A Randomized, Double-blind, Placebo-controlled Phase 1/2a Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of Ad26COVS1 in Adults Aged 18 to 55 Years Inclusive and Adults Aged 65 Years and Older
Phase: PHASE1
Conditions: Covid-19 Prevention
Sponsor: Janssen Vaccines & Prevention B.V.

CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
1
Status: Approved, Date: 16 August 2022
Janssen Vaccines & Prevention B.V.*
Clinical Protocol
Protocol Title
A Randomized, Double-blind, Placebo-controlled Phase 1/2a Study to Evaluate the Safety,
Reactogenicity, and Immunogenicity of Ad26COVS1 in Adults Aged 18 to 55 Years
Inclusive and Adults Aged 65 Years and Older
Protocol VAC31518COV1001; Phase 1/2a
Amendment 16
VAC31518  JNJ-78436735
* 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: 2020-001483-28
Status: 
Approved
Date: 
16 August 2022
EDMS number: 
EDMS-ERI-207834851, 20.0
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.
NCT04436276

VAC31518 JNJ-78436735 
Clinical Protocol VAC31518COV1001 Amendment 16
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
2
Status: Approved, Date: 16 August 2022
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE
DOCUMENT HISTORY
Document 
Date
Amendment 16 
This Document
Amendment 15 
7 October 2021
Amendment 14  
29 July 2021
Amendment 13 
04 June 2021
Amendment 12 
27 May 2021
Amendment 11  
6 May 2021
Amendment 10 
25 February 2021
Amendment 9 
18 December 2020
Amendment 8 
08 December 2020
Amendment 7 
03 November 2020
Amendment 6 
19 September 2020
Amendment 5 
13 August 2020
Amendment 4 
6 August 2020
Amendment 3 
8 July 2020
Amendment 2 
5 June 2020
Amendment 1 
20 May 2020
Original Protocol 
4 May 2020
Amendment 16 (This Document)
Overall Rationale for the Amendment: The main purpose of this amendment is to remove planned
Ad26.COV2.S booster vaccinations at 24 months after the primary regimen for Cohort 2 participants, due
to the smaller number of participants remaining than expected, mostly related to severe acute respiratory
syndrome (coronavirus-2SARS-CoV-2) infections and receiving authorized/licensed coronavirus
disease-2019 (COVID-19) vaccines outside of the study. The primary analysis was completed. Operational
challenges have impacted the feasibility of a strict follow-up of any COVID-19 episode and active
follow-up cannot be sustained. Therefore, the protocol has been amended to reduce the number of on-site
visits and to change the requirements for reporting new COVID-19 episode by applying a passive follow-up
approach. There will be no changes to the safety follow-up of serious adverse events (SAEs) and adverse
events of special interest (AESIs).
Additionally, changes included in the Belgium-specific Amendment 15 are now included in this global
amendment. These include changes requested by the Federal Agency for Medicines and Health Products
(FAMHP) to restrict the Ad26.COV2.S booster vaccine administration to participants ≥65 years of age.
Also, reference to the thrombosis with thrombocytopenia syndrome (TTS) case definition was updated, and
reference was made to the approval by EMA of the Ad26.COV2.S booster posology.
Section Number 
and Name
Description of Change 
Brief Rationale
1.1 Synopsis
1.2 Schema
1.3.3 Cohort 2a
1.3.4 Cohort 2b
3 Objectives and Endpoints
4.1 Overall Design
4.2 Scientific Rationale for
Study Design
5.5 Criteria for Temporarily
Delaying Administration of
Study Vaccination
6 Study Vaccination and
Concomitant Therapy
Text was added to indicate that participants in
Cohort 2 will no longer be offered
Ad26.COV2.S booster vaccination at
24 months after completion of their primary
regimen, as initially planned.
Cohort 2 results following
booster vaccination at 24 months
removed due to the smaller
number of participants
remaining than expected, mostly
related to SARS-CoV-2
infections and receiving
authorized/licensed COVID-19
vaccines outside of the study

VAC31518 JNJ-78436735 
Clinical Protocol VAC31518COV1001 Amendment 16
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Status: Approved, Date: 16 August 2022
Section Number 
and Name
Description of Change 
Brief Rationale
7.1 Discontinuation of
Study Vaccination
8 Study Assessments and
Procedures
1.2 Schema 
1.3.10 Procedures for 
Participants Receiving an 
Ad Hoc Booster 
Vaccination of 5x1010 vp 
Ad26.COV2.S  
Table 9 
Text was added to clarify that participants, 
who did not complete Booster FU2 visit 
before local approval of protocol 
Amendment 16, will attend Booster FU2 visit 
as their last visit, as scheduled in the Schedule 
of Activities. 
Text was added to clarify that participants who 
had completed Booster FU2 visit before the 
local approval of protocol Amendment 16 will 
attend an on-site last visit within 6 weeks
(+7days) from the local approval of protocol
Amendment 16, for reconsenting and safety
follow-up.
There is no placebo comparison
for the ad hoc booster
vaccination group, due to
unblinding and offered
open-label ad hoc booster
vaccination to participants.
Moreover, the post-booster
safety and immunogenicity
follow-up are explored in larger
Phase 3 studies.
1.1 Synopsis 
1.3.6.1 Passive Follow-up 
(As of Local Approval of 
Protocol Amendment 16) 
4.1 Overall Design  
8.1.2.1 Passive Follow-up 
(As of Amendment 16)
8.1.3 Procedures in Case of
Asymptomatic COVID-19
RT-PCR Confirmed
Infection
8.3.1 Time Period and
Frequency for Collecting
Adverse Event and Serious
Adverse Event Information
Text was updated to indicate that the 
management of new suspected COVID-19 
episodes has been changed from active to 
passive follow-up, defined as safety follow-up 
on-site visits to document COVID-19 events 
as (S)AEs. 
Constant evolution of the
COVID-19 pandemic has
impacted the practical
implementation of a strict
follow-up of new suspected
COVID-19 episodes.
1.1 Synopsis 
1.3.10 Procedures for 
Participants Receiving an 
Ad Hoc Booster 
Vaccination of 5x1010 vp
Ad26.COV2.S
3 Objectives and Endpoints
4.1 Overall Design
4.4 End of Study Definition
5 STUDY POPULATION
5.2 Exclusion Criteria
5.5 Criteria for Temporarily
Delaying Administration of
Study Vaccination
6.1 Study Vaccinations
Administered
6.3 Measures to Minimize
Bias: Randomization and
Blinding
7.1 Discontinuation of
Study Vaccination
Text was added to specify that in Belgium, the 
booster vaccination with Ad26.COV2.S will
only be offered to participants ≥65 years of
age
Based on FAMHP feedback

VAC31518 JNJ-78436735 
Clinical Protocol VAC31518COV1001 Amendment 16
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 16 August 2022
Section Number 
and Name
Description of Change 
Brief Rationale
7.5 Discontinue form
Cohort Vaccination
8 Study Assessments and
Procedures - Table 9
8.3.5 Pregnancy
8.7Assessments and
Procedures after Protocol
Amendment 15 Approval
(Ad Hoc Booster
Vaccination)
1.2 Schema 
1.3.3.2 Booster Vaccination 
Cohort 2a 
1.3.4.2 Booster Vaccination 
Cohort 2b 
8 STUDY ASSESSMENTS 
AND PROCEDURES  
Table 6 
Table 7 
Text was updated to indicate that Visits 12, 
13, and 14-15 (Cohort 2a) and Visits 15, 16 
and 17-18 (Cohort 2b) have been removed. 
Footnotes were added to Schema Cohort 2a 
and Cohort 2b, Schedule of Activities for 
booster vaccination for Cohort 2a and 2b. 
Text in Tables 6 and 7 was updated to indicate 
that Visit 11 will be the last visit for Cohort 2a
and Visit 14 will be the last visit for
Cohort 2b, and that no vaccination will be
offered at these visits and only safety
assessment will be performed.
Clarification. Safety and
immunogenicity follow-up
visits; Visits 12, 13, and 14-15
(Cohort 2a) and Visits 15, 16
and 17-18 (Cohort 2b),
respectively, are no longer
applicable, as no booster will be
given at Visit 11 (Cohort 2a) and
Visit 14 (Cohort 2b).
4.4 End of Study Definition 
The last scheduled visit for Cohort 2 
participants will be at 24 months after 
completion of the primary regimen. 
As booster vaccinations at
24 months after completion of
the primary regimen will not be
administered to Cohort 2
participants, the timing of the
final scheduled visit for such
participants has been updated.
10.4.3 Severity Criteria 
The AESI definition of thrombocytopenia has 
been updated based on the Brighton 
Collaboration definition.
To align across the
Ad26.COV2.S program.
1.1 Synopsis 
11 REFERENCES  
The reference to the Brighton Collaboration 
case definition of thrombotic events and
thrombocytopenia was updated.
Update
Throughout the protocol 
Minor errors and inconsistencies were 
corrected, and minor clarifications were added 
throughout the protocol. 
Correction of minor errors and
inconsistencies. Addition of
minor clarifications.

VAC31518 JNJ-78436735 
Clinical Protocol VAC31518COV1001 Amendment 16
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 16 August 2022
TABLE OF CONTENTS
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ............................................................... 2
TABLE OF CONTENTS ............................................................................................................................... 5
LIST OF IN-TEXT TABLES AND FIGURES................................................................................................ 8
1. 
PROTOCOL SUMMARY..................................................................................................................... 9
1.1. 
Synopsis........................................................................................................................................... 9
1.2. 
Schema.......................................................................................................................................... 30
1.3. 
Schedule of Activities (SoA)........................................................................................................... 37
1.3.1. 
Cohort 1a.................................................................................................................................... 37
1.3.2. 
Cohort 1b.................................................................................................................................... 41
1.3.2.1. 
Optional Lymph Node Aspirates for Cohort 1b Participants (Beth Israel Deaconess
Medical Center [BIDMC])......................................................................................................... 44
1.3.3. 
Cohort 2a.................................................................................................................................... 45
1.3.3.1. 
Primary Regimen Cohort 2a.................................................................................................... 45
1.3.3.2. 
Booster Vaccination Cohort 2a................................................................................................ 48
1.3.4. 
Cohort 2b.................................................................................................................................... 51
1.3.4.1. 
Primary Regimen Cohort 2b.................................................................................................... 51
1.3.4.2. 
Booster Vaccination Cohort 2b................................................................................................ 54
1.3.5. 
Cohort 3 ...................................................................................................................................... 57
1.3.6. 
Procedures for Participants with COVID-19-like Signs and Symptoms ..................................... 60
1.3.6.1. 
Passive Follow-up (As of Local Approval of Protocol Amendment 16)................................... 60
1.3.6.2. 
Active Follow-up (Prior to Local Approval of Protocol Amendment 16) .................................. 60
1.3.7. 
Procedures for Group 5 (Placebo Only) Participants Receiving a Single Dose of 5x1010
vp Ad26.COV2.S (Placebo Crossover Vaccination) after EUA or Approval in any
Country ....................................................................................................................................... 62
1.3.8. 
Procedures for Participants with a Suspected AESI .................................................................. 63
1.3.9. 
Additional Follow-up for Cohorts 1a, 1b and 3 ........................................................................... 64
1.3.10. 
Procedures for Participants Receiving an Ad Hoc Booster Vaccination of 5x1010 vp
Ad26.COV2.S ............................................................................................................................. 66
2. 
INTRODUCTION................................................................................................................................ 69
2.1. 
Study Rationale.............................................................................................................................. 70
2.2. 
Background.................................................................................................................................... 72
2.3. 
Benefit-Risk Assessment............................................................................................................... 75
2.3.1. 
Risks Related to Study Participation .......................................................................................... 75
2.3.2. 
Benefits of Study Participation.................................................................................................... 81
2.3.3. 
Benefit-Risk Assessment of Study Participation ........................................................................ 81
3. 
OBJECTIVES AND ENDPOINTS ..................................................................................................... 83
4. 
STUDY DESIGN ................................................................................................................................ 87
4.1. 
Overall Design................................................................................................................................ 87
4.2. 
Scientific Rationale for Study Design............................................................................................. 96
4.2.1. 
Study-Specific Ethical Design Considerations ........................................................................... 97
4.3. 
Justification for Dose...................................................................................................................... 98
4.4. 
End of Study Definition................................................................................................................... 98
5. 
STUDY POPULATION ...................................................................................................................... 99
5.1. 
Inclusion Criteria.......................................................................................................................... 100
5.2. 
Exclusion Criteria......................................................................................................................... 102
5.3. 
Lifestyle Considerations............................................................................................................... 106
5.4. 
Screen Failures............................................................................................................................ 107
5.5. 
Criteria for Temporarily Delaying Administration of Study Vaccination ....................................... 107
6. 
STUDY VACCINATION AND CONCOMITANT THERAPY ........................................................... 108

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Status: Approved, Date: 16 August 2022
6.1. 
Study Vaccinations Administered ................................................................................................ 108
6.2. 
Preparation/Handling/Storage/Accountability .............................................................................. 109
6.3. 
Measures to Minimize Bias: Randomization and Blinding........................................................... 110
6.4. 
Study Vaccine Compliance .......................................................................................................... 112
6.5. 
Dose Modification......................................................................................................................... 113
6.6. 
Continued Access to Study Vaccine After the End of the Study ................................................. 113
6.7. 
Treatment of Overdose ................................................................................................................ 114
6.8. 
Prestudy and Concomitant Therapy ............................................................................................ 114
6.9. 
Study Vaccination Pausing Rules................................................................................................ 116
7. 
DISCONTINUATION OF STUDY VACCINATION AND PARTICIPANT
DISCONTINUATION/WITHDRAWAL............................................................................................. 118
7.1. 
Discontinuation of Study Vaccination........................................................................................... 118
7.2. 
Participant Discontinuation/Withdrawal From the Study.............................................................. 119
7.2.1. 
Withdrawal From the Use of Research Samples ..................................................................... 119
7.3. 
Lost to Follow-up.......................................................................................................................... 119
7.4. 
Discontinue from Placebo Group Participation ............................................................................ 120
7.5. 
Discontinue from Cohort Vaccination........................................................................................... 120
8. 
STUDY ASSESSMENTS AND PROCEDURES ............................................................................. 121
8.1. 
Immunogenicity and Efficacy Assessments................................................................................. 128
8.1.1. 
Immunogenicity Assessments .................................................................................................. 128
8.1.1.1. 
Optional Lymph Node Aspiration........................................................................................... 131
8.1.2. 
Procedures in Case of COVID-19-like Signs and Symptoms................................................... 132
8.1.2.1. 
Passive Follow-up (As of Local Approval of Protocol Amendment 16)................................. 132
8.1.2.2. 
Active Follow-up (Prior to Local Approval of Protocol Amendment 16) ................................ 132
8.1.2.3. 
Prespecified Criteria for Suspected COVID-19 ..................................................................... 133
8.1.3. 
Procedures in Case of Asymptomatic COVID-19 RT-PCR Confirmed Infection...................... 134
8.1.4. 
Efficacy Assessments............................................................................................................... 135
8.2. 
Safety Assessments..................................................................................................................... 135
8.2.1. 
Physical Examinations.............................................................................................................. 135
8.2.2. 
Vital Signs................................................................................................................................. 136
8.2.3. 
Pregnancy Testing.................................................................................................................... 136
8.2.4. 
Clinical Laboratory Assessments ............................................................................................. 136
8.3. 
Adverse Events, Adverse Events of Special Interest, Serious Adverse Events, and Other
Safety Reporting .......................................................................................................................... 137
8.3.1. 
Time Period and Frequency for Collecting Adverse Event, Adverse Events of Special
Interest, and Serious Adverse Event Information..................................................................... 137
8.3.2. 
Method of Detecting Adverse Events, Adverse Events of Special Interest, and Serious
Adverse Events......................................................................................................................... 139
8.3.3. 
Follow-up of Adverse Events, Adverse Events of Special Interest, and Serious Adverse
Events....................................................................................................................................... 140
8.3.4. 
Regulatory Reporting Requirements for Serious Adverse Events ........................................... 140
8.3.5. 
Pregnancy................................................................................................................................. 140
8.3.6. 
Adverse Events of Special Interest........................................................................................... 141
8.3.6.1. 
Thrombosis with Thrombocytopenia Syndrome.................................................................... 141
8.4. 
Medical Resource Utilization and Health Economics .................................................................. 142
8.5. 
Biomarkers................................................................................................................................... 142
8.6. 
Assessments and Procedures after EUA or Approval in any Country......................................... 142
8.7. 
Assessments and Procedures after Protocol Amendment 15 Approval (Ad Hoc Booster
Vaccination) ................................................................................................................................. 144
9. 
STATISTICAL CONSIDERATIONS................................................................................................ 146
9.1. 
Statistical Hypotheses.................................................................................................................. 146
9.2. 
Sample Size Determination ......................................................................................................... 146
9.3. 
Populations for Analysis Sets ...................................................................................................... 147
9.4. 
Statistical Analyses ...................................................................................................................... 147
9.4.1. 
General Considerations............................................................................................................ 147

VAC31518 JNJ-78436735 
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CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 16 August 2022
9.4.2. 
Primary Endpoints .................................................................................................................... 147
9.4.3. 
Secondary Endpoints................................................................................................................ 148
9.4.4. 
Tertiary/Exploratory Endpoint(s)............................................................................................... 149
9.4.5. 
Other Analyses ......................................................................................................................... 149
9.5. 
Planned Analysis.......................................................................................................................... 149
9.6. 
Analyses for Participants Requesting Unblinding to Receive an Authorized/Licensed
COVID-19 Vaccine....................................................................................................................... 153
9.7. 
Analyses after Unblinding all Participants Following EUA or Approval in any Country............... 153
9.7.1. 
Cohorts 1a, 1b, and 3 ............................................................................................................... 153
9.7.2. 
Cohorts 2a and 2b.................................................................................................................... 154
9.8. 
Analysis After Receipt of the Ad Hoc Booster Vaccination.......................................................... 156
10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS.......................... 157
10.1. 
Appendix 1: Abbreviations ........................................................................................................... 157
10.2. 
Appendix 2: Clinical Laboratory Tests ......................................................................................... 159
10.2.1. 
All Cohorts ................................................................................................................................ 159
10.2.2. 
Additional Hematology and Coagulation Testing ..................................................................... 160
10.3. 
Appendix 3: Regulatory, Ethical, and Study Oversight Considerations....................................... 161
10.3.1. 
Regulatory and Ethical Considerations .................................................................................... 161
10.3.2. 
Financial Disclosure.................................................................................................................. 164
10.3.3. 
Informed Consent Process ....................................................................................................... 164
10.3.4. 
Data Protection ......................................................................................................................... 165
10.3.5. 
Long-Term Retention of Samples for Additional Future Research .......................................... 166
10.3.6. 
Committees Structure............................................................................................................... 166
10.3.7. 
Publication Policy/Dissemination of Clinical Study Data.......................................................... 167
10.3.8. 
Data Quality Assurance............................................................................................................ 168
10.3.9. 
Case Report Form Completion................................................................................................. 169
10.3.10. Source Documents ................................................................................................................... 169
10.3.11. Monitoring ................................................................................................................................. 170
10.3.12. On-Site Audits........................................................................................................................... 170
10.3.13. Record Retention...................................................................................................................... 171
10.3.14. Study and Site Start and Closure ............................................................................................. 171
10.4. 
Appendix 4: Adverse Events, Adverse Events of Special Interest, Serious Adverse
Events, Product Quality Complaints, and Other Safety Reporting: Definitions and
Procedures for Recording, Evaluating, Follow-up, and Reporting............................................... 173
10.4.1. 
Adverse Event Definitions and Classifications ......................................................................... 173
10.4.2. 
Attribution Definitions................................................................................................................ 174
10.4.3. 
Severity Criteria........................................................................................................................ 175
10.4.4. 
Special Reporting Situations .................................................................................................... 175
10.4.5. 
Procedures ............................................................................................................................... 176
10.4.6. 
Product Quality Complaint Handling......................................................................................... 177
10.4.7. 
Contacting Sponsor Regarding Safety, Including Product Quality........................................... 178
10.5. 
Appendix 5: Contraceptive Guidance and Collection of Pregnancy Information......................... 179
10.6. 
Appendix 6: Toxicity Grading Scale............................................................................................. 180
10.7. 
Appendix 7: Symptoms of Infection with Coronavirus-19 (SIC)................................................... 184
10.8. 
Appendix 8: Case Definitions for COVID-19................................................................................ 188
10.8.1. 
Case Definition for Moderate to Severe COVID-19.................................................................. 188
10.8.2. 
Case Definition for Mild COVID-19........................................................................................... 189
10.8.3. 
US FDA Harmonized Case Definition for COVID-19................................................................ 189
10.8.4. 
Case Definition for Asymptomatic or Undetected COVID-19................................................... 190
10.9. 
Appendix 9: Symptoms of Coronavirus (US Centers for Disease Control and Prevention)........ 191
10.10. Appendix 10: Summary of Guidance from CDC Website on Underlying Medical
Conditions That Lead or Might Lead to Increased Risk for Severe Illness From COVID-19....... 192
10.11. Appendix 11: TTS AESI Form...................................................................................................... 193
10.12. Appendix 12: Thrombotic Events to be Reported as AESIs ........................................................ 197
10.13. Appendix 13: Protocol Amendment History................................................................................. 198
11. REFERENCES................................................................................................................................. 223

