Ad26.COV2.S vaccine. 
Based on the emerging data
following use of the
Ad26.COV2.S vaccine, GBS has
been identified as an adverse drug
reaction for the use of
Ad26.COV2.S vaccine.
1.1 Synopsis 
11 REFERENCES  
The reference to the Brighton Collaboration
case definition of thrombotic events and
thrombocytopenia was updated.
Update 
8 STUDY 
ASSESSMENTS AND 
PROCEDURES  
Blood volumes have been corrected and it is
clarified that for participants at the BIDMC
site, up to an additional 50 mL of blood is
taken per blood draw (and not in total) for
experimental research amounting to an
additional total approximate blood volume of
200 mL.
Correction and clarification
1.3.1 All Participants 
It is clarified that the e-diary review at Day 8
is only applicable for participants in blood
collection Subset 1. The e-diary will be
reviewed at the Day 15 visit for all
Clarification

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
168
Status: Approved,  Date: 20 April 2022
Section number 
and Name
Description of Change 
Brief Rationale
participants, including repeated review for the
participants in Subset 1.
1.3.2 Participants with a 
Suspected AESI 
It is clarified that also in the event of 
thrombocytopenia, laboratory assessments (to
be performed locally) are required to facilitate
diagnosis and determine treatment options,
including but not limited to platelet count and
anti-PF4 tests.
Clarification
Throughout the protocol 
Minor grammatical, formatting, or spelling 
changes were made and minor clarifications,
including alignment across sections, were
added.
Minor errors were noted
Amendment 1 (16 August 2021)
Overall Rationale for the Amendment: This amendment is written to address HA feedback, including
the increase of the sample size of study groups of interest and adjustment of the assumption in the sample
size calculation for the non-inferiority comparisons of a seroresponse rate of 95% post booster versus 90%
post primary vaccination and a geometric mean titer (GMT) ratio of 1.5 for the booster to using the
conventional assumption of no difference between the virus neutralization assay (VNA) data post booster
and post primary vaccination.
Section number 
and Name
Description of Change 
Brief Rationale
1.1 Synopsis
1.2 Schema
4.1 Overall Design
8 STUDY
ASSESSMENTS
AND
PROCEDURES
9.2 Sample Size
Determination
9.4.3 Secondary
Endpoint(s)
The sample size of study groups 1, 2, 4 and 5,
including a booster dose at the 5x1010 vp or
2.5x1010 vp dose level was increased to ~330
participants per study group.
In each of the cohorts, participants will initially be
randomized in a 1:1:1 ratio into 3 groups to receive
a 1-dose booster vaccination regimen with
Ad26.COV2.S until group 3 (Cohort 1) or group 6
(Cohort 2) is fully enrolled. Thereafter,
randomization will continue in a 1:1 ratio in groups
1 and 2 (Cohort 1) or groups 4 and 5 (Cohort 2).
The size of the subsets (subsets 1 to 4) for humoral
immunogenicity at intermediate timepoints and
cellular immunogenicity remains unchanged. The
first ~330 randomized participants per cohort will
be assigned to 1 of the 4 blood collection subsets.
Once the subsets are enrolled, the subsequent
participants will not be in a subset. They will only
have the immunogenicity samples taken at Day 1,
Day 15 and Day 181.
To increase the safety database of
the final chosen booster dose level
for each primary series cohort
(either 1 dose of Ad26.COV2.S or 2
doses of BNT162b2) to allow for
potential assessment of safety
events that may occur at a rate of
1% and to accommodate for the
revised assumption of no difference
between the VNA data post booster
and post primary vaccination in the
sample size calculation for the non-
inferiority comparisons. (see
description of change in next row)
1.1 Synopsis
9.2 Sample Size
Determination
The assumptions for the non-inferiority
comparison of a seroresponse rate of 95% post
booster versus 90% post primary vaccination and a
GMT ratio (Day 15 post-booster/Day 29 post
primary regimen) of 1.5 have been revised to
assume no difference between VNA data post
booster and post primary vaccination, ie, 90%
seroresponse rate post booster and post primary
vaccination and a GMT ratio of 1.0.
Upon recommendation of the
Health Authority to use the
conventional assumption of no
difference between the VNA data
post booster and post primary
vaccination in the sample size
calculation for the non-inferiority
comparisons.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
169
Status: Approved,  Date: 20 April 2022
Section number
and Name
Description of Change 
Brief Rationale
1.1 Synopsis
9.4.2 Primary
Endpoints
It is clarified that the non-inferiority analysis on 
responder rate will be based on Agresti-Min
(Agresti 2005) method to estimate the difference in
proportions and its confidence interval.