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CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 16 August 2022
INVESTIGATOR AGREEMENT............................................................................................................... 227
LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1: 
Vaccination Schedulesa............................................................................................................ 89
Table 2: 
Cohort 2a Vaccination Schedule –Primary Regimen and Single Booster Vaccination........... 93
Table 3: 
Cohort 2b Vaccination Schedule –Primary Regimen and Single Booster Vaccination........... 93
Table 4: 
Visit Windows Cohort 1a......................................................................................................... 122
Table 5: 
Visit Windows Cohort 1b......................................................................................................... 123
Table 6: 
Visit Windows Cohort 2a......................................................................................................... 124
Table 7: 
Visit Windows Cohort 2b......................................................................................................... 125
Table 8: 
Visit Windows Cohort 3........................................................................................................... 126
Table 9: 
Visit Windows Ad Hoc Booster Vaccination .......................................................................... 126
Table 10: Summary of Humoral Immunogenicity Assays....................................................................... 129
Table 11: Summary of Cellular Immunogenicity Assays ........................................................................ 130
Table 12: Summary of Humoral Immunogenicity Assays....................................................................... 130
Table 13: Summary of Cellular Immunogenicity Assays ........................................................................ 131
Table 14: Probability of Observing at Least One Adverse Event Given a True Adverse Event
Incidence................................................................................................................................. 146
FIGURES
Figure 1: Schematic Overview of Cohort 1a............................................................................................ 30
Figure 2: Schematic Overview of Cohort 1b............................................................................................ 31
Figure 3: Schematic Overview of Cohort 2a............................................................................................ 33
Figure 4: Schematic Overview of Cohort 2b............................................................................................ 34
Figure 5: Schematic Overview of Cohort 3 .............................................................................................. 35
Figure 6: Schematic Overview of Placebo Crossover Vaccination.......................................................... 36
Figure 7: Schematic Overview of Ad Hoc Booster Vaccination ............................................................... 36
Figure 8: Participant Enrollment and First Dose Safety Strategy in Cohorts 1 and 3.............................. 92
Figure 9: Interim and Primary Analyses................................................................................................. 152
Figure 10: Analysis strategy after unblinding, depicted by scenario........................................................ 155

VAC31518 JNJ-78436735 
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Status: Approved, Date: 16 August 2022
1.
PROTOCOL SUMMARY
1.1. 
Synopsis
A Randomized, Double-blind, Placebo-controlled Phase 1/2a Study to Evaluate the Safety, Reactogenicity,
and Immunogenicity of Ad26COVS1 in Adults Aged 18 to 55 Years Inclusive and Adults Aged 65 Years
and Older
Ad26.COV2.S (also known as Ad26COVS1) is a monovalent vaccine composed of a recombinant,
replication incompetent adenovirus type 26 (Ad26) vector, constructed to encode the severe acute
respiratory syndrome coronavirus-2 (SARS-CoV-2) virus spike (S) protein, which will be assessed in this
study. This will be the first-in-human (FIH) study for Ad26.COV2.S.
OBJECTIVES AND ENDPOINTS
A description of study cohorts is provided in the Overall Design section below.
Objectives 
Endpoints
Primary

To assess the safety and reactogenicity
of Ad26.COV2.S  at 2 dose levels,
5×1010 virus particles (vp) and
1×1011 vp, 
administered
intramuscularly (IM) as a single-dose 
or 2-dose schedule in healthy adults 
aged ≥18 to ≤55 years and in adults
aged ≥65 years in good health with or
without stable underlying conditions.
All participants* in Cohorts 1, 2, and 3:

Solicited local and systemic adverse events (AEs) for
7 days after each vaccination in the primary regimen

Unsolicited AEs for 28 days after each vaccination in
the primary regimen

For the primary endpoint: Serious adverse events
(SAEs) and AESIs from the first vaccination until
2 years after the second vaccination for Cohorts 1 and
3, and until 6 months after the primary regimen for
Cohort 2

VAC31518 JNJ-78436735 
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CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 16 August 2022
Objectives 
Endpoints
Secondary
 
To assess the humoral and cellular
immune response to Ad26.COV2.S
Humoral Immune Response
All participants* in Cohorts 1, 2, and 3:
 
SARS-CoV-2 
neutralization: 
SARS-CoV-2
neutralizing titers in serum measured by a virus
neutralization assay (VNA [wild-type virus and/or
pseudovirion expressing S protein])
 
SARS-CoV-2-binding 
antibodies 
measured 
by
enzyme-linked immunosorbent assay (ELISA):
Analysis of antibodies binding to the SARS-CoV-2
S protein.
Cellular Immune Response
A subset of participants* in Cohorts 1, 2, and 3:
 
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 (PBMCs) and intracellular staining
[ICS] including CD4+/CD8+, interferon gamma
[IFNγ], interleukin [IL] 2, tumor necrosis factor alpha
[TNFα], IL-4, IL-5, IL-13, and/or other Th1/Th2
markers.
Exploratory
 
To further assess the safety and
reactogenicity of Ad26.COV2.S  at a
dose level of 5×1010 vp administered
IM as a single booster vaccination at
6 months, 12 months, or 24 months
after the primary regimen in healthy
adults aged ≥18 to ≤55 years
All participants* in Cohort 2:
 
Solicited local and systemic AEs for 7 days after each
booster vaccination time point
 
Unsolicited AEs for 28 days after each booster
vaccination time point
 
SAEs and AESIs until the end of the study
 
Following Amendment 16, booster vaccination at
24 months will not be performed

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 
To further assess the humoral and 
cellular 
immune 
response 
to
Ad26.COV2.S in various regimens
Humoral Immune Response:
Exploratory analyses may include the following assays for
a subset of participants* in Cohorts 1 and 3:
 
SARS-CoV-2 
neutralization 
as 
assessed 
by
alternative SARS-CoV-2 neutralization assays
(different from the VNA used for the secondary
endpoint).
 
Analysis of antibodies binding to SARS-CoV-2
S protein and the receptor-binding domain (RBD) of
the SARS-CoV-2 S protein by Meso Scale Discovery
(MSD) assay
 
Adenovirus neutralization.
 
Functional and molecular antibody characterization
(eg, avidity, Fc receptor interaction, antibody
isotyping).
 
Epitope-specificity characterization for B- and
T-cells.
 
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 neutralizing and binding antibodies
against emerging SARS-CoV-2 virus lineages.
Cellular Immune Response:
Exploratory analyses may include the following assays for
a subset of participants* in Cohorts 1, 2, and 3:
 
Single IFNγ and IL-4 enzyme-linked immunospot
(ELISpot) assay after stimulation of PBMCs with
SARS-CoV-2 S protein peptides.
 
Analysis of gene expression in cells stimulated with
SARS-CoV-2 S protein peptides, or in unstimulated
cells (ex vivo).
 
Cytokine 
profiling: 
Analysis 
of cytokines,
chemokines, and other proteins of the innate or
adaptive immune response in cells stimulated with
SARS-CoV-2 S protein peptides, or in unstimulated
cells (ex vivo).
A subset of participants* in Cohort 2 only:
 
Analysis of the phenotype of antigen-specific T and
B cells, assessed by single cell analysis (on frozen or
Smart tube-isolated PBMCs).

VAC31518 JNJ-78436735 
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Objectives 
Endpoints

To perform a preliminary analysis of
vaccine efficacy in the prevention of
molecularly confirmed coronavirus
disease-2019 (COVID-19)

The number of molecularly confirmed COVID-19
cases in Ad26.COV2.S versus placebo recipients in
the overall study

To perform preliminary analysis of
vaccine efficacy in the prevention of
asymptomatic SARS-CoV-2 infection

The number of participants with positive non-S
protein ELISA (eg, N ELISA), if such an assay can
be developed, in the Ad26.COV2.S  and placebo
groups

To 
evaluate 
the 
presence 
of
SARS-CoV-2 
infection 
and 
the
presence and severity of COVID-19
signs and symptoms

Presence and severity of COVID-19 signs and
symptoms

Confirmation 
of SARS-CoV-2 
infection 
by
molecular testing

To examine the immune response in
vaccinated individuals after natural
infection and to explore 
other
potentially informative biomarkers
(eg, those associated with more severe
disease)

Confirmation 
of SARS-CoV-2 
infection 
by
molecular testing

SARS-CoV-2 neutralizing titers in serum measured
by a VNA (wild-type virus and/or pseudovirion
expressing S protein)

SARS-CoV-2-binding antibodies measured by
ELISA: Analysis of antibodies binding to the
SARS-CoV-2 S protein

Functional and molecular antibody characterization

Analysis of gene expression by RNA transcript
profiling

To explore the immune responses in
fine needle lymph node aspirations
(LNAs) in Cohort 1b participants

Magnitude, phenotype, antigen specificity and subset
distribution of immune and stromal cells in lymph
nodes and peripheral blood

Molecular network analysis of functional regulation
of T- and B-cell subsets in lymph nodes
* Excluding Group 5 (placebo only) participants who received a single dose of 5×1010 vp Ad26.COV2.S at the time
of unblinding, after Emergency Use Authorization (EUA) or approval in any country and local approval of
protocol Amendment 10.
Hypothesis
No formal hypothesis testing is planned. Descriptive statistics will be used to summarize the safety,
reactogenicity, and immunogenicity endpoints.
Ad Hoc Booster Vaccination
Following local approval of protocol Amendment 15, the following objectives are applicable for all eligible
participants who consent to receive a single ad hoc booster dose of 5x1010 vp Ad26.COV2.S. The ad hoc
booster vaccination will be provided to participants who have previously received 1 or more doses of any
COVID-19 vaccine (ie, the Ad26.COV2.S vaccine, an mRNA vaccine and/or another COVID 19 vaccine
authorized for primary vaccination including protein, inactivated, and adenovector-based vaccines) if the
last vaccination was ≥6 months ago. See study design section below for more details.

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Objectives 
Endpoints
Primary
 
To assess the safety and reactogenicity of
Ad26.COV2.S at the 5×1010 vp dose level
administered as ad hoc booster vaccination in
healthy adults aged ≥18 to ≤55 years and in
adults aged ≥65 years in good health with or
without stable underlying conditions.
 
Solicited local and systemic AEs for 7days
after ad hoc booster vaccination.
 
Unsolicited AEs for 28 days after ad hoc
booster vaccination.
 
SAEs and AESIs from ad hoc booster
vaccination until the end of the study.
Secondary
 
To obtain samples to evaluate potential
thromboembolic events following ad hoc
booster vaccination by obtaining platelet
counts and sufficient extra sera for specialized
studies at the day of booster vaccination and
28 days later.
 
Platelet count on the day of ad hoc booster
vaccination and 28 days after ad hoc booster
vaccination. Additional analysis on collected
sera 
samples 
in 
case 
of potential
thromboembolic events.
Exploratory
 
To assess the humoral and cellular immune
response to Ad26.COV2.S ad hoc booster
dose.
Humoral immune response assessment may
include, and is not limited to:
 
SARS-CoV-2 neutralization: SARS-CoV-2
neutralizing titers in serum measured by a
virus neutralization assay (VNA [wild-type
virus 
and/or 
pseudovirion 
expressing
S protein]) against the original strain and
emerging variants.
 
SARS-CoV-2-binding antibodies measured
by ELISA: Analysis of antibodies binding to
the SARS-CoV-2 S and RBD protein from the
original strain and emerging variants.
 
Adenovirus neutralization.
 
Functional 
and 
molecular 
antibody
characterization (eg, avidity, Fc receptor
interaction, antibody isotyping).
 
Epitope-specificity characterization for B-
and T cells.
 
Passive transfer: Analysis of immune
mediators correlating with protection against
experimental SARS-CoV-2 challenge in a
suitable animal model.
In a subset of participants, cellular immune
response assessment may include, and is not
limited to:
 
Th1 and Th2 immune responses as assessed
by flow cytometry after SARS-CoV-2
S protein peptide stimulation of PBMCs and
ICS including CD4+/CD8+, IFNγ, IL-2,

VAC31518 JNJ-78436735 
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Objectives 
Endpoints
TNFα, IL-4, IL-5, IL-13, and/or other
Th1/Th2 markers.
 
To examine the immune response in
vaccinated individuals after natural infection
and to explore other potentially informative
biomarkers (eg, those associated with more
severe disease).
 
Confirmation of SARS-CoV-2 infection by
molecular testing
 
SARS-CoV-2 neutralizing titers in serum
measured by a VNA (wild-type virus and/or
pseudovirion expressing S protein)
 
SARS-CoV-2-binding antibodies measured
by ELISA: Analysis of antibodies binding to
the SARS-CoV-2 S protein
 
Functional 
and 
molecular 
antibody
characterization
OVERALL DESIGN
This is a randomized, double-blind, placebo-controlled, FIH Phase 1/2a multicenter study in adults aged
≥18 to ≤55 years and aged ≥65 years. The safety, reactogenicity, and immunogenicity of Ad26.COV2.S
will be evaluated at 2 dose levels, administered IM as a single dose or 2 dose schedule, with a single booster
vaccination.
Following Emergency Use Authorization (EUA), conditional licensure, or approval in any country for the
single-dose regimen of 5×1010 vp Ad26.COV2.S, all participants from countries where Amendment 10 is
locally approved by the Health Authority and Independent Ethics Committees (IEC)/Institutional Review
Board (IRB), will be unblinded to disclose who received placebo only  during primary  regimen. After
unblinding, enrolled participants who initially received placebo only will be offered a single dose of
5×1010 vp Ad26.COV2.S. If willing to receive, they  will discontinue from participation in the placebo
groups.
Following local approval of protocol Amendment 15, all ongoing eligible participants will be offered a
single ad hoc booster dose of 5×1010 vp Ad26.COV2.S. The ad hoc booster vaccination will be provided to
participants who have previously received 1 or more doses of any COVID-19 vaccine (ie, the
Ad26.COV2.S vaccine, an mRNA vaccine and/or another COVID-19 vaccine authorized for primary
vaccination including protein, inactivated, and adenovector-based vaccines) if the last vaccination was
≥6 months ago. Participants who choose to receive an outside of the study booster vaccination with the
Ad26.COV2.S vaccine (if recommended by local authorities and available) or another authorized
COVID-19 vaccine, choose not to receive an ad hoc booster vaccination, or are not eligible to receive the
ad hoc booster vaccination, will not be withdrawn from the study and will be encouraged to remain in the
study.
The following ongoing participants will not be eligible to receive this ad hoc booster vaccination:
− Group 5 participants (all cohorts) who crossed over from placebo to receive Ad26.COV2.S at the 5x1010
vp dose level (ie, placebo crossover vaccination).
− Group 5 participants (all cohorts) who did not opt for the placebo crossover vaccination and therefore
have not received any vaccination with the Ad26.COV2.S vaccine.
− Cohort 2 participants who will receive a booster vaccination according to their initial schedule at 6 and
12 months after the primary regimen (Groups 2 and 3, respectively).

VAC31518 JNJ-78436735 
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Status: Approved, Date: 16 August 2022
− Applicable to Belgium only: Per the Belgian-specific protocol Amendment 15, participants aged <65
years enrolled at Belgian sites.
The safety, reactogenicity, and immunogenicity will be evaluated in a cohort of adults aged ≥18 to
≤55 years. Safety, reactogenicity, and immunogenicity will also be evaluated in an expanded cohort in this
age group. In addition, safety, reactogenicity, and immunogenicity will be evaluated in a cohort of adults
aged ≥65 years.
The study includes the following cohorts:
1) Cohort 1:
a. Cohort 1a: approximately 375 participants (75 participants per group) aged ≥18 to ≤55 years who
will be randomized in parallel in a 1:1:1:1:1 ratio to 1 of 5 vaccination groups.
b. Cohort 1b: 25 participants (5 participants per group) aged ≥18 to ≤55 years who will be enrolled at
the Beth Israel Deaconess Medical Center (BIDMC) and randomized in parallel in a 1:1:1:1:1 ratio
to 1 of 5 vaccination groups. Additional exploratory immunogenicity evaluations (eg, epitope
mapping, passive transfer, and certain analyses of functional and molecular antibody
characteristics) will be performed for Cohort 1b. Optional fine needle LNA will be collected from
consenting participants approximately 12 months after their 2nd vaccination (active or placebo) or
approximately 6 months after the ad hoc crossover vaccination (for participants who crossed over
from placebo to receive active Ad26.COV2.S 5x1010 vp vaccination), to further explore the immune
responses in lymph nodes.
2) Cohort 2: approximately 270 participants aged ≥18 to ≤55 years will be randomized to receive
Ad26.COV2.S (approximately 240 participants) or a placebo (approximately 30 participants) in the
primary regimen. Cohort 2 will include an evaluation of a single booster vaccination (see below for
further details).
3) Cohort 3: approximately 375 participants (approximately 75 participants per group) aged ≥65 years
who will be randomized in parallel in a 1:1:1:1:1 ratio to 1 of 5 vaccination groups.
Table: Vaccination Schedulesa
Cohort 1a (Adults ≥18 to ≤55 years)
Group  
N 
Day 1 (Vaccination 1) 
Day 57 (Vaccination 2)
1 
75 
Ad26.COV2.S 5×1010 vp 
Ad26.COV2.S 5×1010 vp
2 
75 
Ad26.COV2.S 5×1010 vp 
Placebo
3 
75 
Ad26.COV2.S 1×1011 vp 
Ad26.COV2.S 1×1011 vp
4 
75 
Ad26.COV2.S 1×1011 vp 
Placebo
5 
75 
Placebo 
Placebo
Cohort 1b (Adults ≥18 to ≤55 years) b
Group  
N 
Day 1 (Vaccination 1) 
Day 57 (Vaccination 2)
1 
5 
Ad26.COV2.S 5×1010 vp 
Ad26.COV2.S 5×1010 vp
2 
5 
Ad26.COV2.S 5×1010 vp 
Placebo
3 
5 
Ad26.COV2.S 1×1011 vp 
Ad26.COV2.S 1×1011 vp
4 
5 
Ad26.COV2.S 1×1011 vp 
Placebo
5 
5 
Placebo 
Placebo
Cohort 2a (Adults ≥18 to ≤55 years)
Group  
N 
Day 1 (Vaccination 1) c 
Day 57 c
1-4 
120 
Ad26.COV2.S 5×1010 vp 
No vaccination
5 
15 
Placebo 
No vaccination

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Cohort 2b (Adults ≥18 to ≤55 years)
Group  
N 
Day 1 (Vaccination 1) c
Day 57 (Vaccination 2) c
1-4 
120 
Ad26.COV2.S 5×1010 vp 
Ad26.COV2.S 5×1010 vp
5 
15 
Placebo 
Placebo
Cohort 3 (Adults ≥65 years)
Group  
N 
Day 1 (Vaccination 1) 
Day 57 (Vaccination 2)
1 
75 
Ad26.COV2.S 5×1010 vp 
Ad26.COV2.S 5×1010 vp
2 
75 
Ad26.COV2.S 5×1010 vp 
Placebo
3 
75 
Ad26.COV2.S 1×1011 vp 
Ad26.COV2.S 1×1011 vp
4 
75 
Ad26.COV2.S 1×1011 vp 
Placebo
5 
75 
Placebo 
Placebo
Total 
1,045
a. Following local approval of protocol Amendment 15, all eligible participants will be offered a single ad hoc booster
dose of 5×1010 vp Ad26.COV2.S. The ad hoc booster vaccination will be provided to participants who have
previously received 1 or more doses of any COVID-19 vaccine (ie, the Ad26.COV2.S vaccine, an mRNA vaccine
and/or another COVID 19 vaccine authorized for primary vaccination including protein, inactivated, and
adenovector-based vaccines) if the last vaccination was ≥6 months ago.
b. Cohort 1b comprises 5 participants in each group who will be enrolled at Beth Israel Deaconess Medical Center
(BIDMC) and for whom additional exploratory immunogenicity analyses will be performed.
c. Study vaccine will be administered as a single-dose (Day 1) or 2-dose (Day 1 and Day 57) primary regimen. Cohort
2 will include an evaluation of a single booster vaccination (see below for further details).
N = number of participants; vp = virus particles.
An internal Data Review Committee (DRC) will be commissioned for this study to evaluate safety data
over the course of the study and to review any events that meet a specific study pausing rule or any other
safety issue that may arise.
Cohort 1 (Adults Aged ≥18 to ≤55 Years)
The first doses of study vaccine will be administered to a sentinel group of 5 participants (1 participant per
group) in Cohort 1a, enrolled at the same study site, to monitor for any unexpected severe adverse reactions.
The sentinel participants will be vaccinated at least 1 hour apart. In Cohort 1a, as for each cohort,
participants will be closely observed for a minimum of 1-hour post-vaccination for the development of
acute reactions. A telephone call will be made to each of these 5 sentinel participants on Day 2
(approximately 24 hours post-vaccination) to collect safety data, which will include solicited and
unsolicited AEs and SAEs. The collected data will be reviewed in a blinded manner by the principal
investigator (PI) and the sponsor’s study responsible physician (SRP). Randomization and vaccination of
additional participants will be halted until the review is completed.
In the absence of clinically significant findings from the review of 24-hour safety data from the first
5 sentinel participants, all participants in Cohort 1a and Cohort 1b will be randomized and vaccinated. The
next 10 participants in Cohort 1a will be enrolled at the same study site as the 5 sentinel participants,
randomly assigned to 1 of the 5 vaccination groups to have an overall 1:1:1:1:1 randomization ratio (ie, a
total of 15 participants including the 5 sentinels, with 3 participants in each vaccination group), and
administered the first vaccination. The DRC will review the blinded 3-day safety data (ie, from Day 1 to
Day 4) and 7-day safety data (ie, from Day 1 to Day 8) following administration of the first vaccination to
these first 15 participants, including solicited and unsolicited AEs and SAEs. In the absence of safety
concerns, enrollment and vaccination of participants in Cohort 3 will begin.

VAC31518 JNJ-78436735 
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Cohort 2 (Adults Aged ≥18 to ≤55 Years)
Cohort 2 will be initiated after the interim or primary analyses of Cohort 1a. In Cohort 2a, approximately
120 participants will receive Ad26.COV2.S at a dose level of 5×1010 vp and approximately 15 participants
will receive a placebo in a single-dose primary regimen. In Cohort 2b, approximately 120 participants will
receive Ad26.COV2.S at a dose level of 5×1010 vp and approximately 15 participants will receive a placebo
in a 2-dose primary regimen. No staggered enrollment will be performed for Cohort 2; however, the DRC
will evaluate safety data from Cohort 2 over the course of the study. If required, Cohort 2 may contribute
to the safety database prior to initiation of larger studies.
If the immunogenicity results obtained after the 1st vaccination in Cohort 1a are not adequately supporting
initiation of Cohort 2, then results obtained after the 2nd vaccination in the 2-dose regimens in Cohort 1a
will be used to select the vaccine regimens to be evaluated in Cohort 2 of this study. If the immunogenicity
results obtained after the 2nd vaccination in the 2-dose regimens in Cohort 1a do not demonstrate an
adequately increased immune response, the sponsor will not provide the 2nd vaccination at Day 57 in
Cohort 2b of this study. The immunogenicity results available from Cohort 1a supported the administration
of the 2nd vaccination at Day 57 in Cohort 2b.
In addition, data obtained after a single booster vaccination will be used to evaluate the effect of a booster
vaccination at different time points and the duration of immune response (see below for further details).
Cohort 3 (Adults Aged ≥65 Years)
The safety, reactogenicity, and immunogenicity of Ad26.COV2.S in adults aged ≥65 years will be assessed
in Cohort 3. Vaccination of participants in Cohort 3 will begin after the DRC review of 7-day safety data
from the first 15 participants in Cohort 1a if no safety concerns are identified.
In Cohort 3, the first doses of study vaccine will be administered to a sentinel group of 5 participants
(1 participant per group) to monitor for any unexpected severe adverse reactions. The sentinel participants
will be vaccinated at least 1 hour apart. A telephone call will be made to each of these 5 sentinel participants
on Day 2 (approximately 24 hours post-vaccination) to collect safety data, which will be reviewed in a
blinded manner by the PI and the sponsor’s SRP. Randomization and vaccination of additional participants
will be halted until the review is completed. In the absence of clinically significant findings, an additional
10 participants will be enrolled at the same study site as the 5 sentinel participants, randomly assigned to
1 of the 5 vaccination groups to have an overall 1:1:1:1:1 randomization ratio, and administered the first
vaccination. The DRC will review the blinded 3-day safety data (ie, from Day 1 to Day 4) and 7-day safety
data (ie, from Day 1 to Day 8) following administration of the first vaccination to these first 15 participants.
Safety data for review will include solicited and unsolicited AEs and SAEs. In the absence of safety
concerns, enrollment and vaccination of the remaining participants in Cohort 3 will proceed.
Booster Vaccinations in Cohort 2
Note: For participants at Belgian sites: per Belgian-specific Protocol Amendment 15, this section is no
longer applicable as participants aged <65 years enrolled at Belgian sites are not eligible to receive a
booster vaccination with Ad26.COV2.S.
To gain preliminary insight into the safety and immunogenicity of a single booster vaccination, designated
participants in Cohort 2 who received Ad26.COV2.S for the single-dose (Cohort 2a) or 2-dose (Cohort 2b)
primary regimen will receive a single booster vaccination of Ad26.COV2.S at 6 months or12 months, after
completion of the primary regimen, and will receive placebo at the other applicable time point. As a control,
a subgroup of participants who received Ad26.COV2.S for the primary regimen will receive placebo at
6 months and 12 months, after completion of the primary regimen. In addition, participants who received

VAC31518 JNJ-78436735 
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placebo for the primary regimen will receive placebo at 6 months and 12 months after completion of the
primary regimen.
See the below tables for further details. An Ad26.COV2.S dose level of 5×1010 vp will be used for the
booster vaccination in Cohorts 2a and 2b.
Table: Cohort 2a Vaccination Schedule –Primary Regimen and Single Booster Vaccination
Primary Regimen 
Booster Vaccination
Group  
N 
Day 1 a 
(Vac 1) 
6 months b 
12 months b 
24 months e
N/A per Amendment 16
1d 
30 
Ad26.COV2.S  
5×1010 vp
Placebo 
Placebo 
Placebo
2 
30 
Ad26.COV2.S  
5×1010 vp 
Ad26.COV2.S  
5×1010 vp
Placebo 
Placebo
3 
30 
Ad26.COV2.S  
5×1010 vp 
Placebo 
Ad26.COV2.S  
5×1010 vp
Placebo
4 d 
30 
Ad26.COV2.S  
5×1010 vp 
Placebo 
Placebo 
Ad26.COV2.S
5×1010 vp
5 c 
15 
Placebo 
Placebo c 
Placebo c 
Placebo c
Total 
135
a. Study vaccine will be administered as a single-dose primary regimen.
b. Study vaccine (Ad26.COV2.S or a placebo) will be administered at 6 months and 12 months after completion of
the single-dose primary regimen.
c. At the time of unblinding, after EUA or approval in any country and local approval of Protocol Amendment 10,
only the Group 5 (placebo only) participants not willing to receive a single dose of 5×1010 vp Ad26.COV2.S or
another authorized/licensed COVID-19 vaccine will continue Group 5 booster vaccinations in Cohort 2a.
d. Applicable to the US only: Following local approval of Protocol Amendment 15, all participants of Groups 1 and
4 not willing to receive a single ad hoc booster dose of 5×1010 vp Ad26.COV2.S  will continue booster
vaccinations in Cohort 2a according to their current schedule.
e. Following local approval of Protocol Amendment 16, booster vaccinations (either placebo or Ad26.COV2.S
5x1010 vp) will not be administered at 24 months after completion of the primary regimen.
EUA = Emergency Use Authorization; N = number of participants; N/A = not applicable; vac = vaccination;
vp = virus particles.
Table: Cohort 2b Vaccination Schedule –Primary Regimen and Single Booster Vaccination
Primary Regimen 
Booster Vaccination
Group  
N 
Day 1 a 
(Vac 1) 
Day 57 a 
(Vac 2) 
8 months b 
14 months b 
26 months e
N/A per
Amendment 16
1d 
30 
Ad26.COV2.S  
5×1010 vp 
Ad26.COV2.S  
5×1010 vp
Placebo 
Placebo 
Placebo
2 
30 
Ad26.COV2.S  
5×1010 vp 
Ad26.COV2.S  
5×1010 vp 
Ad26.COV2.S  
5×1010 vp
Placebo 
Placebo
3 
30 
Ad26.COV2.S  
5×1010 vp 
Ad26.COV2.S  
5×1010 vp 
Placebo 
Ad26.COV2.S  
5×1010 vp
Placebo
4 d 
30 
Ad26.COV2.S  
5×1010 vp 
Ad26.COV2.S  
5×1010 vp 
Placebo 
Placebo 
Ad26.COV2.S
5×1010 vp
5 c 
15 
Placebo 
Placebo 
Placebo c 
Placebo c 
Placebo c
Total 
135
a. Study vaccine will be administered as a 2-dose (Day 1 and Day 57) primary regimen.

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b. Study vaccine (Ad26.COV2.S or a placebo) will be administered at 6 months and 12 months after completion of
the 2-dose primary regimen. If the 2nd vaccination at Day 57 is not provided, then participants will discontinue
the study.
c. At the time of unblinding, after EUA or approval in any country and local approval of Protocol Amendment 10,
only the Group 5 (placebo only) participants not willing to receive a single dose of 5×1010 vp Ad26.COV2.S or
another authorized/licensed COVID-19 vaccine will continue Group 5 booster vaccinations in Cohort 2b.
d. Applicable to the US only: Following local approval of Protocol Amendment 15, all participants of Groups 1 and
4 not willing to receive a single ad hoc booster dose of 5×1010 vp Ad26.COV2.S will continue booster
vaccinations in Cohort 2b according to their current schedule.
e. Following local approval of Protocol Amendment 16, booster vaccinations (either placebo or Ad26.COV2.S
5x1010 vp) will not be administered at 26 months after completion of the primary regimen.
EUA = Emergency Use Authorization; N = number of participants; N/A = not applicable; vac = vaccination; vp = virus
particles.
Procedures in Case of COVID-19-like Signs and Symptoms
Passive Follow-up (As oflocal approval of Protocol Amendment 16)
As of Amendment 16, active follow-up of suspected COVID-19 episodes will be replaced by a passive
follow-up approach. New suspected COVID-19 episodes will be participant-reported and may include
available laboratory findings from testing outside the clinical study. Site staff will collect information on
the new COVID-19 episodes at scheduled visits and report these as SAEs, or AEs, as applicable.
Participants may also contact the site at any time in between scheduled visits to report a safety concern
(eg, hospitalization) or COVID-19 episodes. Concomitant therapies related to these events are to be
reported, as well as any confirmatory COVID-19 laboratory information, if available. Some participants
may have an ongoing COVID-19 episode at time of local approval of Protocol Amendment 16. Also, under
Protocol Amendment 16, the SIC will no longer be completed. Hence, participants with an ongoing
COVID-19 episode will stop completing the SIC as of local approval of Protocol Amendment 16. The
outstanding activities planned for the follow-up of COVID-19 episodes will also end on that date for the
participants (eg, no further samples and no further visit in the context of the COVID-19 follow-up).
Active Follow-up (Prior to local approval of Protocol Amendment 16)
Participants will be provided with a booklet including a daily question on whether they are experiencing
COVID-19-like symptoms. Following local approval of protocol Amendment 15, participants will not be
required to complete the booklet but will be contacted by the site regularly  to check whether they
experienced COVID-19 like symptoms.
If a participant experiences COVID-19-like symptoms, the following should take place:
 
Participants should contact the study site at the time of symptom onset.
 
A nasal swab should be collected by a health care professional from the participant at home (using
available material for home swabs) or at the study site as soon as possible and preferably no longer
than 2 to 3 days after the onset of symptoms and stored appropriately. The sample should be transferred
to the study site by an appropriate method as soon as possible after being collected. A second nasal
swab will be obtained 2 to 4 days after the first swab following the same procedures as the first nasal
swab. The presence of SARS-CoV-2 infection and influenza infection will be assessed at the study
site by molecular testing using the nasal swab sample.

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 
Participants should complete the Symptoms of Infection with Coronavirus-19 (SIC) and record their
highest body temperature daily starting on the first day they experience symptoms. If either nasal swab
is positive for SARS-CoV-2 or influenza, collection of data will continue until sign and symptom
resolution. If the first nasal swab is negative, collection of data will continue until the negative test is
confirmed by the second nasal swab or until sign and symptom resolution, whichever comes first.
Long-term sequelae of COVID-19 (eg, anosmia, headache, fatigue, and other symptoms at the
investigator's judgement) will not be followed until their resolution if not resolved within a month.
 
For participants with a positive test result for SARS-CoV-2 infection, a study visit will be conducted
28 days after symptom onset to assess the clinical course of the infection, record concomitant
medications since symptom onset, and obtain a blood sample for evaluation of the immune response
and other biomarkers. The sponsor recommends to follow these participants until 2 consecutive
negative nasal swabs could be obtained.
If a participant has a positive test result for SARS-CoV-2 infection, the participant may be requested to
remain at home and not visit the study site. If necessary, study site personnel will visit the participant at
home. 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. The participant will not receive further study
vaccinations but should remain on study for follow-up with assessments of safety and immunogenicity,
unless they withdraw consent from the study. The participant will be followed until resolution of clinical
symptoms (except for long-term sequelae of COVID-19).
Procedures in Case of Asymptomatic COVID-19 RT-PCR Confirmed Infection
Passive Follow-up (As of local approval of Protocol Amendment 16)
 
Participants will report any positive RT-PCR SARS-CoV-2 test results during their scheduled visit.
Active Follow-up (Prior to local approval of Protocol Amendment 16)
For each cohort, if participants receive a positive SARS-CoV-2 result from a private/off-study test, without
experiencing any COVID-19 symptoms, the following should take place:
 
Participants should contact the study site at the time the positive RT-PCR SARS-CoV-2 test result is
obtained.
 
The study staff should ensure the participant’s medical care provider has been/will be informed. The
sponsor recommends to contact the participant at least once per week, and recommends to follow these
participants until 2 consecutive negative nasal swabs could be obtained.
In the event a participant experiences COVID-19-like signs or symptoms after obtaining a positive RT-PCR
SARS-CoV-2 test result, procedures as described above should be followed with the exception of nasal
swab collection to assess the presence of SARS-CoV-2 infection or influenza infection.
The above must be done in accordance with local country and site level recommendations for COVID-19,
and these participants will not be permitted to receive further study vaccination administrations. The
participant can continue in the study for safety and immunogenicity assessments, unless they withdraw
consent from the study.

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Assessments and Procedures after Emergency Use Authorization (EUA) or Approval in any Country
Procedures installed at the time of unblinding all participants after EUA or approval in any country and
local approval of protocol Amendment 10, will also apply to participants who were unblinded at their own
request prior to Amendment 10.
All currently enrolled participants will be contacted by the study site to inform them whether they received
active vaccine or placebo only. Participants will be counseled regarding the importance to continue
practicing preventative measures to limit the spread of the disease including social distancing, wearing face
masks, and frequent hand washing, in compliance with local and national guidelines. This contact will be
documented in the source documents.
Participants in the active vaccine groups will be informed they received at a minimum the dose level
approved for Emergency Use (single-dose regimen of 5x1010 vp Ad26.COV2.S), and will be asked to
continue to be followed in this study in line with the Schedule of Activities (SoA). Participants who were
unblinded (at any time) and did not receive an authorized/licensed COVID-19 vaccine outside of the study,
will be permitted to receive the Cohort 2 booster vaccinations. If they opt to receive an authorized/licensed
COVID-19 vaccine outside of the study, they will be discontinued from further study vaccinationa.
Participants who received placebo only during primary regimen and who are still actively enrolled in the
study, will be offered a single dose of 5×1010 vp Ad26.COV2.S  (ie, placebo crossover vaccination). If
willing to receive, they will discontinue from participation in the placebo groups and will be redirected to
the SoA "Procedures for Group 5 (Placebo Only) Participants Receiving a Single Dose of 5x1010 vp
Ad26.COV2.S (Placebo Crossover Vaccination) after EUA or Approval in any Country". If they opt to
receive an authorized/licensed COVID-19 vaccine outside of the study, they will discontinue the study. If
they choose not to receive any additional vaccinations, they will be asked to continue to be followed in this
study in line with the SoA.
Assessments and Procedures after Protocol Amendment 15 Approval (Ad Hoc Booster Vaccination)
Following local approval of protocol Amendment 15, all eligible participants will be offered a single ad
hoc booster dose of 5×1010 vp Ad26.COV2.S.
As soon as possible, but no later than 120 days post local approval of protocol amendment 15, the ad hoc
booster vaccination will be provided to participants who have previously received 1 or more doses of any
COVID-19 vaccine (ie, the Ad26.COV2.S vaccine, an mRNA vaccine and/or another COVID 19 vaccine
authorized for primary vaccination including protein, inactivated, and adenovector-based vaccines) if the
last vaccination was ≥6 months ago.
The following ongoing participants will not be eligible to receive this ad hoc booster vaccination:
− Group 5 participants (all cohorts) who crossed over from placebo to receive Ad26.COV2.S at the 5x1010
vp dose level (ie, placebo crossover vaccination).
− Group 5 participants (all cohorts) who did not opt for the placebo crossover vaccination and therefore
have not received any vaccination with the Ad26.COV2.S vaccine.
a Following local approval of protocol Amendment 15, participants who received an authorized/licensed COVID-19
vaccine outside of the study are allowed to receive a single ad hoc booster dose of Ad26.COV2.S vaccine
(5×1010 vp) if the last vaccination was ≥6 months ago.

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− Cohort 2 participants who will receive a booster vaccination according to their initial schedule at 6 and
12 months after the primary regimen (Groups 2 and 3, respectively).
− Applicable to Belgium only: Per the Belgian-specific protocol Amendment 15, participants aged
<65 years enrolled at Belgian sites.
NUMBER OF PARTICIPANTS
Overall, a target of approximately 1,045 adult male and female participants aged ≥18 to ≤55 years or
≥65 years will be randomly assigned in this study.
DOSAGE AND ADMINISTRATION
Participants will be vaccinated at the study site according to the schedules detailed above:
 
Ad26.COV2.S supplied at a concentration of 1×1011 vp/mL as a suspension in single-use vials, and
dosed at 5×1010 vp and 1×1011 vp
 
Placebo: 0.9% NaCl solution
For blinding purposes, the same volume (1 mL) will be administered to all participants in a cohort.
For participants who received placebo only during primary regimen and who are offered a single dose of
5×1010 vp Ad26.COV2.S at the time of unblinding (ie, after Emergency Use Authorization or approval in
any country and local Amendment 10 approval), a dose level of5×1010 vp in a volume of 0.5 mL will be
administered.
Following local approval of protocol Amendment 15, for all eligible participants who are offered a single
ad hoc booster dose of 5×1010 vp Ad26.COV2.S, a dose level of 5×1010 vp in a volume of 0.5 mL will be
administered.
IMMUNOGENICITY EVALUATIONS
Blood for evaluation of humoral and cellular immune responses will be drawn from participants at the time
points specified in the Schedule of Activities. Immunogenicity assessments may include, but are not limited
to, the humoral and cellular immunogenicity assays (as available and feasible) summarized in the below
tables.
Optional exploratory assessments on lymph node samples for Cohort 1b (Beth Israel Deaconess Medical
Center [BIDMC]) may include, but are not limited to characterization of resident immune cells by flow
cytometry, gene expression, and cytokine release.
Summary of Immunogenicity Assays Used for the Double-blind Phase and Post Unblinding of the Study
Assay 
Purpose
Humoral Immunogenicity
SARS-CoV-2 neutralization 
(VNA) 
Analysis of neutralizing antibodies to the wild-type virus and/or
pseudovirion expressing S protein
SARS-CoV-2 binding antibodies 
(ELISA) 
Analysis of antibodies binding to the SARS-CoV-2 S protein and, if such
an assay can be developed, SARS-CoV-2 N protein
SARS-CoV-2 binding antibodies 
to S protein (MSD) 
Analysis of antibodies binding to SARS-CoV-2 S protein and the RBD of
SARS-CoV-2 S protein
SARS-CoV-2 neutralization 
(neutralization assay) 
Analysis of neutralizing antibodies to the vaccine strain (or other lineage),
as measured by an alternative neutralization assay (different from the VNA
used for the secondary endpoint)
Adenovirus neutralization 
(neutralization assay)
Analysis of neutralizing antibodies to adenovirus