Clarification
1.1 Synopsis
1.3 Schedule of
Activities
3 OBJECTIVES
AND ENDPOINTS
8 STUDY
ASSESSMENTS
AND
PROCEDURES
It is clarified that in-depth humoral and cellular 
immunogenicity assessments may be performed on
participants enrolled at the BIDMC site and in a
subset of participants enrolled at other sites. It is
also clarified that for participants enrolled at
BIDMC, additional blood draws are required for
this exploratory analysis at Day 1, Day 15 and Day
181.
Clarification
Throughout the
protocol
Minor grammatical, formatting, or spelling 
changes were made.
Minor errors were noted

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
170
Status: Approved,  Date: 20 April 2022
11. 
REFERENCES
Agrawal AS (2016), Tao X, Algaissi A, et al. Immunization with inactivated Middle East Respiratory Syndrome
coronavirus vaccine leads to lung immunopathology on challenge with live virus. Hum Vaccin Immunother.
2016;12(9):2351-2356.
Agresti, A. & Min, Y. (2005). Simple improved confidence intervals for comparing matched proportions. Statistics
in Medicine, 24, 729-740.
American Society of Hematology (2021). COVID-19 resources. Thrombosis with Thrombocytopenia Syndrome
(also termed Vaccine-induced Thrombotic Thrombocytopenia). https://www.hematology.org/covid-19/vaccine-
induced-immune-thrombotic-thrombocytopenia. Accessed: 27 April 2021.
Anywaine Z (2019), Whitworth H, Kaleebu P, et al. Safety and Immunogenicity of a 2-Dose Heterologous
Vaccination Regimen With Ad26.ZEBOV and MVA-BN-Filo Ebola Vaccines: 12-Month Data From a Phase 1
Randomized Clinical Trial in Uganda and Tanzania. J Infect Dis. 2019;220(1):46-56.
Baden LR (2020b), El Sahly HM, Essink B, et al. Efficacy and safety of the mrna-1273 sars-cov-2 vaccine. N Engl J
Med. Published online December 30, 2020:NEJMoa2035389.
Barouch DH (2013), 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(2);248-256.
Barouch DH (2018), 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.
Bolles M (2011), Deming D, Long K, et al. A double-inactivated severe acute respiratory syndrome coronavirus
vaccine provides incomplete protection in mice and induces increased eosinophilic proinflammatory pulmonary
response upon challenge. J Virol. 2011;85(23):12201-12215.
Brighton Collaboration (2021) Updated Proposed Brighton Collaboration process for developing a standard case
definition for study of new clinical syndrome X, as applied to Thrombosis with Thrombocytopenia Syndrome
(TTS). 18 May 2021. https://brightoncollaboration.us/wp-content/uploads/2021/05/TTS-Interim-Case-Definition-
v10.16.3-May-23-2021.pdf.Accessed: 02 September 2021.
British Society for Haematology (2021). Guidance produced from the Expert Haematology Panel (EHP) focussed on
Covid-19 Vaccine induced Thrombosis and Thrombocytopenia (VITT). https://b-s-h.org.uk/media/19530/guidance-
version-13-on-mngmt-of-thrombosis-with-thrombocytopenia-occurring-after-c-19-vaccine 20210407.pdf. Version
1.3; 7 April 2021.  Accessed: 27 April 2021.
Center for Disease Control and Prevention (CDC 2020b). Symptoms of Coronavirus.
https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html. Accessed 21 January 2021.
Center for Disease Control and Prevention (CDC 2020g). Multisystem Inflammatory Syndrome in Children (MIS C)
Associated with Coronavirus Disease 2019 (COVID-19). https://emergency.cdc.gov/han/2020/han00432.asp.
Accessed 21 January 2021.
Center for Disease Control and Prevention (CDC 2020h). Transcript - CDC Media Telebriefing: Update on
COVID-19. https://www.cdc.gov/media/releases/2020/t0309-covid-19-update.html. Accessed 21 January 2021.
Centers for Disease Control and Prevention (CDC 2021a). Coronavirus Disease 2019 (COVID-19) Groups at Higher
Risk for Severe Illness. https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/groups-at-higher-
risk.html. Updated: 29 March 2021. Accessed 6 April 2021.
Centers for Disease Control and Prevention (CDC 2021c). SARS-CoV-2 Variant Classifications and Definitions.
https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/variant-surveillance/variant-info.html#Consequence.
Accessed 21 April 2021; 24 August 2021.