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Assay 
Purpose
Functional and molecular antibody 
characterization  
Analysis of antibody characteristics including Fc-mediated viral clearance,
avidity, Fc characteristics, Ig subclass and IgG isotype
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
Cellular Immunogenicity
Flow cytometry (ICS) 
Analysis of T-cell responses to SARS-CoV-2 S protein, and/or other protein
peptides by ICS including CD4+/CD8+, IFNγ, IL-2,TNFα, IL-4, IL-5, IL-13,
and/or other Th1/Th2 markers
ELISpot 
IFNγ and IL-4 responses to SARS-CoV-2 S protein peptides by PBMCs,
based on single 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-2
S protein peptides or in unstimulated cells or whole blood (ex vivo)
Cytokine profiling (ELISA or 
multiplexed arrays) 
Analysis of cytokines, chemokines, and other proteins of the innate or
adaptive immune response in cells or whole blood stimulated with
SARS-CoV-2 S protein peptides, or in unstimulated cells or whole blood,
by ELISA or multiplexed arrays and confirmation by functional in vitro
assays
T and B cell phenotyping 
Analysis of the phenotype of antigen-specific T and B cells, assessed by
single cell analysis (on frozen or Smart tube isolated PBMCs)
Evaluation of germinal centers in 
lymph nodes
Analysis of the immune responses in lymph nodes
ELISA = enzyme-linked immunosorbent assay; ELISpot = enzyme-linked immunospot (assay); ICS = intracellular
cytokine staining; IFNγ = interferon gamma; Ig = immunoglobulin; IL = interleukin; MSD = Meso Scale Discovery;
PBMC = peripheral blood mononuclear cell; RBD = receptor-binding domain; RNA = ribonucleic acid; S = spike;
SARS-CoV-2 = severe acute respiratory syndrome coronavirus-2; TNFα = tumor necrosis factor alpha; VNA = virus
neutralization assay.
Summary of Immunogenicity Assays Used for the Ad Hoc Booster Vaccination
Assay 
Purpose
Humoral Immunogenicity
SARS-CoV-2 neutralization (VNA) 
Analysis of neutralizing antibodies to the wild-type virus and/or
pseudovirion expressing S protein from the original strain and/or
emerging variants
SARS-CoV-2 binding antibodies (ELISA) 
Analysis of antibodies binding to the SARS-CoV-2 S and RBD
protein from the original strain and/or emerging variants
SARS-CoV-2 binding antibodies (ELISA) 
Analysis of antibodies binding to the SARS-CoV-2 N protein
Adenovirus neutralization (neutralization 
assay)
Analysis of neutralizing antibodies to adenovirus
Functional and molecular antibody 
characterization  
Analysis of antibody characteristics including Fc-mediated viral
clearance, avidity, Fc characteristics, Ig subclass and IgG isotype
Epitope-specificity characterization 
Analysis of site-specificity, epitope mapping
Passive transfer 
Analysis of immune mediators correlating with protection against
experimental SARS-CoV-2 challenge in a suitable animal model
Cellular Immunogenicity
Flow cytometry (ICS) 
Analysis of T-cell responses to SARS-CoV-2 S protein, and/or other
protein peptides by ICS including CD4+/CD8+, IFNγ, IL-2, TNFα,
IL-4, IL-5, IL-13, and/or other Th1/Th2 markers
ELISA = enzyme-linked immunosorbent assay; ICS = intracellular cytokine staining; IFNγ = interferon gamma;
IL = interleukin; RBD = receptor-binding domain; S = spike; SARS-CoV-2 = severe acute respiratory syndrome
coronavirus-2; TNFα = tumor necrosis factor alpha; VNA = virus neutralization assay

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SAFETY EVALUATIONS
After each vaccination, participants will remain under observation at the study site for at least 15 minutes
to 1 hour depending on the vaccination being administered (see SoAs for details) for the presence of any
acute reactions and solicited events. Participants will be asked to note in the 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).
Participants will be instructed on how to record daily temperature using a thermometer provided for home
use. Participants should record the temperature in the diary in the evening of the day of vaccination, and
then daily for the next 7 days approximately at the same time each day. Participants will also be instructed
on how to note signs and symptoms in the 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.
For all cohorts, AEs and special reporting situations, whether serious or non-serious, that are related to
study procedures or that are related to non-investigational sponsor products will be reported from the time
a signed and dated informed consent form (ICF)is obtained until the end of the study/early withdrawal. All
other unsolicited AEs will be reported for each vaccination from the time of vaccination until 28 days
post-vaccination. All other SAEs and AEs leading to discontinuation from the study/vaccination (regardless
of the causal relationship) will be reported from the moment of first vaccination until completion of the
participant’s last study-related procedure. Adverse events of special interest (AESI) will be reported from
local approval of protocol Amendment 11 until the end of the study/early withdrawal.
For enrolled participants who received placebo only during primary regimen and who are accepting a single
dose of 5×1010 vp Ad26.COV2.S offered at the time of unblinding (ie, after Emergency Use Authorization
(EUA) or approval in any country and local approval of protocol Amendment 10), different procedures
apply. A single dose of 5×1010 vp Ad26.COV2.S will be administered during an ad hoc crossover visit and
participants will remain under observation at the study site for at least 15 minutes following vaccination.
SAEs, special reporting situations (whether serious or non-serious, that are related to study procedures or
that are related to non-investigational sponsor products), and COVID-19-like signs and symptoms will be
reported from the time of unblinding until the end-of-safety-follow-up phone call. In addition, suspected
AESIs will be reported after local approval of protocol Amendment 11 is obtained.
From the time of local approval of protocol Amendment 11 onwards, TTS is considered an AESI. Suspected
AESIs (thrombotic events and/or thrombocytopenia [defined as platelet count below 150,000/µLa]) will be
reported 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.
STATISTICAL METHODS
Sample Size Calculation
The number of participants chosen for this study will provide a preliminary safety and immunogenicity
assessment. While mild-to-moderate vaccine reactions (local site and systemic responses) are expected,
AEs that preclude further dose administration or more serious ones that would limit product development
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). 11 November 2021.
https://brightoncollaboration.us/wp-content/uploads/2021/11/TTS  Updated-Brighton-Collaboration-Case-Defintion-
Draft-Nov-11-2021.pdf. Accessed: 25 February 2022.

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are not anticipated. When 75 and 120 participants are vaccinated, the observation of 0 such reactions would
be associated with a 95% confidence that the true rate is less than 3.9% and <2.5% respectively.
Populations for Analysis Sets
For purposes of analysis, the following populations are defined:
FAS: The full analysis set will include all participants with at least one vaccine administration documented.
PPIa: The per protocol immunogenicity population will include all randomized and vaccinated participants
for whom immunogenicity data are available excluding participants with major protocol deviations
expecting to impact the immunogenicity outcomes. In addition, samples obtained after missed vaccinations
or from participants with natural infection occurring after screening (if applicable) will be excluded from
the analysis set.
PPE: The per protocol efficacy population will include all randomized participants having received at least
1 vaccination for whom efficacy data concerning endpoint measures are available. All efficacy analyses
will be done according to the as treated principle (ie, actually received vaccinations).
Primary Endpoint
No formal statistical testing of safety data is planned. Safety data will be analyzed descriptively by vaccine
group. In addition, for selected tables, tabulations pooled by vaccine dose will also be provided. All safety
analyses will be made on the FAS.
Secondary Endpoints
No formal hypothesis on immunogenicity will be tested. Descriptive statistics (geometric mean and 95%
confidence interval, or median and interquartile range Q1-Q3, as appropriate) will be calculated for
continuous immunologic parameters at all available time points. 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 protein
ELISA, respectively, will be calculated.
The immunogenicity analyses will be performed on the PPI population. Immunogenicity analyses will also
be done on the FAS (participants who became infected during the study will be analyzed as a subgroup and
shown in the graphs using different colors and symbols).
Planned Analyses
Interim and primary analyses for each cohort are presented in the figure below. Additional interim analyses
may be conducted by the sponsor as needed.
a If a participant would be vaccinated out of window due to a study pause (per Section 6.9), this will not by default be
a reason for excluding this participant from the PPI. A sensitivity analysis might also be performed. Further details
will be described in the Statistical Analysis Plan.

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Figure:Interim and Primary Analyses
*May be performed based on operational availability of data.
**Analysis of VNA/ELISA may be performed before availability of Th1/Th2 data, which may not be available at
the time of this analysis.
ELISA = enzyme-linked immunosorbent assay; Th = T-helper; VNA = virus neutralization assay
The end-of-study analysis will be performed when all included participants have completed the last visit or
last booster vaccination follow-up visit or discontinued the study earlier.
Analyses for Participants Requesting Unblinding in Order to Receive an Authorized/Licensed
COVID-19 Vaccine
Investigators may receive requests to unblind study participants who become eligible to receive an
authorized/licensed COVID-19 vaccine if/when these become available. In these cases, the investigator will
discuss with the participant available options and ramifications. If the participant is eligible for an
authorized/licensed vaccine according to local immunization guidelines or recommendations and if the

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participant wishes to proceed with the unblinding, the investigator will follow the unblinding procedures.
The reason for the unblinding request should be documented. The name and date(s) of administration of
the other COVID-19 vaccine should be recorded (see body of the protocol for more details).
When unblinding, if it is determined that the participant received the Ad26.COV2.S vaccine (and not
placebo), the participant will be informed that there are no clinical data on the safety of receiving a different
COVID-19 vaccine after receiving Ad26.COV2.S. In the event of participant unblinding to obtain an
authorized/licensed COVID-19 vaccine and the participant received an authorized/licensed COVID-19
vaccine outside of the study, no further study vaccination will be permitteda. Unblinded participants,
whether in the vaccine or control group that did not receive an authorized/licensed COVID-19 vaccine
outside of the study will be asked to continue to be followed in this study in line with the schedule of
activities to the extent that they permit, including Cohort 2 booster vaccinations. Safety and
immunogenicity evaluations will be identical for all participants, including participants that are unblinded
to obtain an authorized/licensed COVID-19 vaccine and who remain in the study, if applicable and feasible.
The statistical analyses will follow the same approach as outlined below.
Analyses after Unblinding all Participants Following Emergency Use Authorization (EUA) or
Approval in any Country
In general, after unblinding, participants who received placebo only during primary regimen, can elect to
receive a single dose of 5×1010 vp Ad26.COV2.S offered at the study site, can opt to receive an
authorized/licensed COVID-19 vaccine outside of the study, or may choose not to receive any additional
vaccinations. Participants who received active vaccine will be asked to continue the study or can opt to
receive an authorized/licensed COVID-19 vaccine outside of the study.
The participants in cohorts 1a, 1b, and 3 have completed the planned study vaccination regimen by the time
of unblinding (or have discontinued earlier). Participants in Cohorts 2a and 2b will not have completed the
planned vaccination schedule by the time of unblinding, because the booster vaccinations will not yet have
occurred.
The safety and efficacy analyses will be censored at the date of unblinding or the receipt of an unscheduled
vaccineb, whichever event occurs first. SAEs reported after unblinding or receipt of an unscheduled vaccine,
whichever comes first, will be listed.
The immunogenicity analyses will be censored at the date of the receipt of an unscheduled vaccine.
Immunogenicity samples taken after the receipt of an unscheduled vaccine will be included in the listings
and flagged.
Analyses pertaining to the booster vaccinations in Cohorts 2a and 2b will be produced as planned.
Post-booster safety or efficacy analyses will not include participants who were unblinded at their own
request, nor participants who received an unscheduled vaccination.
a Following local approval of protocol Amendment 15, participants who received an authorized/licensed COVID-19
vaccine outside of the study are allowed to receive a single ad hoc booster dose of Ad26.COV2.S vaccine
(5×1010 vp) if the last vaccination was ≥6 months ago.
b Unscheduled vaccine: for placebo participants: a single dose of 5×1010 vp Ad26.COV2.S offered at the study site or
an authorized/licensed COVID-19 vaccine offered outside of the study; for participants in the active vaccine
groups: an authorized/licensed COVID-19 vaccine offered outside of the study.

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The analysis strategy is depicted graphically in the figure below.
Analysis After Receipt of the Ad Hoc Booster Vaccination
Amendment 15 of this protocol offers eligible study participants a single ad hoc booster vaccination with
the Ad26.COV2.S vaccine at the 5×1010 vp dose level. The main analyses will be conducted as described
above, in which censoring is applied for the various statistical analyses depending on the date of unblinding
or receipt of an unscheduled vaccine. In addition, receipt of the ad hoc booster vaccination will also be a
reason for censoring data from the main analyses.
For safety and reactogenicity, additional analyses will be conducted on study participants who received the
ad hoc booster vaccination. Safety and reactogenicity analyses will be presented from the start of the ad
hoc booster vaccination until 7 days post vaccination for reactogenicity, until 28 days post vaccination for
unsolicited AEs, and until the end of the study for SAEs and AESIs.
For immunogenicity, an additional analysis will be conducted on study participants who received the ad hoc
booster vaccination. Immunogenicity analyses will be presented from the start of the ad hoc booster
vaccination and will show their immune responses at each subsequent time point, as available.
The analyses will be descriptive, presenting study participants according to their original vaccination
regimen. In addition, the analyses may also be conducted separately by subgroups of study participants who
received a COVID-19 vaccine outside of the study versus study participants who did not receive a
COVID-19 vaccine outside of the study. Additional exploratory analyses may be conducted.
Details for the analysis of the ad hoc booster vaccination will be provided in an amendment to the study
Statistical Analysis Plan.

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Figure: 
Analysis strategy after unblinding, depicted by scenario
AESI = adverse event of special interest; C = cohort; SAE = serious adverse event

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Figure 2: 
Schematic Overview of Cohort 1b
VISIT
1
Screening:
Days -28 to 1
2 
Vaccination 1: Day 1
3 
Safety and Immunogenicity: 1 day post vaccination 1
4 
Safety and Immunogenicity: 7 days post vaccination 1
5 
Safety and Immunogenicity: 14 days post vaccination 1
6 
Safety and Immunogenicity: 28 days post vaccination 1
7 
Vaccination 2: Target Visit Day 57
8 
Safety and Immunogenicity: 1 day post vaccination 2
9 
Safety and Immunogenicity: 7 days post vaccination 2
10 
Safety and Immunogenicity: 14 days post vaccination 2
11 
Safety and Immunogenicity: 28 days post vaccination 2
12 
Safety and Immunogenicity: 6 months post vaccination 2
13 
Safety and Immunogenicity: 12 months post vaccination 2
13a
Safety and Immunogenicity: ~12
months post vaccination 2
13b 
Safety: 72 hr post LNA
13c 
Safety: 7 days post LNA
FU1 
Safety: 15 months post vaccination 2 (telephone call [visit if necessary])

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FU2 
Safety and Immunogenicity: 18 months post vaccination 2
FU3 
Safety: 21 months post vaccination 2 (telephone call [visit if necessary])
FU4 
Safety and Immunogenicity: 24 months post vaccination 2

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Figure 3: 
Schematic Overview of Cohort 2a
VISIT
1 
Screening:
Days -28 to 1
2 
Vaccination 1: Day 1
3 
Safety and Immunogenicity: 7 days post-vaccination 1
4 
Safety and Immunogenicity: 28 days post-vaccination 1
5 
Time Point for Single Booster Vaccination: 6 months post-vaccination 1 a
6 
Safety and Immunogenicity: 7 days post-booster vaccination
7 
Safety and Immunogenicity: 28 days post-booster vaccination
8 
Time Point for Single Booster Vaccination: 12 months post-vaccination 1 a
9 
Safety and Immunogenicity: 7 days post-booster vaccination
10 
Safety and Immunogenicity: 28 days post-booster vaccination
11 
24 months post-vaccination 1 a, b
a. Participants designated to receive a single booster vaccination will receive Ad26.COV2.S at 6 months, or 12 months after
completion of the single dose primary regimen and will receive placebo at the other indicated time point. Participants not
designated to receive a booster vaccination will receive placebo at both time points. See Table 2 for further details.
b. Visit 11 is the last visit.

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Figure 5: 
Schematic Overview of Cohort 3
VISIT
1
Screening:
Days -28 to 1
2 
Vaccination 1: Day 1
3
1 day post vaccination 1
(Sentinel participants: safety telephone call)
4 
Safety: 7 days post vaccination 1
5 
Safety and Immunogenicity: 14 days post vaccination 1
6 
Safety and Immunogenicity: 28 days post vaccination 1
7 
Vaccination 2: Target Visit Day 57
8
1 day post vaccination 2
(Sentinel participants: safety telephone call)
9 
Safety: 7 days post vaccination 2
10 
Safety and Immunogenicity: 14 days post vaccination 2
11 
Safety and Immunogenicity: 28 days post vaccination 2
12 
Safety and Immunogenicity: 6 months post vaccination 2
13 
Safety and Immunogenicity: 12 months post vaccination 2
FU1 
Safety: 15 months post vaccination 2 (telephone call [visit if necessary])
FU2 
Safety and Immunogenicity: 18 months post vaccination 2
FU3 
Safety: 21 months post vaccination 2 (telephone call [visit if necessary])
FU4 
Safety and Immunogenicity: 24 months post vaccination 2

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Figure 6: 
Schematic Overview of Placebo Crossover Vaccination
VISIT
Ad Hoc Visit
Placebo Crossover
Vaccination
End-of-Safety-Follow-Up  
Phone Call 
Cohorts 1a, 1b a, and 3: Day 422 b±21d
Cohorts 2a, 2b: Ad Hoc Vaccination Visit +182 d ±21 d
a. At this visit, optional fine needle LNA procedure will be performed on Cohort 1b participants who have provided
consent. In this case, the visit will take place onsite instead of a telephone call. This onsite visit will not be the
final visit, as there will be 2 other follow-up visits (see Section 1.3.2.1).
b. Or ad hoc vaccination visit +182 d ± 21 d, whichever comes first. Day 422 was the initially planned study completion date
(based on the participant's initial SoA).
Figure 7: 
Schematic Overview of Ad Hoc Booster Vaccination
VISIT
Ad Hoc Booster Visit 
Ad Hoc Booster
Vaccination
Booster FU1 
Safety and Immunogenicity: 28 days post booster vaccination
Booster FU2 
Safety and Immunogenicity: 6 months post booster vaccination

VAC31518 JNJ-78436735 
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Status: Approved, Date: 16 August 2022
1.3. 
Schedule of Activities (SoA)
1.3.1. 
Cohort 1a
Participants who consent for the additional follow-up will follow the additional procedures as specified in Section 1.3.9. Participants who
consent for the ad hoc booster vaccination will discontinue from the current schedule and follow the procedures as specified in Section 1.3.10.
If not willing to do the additional follow-up or receive the ad hoc booster vaccination, they will continue to follow the assessments according
to the schedule below.
Phase 
Screening a 
Study Period b
Visit # 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
Exit b
Visit Timing
Vac 1 
Vac 1 
+ 1 d  
Vac 1 
+ 3 d  
Vac 1 
+ 7 d  
Vac 1 
+ 14 d  
Vac 1 
+ 28 d  
Vac 2
Vac 2 
+ 1 d  
Vac 2 
+ 7 d  
Vac 2 
+ 14 d  
Vac 2 
+ 28 d  
Vac 2 
+6 mo 
Vac 2
+12 mo
Target Visit Day ±Window
-28 to 1 
1 
2 
4 
8±2 c 
15±3 
29±3 
57-3/+7 
58* 
64*±2 c 
71*±3 
85*±3
239* 
±21 
422*
±21
Visit Type
Screening
Vaccine 
1 
(Safety 
tel.) d 
(Safety 
tel.) d 
Safety  
Safety and 
Immuno 
Vaccine 
2 
(Safety 
tel.) d 
Safety
Safety and Immuno
Early
Exit
Written informed consent e 

Inclusion/exclusion criteria 
 

Demographics 

Medical history/prestudy
meds
 

Physical examination f 

Vital signs g, l incl. body
temperature
 
 
 
 
 
 
 
 
 

Nasal swab sample 
 

Serological test for
SARS CoV 2 specific 
antibodies
 

Randomization 

Pre vaccination symptoms h 
 

Urine pregnancy test i 
 
 

Clinical lab blood sample, mL 
  
10 
10 
10 
10
Urinalysis 
 
 
 
 

Humoral immunity (serum),
mL
30 
30 
30 
30 
30 
30 
30 
30 
20
Cellular immunity (PBMC),
mL j
60 
60 
60 
60 
60 
60 
60 
60 
60

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b. For those participants who are unable to continue participation in the study up to Visit 14, 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 discontinue study vaccination for reasons listed in Section 7.1, will be
offered all safety and immunogenicity follow-up visits according to the current SoA. Participants who wish to withdraw consent from participation in the study (see
section 7.2) 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).
c. If a participant comes in early for Visit 5 or 10, ie, 1 or 2 days prior to the Target Visit Day per the allowed visit window, a subsequent phone call will be made at the
end of the diary period to collect diary information recorded between the actual visit and the end of the diary period. The diary will be returned by the participant at
the next visit.
d. Telephone contact on Day 2 and Day 58 for the 5 sentinel participants. Telephone contact on Day 4 for the first 15 participants including the 5 sentinel participants.
e. Signing of the ICF should be done before any study-related activity.
f. A full physical examination, including height and body weight, will be carried out at screening. At other visits, an abbreviated, symptom-directed examination will
be performed if determined necessary by the investigator.
g. Heart rate, systolic and diastolic blood pressure, respiratory rate, and body temperature. Heart rate and blood pressure measurements should be taken in the supine
position 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.
h. 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 windows (see Section 5.5 and Table 4). 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. In addition, the
investigator must check the criteria for withdrawal of study vaccinations as noted in Section 7.1.
i. 
For women of childbearing potential only.
j. 
Samples to be taken from approximately 200 seronegative participants at selected sites.
k. Sample to be taken from all participants pre-vaccination on Day 1. At subsequent time points, samples to be taken only from approximately 200 seronegative
participants at selected sites.
l. 
Participants will be closely observed for a minimum of 1-hour post-vaccination. Any solicited local (at injection site) and systemic AEs, unsolicited AEs, 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 1-hour 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 for each
vaccination 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 first vaccination until completion of the
participant’s last study-related procedure. Suspected AESIs are to be reported from the time of local approval of protocol Amendment 11 onwards (see Section 8.3.1).
For schedule of activities related to AESI, see Section 1.3.8 for more details.
o. Concomitant therapies such as analgesic/antipyretic medications and non-steroidal anti-inflammatory drugs, corticosteroids, antihistamines, and vaccinations must be
recorded from the first dose of study vaccine until 28 days after administration of study vaccine, and thereafter, pre-dose on the day of vaccination and for 28 days
after the subsequent dose of study vaccine. Receipt of a licensed/authorized COVID-19 vaccine must be recorded at any timepoint during the study. The name and
date(s) of administration of the COVID-19 vaccine should be recorded. 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 8.3.1.
p. At Visit 2, in addition to the diary, a ruler and thermometer will be distributed to each participant.
q. If an event is still ongoing on Day 8 or Day 64, the participant should keep the diary after the review and collect information until resolution. The diary should be
reviewed again at the next visit.

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r. If a participant develops COVID-19-like signs and symptoms, refer to Section 1.3.6.
AE = adverse event; AESI = adverse event of special interest; COVID-19 = coronavirus disease-2019; d = day(s); ICF = informed consent form; mo = months;
PBMC = peripheral blood mononuclear cell; SAE = serious adverse event; SARS-CoV-2 = severe acute respiratory syndrome coronavirus-2; SoA = schedule of
activities; tel = telephone contact; vac = vaccination.

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Status: Approved, Date: 16 August 2022
1.3.2. 
Cohort 1b
Participants who consent for the additional follow-up will follow the additional procedures as specified in Section 1.3.9. Participants who
consent for the ad hoc booster vaccination will discontinue from the current schedule and follow the procedures as specified in Section 1.3.10.
If not willing to do the additional follow-up or receive the ad hoc booster vaccination, they will continue to follow the assessments according
to the schedule below.
Phase 
Screening a 
Study Period b
Visit # 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
Exit b
Visit Timing
Vac 1 
Vac 1 
+ 1 d  
Vac 1 
+ 7 d  
Vac 1 
+ 14 d  
Vac 1 
+ 28 d  
Vac 2
Vac 2 
+ 1 d  
Vac 2 
+ 7 d  
Vac 2 
+ 14 d  
Vac 2 
+28 d  
Vac 2 
+ 6 mo 
Vac 2
+12 mo d
Target Visit Day ±Window  
-28 to 1 
1 
2 
8±2 c 
15±3 
29±3 
57-3/+7 
58* 
64*±2 c 
71*±3 
85*±3 
239*±21 
422*±21
Visit Type
Screening 
Vaccine 
1 
Safety and Immuno 
Vaccine 
2 
Safety and Immuno
Early
Exit
Written informed consent e 

Inclusion/exclusion criteria 
 

Demographics 

Medical history/prestudy meds 
 

Physical examination f 

Vital signs g, j incl. body
temperature
 
 
 
 
 
 
 
 
 
 
 

Nasal swab sample 
 

Serological test for
SARS CoV 2 specific 
antibodies
 

Randomization 

Pre vaccination symptoms h 
 

Urine pregnancy test i 
 
 

Clinical lab blood sample, mL 
  
10 
10 
10 
10
Urinalysis 
 
 
 
 

Humoral immunity (serum),
mL
40 
20 
40 
40 
40 
20 
20 
40 
40 
40 
20 
20 
20
Cellular immunity (PBMC),
mL
60 
60 
60 
60 
60 
60 
60 
60 
60 
60 
60
Cellular immunity (whole
blood, PAXgene® tubes), mL
2.5 
2.5 
2.5 
2.5 
2.5 
2.5
Vaccination 
 

1 hour post vaccination
observation j
 


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g. Heart rate, systolic and diastolic blood pressure, respiratory rate, and body temperature. Heart rate and blood pressure measurements should be taken in the supine
position 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.
h. 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 windows (see Section 5.5 and Table 5). 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. In addition, the
investigator must check the criteria for withdrawal of study vaccinations as noted in Section 7.1.
i. For women of childbearing potential only.
j. Participants will be closely observed for a minimum of 1-hour post-vaccination. Any solicited local (at injection site) and systemic AEs, unsolicited AEs, 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 1-hour post-vaccination observation period is complete.
k. 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 for each
vaccination from the time of vaccination until 28 days post-vaccination.
l. 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 first vaccination until completion of the
participant’s last study-related procedure. Suspected AESIs are to be reported from the time of local approval of protocol Amendment 11 onwards (see Section 8.3.1).
For schedule of activities related to AESI, see Section 1.3.8 for more details.
m. Concomitant therapies such as analgesic/antipyretic medications and non-steroidal anti-inflammatory drugs, corticosteroids, antihistamines, and vaccinations must be
recorded from the first dose of study vaccine until 28 days after administration of study vaccine, and thereafter, pre-dose on the day of vaccination and for 28 days
after the subsequent dose of study vaccine. Receipt of a licensed/authorized COVID-19 vaccine must be recorded at any timepoint during the study. The name and
date(s) of administration of the COVID-19 vaccine should be recorded. 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 8.3.1.
n. At Visit 2, in addition to the diary, a ruler and thermometer will be distributed to each participant.
o. If an event is still ongoing on Day 8 or Day 64, the participant should keep the diary after the review and collect information until resolution. The diary should be
reviewed again at the next visit.
p. If a participant develops COVID-19-like signs and symptoms, refer to Section 1.3.6.
AE = adverse event; AESI = adverse event of special interest; COVID-19 = coronavirus disease-2019; d = day(s); ICF = informed consent form; LNA = lymph node
aspirate; mo = months; PBMC = peripheral blood mononuclear cell; SAE = serious adverse event; SARS-CoV-2 = severe acute respiratory syndrome coronavirus-2;
SoA = schedule of activities; vac = vaccination.

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i. Samples will be collected from 27 seronegative participants at selected sites.
j. Sample to be taken from all participants pre-vaccination on Day 1. At subsequent time points, samples to be taken only from 27 seronegative participants at selected
sites.
k. Participants will be closely observed for a minimum of 1-hour post-vaccination. Any solicited local (at injection site) and systemic AEs, unsolicited AEs, 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 1-hour post-vaccination observation period is complete.
l. Participants will record solicited symptoms in a diary for 7 days post-vaccination.
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 for each
vaccination 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 first vaccination until completion of the
participant’s last study-related procedure. Suspected AESIs are to be reported from the time of local approval of protocol Amendment 11 onwards.  (see Section 8.3.1).
For schedule of activities related to AESI, see Section 1.3.8 for more details.
o. Concomitant therapies such as analgesic/antipyretic medications and non-steroidal anti-inflammatory drugs, corticosteroids, antihistamines, and vaccinations must be
recorded from the first dose of study vaccine until 28 days after administration of study vaccine, and thereafter, pre-dose on the day of vaccination and for 28 days
after the subsequent dose of study vaccine. Receipt of a licensed/authorized COVID-19 vaccine must be recorded at any timepoint during the study. The name and
date(s) of administration of the COVID-19 vaccine should be recorded. 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 8.3.1.
p. At Visit 2, in addition to the diary, a ruler and thermometer will be distributed to each participant.
q. If an event is still ongoing on Day 8, the participant should keep the diary after the review and collect information until resolution. The diary should be reviewed again
at the next visit.
r. If a participant develops COVID-19-like signs and symptoms, refer to Section 1.3.6.
s. Vaccination and randomization may be done on the same day.
AE = adverse event; AESI = adverse event of special interest; COVID-19 = coronavirus disease-2019; d = day(s); ICF = informed consent form; PBMC = peripheral
blood mononuclear cell; SAE = serious adverse event; SARS-CoV-2 = severe acute respiratory syndrome coronavirus-2; SoA = schedule of activities; vac = vaccination.

VAC31518 JNJ-78436735 
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i. Participants will be closely observed for a minimum of 1-hour post-vaccination. Any solicited local (at injection site) and systemic AEs, unsolicited AEs, 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 1-hour post-vaccination observation period is complete.
j. Participants will record solicited symptoms in a diary for 7 days post-vaccination.
k. 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 for each
vaccination from the time of vaccination until 28 days post-vaccination.
l. 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 first vaccination until completion of the
participant’s last study-related procedure. Suspected AESIs are to be reported from the time of local approval of protocol Amendment 11 onwards (see Section 8.3.1).
For schedule of activities related to AESI, see Section for more details.
m. Concomitant therapies such as analgesic/antipyretic medications and non-steroidal anti-inflammatory drugs, corticosteroids, antihistamines, and vaccinations must be
recorded from the first dose of study vaccine until 28 days after administration of study vaccine, and thereafter, pre-dose on the day of vaccination and for 28 days
after the subsequent dose of study vaccine. Receipt of a licensed/authorized COVID-19 vaccine must be recorded at any timepoint during the study. The name and
date(s) of administration of the COVID-19 vaccine should be recorded. 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 8.3.1.
n. If an event is still ongoing on Day 190, or Day 373, the participant should keep the diary after the review and collect information until resolution. The diary should
be reviewed again at the next visit.
o. If a participant develops COVID-19-like signs and symptoms, refer to Section 1.3.6.
p. Following local approval of Protocol Amendment 16, participants will have on-site Visit 11 as scheduled. Visit 11 will be the last visit for Cohort 2a, at which only
safety evaluations will be performed.
AE = adverse event; AESI = adverse event of special interest; Cont = continuous; COVID-19 = coronavirus disease-2019; d = day(s); ICF = informed consent form;
mo = months; PBMC = peripheral blood mononuclear cell; SAE = serious adverse event; SARS-CoV-2 = severe acute respiratory syndrome coronavirus-2;
vac = vaccination

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h. For women of childbearing potential only.
i. Samples will be collected from 27 seronegative participants at selected sites.
j. Sample to be taken from all participants pre-vaccination on Day 1. At subsequent time points, samples to be taken only from 27 seronegative participants at selected
sites.
k. Participants will be closely observed for a minimum of 1-hour post-vaccination. Any solicited local (at injection site) and systemic AEs, unsolicited AEs, 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 1-hour post-vaccination observation period is complete.
l. Participants will record solicited symptoms in a diary for 7 days post-vaccination.
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 for each
vaccination 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 first vaccination until completion of the
participant’s last study-related procedure. Suspected AESIs are to be reported from the time of local approval of protocol Amendment 11 onwards (see Section 8.3.1).
For schedule of activities related to AESI, see Section 1.3.8 for more details.
o. Concomitant therapies such as analgesic/antipyretic medications and non-steroidal anti-inflammatory drugs, corticosteroids, antihistamines, and vaccinations must be
recorded from the first dose of study vaccine until 28 days after administration of study vaccine, and thereafter, pre-dose on the day of vaccination and for 28 days
after the subsequent dose of study vaccine. Receipt of a licensed/authorized COVID-19 vaccine must be recorded at any timepoint during the study. The name and
date(s) of administration of the COVID-19 vaccine should be recorded. 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 8.3.1.
p. At Visit 2, in addition to the diary, a ruler and thermometer will be distributed to each participant.
q. If an event is still ongoing on Day 8 or Day 64, the participant should keep the diary after the review and collect information until resolution. The diary should be
reviewed again at the next visit.
r. If a participant develops COVID-19-like signs and symptoms, refer to Section 1.3.6.
s. Vaccination and randomization may be done on the same day.
AE = adverse event; AESI = adverse event of special interest; Cont = continuous; COVID-19 = coronavirus disease-2019; d = day(s); ICF = informed consent form;
PBMC = peripheral blood mononuclear cell; SAE = serious adverse event; SARS-CoV-2 = severe acute respiratory syndrome coronavirus-2; SoA = schedule of activities;
vac = vaccination

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be rescheduled within the allowed window or the contraindications to vaccination persist, the sponsor should be contacted for further guidance. In addition, the
investigator must check the criteria for withdrawal of study vaccinations as noted in Section 7.1.
f. For women of childbearing potential only.
g. Samples will be collected from 27seronegative participants at selected sites.
h. A blood sample will be used for a platelet count (as part of a complete blood count if applicable) in a local laboratory. A serum sample will be stored for potential
future coagulation-related testing in a central laboratory if the participant experiences a suspected AESI (see Section 10.2.2, Appendix 2). If the blood and serum
samples have been taken within 5 days before vaccination and platelet results are available, sample collection does not need to be repeated before vaccination.
i. 
Participants will be closely observed for a minimum of 1-hour post-vaccination. Any solicited local (at injection site) and systemic AEs, unsolicited AEs, 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 1-hour post-vaccination observation period is complete.
j. 
Participants will record solicited symptoms in a diary for 7 days post-vaccination.
k. 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 for each
vaccination from the time of vaccination until 28 days post-vaccination.
l. 
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 first vaccination until completion of the
participant’s last study-related procedure. Suspected AESIs are to be reported from the time of local approval of protocol Amendment 11 onwards (see Section 8.3.1.
For schedule of activities related to AESI, see Section 1.3.8 for more details.
m. Concomitant therapies such as analgesic/antipyretic medications and non-steroidal anti-inflammatory drugs, corticosteroids, antihistamines, and vaccinations must be
recorded from the first dose of study vaccine until 28 days after administration of study vaccine, and thereafter, pre-dose on the day of vaccination and for 28 days
after the subsequent dose of study vaccine. Receipt of a licensed/authorized COVID-19 vaccine must be recorded at any timepoint during the study. The name and
date(s) of administration of the COVID-19 vaccine should be recorded. 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 8.3.1.
n. If an event is still ongoing on Day 246, or Day 429, the participant should keep the diary after the review and collect information until resolution. The diary should
be reviewed again at the next visit.
o. If a participant develops COVID-19-like signs and symptoms, refer to Section 1.3.6.
p. Following local approval of Protocol Amendment 16, participants will have on-site Visit 14 as scheduled. Visit 14 will be the last visit for Cohort 2b, at which only
safety evaluations will be performed.
AE = adverse event; AESI = adverse event of special interest; Cont = continuous; COVID-19 = coronavirus disease-2019; d = day(s); ICF = informed consent form;
mo = months; PBMC = peripheral blood mononuclear cell; SAE = serious adverse event; SARS-CoV-2 = severe acute respiratory syndrome coronavirus-2;
vac = vaccination

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1.3.5. 
Cohort 3
Participants who consent for the additional follow-up will follow the additional procedures as specified in Section 1.3.9. Participants who
consent for the ad hoc booster vaccination will discontinue from the current schedule and follow the procedures as specified in Section 1.3.10.
If not willing to do the additional follow-up or receive the ad hoc booster vaccination, they will continue to follow the assessments according
to the schedule below.
Phase Screening a 
Study Period b
Visit # 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
Exit b
Visit Timing
Vac 1 
Vac 1 
+ 1 d  
Vac 1 
+ 7 d  
Vac 1 
+ 14 d  
Vac 1 
+ 28 d  
Vac 2
Vac 2 
+ 1 d  
Vac 2 
+ 7 d  
Vac 2 
+ 14 d  
Vac 2 
+ 28 d  
Vac 2 
+ 6 mo 
Vac 2
+ 12 mo
Target Visit Day ±Window  
-28 to 1 
1 
2 
8±2 c 
15±3 
29±3 
57-3/+7 
58* 
64*±2 c 
71*±3 
85*±3 
239*±21 
422*±21
Visit Type
Screening 
Vaccine 
1 
(Safety 
tel.) d 
Safety
Safety and 
Immuno 
Vaccine 
2 
(Safety 
tel.) d 
Safety  
Safety and Immuno
Early
Exit
Written informed consent e 

Inclusion/exclusion criteria 
 

Demographics 

Medical history/prestudy meds 
 

Physical examination f 

Vital signs g, k incl. body
temperature
 
 
 
 
 
 
 
 
 

Nasal swab sample 
 

Serological test for
SARS CoV 2 specific 
antibodies
 

Randomization 

Pre vaccination symptoms h 
 

Clinical lab blood sample, mL 
  
10 
10 
10 
10
Urinalysis 
 
 
 
 

Humoral immunity (serum),
mL
30 
30 
30 
30 
30 
30 
30 
30 
20
Cellular immunity (PBMC),
mL i
60 
60 
60 
60 
60 
60 
60 
60 
60
Cellular immunity (whole
blood, PAXgene® tubes), mL j 
2.5 
2.5 
2.5 
2.5 
2.5 
2.5
Vaccination 
 

1 hour post vaccination
observation k
 
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c. If a participant comes in early for Visit 4 or 9, ie, 1 or 2 days prior to the Target Visit Day per the allowed visit window, a subsequent phone call will be made at the
end of the diary period to collect diary information recorded between the actual visit and the end of the diary period. The diary will be returned by the participant at
the next visit.
d. Telephone contact on Day 2 and Day 58 for the 5 sentinel participants.
e. Signing of the ICF should be done before any study-related activity.
f. A full physical examination, including height and body weight, will be carried out at screening. At other visits, an abbreviated, symptom-directed examination will
be performed if determined necessary by the investigator.
g. Heart rate, systolic and diastolic blood pressure, respiratory rate, and body temperature. Heart rate and blood pressure measurements should be taken in the supine
position and preceded by at least 5 minutes of rest. Vital signs measurements are recommended before blood sampling. Bodytemperatures will be measured preferably
via the oral route.
h. 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 windows (see Section 5.5 and Table 8). 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. In addition, the
investigator must check the criteria for withdrawal of study vaccinations as noted in Section 7.1.
i. Samples to be taken from approximately 200 seronegative participants at selected sites.
j. Sample to be taken from all participants pre-vaccination on Day 1. At subsequent time points, samples to be taken only from approximately 200 seronegative
participants at selected sites.
k. Participants will be closely observed for a minimum of 1-hour post-vaccination. Any solicited local (at injection site) and systemic AEs, unsolicited AEs, 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 1-hour post-vaccination observation period is complete.
l. 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 for each
vaccination from the time of vaccination until 28 days post-vaccination.
m. 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 first vaccination until completion of the
participant’s last study-related procedure. Suspected AESIs are to be reported from the time of local approval of protocol Amendment 11 onwards (see Section 8.3.1).
For schedule of activities related to AESI, see Section 1.3.8 for more details.
n. Concomitant therapies such as analgesic/antipyretic medications and non-steroidal anti-inflammatory drugs, corticosteroids, antihistamines, and vaccinations must be
recorded from the first dose of study vaccine until 28 days after administration of study vaccine, and thereafter, pre-dose on the day of vaccination and for 28 days
after the subsequent dose of study vaccine. Receipt of a licensed/authorized COVID-19 vaccine must be recorded at any timepoint during the study. The name and
date(s) of administration of the COVID-19 vaccine should be recorded. 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 8.3.1.
o. At Visit 2, in addition to the diary, a ruler and thermometer will be distributed to each participant.
p. If an event is still ongoing on Day 8 or Day 64, the participant should keep the diary after the review and collect information until resolution. The diary should be
reviewed again at the next visit.
q. If a participant develops COVID-19-like signs and symptoms, refer to Section 1.3.6.
AE = adverse event; AESI = adverse event of special interest; COVID-19 = coronavirus disease-2019; d = day(s); ICF = informed consent form; mo = months;
SAE = serious adverse event; PBMC = peripheral blood mononuclear cell; SARS-CoV-2 = severe acute respiratory syndrome coronavirus-2; SoA = schedule of
activities; tel = telephone contact; vac = vaccination

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b. A nasal swab should be collected by a health care professional from the participant at home (using available material for home swabs) or at the study site as soon as
possible and preferably no longer than 2 to 3 days after the onset of symptoms (see Section 8.1.2.3, Prespecified Criteria for Suspected COVID-19). The sample
should be transferred to the study site by an appropriate method as soon as possible after collection.
c. An abbreviated, symptom-directed examination will be performed if determined necessary by the investigator.
d. Heart rate, systolic and diastolic blood pressure, respiratory rate, and body temperature. Heart rate and blood pressure measurements should be taken in the supine
position and preceded by at least 5 minutes of rest. Vital signs measurements are recommended before blood sampling. Body temperature will be measured preferably
via the oral route.
e. Participant should measure body temperature daily and record the highest temperature each day.
f. Participants should complete the SIC starting on the first day they experience symptoms (See Section 10.7, Appendix 7, for an example of the SIC).
g. If a participant has a positive test result for SARS-CoV-2 infection, the participant may be requested to remain at home and not visit the study site. If necessary,
study-site personnel will visit the participant at home. 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. The sponsor recommends to follow these participants until 2 consecutive negative nasal swabs could be obtained.
COVID-19 = coronavirus disease-2019; SARS-CoV-2 = severe acute respiratory syndrome coronavirus-2 SoA = schedule of activities.