Centers for Disease Control and Prevention (CDC 2021d). Cases of cerebral venous sinus thrombosis with
thrombocytopenia after receipt of the Johnson & Johnson COVID-19 Vaccine. 13 April 2021.
https://emergency.cdc.gov/han/2021/han00442.asp. Accessed: 27 April 2021.
Chen G (2020), Wu D, Guo WZ, Cao Y, Huang D, Wang H, et al. Clinical and immunologic features in severe and
moderate coronavirus disease 2019. J Clin Investig. 2020;130:2620-2629.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
171
Status: Approved,  Date: 20 April 2022
Chen N (2020), Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel
coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507-513.
Copaescu A (2020), Smibert O, Gilson A, Philips EJ, and Trubiano JA. The role of IL-6 and other mediators in the
cytokine storm associated with SARS-CoV-2 infection. J Allergy Clin Immunol 2020; 146(3): 518-534.
Coronaviridae Study Group of the International Committee on Taxonomy of Viruses (2020). The species Severe
acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol.
2020;5(4):536-544.
Deming D (2006), Sheahan T, Heise M, et al. Vaccine efficacy in senescent mice challenged with recombinant
SARS CoV bearing epidemic and zoonotic spike variants. PLoS Med. 2006;3(12):e525.
ECDC (2021). European Centre for Disease Prevention and Control. COVID-19 country overviews. https://covid19-
country-overviews.ecdc.europa.eu/. Accessed 12 February 2021.
European Medicines Agency (2021). Adapting COVID-19 vaccines to SARS-CoV-2 variants: guidance for vaccine
manufacturers. February 2021. https://www.ema.europa.eu/en/news/adapting-covid-19-vaccines-sars-cov-2-
variants-guidance-vaccine-manufacturers. Accessed 12 April 2021.
European Commission (1998) 98/463/EC: Council Recommendation of 29 June 1998 on the suitability of blood and
plasma donors and the screening of donated blood in the European Community.
Faria NR (2021), Claro IM, Candido D et al. Genomic characterisation of an emergent SARS-CoV-2 lineage in
Manaus: Preliminary Findings. nCoV-2019 Genomic Epidemiology, 2021.
Garg S (2020), Kim L, Whitaker M, et al. Hospitalization rates and characteristics of patients hospitalized with
laboratory-confirmed coronavirus disease 2019 — COVID-NET, 14 States. Morb Mortal Wkly Rep.
2020;69(15):458–464.
Gidudu JF (2012), 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.
Guan WJ (2020), Ni ZY, Hu Y, et al, for the China Medical Treatment Expert Group for Covid-19. Clinical
Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020;382:1708-1720.
He X (2021), Chandrashekar A, Zahn RC, et al. Low-dose Ad26.COV2.S protection against SARS-CoV-2 challenge
in rhesus macaques. BioRxiv 2021; doi:10.1101/2021.01.27.428380. [preprint]
Honda-Okubo Y (2015), Barnard D, Ong CH, Peng BH, Tseng CT, Petrovsky N. Severe acute respiratory
syndrome-associated coronavirus vaccines formulated with delta inulin adjuvants provide enhanced protection while
ameliorating lung eosinophilic immunopathology. J Virol. 2015;89(6):2995-3007.
Houser KV (2017), Broadbent AJ, Gretebeck L, et al. Enhanced inflammation in New Zealand white rabbits when
MERS-CoV reinfection occurs in the absence of neutralizing antibody. PLoS Pathog. 2017;13(8):e1006565.
Hu B (2021), Guo H, Zhou P and Shi Z-L. Characteristics of SARS-CoV-2 and COVID-19. Nat Rev Microbiol.
2021;19(3):141-154.
Huang C (2020), Wang, Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel
coronavirus in Wuhan. China. Lancet 2020;395:497-506.
Huang I (2020) and Pranata R. Journal of Intensive Care 2020 vole 8 (36) Lymphopenia in severe coronavirus
disease-2019 (COVID-19): systematic review and meta analysis.
Investigator's Brochure: Ad26.COV2.S (VAC31518), Edition 4, Janssen Vaccines & Prevention B.V (19 February
2021). Janssen Vaccines & Prevention B.V. Data on file.
Investigator's Brochure: Ad26.COV2.S (VAC31518), Edition 4, Addendum 1, Janssen Vaccines & Prevention B.V
(23 April 2021). Janssen Vaccines & Prevention B.V. Data on file.