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1.3.8. 
Procedures for 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
Hematology3, British Society of Haematology - Expert Haematology Panel10, and the CDC15). 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-platelet factor 4 (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, AESI Day 29
visit will therefore become 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
(see Section 8.3.6).
d. On AESI Day 1 and again on Day 29, whole blood samples will be used for a platelet count (as part of a complete blood count, if applicable) in a local laboratory.
Serum (3.5 mL) and plasma (1.5 mL) samples will be derived from the whole blood samples (7 mL and 3 mL, respectively) for coagulation-related testing in a central
laboratory (see Section 10.2.2, Appendix 2). For the follow-up visit, the volume of blood to be collected may vary depending on the clinical evaluation of the case.
Low platelet counts are to be recorded as a suspected AESI (thrombocytopenia).
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 8.3.6 and Section 10.11, Appendix 11 for further details.
f. Refer to Section 6.8 for collection and recording of concomitant therapies associated with suspected AESIs.
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 1 a 
AESI
Day 29 b
Visit Window  
±7 d
Site to report AESI c 

Blood samples, mL (approx.) d 
15 
15
TTS AESI form e 
- - - - Continuous- - - - -
Concomitant therapies f 
 
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after the subsequent dose of study vaccine. Receipt of a licensed/authorized COVID-19 vaccine must be recorded at any timepoint during the study. The name and
date(s) of administration of the COVID-19 vaccine should be recorded. 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 8.3.1.
Participants who receive COVID-19 vaccines, outside of the study, should be allowed to stay in the study (if willing), however these vaccines should be recorded in
the Concomitant Medications section of the eCRF.
f. If a participant develops COVID-19-like signs and symptoms, refer to Section 1.3.6.
g. An abbreviated, symptom-directed examination will be performed, if determined necessary by the investigator.
AESI = adverse event of special interest; COVID-19 = coronavirus disease-2019; eCRF= electronic case report form; FU = follow-up; ICF = informed consent form;
mo= months; PBMC = peripheral blood mononuclear cell; SAE = serious adverse event; SoA = schedule of activities; vac = vaccination

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** The timings of visits after the ad hoc booster vaccination will be determined relative to the actual day of that vaccination.
a. For those participants who are unable to continue participation in the study up to Booster follow-up visit 2 (Booster FU2), 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 discontinue study vaccination for
reasons listed in Section 7.1, will be offered all safety and immunogenicity follow-up visits according to the current SoA. Participants who wish to withdraw consent
from participation in the study (see Section 7.2) 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).
b. Signing of the ICF should be done before any visit-related procedure.
c. Heart rate, systolic and diastolic blood pressure, respiratory rate, and body temperature. Heart rate and blood pressure measurements should be taken in the supine
position 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.
d. 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 windows (see Section 5.5 and Table 9). 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. In addition, the
investigator must check the criteria for withdrawal of study vaccinations as noted in Section 7.1.
e. For women of childbearing potential in Cohorts 1 and 2 only. Applicable to the US only: Participants who are pregnant may receive ad hoc booster vaccination with
Ad26.COV2.S, if allowed by local regulations and if the investigator considers that the potential benefits outweigh the potential risks to the mother and fetus (see
Section 8.7).
f. 
For Cohort 1a and 3, samples to be taken from approximately 200 seronegative participants at selected sites. For cohort 1b, samples will be collected in all participants
if feasible. For cohorts 2a and 2b, samples will be collected from 27 seronegative participants at selected sites.
g. Whole blood samples will be used for a complete blood count, including platelets, in a local laboratory. Serum 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 Section 10.2.2, Appendix 2). If
the blood and serum samples have been taken within 5 days before vaccination, and platelet results are available, sample collection does not need to be repeated
before vaccination.
h. Participants will be closely observed for a minimum of 15 minutes post-vaccination. Any solicited local (at injection site) and systemic AEs, unsolicited AEs, 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 15 minutes post-vaccination observation period is complete.
i. 
Participants will record solicited symptoms in a diary for 7 days post-vaccination. If an event is still ongoing 7 days post-vaccination, the participant should collect
information until resolution.
j. 
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 for each
vaccination from the time of vaccination until 28 days post-vaccination.
k. 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 first vaccination until completion of the
participant’s last study-related procedure. Suspected AESIs are to be reported from the time of local approval of protocol Amendment 11 onwards (see Section 8.3.1).
For schedule of activities related to AESI, see Section 1.3.8 for more details.
l. 
Concomitant therapies such as analgesic/antipyretic medications and non-steroidal anti-inflammatory drugs, corticosteroids, antihistamines, and vaccinations must be
recorded from the first dose of study vaccine until 28 days after administration of study vaccine, and thereafter, pre-dose on the day of vaccination and for 28 days
after the subsequent dose of study vaccine. Receipt of a licensed/authorized COVID-19 vaccine must be recorded at any timepoint during the study. The name and

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date(s) of administration of the COVID-19 vaccine should be recorded. 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 8.3.1.
m. The participants should keep the diary and bring it to the study site for review of solicited signs and symptoms after vaccination by the investigator at the next visit.
n. If a participant develops COVID-19-like signs and symptoms, refer to Section 1.3.6.
o. Participants receiving the ad hoc booster who did not complete Booster FU2 visit before local approval of Protocol Amendment 16 will attend the Booster FU2 visit
as per the SoA. This will be their last visit and they will be reconsented for updated safety follow-up and removal of Booster FU3 visit.
p. Participants who have already completed Booster FU2 visit before local approval of protocol Amendment 16 will attend on-site last visit within 6 weeks (+7 days)
from approval of protocol amendment 16. The following assessments will be performed at this last visit: reconsenting and safety follow-up.
AE = adverse event; AESI = adverse event of special interest; AHBV = ad hoc booster visit; Cont = continuous; COVID-19 = coronavirus disease-2019; d = day(s);
FU = follow-up; ICF = informed consent form; mo= months; PBMC = peripheral blood mononuclear cell; SAE = serious adverse event; SARS-CoV-2 = severe acute
respiratory syndrome coronavirus-2; SoA = schedule of activities

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2. 
INTRODUCTION
Ad26.COV2.S (also known as Ad26COVS1) is a monovalent vaccine composed of a recombinant,
replication-incompetent adenovirus type 26 (Ad26) vector, constructed to encode the severe acute
respiratory syndrome coronavirus-2 (SARS-CoV-2) virus spike (S) protein, which will be assessed
in this study. This will be the first-in-human (FIH) study for Ad26.COV2.S.
For the most comprehensive nonclinical and clinical information regarding Ad26.COV2.S, refer
to the latest version of the Investigator's Brochure (IB)for Ad26.COV2.S.31
The term “study vaccine” throughout the protocol, refers to Ad26.COV2.S or a placebo as defined
in Section 6.1, Study Vaccinations Administered. 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. The term "participant" throughout the protocol refers to the common term
"subject".
COVID-19 Vaccine and Considerations
Currently, there are no available vaccines for the prevention of coronavirus disease-2019
(COVID-19). The development of a safe and effective COVID-19 vaccine is considered critical to
contain the current outbreak and help prevent future outbreaks.
Although the quantitative correlate of protection against SARS-CoV-2 infection has not yet been
identified, neutralizing antibody responses against the severe acute respiratory syndrome
coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV)
S protein have been associated with protection against experimental SARS-CoV and MERS-CoV
infection in nonclinical models.18,54 Recent studies suggest that SARS-CoV-2 has several
similarities to SARS-CoV based on the full-length genome phylogenetic analysis and the
putatively similar cell entry mechanism and human cell receptor usage.38,40,55 Therefore, a
neutralizing antibody response against the SARS-CoV-2 S protein may also have a protective
effect.
Adenoviral-vectored Vaccines
Recombinant, replication-incompetent adenoviral vectors are attractive candidates for expression
of foreign genes for a number of reasons. The adenoviral genome is well characterized and
comparatively easy to manipulate. Adenoviruses exhibit broad tropism, infecting a variety of
dividing and non-dividing cells. The adenoviral vaccine (AdVac®) vector platform, developed by
Crucell Holland B.V. (now Janssen Vaccines & Prevention B.V.) allows for high-yield production
of replication-incompetent adenovirus vectors, eg, Ad26, with desired inserts. The adenovirus
E1 region is deleted to render the vector replication-incompetent and create space for transgenes,
with viral replication taking place in cells that complement for the E1 deletion in the virus genome.
Ad26 has been selected as a potential vaccine vector because there is substantial nonclinical and
clinical experience with Ad26-based vaccines that demonstrate their capacity to elicit strong
humoral and cellular immune responses and their acceptable safety profile, irrespective of the
antigen transgene (see also Section 2.3.1, Risks Related to Study Participation).

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The immunogenicity profile of adenoviral vectors is illustrated by data obtained following the
immunization of adults with Ad26-vectored human immunodeficiency virus (HIV) vaccines
(Ad26.ENVA.01, Ad26.Mos.HIV, and Ad26.Mos4.HIV), an Ad26-vectored Ebola virus vaccine
(Ad26.ZEBOV), Ad26-vectored respiratory syncytial virus (RSV) vaccines (Ad26.RSV.FA2 and
Ad26.RSV.preF), an Ad26-vectored Zika virus vaccine (Ad26.ZIKV.001), and an Ad26-vectored
malaria vaccine (Ad26.CS.01). Antigen-specific antibody responses are observed in almost all
participants after one dose, in both naïve and pre-immune individuals (RSV). These antibodies
may persist for a year or more (RSV) after a single dose in pre-immune participants. They have
functional properties of neutralization (RSV, Zika), Fc-mediated antibody-dependent cellular
cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) (HIV, Malaria).
Furthermore, these data support an immunogenicity profile with emphasis on T-helper (Th)1
responses and demonstrate predominantly interferon gamma (IFN-γ) and tumor necrosis factor
alpha (TNF-α) production in CD4+ and CD8+ T cells.5,32,42
Ad26.COV2.S Candidate Vaccine
The aim of the COVID-19 vaccine clinical development program is to develop a safe and
efficacious vaccine for the prevention of COVID-19. The initial effort will be to rapidly
demonstrate safety and immunogenicity in adults aged ≤55 years, in order to initiate an efficacy
trial in this age group as soon as possible, and to evaluate safety and immunogenicity in older
adults aged ≥65 years. The candidate vaccine to be assessed in this study is Ad26.COV2.S, which
is a recombinant, replication-incompetent Ad26 encoding a stabilized variant of the SARS-CoV-2
S protein. The parental S protein sequence was derived from a SARS-CoV-2 clinical isolate
(Wuhan, 2019, whole genome sequence NC_045512). The selection of antigen was based on
previous work on the SARS-CoV and MERS-CoV candidate vaccines.18,25,43 The protein is the
major surface protein on coronaviruses and is responsible for binding to the host cell receptor and
mediating the fusion of host and viral membranes, thereby facilitating virus entry into the cell.56
2.1. 
Study Rationale
SARS-CoV-2 is an enveloped, positive-sense, single-stranded ribonucleic acid (RNA)
betacoronavirus.21,53 It was first identified following reports of a cluster of acute respiratory illness
cases in Wuhan, Hubei Province, China in December 2019.39 Epidemiological investigations
indicated that the majority of early cases were linked to a seafood market, with patients infected
through zoonotic or environmental exposure, followed by the subsequent spread of infection by
human-to-human transmission among close contacts.39 Genomic sequencing was performed on
bronchoalveolar lavage fluid samples collected from patients with viral pneumonia admitted to
hospitals in Wuhan, which identified a novel RNA virus from the family Coronaviridae.40,53
Phylogenetic analysis of the complete viral genome revealed that the virus, SARS-CoV-2, is part
of the subgenus Sarbecovirus of the genus Betacoronavirus, and is most closely related
(approximately 88% identity) to a group of SARS-CoV-like coronaviruses previously sampled
from bats in China.40
SARS-CoV-2 has spread rapidly and globally since its emergence. The World Health Organization
(WHO) declared that the outbreak constituted a public health emergency of international concern

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on January 30, 2020, and declared the outbreak to be a pandemic on March 11, 2020.50,51 As of
April 29, 2020, approximately 3,170,000 cases of COVID-19 had been reported.33
Symptoms of infection may appear from 2 to 14 days following exposure, with the clinical
manifestations ranging from mild symptoms to severe illness or death.12 Severe clinical
presentations have been reported in as many as 20 25% of laboratory-confirmed cases.24 In a study
of 99 patients in a single center in Wuhan with SARS-CoV-2 infection confirmed by real-time
reverse-transcriptase polymerase chain reaction (RT-PCR), the most commonly reported clinical
manifestations were fever (83%), cough (82%), shortness of breath (31%), and muscle aches
(11%).17 In chest x-rays and computed tomographic (CT) scans, 75% of patients showed bilateral
pneumonia and 14% of patients showed diffuse mottling and ground-glass opacities. In a further
study of 138 patients with novel coronavirus-induced pneumonia in a single center in Wuhan,
common symptoms included fever (98.6%), fatigue (69.6%), and dry cough (59.4%).47
Lymphopenia occurred in 70.3% of patients, and chest CT scans showed bilateral patchy shadows
or ground-glass opacities in the lungs of all patients. Thirty-six patients (26%) were transferred to
the intensive care unit because of complications, including acute respiratory distress syndrome,
arrhythmia, and shock.
At present, it appears that individuals aged 65 years or older, especially those with comorbid
diseases, are subject to the highest incidence of morbidity and mortality.27In contrast, a study of
2,143 children aged <18 years in China with laboratory-confirmed (34.1%) or suspected (65.9%)
COVID-19 indicated that the clinical manifestations of the disease may be less severe in children
than adults, with approximately 94% of cases being asymptomatic, mild, or moderate.23 However,
young children, particularly infants, were susceptible to severe disease, with the highest proportion
of severe and critical cases by age group reported for children aged <1 year (10.6% of cases in this
age group). Consistent with these findings was a study of 149,082 COVID-19 cases reported in
the US.15 Although persons aged <18 years account for 22% of the US population, only 1.7% of
these cases occurred in this age group. Furthermore, relatively few pediatric COVID-19 cases were
hospitalized indicating that COVID-19 might have a mild course among younger patients.
Hospitalization was most common among pediatric patients aged <1 year and those with
underlying conditions.
The identification of SARS-CoV-2 follows the emergence of 2 other novel betacoronaviruses
capable of causing severe human disease over the past 18 years: SARS-CoV and MERS-CoV,
which have nucleotide sequence identity with SARS-CoV-2 of approximately 79% and 50%,
respectively.40 The first known cases of severe acute respiratory syndrome (SARS) occurred in
Southern China in November 2002.52 The etiological agent, SARS-CoV, is believed to be an
animal virus that crossed the species barrier to humans followed by human-to-human transmission,
leading to SARS cases in >25 countries. The MERS-CoV was isolated from a patient in Saudi
Arabia who died of severe pneumonia and multi-organ failure in June 2012.56 MERS-CoV is
considered to be a zoonotic virus capable of non-sustained human-to-human transmission. Since
2012, sporadic cases and community and health-care-associated clusters of infected individuals
have been reported in the Middle East.

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Patients with SARS or Middle East respiratory syndrome (MERS) present with various clinical
features, ranging from asymptomatic or mild respiratory illness to fulminant severe acute
respiratory disease with extrapulmonary manifestations.16,56 Both diseases have predominantly
respiratory manifestations, but extrapulmonary features may occur in severe cases. By July 2003,
the international spread of SARS-CoV resulted in 8,098 SARS cases and 774 deaths (case-fatality
rate: 10%) with substantial social, economic and health service disruption in some affected
countries.16,52 The case-fatality rate of MERS-CoV infections is estimated to be 35%.16
Therefore, while the understanding of the epidemiology and clinical spectrum of COVID-19 is
still evolving during the ongoing pandemic, the current knowledge of the disease burden highlights
the urgent medical need for a prophylactic vaccine.
2.2. 
Background
Nonclinical Pharmacology
Nonclinical studies were performed to test the immunogenicity of different vaccine candidates,
leading to the selection of the current vaccine for this Phase 1/2a clinical study. Details of the
nonclinical immunogenicity of Ad26.COV2.S are provided in the IB.31
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 HIV vaccine,
Ad26.ENVA.01, and an Ad26-based RSV vaccine, Ad26.RSV.preF. In the available
biodistribution studies, the Ad26 vector did not widely distribute following IM administration in
rabbits. Ad26 vector deoxyribonucleic acid (DNA) was primarily detected at the site of injection,
draining lymph nodes and (to a lesser extent) the spleen. Clearance of the Ad26 vector from the
tissues was observed. Both Ad26 vectors showed a comparable biodistribution profile despite
carrying different antigen transgenes. These data further indicate that the Ad26 vector does not
replicate and/or persist in the tissues following IM injection. These platform data are considered
sufficient to inform on the biodistribution profile of Ad26.COV2.S  for which the same
Ad26 vector backbone is used.
Toxicology
The sponsor has significant nonclinical experience with Ad26-vectored vaccines using various
transgenes encoding HIV, RSV, Ebola virus, filovirus, human papilloma virus, Zika, influenza
(universal flu [Uniflu]), and malaria antigens. To date, more than 10 Good Laboratory Practice
(GLP) combined repeated dose toxicology and local tolerance studies have been performed in
rabbits (and 1 study in rats), testing the nonclinical safety of various homologous and heterologous
regimens with Ad26-based vaccines at full human doses up to 1.2×1011 virus particles (vp). No
adverse effects have been observed in these studies. The vaccine-related effects observed were
similar across studies, considered to be reflective of a physiological response to the vaccines
administered, and seem to be independent of the antigen transgene. Overall, there were no safety

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signals detected in any of the available GLP toxicology studies with Ad26-based vaccines up to
the highest dose tested (1.2×1011 vp).
Clinical Studies
At the time of initial protocol writing, no clinical data with the Ad26.COV2.S vaccine were
available. Recent data generated from the ongoing clinical studies VAC31518COV1001,
VAC31518COV1002, VAC31518COV2001 and VAC31518COV3001, demonstrated that a
single dose of Ad26.COV2.S has an acceptable safety and reactogenicity profile and is sufficient
to elicit SARS-CoV-2 neutralizing antibodies in adults ≥18 years of age, including adults
≥60 years of age.
Clinical Safety Experience With Ad26-based Vaccines
As described above, replication-incompetent Ad26 is being used as a vector in the development of
vaccine candidates against diseases such as malaria, RSV, HIV, Ebola virus, and filovirus.
As of 27 March 2020, Ad26-based vaccines had been administered to approximately  67,000
participants in ongoing and completed studies, including more than 50,000 participants in an
ongoing 
Ebola 
vaccine 
study 
in 
the 
Democratic 
Republic 
of the 
Congo
(VAC52150EBL3008/DRC-EB-001) and an ongoing immunization campaign in  Rwanda
(UMURINZI Ebola Vaccine Program campaign).
The sponsor’s clinical AdVac® safety database report (V5.0, dated 10 April 2020, cutoff date
20 December 2019) describes integrated safety data from 26 completed clinical studies using
Ad26-based vaccines for which the database was locked for final analysis. In these 26 studies,
4,224 adult participants were vaccinated with an Ad26-based vaccine and 938 adult participants
received a placebo. A total of 6,004 Ad26-based vaccine doses were administered to adults. Most
adult participants (3,557 out of 4,224; 84.2%) received Ad26-based vaccine at a dose level of
5×1010 vp, while 284 adult participants (6.7%) received Ad26-based vaccine at the 1×1011 vp dose
level (the highest dose level tested).
As of 27 March 2020, more than 62,000 participants were enrolled in ongoing studies. However,
their safety data were not included in the AdVac® safety database report V5.0 because the studies
were still blinded, the studies were unblinded but their analysis took place after the AdVac® safety
database report cutoff date, or the study data were not integrated in the Ad26-based vaccine
database used for the report.
Overall, the Ad26-based vaccines were well tolerated irrespective of the antigen transgene, without
significant safety issues identified to date. See Section 2.3.1, Risks Related to Study Participation
for a summary of data from the AdVac® safety database report.

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Ad26-based Vaccines in Adults Aged 60 Years and Older
In the RSV vaccine clinical development program, Ad26.RSV.preF has been evaluated in studies
with participants aged ≥60 years, including the Phase 1 studies VAC18193RSV1003 and
VAC18193RSV1005, 
Phase 
1/2a 
study 
VAC18193RSV1004, 
Phase 
2a 
study
VAC18193RSV2003, and Phase 2b study VAC18193RSV2001. Up to a cutoff date of
27October 2019, more than 3,600 participants aged ≥60 years received an Ad26.RSV.preF-based
regimen  in completed and ongoing studies. An acceptable safety and tolerability profile in
participants aged ≥60 years has been reported for the Ad26.RSV.preF-based regimens assessed in
these studies, and no safety concerns have been raised to date.
T-helper (Th)1/Th2 Profile of Ad26-based Vaccines in Clinical Studies
In the 1960s, a formalin-inactivated (FI) RSV vaccine was associated with enhanced respiratory
disease (ERD) in young children, characterized by an increased rate of RSV-mediated, severe
lower respiratory tract infection in the vaccinated individuals compared with the control
group.20,26,34,35 Although the mechanisms for ERD are not fully understood, it is thought that
FI-RSV may have: 1) failed to induce adequate neutralizing antibody titers; 2) led to an
overproduction of binding antibodies promoting immune complex deposition and hypersensitivity
reactions; 3) failed to induce adequate numbers of memory CD8+ T cells important for viral
clearance; and 4) induced a Th2-skewed type T-cell response.44 Vaccine-induced ERD has also
been described for SARS-CoV and MERS-CoV in animal models.45
The immunogenicity profile of adenoviral vectors, with particular emphasis on Th1 responses, is
illustrated by data obtained from immunization of adults with Ad26-vectored HIV vaccines
(Ad26.ENVA.01 and Ad26.Mos.HIV) and Ad26-vectored Ebola vaccine (Ad26.ZEBOV). These
data show predominantly IFNγ and TNFα production in CD4+ and CD8+ T cells.4,5,6 In the RSV
vaccine clinical development program, Ad26.RSV.preF is being evaluated in healthy
RSV-seropositive toddlers aged 12 to 24 months (Phase 1/2a study VAC18194RSV2001). Safety
data from the primary analysis at 28 days after the second study vaccination revealed no safety
concerns following Ad26.RSV.preF dosing at 5×1010 vp or a placebo. The immunogenicity of a
single immunization with Ad26.RSV.preF in RSV-seropositive toddlers aged 12 to 24 months,
including favorable Th1 bias, was confirmed. In a further study of Ad26.RSV.preF in
RSV-seronegative toddlers aged 12 to 24 months (Phase 1/2a study VAC18194RSV2002), initial
safety data have not revealed concerns after Ad26.RSV.preF dosing.

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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 IB.31
2.3.1. 
Risks Related to Study Participation
This clinical study is a FIH study for Ad26.COV2.S. 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 protocol Amendment 10 writing, immunogenicity and safety data were available
from 
the 
ongoing 
clinical 
studies 
VAC31518COV1001, 
VAC31518COV1002,
VAC31518COV2001 and VAC31518COV3001 (Section 2.2). For emerging clinical data and the
most comprehensive nonclinical information regarding Ad26.COV2.S, refer to the latest version
of the IB and its addenda (if applicable).31
Sites should advice 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. This is based on emerging data
from Cohorts 1a and 3 that became available at the time of writing of protocol Amendment 6.
Anaphylaxis is considered an important identified risk for Ad26.COV2.S. Individuals should be
observed by a healthcare provider after vaccination per protocol requirements. Refer to the latest
version of the IB and its addenda (if applicable) for further details.
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. Reports include severe cases of venous thrombosis at unusual
sites such as cerebral venous sinus thrombosis (CVST), splanchnic vein thrombosis, and arterial
thrombosis, in combination with thrombocytopenia. These cases occurred within the first 3 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, and 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 Hematology3, British Society of
Haematology - Expert Haematology Panel10, and the CDC14). 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. Refer to the latest version of the IB and its addenda (if applicable)
for further details. Due to the possibility of the occurrence of TTS after vaccination with

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Ad26.COV2.S, additional reporting and data collection procedures have been included in the study
for thrombotic events, thrombocytopenia, and TTS (see Section 8.3.6), which  may  facilitate
diagnosis and clinical management of the event.
Guillain-Barré syndrome (GBS) is considered an important identified risk for Ad26.COV2.S.
Cases of GBS following use of the Ad26.COV2.S vaccine have been reported during the 42 days
following vaccination. Investigators should be alert to GBS signs and symptoms to facilitate
diagnosis, to initiate adequate supportive care and treatment, and to rule out other causes. Refer to
the latest version of the IB and its addenda (if applicable) for further details.
Risks Related to Ad26.COV2.S Administration after Previous Vaccination with
Ad26.COV2.S
Preliminary safety data of an Ad26.COV2.S booster (5×1010 vp, 2.5×1010 vp, or 1×1010 vp)
administered ≥6 months post-primary single-dose Ad26.COV2.S (5×1010 vp) vaccination are
available from 244 participants (dose-level blinded data). The data indicate that the safety and
reactogenicity of a second Ad26.COV2.S dose is acceptable and in line with the safety and
reactogenicity observed after the first Ad26.COV2.S dose. There is no indication of increased
reactogenicity upon administration of a second dose of Ad26.COV2.S and no safety concerns have
been observed.
In addition, the primary analysis of study VAC31518COV3009 indicated that the safety profile of
the vaccine remained consistent and was generally well-tolerated when administered as a second
dose according to the study schedule (vaccinations at Day 1 and Day 57).a
Risks Related to Ad26.COV2.S Administration after Previous Vaccination with a Different
COVID-19 Vaccine
To date, limited clinical data have not shown any safety issues when the Ad26.COV2.S vaccine is
administered after previous vaccination or booster vaccination with a different COVID-19 vaccine.
The overall benefit-risk balance assessment is ongoing.
Risks Related to Adenoviral-vectored Vaccines
The clinical AdVac® safety database (report version 5.0, dated 10 April 2020, cutoff date
20 December 2019) contains pooled safety data from 26 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
a Johnson & Johnson News Release. Johnson & Johnson Announces Real-World Evidence and Phase 3 Data
Confirming Strong and Long-Lasting Protection of Single-Shot COVID-19 Vaccine in the U.S. Press Release,
New Brunswick, N.J., 21 September 2021. Available at:
https://www.janssen.com/emea/sites/www janssen com emea/files/johnson johnson announces real-
world evidence and phase 3 data confirming strong and long-lasting prote.pdf. Accessed on 28 September
2021.

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Ad26.RSV.preF (RSV; 6 studies), and Ad26.Filo (filovirus; 1 study). In these studies, 4,224 adult
participants and 650 children received at least 1 vaccination with an Ad26-based vaccine. The
AdVac® safety database report includes data only from studies for which the database has been
locked for the final analysis; therefore, of the studies including an Ad26.RSV.preF-based regimen
mentioned in Section 2.2, Background, only data for approximately 230 participants aged
≥60 years from studies VAC18193RSV1003, VAC18193RSV1005, and VAC18193RSV2003
were included.
Overall, the Ad26-based vaccines were well tolerated, without significant safety issues identified.
The majority of solicited local and systemic adverse events (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 (56.9% of
Ad26 participants, compared with 22.5% of placebo participants). All other solicited local AEs
were experienced by less than 25% of adult participants. The most frequently experienced solicited
local AE in children was injection site pain, reported in 13.9% of children aged 1-3 years, 29.8%
of children aged 4-11 years, and 24.8% of children aged 12-17 years after vaccination with an
Ad26-based vaccine. For placebo, these percentages were 29.2% in children aged 4-11 years and
14.3% in children aged 12-17 years. No children aged 1-3 years have received placebo.
Severe injection site pain was experienced by 1.0% of adult Ad26 participants and 0.8% of children
aged 4-11 years. No children in the other 2 age groups and no placebo participants experienced
severe injection site pain.
There was a trend towards 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).
The most frequently reported solicited systemic AEs (ie, reported in more than 30% of
participants) for adult Ad26 participants were malaise (53.8%), fatigue (48.3%), headache
(45.7%), and myalgia (38.3%), all of which were more frequent for Ad26 participants compared
with placebo (36.4%, 30.7%, 30.0%, and 17.7% of placebo participants, respectively). Most of
these events were considered related to the study vaccine. Pyrexia (9.9%) and vaccine-related
pyrexia (9.0%) were also reported more frequently after administration of an Ad26-based vaccine
compared with placebo (3.5% and 2.9%, respectively).

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Solicited systemic AEs reported in ≥10% of children aged 1-3 years were decreased appetite
(13.9%), decreased activity (13.2%), pyrexia (11.1%), and irritability (10.4%). The most
frequently reported solicited systemic AEs in children aged 4-11 years (reported in ≥15% of
Ad26 participants) were headache (23.6%; no data are available for the placebo arm in this age
group), and decreased activity (18.5%) and irritability (17.6%), which were both reported in 4.2%
(N 1) of placebo participants. The most frequently reported solicited systemic AEs in children
aged 12-17 years (reported in ≥15% of Ad26 participants) were headache (34.6%) and fatigue
(24.0%), compared to 33.3% and 19.0% of placebo participants, respectively. Most of the
frequently experienced solicited systemic AEs in children were considered related to the study
vaccine.
The majority of solicited systemic AEs were of mild or moderate severity. For adults, 6.5% of
Ad26 participants and 2.0% of placebo participants reported severe solicited systemic AEs, mostly
malaise and fatigue. Other severe solicited systemic AEs were reported in less than 3% of adult
Ad26 participants.
There was a trend towards an increase in the frequency of solicited systemic AEs with an increase
in Ad26 dose (35.3% at the 0.8×1010 vp dose level, 49.3% at the 2×1010 vp dose level, 64.5% at
the 5×1010 vp dose level, and 70.4% at the 1×1011 vp dose level). The frequency of severe solicited
systemic AEs also tended to increase with higher Ad26 dose, ie, 1.3% of participants at the
0.8×1010 vp and the 2×1010 vp dose level, 5.3% of participants at the 5×1010 vp dose level, and
14.4% of participants at the 1×1011  vp dose level. 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).
The most frequently reported unsolicited AE in adult Ad26 participants was upper respiratory tract
infection (5.3% vs. 7.0% in adult placebo participants). The most frequently reported unsolicited
AEs considered related to the vaccine were neutropenia (1.0% of adult Ad26 participants vs. 0.5%
of adult placebo participants) and dizziness (0.7% vs. 0.2%, respectively).
In children for Ad26, the most frequently reported unsolicited AE was malaria,a reported in 36.8%
of children aged 1-3 years, in 19.0% of children aged 4-11 years, and in 10.6% of children aged
12-17 years. One child in the 12-17years group (4.8%) experienced malaria after placebo
vaccination. There were no other children in the placebo groups who experienced malaria. The
most frequently reported related unsolicited AE was hypernatremia (1.6% of children aged
4-11 years [vs. 4.2% with placebo] and 2.4% of children aged 12-17 years [vs. 4.8% with
placebo]). No AEs in children aged 1-3 years were considered related to the vaccine.
aThis was expected as the pediatric studies were conducted in malaria-endemic regions. The imbalance in the
frequency of malaria between Ad26 participants and placebo participants can largely be explained by the fact that the
active control group of study VAC52150EBL3001 was not included in the pooling.

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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 a 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 6.8.
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 each vaccination, participants will remain at the study site for at least 15 minutes to 1 hour
depending on the vaccination being administered (see SoAs for details) 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 foetus or on nursing baby is unknown.
Women of childbearing potential will be required to agree to practicing a highly effective method
of contraception and agree to remain on such a method of contraception from signing the informed
consent form (ICF) until 3 months after the last dose of study vaccine (See Section 5.1, Inclusion
Criteria). Women who are pregnant or breast-feeding will be excluded from the study. Women
who become pregnant while enrolled in the study will not receive further study vaccine but may
continue other study procedures at the discretion of the investigator (see Section 7.1,
Discontinuation of Study Vaccination).
Applicable to the US only: Following local approval of protocol Amendment 15, participants who
are pregnant may receive ad hoc booster vaccination with Ad26.COV2.S, if allowed by local
regulations and if the investigator considers that the potential benefits outweigh the potential risks
to the mother and fetus (See Section 8.7).
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.

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Risks from Collection of Nasal Swabs
Collection of a nasal swab may cause a nosebleed.
Theoretical Risk of Enhanced Disease
Vaccine-associated enhanced disease has been described for SARS-CoV and MERS-CoV in some
animal models,2,8,22,29,30 and is associated with non-neutralizing antibodies and a Th2-skewed
immune response. In contrast, the Ad26-based vaccines have been shown to induce a clear
Th1-skewed immune response and generate potent neutralizing antibody responses in both humans
and animal models (see Section 2.2). Participants in the present study will be informed of the
theoretical risk of disease enhancement in the ICF. The initial cohort in this study (Cohort 1a) will
include healthy adults aged ≥18 to ≤55 years of age. As a risk mitigation strategy, all participants
in the study will be passively and actively monitored for acquisition of molecularly confirmed
COVID-19 (see Section 4.1, Section 8.1.2, and Section 10.8, Appendix 8, Case Definitions for
COVID-19). This active and passive surveillance system for detection of COVID-19, with
influenza serving as a control to monitor the effectiveness of the surveillance system, will ensure
rapid identification of COVID-19 and will ensure that appropriate treatment procedures can be
initiated to reduce the risk of enhanced disease if it should occur. Selected members of the
statistical programming and the statistics group will receive individual level unblinded data
pertaining to study VAC31518COV1001 when unblinding at the participant level is required. They
will monitor the number and severity of molecularly confirmed COVID-19 cases in the
Ad26.COV2.S and placebo groups to identify an imbalance between groups if it occurs. They will
inform the Data Review Committee (DRC) as soon as an imbalance between groups is detected.
A prespecified threshold (imbalance above a certain percentage and/or number of cases) that will
trigger notification of the DRC will be described in the Statistical Analysis Plan.
Risks from Optional Lymph Node Aspiration
Most common risks and discomforts associated with fine needle LNA include swelling, pain,
tenderness, bruising and soreness at the procedure site. These symptoms usually do not last long
(1 to 2 days). Rare side effects include developing an infection, or damage to surrounding nerves
or blood vessels.
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.

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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. The overall benefit and risk balance for individual
participants is ongoing.
Preliminary  immunogenicity and safety data for a Ad26.COV2.S booster dose (5×1010 vp) at
≥6 months post-primary single-dose Ad26.COV2.S administration and efficacy data for a 2nd dose
of Ad26.COV2.S 2-3 months post-primary single-dose Ad26.COV2.S administration support a
favorable benefit-risk profile in participants who received a single dose of Ad26.COV2.S.
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:
 Only participants who meet all inclusion criteria and none of the exclusion criteria (specified in
Section 5, Study Population) will be allowed to participate in this study. The selection criteria
include adequate provisions to minimize the risk and 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 (SoA)
 After each vaccination, participants will remain at the study site for at least 15 minutes to
1 hour depending on the vaccination being administered (see SoAs for details) 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 a diary to
document solicited signs and symptoms. Details are provided in Section 8.2, Safety
Assessments and Section 8.3, Adverse Events, Serious Adverse Events, and Other Safety
Reporting.
 The investigator or the designee will document unsolicited AEs as indicated in Section 8.2,
Safety Assessments; Section 8.3, Adverse Events, Serious Adverse Events, and Other
Safety Reporting; and Section 10.4, Appendix 4, Adverse Events, Serious Adverse Events,
Product Quality Complaints, and Other Safety Reporting: Definitions and Procedures for
Recording, Evaluating, Follow-Up, and Reporting.
 From the time of local approval of protocol Amendment 11 onwards, TTS is considered an
adverse event of special interest (AESI) (Section 8.3.6). Suspected AESIs (thrombotic
events and/or thrombocytopenia [defined as platelet count below 150,000/µL9]) must be
reported to the sponsor within 24 hours of awareness. Suspected AESIs will be followed
up as described in the Schedule of Activities in Section 1.3.8.

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 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.
 AEs related to the optional LNA procedure will be monitored.
 Several safety measures are included in this protocol to minimize the potential risk to
participants, including the following:
 Eligibility will be reassessed pre-vaccination on Day 1.
 Clinical laboratory assessment (blood and urine) will be performed at screening,
pre-vaccination at each day of vaccination (pre-dose 1 and pre-dose 2), and at the Day 7 post
vaccination visit for the primary regimens (Day 8 and Day 64). Details are provided in
Section 10.2, Appendix 2, Clinical Laboratory Tests.
 In Cohorts 1a and 3, five sentinel participants will be evaluated for safety before extending
enrollment in each cohort. The sentinel participants will be vaccinated at least 1 hour apart.
A telephone call will be made to each of the sentinel participants 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). Randomization and vaccination of additional
participants will be halted until this 24-hour sentinel safety evaluation is completed. Refer
to Section 4.1, Overall Design, for further details. For Cohorts 1a and 3, the second
vaccination will be administered to the sentinel participants first. The PI and SRP will also
review blinded safety data from the 5 sentinel participants following the second vaccination
but randomization and vaccination of participants will not be halted during this review.
 For Cohorts 1a and 3, an internal DRC will review blindeda safety data following
administration of the first vaccination to the first 15 participants. Refer to Section 4.1,
Overall Design, for further details.
 There are prespecified rules for all participants, that if met would result in pausing of further
vaccinations, preventing exposure of new participants to study vaccine until the DRC
reviews all safety data (see Committees Structure in Section 10.3, Appendix 3, Regulatory,
Ethical, and Study Oversight Considerations).
 Study vaccinations will be discontinued in participants for the reasons included in Section 7,
Discontinuation of Study Vaccination and Participant Discontinuation/Withdrawal.
 Contraindications to vaccination are included in Section 5.5, Criteria for Temporarily
Delaying Administration of Study Vaccination.
a The DRC will review blinded data first but may review unblinded data if deemed necessary.

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3. 
OBJECTIVES AND ENDPOINTS
A description of study cohorts is provided in Section 4.1.
Objectives 
Endpoints
Primary
 
To assess the safety and reactogenicity 
of Ad26.COV2.S  at 2 dose levels,
5×1010 vp and 1×1011 vp, administered
IM as a single-dose or 2-dose schedule
in healthy adults aged ≥18 to ≤55 years 
and in adults aged ≥65 years in good 
health 
with 
or 
without 
stable
underlying conditions.
All participants* in Cohorts 1, 2, and 3:
 
Solicited local and systemic AEs for 7 days after each
vaccination in the primary regimen
 
Unsolicited AEs for 28 days after each vaccination in
the primary regimen
For the primary endpoint: Serious adverse events (SAEs)
and adverse events of special interest (AESIs)from the first
vaccination until 2 years after the second vaccination for
Cohorts 1 and 3, and until 6 months after the primary
regimen for Cohort 2
Secondary
 
To assess the humoral and cellular 
immune response to Ad26.COV2.S
Humoral Immune Response
All participants* in Cohorts 1, 2, and 3:
 
SARS-CoV-2 
neutralization: 
SARS-CoV-2
neutralizing titers in serum measured by a virus
neutralization assay (VNA  [wild-type virus and/or
pseudovirion expressing S protein])
 
SARS-CoV-2-binding 
antibodies 
measured 
by
enzyme-linked 
immunosorbent 
assay 
(ELISA):
Analysis of antibodies binding to the SARS-CoV-2
S protein.
Cellular Immune Response
A subset of participants* in Cohorts 1, 2, and 3:
 
Th1 and Th2 immune responses as assessed by flow
cytometry after SARS-CoV-2 S protein peptide
stimulation of peripheral blood mononuclear cells
(PBMCs) and intracellular staining [ICS] including
CD4+/CD8+, IFNγ, interleukin [IL] 2, TNFα, IL-4,
IL-5, IL-13, and/or other Th1/Th2 markers.
Exploratory
 
To further assess the safety and 
reactogenicity of Ad26.COV2.S  at a
dose level of 5×1010 vp administered
IM as a single booster vaccination at
6 months, 12 months, or 24 months 
after the primary regimen in healthy 
adults aged ≥18 to ≤55 years
All participants* in Cohort 2:
 
Solicited local and systemic AEs for 7 days after each
booster vaccination time point
 
Unsolicited AEs for 28 days after each booster
vaccination time point
 
SAEs and AESIs until the end of the study
 
Following Amendment 16, booster vaccination at
24 months will not be performed

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Objectives 
Endpoints
 
To further assess the humoral and
cellular 
immune 
response 
to
Ad26.COV2.S in various regimens
Humoral Immune Response:
Exploratory analyses may include the following assays for
a subset of participants* in Cohorts 1 and 3:
 
SARS-CoV-2 neutralization as assessed by alternative
SARS-CoV-2 neutralization assays (different from the
VNA used for the secondary endpoint).
 
Analysis of antibodies binding to SARS-CoV-2
S protein and the receptor-binding domain (RBD) of
the SARS-CoV-2 S protein by Meso Scale Discovery
(MSD) assay.
 
Adenovirus neutralization.
 
Functional and molecular antibody characterization
(eg, avidity, Fc receptor interaction, antibody
isotyping).
 
Epitope-specificity characterization for B- and T-cells.
 
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 neutralizing and binding antibodies
against emerging SARS-CoV-2 virus lineages.
Cellular Immune Response:
Exploratory analyses may include the following assays for
a subset of participants* in Cohorts 1, 2, and 3:
 
Single IFNγ and IL-4 enzyme-linked immunospot
(ELISpot) assay after stimulation of PBMCs with
SARS-CoV-2 S protein peptides.
 