Investigator's Brochure: Ad26.COV2.S (VAC31518), Edition 4, Addendum 2, Janssen Vaccines & Prevention B.V
(21 May 2021). Janssen Vaccines & Prevention B.V. Data on file.
Investigator's Brochure: Ad26.COV2.S (VAC31518), Edition 4, Addendum 3, Janssen Vaccines & Prevention B.V
(1 June 2021). Janssen Vaccines & Prevention B.V. Data on file.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
172
Status: Approved,  Date: 20 April 2022
International Coalition of Medicines Regulatory Authorities ICMRA COVID-19 Virus Variants Workshop guidance
(2021). http://www.icmra.info/drupal/en/covid-19/10february2021. Accessed 11 April 2021.
Johns Hopkins CSSE (2021). Coronavirus COVID-19 Global Cases. Available from:
https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6.
Accessed 17 April 2021.
Kohl KS (2007), Walop W, Gidudu J, et al. The 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.
Leung L (2021), Shum HH, Leung GM, et al. Early transmissibility assessment of the N501Y mutant strains of
SARS-CoV-2 in the United Kingdom, October to November 2020. Eurosurveilance. 2021;26(1).
Linton NM (2020), Kobayashi T, Yang Y, et al. Incubation Period and Other Epidemiological Characteristics of
2019 Novel Coronavirus Infections with Right Truncation: A Statistical Analysis of Publicly Available Case Data. J
Clin Med. 2020;9(2):1-9.
Li Q (2020), Guan X, Wu P, et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected
Pneumonia. N Engl J Med. 2020;382(13):1199-1207.
Lu R (2020), Zhao X, Li J, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus:
implications for virus origins and receptor binding. Lancet. 2020 Jan 30. pii: S0140-6736(20)30251-30258.
Marcy SM (2004), Kohl KS, Dagan R, et al./The 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(5-6);551-556.Polack FP (2020), Thomas SJ, Kitchin N, et al. Safety and efficacy of the bnt162b2 mrna
covid-19 vaccine. N Engl J Med. 2020;383(27):2603-2615.
Rambaut A, Loman N, Pybus O, et al. Preliminary genomic characterisation of an emergent SARS-CoV-2 lineage in
the UK defined by a novel set of spike mutations. Virological. 2020. https://virological.org/t/preliminary-genomic-
characterisation-of-an-emergent-sars-cov-2-lineage-in-the-uk-defined-by-a-novel-set-of-spike-mutations/563.
Accessed 21 April 2021.
Reed, JF. III (2009). Closed Form Confidence Intervals for Small Sample Matched Proportions, Journal of Modern
Applied Statistical Methods. 2009;8(2):511-519.
Riphagen S (2020), Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in
children during COVID-19 pandemic. Lancet 2020;395:1607-1608.
Rüggeberg JU (2007), Gold MS, Bayas J, et al. Anaphylaxis: case definition and guidelines for data collection,
analysis, and presentation of immunization safety data. Vaccine; 2007;25(31):5675-5684.
Sadoff J (2021a), Le Gars M, Shukarev G, et al. Interim Results of a Phase 1-2a Trial of Ad26.COV2.S Covid-19
Vaccine. N Engl J Med. Published online January 13, 2021:NEJMoa2034201.
Sadoff J (2021b), Gray G, Vandebosch An, et al. Safety and Efficacy of Single-Dose Ad26.COV2.S Vaccine against
Covid-19. Published online April 21, 2021:NEJMoa2101544.
Salisch NC (2019), Izquierdo gil A, Czapska-casey DN, et al. Adenovectors encoding RSV-F protein induce durable
and mucosal immunity in macaques after two intramuscular administrations. NPJ Vaccines. 2019;4:54.
Tegally H (2020), Wilkinson E, Giovanetto M, et al. Emergence and rapid spread of a new severe acute respiratory
syndrome-related coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa. MedRxiv
preprint doi: https://doi.org/10.1101/2020.12.21.2024864.
US Department of Health and Human Services. Office for Human Research Protections - OHRP Expedited Review
Categories (1998). https://www.hhs.gov/ohrp/regulations-and-policy/guidance/categoriesof-research-expedited-
review-procedure-1998/index.html. Accessed 6 April 2021.
US Food and Drug Administration. Conditions for IRB Use of Expedited Review. Federal Register: November 9,
1998 (Volume 63, Number 216). https://www.fda.gov/science-research/guidance-documentsincluding-information-
sheets-and-notices/conditions-irb-use-expedited-review. Accessed 6 April 2021.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
173
Status: Approved,  Date: 20 April 2022
US Department of Health and Human Services (2007), 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.
https://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/V
accines/ucm091977.pdf. Accessed 2 April 2021.
US Food and Drug Administration (2020b). Development and Licensure of Vaccines to Prevent COVID-19.
Guidance for Industry. June 2020. https://www.fda.gov/media/139638/download. Accessed 2 April 2021.
US Food and Drug Administration (2021a). COVID-19: Developing Drug and Biological Products for Treatment or
Prevention. Guidance for Industry. February 2021. https://www.fda.gov/media/137926/download. Accessed
2 April 2021.
US Food and Drug Administration (2021b). Coronavirus (COVID-19) Update: FDA Issues Policies to Guide
Medical Product Developers Addressing Virus Variants. February 2021. https://www.fda.gov/news-events/press-
announcements/coronavirus-covid-19-update-fda-issues-policies-guide-medical-product-developers-addressing-
virus. Accessed 12 April 2021.
US San Diego Health (2020). Coronavirus (COVID-19) updates for UC San Diego Health patients and visitors.
Available at: https://health.ucsd.edu/coronavirus/Pages/FAQ.aspx. Accessed: 18 September 2020.
van der Fits L (2020), Bolder R, Heemskerk-van der Meer M, et al. Adenovector 26 encoded prefusion
conformation stabilized RSV-F protein induces long-lasting Th1-biased immunity in neonatal mice. NPJ Vaccines.
2020;5:49
van der Lubbe JEM (2021), Rosendahl Huber SK, Vijayan A, et al. Ad26.COV2.S-elicited immunity protects
against G614 spike variant SARS2 CoV-2 infection in Syrian hamsters and does not enhance respiratory disease in
challenged animals with breakthrough infection after sub-optimal vaccine dosing. BioRxiv. 2021:doi:
10.1101/2021.01.08.425915. [preprint]
Verity R (2020), Okell LC, Dorigatti I, et al. Estimates of the severity ofcoronavirus disease 2019: a model-based
analysis. Lancet Infect Dis. 2020;20(6):669-677.
Voysey M (2021), Clemens SAC, Madhi S. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222)
against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa and the UK.
Lancet.2021;397:99-111.
Widjojoatmodjo MN (2015), Bogaert L, Meek B, et al. Recombinant low-seroprevalent adenoviral vectors Ad26
and Ad35 expressing the respiratory syncytial virus (RSV) fusion protein induce protective immunity against RSV
infection in cotton rats. Vaccine. 2015;33(41):5406-5414.
Wibmer CK (2021), Ayres F, Hermanus T, et al. SARS-CoV-2 501Y.V2 escapes neutralization by South African
COVID-19 donor plasma. Nat Med 2021;27:622-625.
Wool GD (2021) and Miller JL. The impact of COVID-19 disease on platelets and coagulation. Pathobiology
2021;88(1):15-27.
World Health Organization (2020a). Coronavirus disease 2019 (COVID-19) Situation Report. Available at:
https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports. Accessed: 06 October 2020.
World Health Organization (2020b). Report of the WHO-China Joint Mission on Coronavirus Disease 2019
(COVID-19). Available at: https://www.who.int/emergencies/diseases/novel-coronavirus-
2019?gclid=EAIaIQobChMIvuDQ2ZfM6QIVxPZRCh2DwguUEAAYASAAEgLP6 D BwE. Accessed:
21 January 2021.
World Health Organization (2020c). WHO Director-General's opening remarks at the media briefing on COVID-19.
11 March 2020. Available from: https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-
at-the-media-briefing-on-covid-19---11-march-2020. Accessed: 21 January 2021.
Wu F (2020), Zhao S, Yu B, et al. A new coronavirus associated with human respiratory disease in China. Nature.
2020;579(7798):265-269.
Zhou P (2020), Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat
origin. Nature. 2020;579:270-273.

VAC31518 (JNJ-78436735 [Ad26.COV2.S])
Clinical Protocol VAC31518COV2008 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
174
Status: Approved,  Date: 20 April 2022
INVESTIGATOR AGREEMENT
I have read this protocol and agree that it contains all necessary details for carrying out this study. I will
conduct the study as outlined herein and will complete the study within the time designated.
I will provide copies of the protocol and all pertinent information to all individuals responsible to me who
assist in the conduct of this study. I will discuss this material with them to ensure that they are fully informed
regarding the study 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 study, written notification will be
provided by the investigator to the sponsor, and a protocol amendment will not be required.
PPD

Signature
User 
Date 
Reason
 
21-Apr-2022
03:56:08
(GMT)
Document Approval
PPD