Analysis of gene expression in cells stimulated with
SARS-CoV-2 S protein  peptides, or in unstimulated
cells (ex vivo).
 
Cytokine 
profiling: 
Analysis 
of 
cytokines,
chemokines, and other proteins of the innate or
adaptive immune response in cells stimulated with
SARS-CoV-2 S protein  peptides, or in unstimulated
cells (ex vivo).
A subset of participants* in Cohort 2 only:
 
Analysis of the phenotype of antigen-specific T and
B cells, assessed by single cell analysis (on frozen or
Smart tube-isolated PBMCs).

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Objectives 
Endpoints
 
To perform a preliminary analysis of
vaccine efficacy in the prevention of
molecularly confirmed COVID-19
 
The number of molecularly confirmed COVID-19
cases in Ad26.COV2.S  versus placebo recipients in
the overall study
 
To perform preliminary analysis of
vaccine efficacy in the prevention of
asymptomatic SARS-CoV-2 infection
 
The number of participants with positive non-S protein
ELISA (eg, N ELISA), if such an assay can be
developed, in the Ad26.COV2.S and placebo groups
 
To 
evaluate 
the 
presence 
of
SARS-CoV-2 
infection 
and 
the
presence and severity of COVID-19
signs and symptoms
 
Presence and severity of COVID-19 signs and
symptoms
 
Confirmation of SARS-CoV-2 infection by molecular
testing
 
To examine the immune response in
vaccinated individuals after natural
infection and to explore 
other
potentially informative biomarkers
(eg, those associated with more severe
disease)
 
Confirmation of SARS-CoV-2 infection by molecular
testing
 
SARS-CoV-2 neutralizing titers in serum measured by
a VNA (wild-type virus and/or pseudovirion
expressing S protein)
 
SARS-CoV-2-binding 
antibodies 
measured 
by
ELISA: Analysis of antibodies binding to the
SARS-CoV-2 S protein
 
Functional and molecular antibody characterization
 
Analysis of gene expression by RNA transcript
profiling
 
To explore the immune responses in
fine needle LNA in Cohort 1b
participants
 
Magnitude, phenotype, antigen specificity and subset
distribution of immune and stromal cells in lymph
nodes and peripheral blood
 
Molecular network analysis of functional regulation of
T- and B-cell subsets in lymph nodes
* Excluding Group 5 (placebo only) participants who received a single dose of 5×1010 vp Ad26.COV2.S at the time
of unblinding, after EUA or approval in any country and local approval of protocol Amendment 10.
HYPOTHESIS
No formal hypothesis testing is planned. Descriptive statistics will be used to summarize the safety,
reactogenicity, and immunogenicity endpoints (see Section 9.4, Statistical Analyses).

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Ad Hoc Booster Vaccination
Following local approval of protocol Amendment 15, the following objectives are applicable for
all eligible participants (see Section 8.7) that consent to receive a single ad hoc booster dose of
5x1010 vpAd26.COV2.S. The ad hoc booster vaccination will be provided to participants who have
previously received 1 or more doses of any COVID-19 vaccine (ie, the Ad26.COV2.S vaccine, an
mRNA vaccine and/or another COVID 19 vaccine authorized for primary vaccination including
protein, inactivated, and adenovector-based vaccines) if the last vaccination was ≥6 months ago.
Objectives 
Endpoints
Primary
 
To assess the safety and reactogenicity of
Ad26.COV2.S at the 5×1010 vp dose level
administered as ad hoc booster vaccination in
healthy adults aged ≥18 to ≤55 years and in
adults aged ≥65 years in good health with or
without stable underlying conditions.
 
Solicited local and systemic AEs for 7days
after ad hoc booster vaccination.
 
Unsolicited AEs for 28 days after ad hoc
booster vaccination.
 
SAEs and AESIs from ad hoc booster
vaccination until the end of the study.
Secondary
 
To obtain samples to evaluate potential
thromboembolic events following ad hoc
booster vaccination  by obtaining platelet
counts and sufficient extra sera for specialized
studies at the day of booster vaccination and
28 days later.
 
Platelet count on the day of ad hoc booster
vaccination and 28 days after ad hoc booster
vaccination. Additional analysis on collected
sera 
samples 
in 
case 
of potential
thromboembolic events.
Exploratory
 
To assess the humoral and cellular immune
response to Ad26.COV2.S ad hoc booster
dose.
Humoral immune response assessment may
include, and is not limited to:
 
SARS-CoV-2 neutralization: SARS-CoV-2
neutralizing titers in serum measured by a
virus neutralization assay (VNA [wild-type
virus 
and/or 
pseudovirion 
expressing
S protein]) against the original strain and
emerging variants.
 
SARS-CoV-2-binding antibodies measured
by ELISA: Analysis of antibodies binding to
the SARS-CoV-2 S and RBD protein from the
original strain and emerging variants.
 
Adenovirus neutralization.
 
Functional 
and 
molecular 
antibody
characterization (eg, avidity, Fc receptor
interaction, antibody isotyping).
 
Epitope-specificity characterization for B-
and T cells.
 
Passive transfer: Analysis of immune
mediators correlating with protection against

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Objectives 
Endpoints
experimental SARS-CoV-2 challenge in a
suitable animal model.
In a subset of participants, cellular immune
response assessment may include, and is not
limited to:
 
Th1 and Th2 immune responses as assessed
by flow cytometry after SARS-CoV-2
S protein peptide stimulation of PBMCs and
ICS including CD4+/CD8+, IFNγ, IL-2,
TNFα, IL-4, IL-5, IL-13, and/or other
Th1/Th2 markers.
 
To examine the immune response in
vaccinated individuals after natural infection
and to explore other potentially informative
biomarkers (eg, those associated with more
severe disease).
 
Confirmation of SARS-CoV-2 infection by
molecular testing
 
SARS-CoV-2 neutralizing titers in serum
measured by a VNA (wild-type virus and/or
pseudovirion expressing S protein)
 
SARS-CoV-2-binding antibodies measured
by ELISA: Analysis of antibodies binding to
the SARS-CoV-2 S protein
 
Functional 
and 
molecular 
antibody
characterization
4. 
STUDY DESIGN
4.1. 
Overall Design
This is a randomized, double-blind, placebo-controlled, FIH Phase 1/2a multicenter study in adults
aged ≥18 to ≤55 years and aged ≥65 years. The safety, reactogenicity, and immunogenicity of
Ad26.COV2.S  will be evaluated at 2 dose levels, administered IM as a single-dose or 2-dose
schedule, with a single booster vaccination.
The safety, reactogenicity, and immunogenicity will be evaluated in a cohort of adults aged ≥18
to ≤55 years. Safety, reactogenicity, and immunogenicity will also be evaluated in an expanded
cohort in this age group. In addition, safety, reactogenicity, and immunogenicity will be evaluated
in a cohort of adults aged ≥65 years. Overall, a target ofapproximately 1,045 adult male and female
participants in these 2 age groups will be randomly assigned in this study.
Participants will receive IM injections of Ad26.COV2.S or a placebo as shown in Table 1, Table 2,
and Table 3. Two dose levels of Ad26.COV2.S will be administered: 5×1010 vp and 1×1011  vp.
Following EUA, conditional licensure, or approval in any country for the single-dose regimen of
5×1010 vp Ad26.COV2.S, all participants from countries where Amendment 10 is approved locally
by the Health Authority and IEC/IRB will be unblinded to disclose who received placebo only
during primary regimen. After unblinding, enrolled participants who initially received placebo

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only will be offered a single dose of 5×1010 vp Ad26.COV2.S. If willing to receive, they will
discontinue from participation in the placebo groups. Refer to Sections 7.4 and8.6 for more details.
Following local approval of protocol Amendment 15, all eligible participants (see Section 8.7) will
be offered a single ad hoc booster dose of 5×1010 vp Ad26.COV2.S. The ad hoc booster
vaccination will be provided to participants who have previously received 1 or more doses of any
COVID-19 vaccine (ie, the Ad26.COV2.S vaccine, an mRNA vaccine and/or another COVID-19
vaccine authorized for primary vaccination including protein, inactivated, and adenovector-based
vaccines) if the last vaccination was ≥6 months ago. Participants who choose to receive an outside
of the study  booster vaccination with the Ad26.COV2.S vaccine (if recommended by local
authorities and available) or another authorized COVID-19 vaccine, choose not to receive an ad
hoc booster vaccination, or are not eligible to receive the ad hoc booster vaccination, will not be
withdrawn from the study and will be encouraged to remain in the study. Refer to Section 8.7for
more details.
The study includes the following cohorts:
1) Cohort 1:
a. Cohort 1a: approximately 375 participants (75 participants per group) aged ≥18 to ≤55
years who will be randomized in parallel in a 1:1:1:1:1 ratio to 1 of 5 vaccination groups.
b. Cohort 1b: 25 participants (5 participants per group) aged ≥18 to ≤55 years who will be
enrolled at the Beth Israel Deaconess Medical Center (BIDMC) and randomized in parallel
in a 1:1:1:1:1 ratio to 1 of 5 vaccination groups. Additional exploratory immunogenicity
evaluations (eg, epitope mapping, passive transfer, and certain analyses of functional and
molecular antibody characteristics) will be performed for Cohort 1b. Optional fine needle
LNA will be collected from consenting participants after their 2nd vaccination (active or
placebo)or approximately 6 months after the ad hoc crossover vaccination (for participants
who crossed over from placebo to receive active Ad26.COV2.S 5x1010 vp vaccination), to
further explore the immune responses in lymph nodes (refer to Section 8.1.1.1 for more
details).
2) Cohort 2: approximately 270 participants aged ≥18 to ≤55 years will be randomized to receive
Ad26.COV2.S (approximately 240 participants) or a placebo (approximately 30 participants)
in the primary regimen. Cohort 2 will include an evaluation of a single booster vaccination
(see below for further details).
3) Cohort 3: approximately 375 participants (approximately 75 participants per group) aged
≥65 years who will be randomized in parallel in a 1:1:1:1:1 ratio to 1 of 5 vaccination groups.

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Table 1: 
Vaccination Schedulesa
Cohort 1a (Adults ≥18 to ≤55 years)
Group  
N 
Day 1 (Vaccination 1) 
Day 57 (Vaccination 2)
1 
75 
Ad26.COV2.S 5×1010 vp 
Ad26.COV2.S 5×1010 vp
2 
75 
Ad26.COV2.S 5×1010 vp 
Placebo
3 
75 
Ad26.COV2.S 1×1011 vp 
Ad26.COV2.S 1×1011 vp
4 
75 
Ad26.COV2.S 1×1011 vp 
Placebo
5 
75 
Placebo 
Placebo
Cohort 1b (Adults ≥18 to ≤55 years) b
Group  
N 
Day 1 (Vaccination 1) 
Day 57 (Vaccination 2)
1 
5 
Ad26.COV2.S 5×1010 vp 
Ad26.COV2.S 5×1010 vp
2 
5 
Ad26.COV2.S 5×1010 vp 
Placebo
3 
5 
Ad26.COV2.S 1×1011 vp 
Ad26.COV2.S 1×1011 vp
4 
5 
Ad26.COV2.S 1×1011 vp 
Placebo
5 
5 
Placebo 
Placebo
Cohort 2a (Adults ≥18 to ≤55 years)
Group  
N 
Day 1 (Vaccination 1) c 
Day 57 c
1-4 
120 
Ad26.COV2.S 5×1010 vp 
No vaccination
5 
15 
Placebo 
No vaccination
Cohort 2b (Adults ≥18 to ≤55 years)
Group  
N 
Day 1 (Vaccination 1) c 
Day 57 (Vaccination 2) c
1-4 
120 
Ad26.COV2.S 5×1010 vp 
Ad26.COV2.S 5×1010 vp
5 
15 
Placebo 
Placebo
Cohort 3 (Adults ≥65 years)
Group  
N 
Day 1 (Vaccination 1) 
Day 57 (Vaccination 2)
1 
75 
Ad26.COV2.S 5×1010 vp 
Ad26.COV2.S 5×1010 vp
2 
75 
Ad26.COV2.S 5×1010 vp 
Placebo
3 
75 
Ad26.COV2.S 1×1011 vp 
Ad26.COV2.S 1×1011 vp
4 
75 
Ad26.COV2.S 1×1011 vp 
Placebo
5 
75 
Placebo 
Placebo
Total 
1,045
a. Following local approval of protocol Amendment 15, all eligible participants (see Section 8.7) will be offered a
single ad hoc booster dose of 5×1010 vp Ad26.COV2.S. The ad hoc booster vaccination will be provided to
participants who have previously received 1 or more doses of any COVID-19 vaccine (ie, the Ad26.COV2.S
vaccine, an mRNA vaccine and/or another COVID 19 vaccine authorized for primary vaccination including
protein, inactivated, and adenovector-based vaccines) if the last vaccination was ≥6 months ago.
b. Cohort 1b comprises 5 participants in each group who will be enrolled at Beth Israel Deaconess Medical Center
(BIDMC) and for whom additional exploratory immunogenicity analyses will be performed.
c. Study vaccine will be administered as a single-dose (Day 1) or 2-dose (Day 1 and Day 57) primary regimen. Cohort
2 will include an evaluation of a single booster vaccination (see Table 2 and Table 3 for further details).
N = number of participants; vp = virus particles.
An internal DRC will be commissioned for this study to evaluate safety data over the course of the
study and to review any events that meet a specific study pausing rule or any other safety issue
that may arise (see Section 6.9, Study Vaccination Pausing Rules). Refer to Committees Structure
in Section 10.3, Appendix 3, Regulatory, Ethical, and Study Oversight Considerations for details.
In Cohorts 1a and 3, participants will be enrolled in a staggered approach with safety evaluations
in place before extending enrollment within the cohort and progressing from one cohort to the next
(Figure 8). A diagram of the study design is provided in Section 1.2, Schema.

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With local approval of Protocol Amendment 16, active follow-up of suspected COVID-19
episodes will be replaced by passive follow-up (ie, follow-up at scheduled visits to document new
COVID‑19 events as SAEs or AEs and to record concomitant therapies associated with
COVID-19). The assay methodology should be documented. During these site visits, the
protocol-required safety information (eg, [S]AEs and AESIs 6 months after the last vaccination)
is also collected. In between the scheduled visits, participants who experienced a (S)AE or AESI
are encouraged to contact the study site.
Cohort 1 (Adults Aged ≥18 to ≤55 Years)
The first doses of study vaccine will be administered to a sentinel group of 5 participants
(1 participant per group) in Cohort 1a, enrolled at the same study site, to monitor for any
unexpected severe adverse reactions. The sentinel participants will be vaccinated at least 1 hour
apart. In Cohort 1a, as for each cohort, participants will be closely observed for a minimum of
1 hour post-vaccination for the development of acute reactions. A telephone call will be made to
each of these 5 sentinel participants on Day 2 (approximately 24 hours post-vaccination) to collect
safety data, which will include solicited and unsolicited AEs and SAEs. The collected data will be
reviewed in a blinded manner by the principal investigator (PI)and the sponsor’s study responsible
physician (SRP). Randomization and vaccination of additional participants will be halted until the
review is completed.
In the absence of clinically significant findings from the review of 24-hour safety data from the
first 5 sentinel participants, all participants in Cohort 1a and Cohort 1b will be randomized and
vaccinated. The next 10 participants in Cohort 1a will be enrolled at the same study site as the
5 sentinel participants, randomly assigned to 1 of the 5 vaccination groups to have an overall
1:1:1:1:1 randomization ratio (ie, a total of 15 participants including the 5 sentinels, with
3 participants in each vaccination group), and administered the first vaccination. The DRC will
review the blinded 3-day safety data (ie, from Day 1 to Day 4) and 7-day safety data (ie, from
Day 1 to Day 8) following administration of the first vaccination to these first 15 participants,
including solicited and unsolicited AEs and SAEs. In the absence of safety concerns, enrollment
and vaccination of participants in Cohort 3 will begin.
Cohort 2 (Adults Aged ≥18 to ≤55 Years)
Cohort 2 will be initiated after interim or primary analyses of Cohort 1a. In Cohort 2a,
approximately 120 participants will receive Ad26.COV2.S  at a dose level of 5×1010 vp and
approximately 15 participants will receive a placebo in a single-dose primary regimen. In
Cohort 2b, approximately 120 participants will receive Ad26.COV2.S at a dose level of 5×1010 vp
and approximately 15 participants will receive a placebo in a 2-dose primary regimen. No
staggered enrollment will be performed for Cohort 2; however, the DRC will evaluate safety data
from Cohort 2 over the course of the study. If required, Cohort 2 may contribute to the safety
database prior to initiation of larger studies.
If the immunogenicity results obtained after the 1st vaccination in Cohort 1a are not adequately
supporting initiation of Cohort 2, then results obtained after the 2nd vaccination in the 2-dose
regimens in Cohort 1a will be used to select the vaccine regimens to be evaluated in Cohort 2 of

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this study. If the immunogenicity results obtained after the 2nd vaccination in the 2-dose regimens
in Cohort 1a do not demonstrate an adequately increased immune response, the sponsor will not
provide the 2nd vaccination at Day 57 in Cohort 2b of this study. The immunogenicity results
available from Cohort 1a supported the administration of the 2nd vaccination at Day 57 in
Cohort 2b.
In addition, data obtained after a single booster vaccination will be used to evaluate the effect of a
booster vaccination at different time points and the duration of immune response (see below for
further details).
Cohort 3 (Adults Aged ≥65 Years)
The safety, reactogenicity, and immunogenicity of Ad26.COV2.S in adults aged ≥65 years will be
assessed in Cohort 3. Vaccination of participants in Cohort 3 will begin after the DRC review of
7-day safety data from the first 15 participants in Cohort 1a if no safety concerns are identified.
In Cohort 3, the first doses of study vaccine will be administered to a sentinel group of
5 participants (1 participant per group) to monitor for any unexpected severe adverse reactions.
The sentinel participants will be vaccinated at least 1 hour apart. A telephone call will be made to
each of these 5 sentinel participants on Day 2 (approximately 24 hours post-vaccination) to collect
safety data, which will be reviewed in a blinded manner by the PI and the sponsor’s SRP.
Randomization and vaccination of additional participants will be halted until the review is
completed. In the absence of clinically significant findings, an additional 10 participants will be
enrolled at the same study site as the 5 sentinel participants, randomly assigned to 1 of the
5 vaccination groups to have an overall 1:1:1:1:1 randomization ratio, and administered the first
vaccination. The DRC will review the blinded 3-day safety data (ie, from Day 1 to Day 4) and
7-day safety data (ie, from Day 1 to Day 8) following administration of the first vaccination to
these first 15 participants. Safety data for review will include solicited and unsolicited AEs and
SAEs. In the absence of safety concerns, enrollment and vaccination of the remaining participants
in Cohort 3 will proceed.
Although it is anticipated that an efficacy study will be initiated in adults aged ≥18 to ≤55 years,
it is important to establish safety and a regimen capable of inducing appropriate immunity for this
candidate vaccine in elderly adults aged ≥65 years, as this group displays the highest incidence of
morbidity and mortality in the current pandemic caused by SARS-CoV-2.

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Figure 8: 
Participant Enrollment and First Dose Safety Strategy in Cohorts 1 and 3
C = cohort; DRC = Data Review Committee; PI = principal investigator; SRP = study responsible physician
Booster Vaccinations in Cohort 2
Note: For participants at Belgian sites: per Belgian-specific Protocol Amendment 15, this section
is no longer applicable as participants aged <65 years enrolled at Belgian sites are not eligible
to receive a booster vaccination with Ad26.COV2.S.
To gain preliminary insight into the safety and immunogenicity of a single booster vaccination,
designated participants in Cohort 2 who received Ad26.COV2.S for the single-dose (Cohort 2a)
or 2-dose (Cohort 2b)primary regimen will receive a single booster vaccination of Ad26.COV2.S
at 6 months or 12 months after completion of the primary regimen, and will receive placebo at the
other applicable time point. As a control, a subgroup of participants who received Ad26.COV2.S
for the primary regimen will receive placebo at 6 months and 12 months after completion of the
primary regimen. In addition, participants who received placebo for the primary regimen will
receive placebo at 6 months and 12 months after completion of the primary regimena (Table 2 and
Table 3). An Ad26.COV2.S dose level of 5×1010 vp will be used for the booster vaccination in
Cohorts 2a and 2b.
a At the time of unblinding, after EUA  or approval in any  country  and local approval of Protocol
Amendment 10, only the Group 5 (placebo only) participants not willing to receive a single dose of 5×1010
vp Ad26.COV2.S or another authorized/licensed COVID-19 vaccine will continue Group 5 booster
vaccinations in Cohort 2 (refer to Section 8.6).

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Table 2: 
Cohort 2a Vaccination Schedule –Primary Regimen and Single Booster Vaccination
Primary Regimen 
Booster Vaccination
Group  
N 
Day 1 a 
(Vac 1) 
6 months b 
12 months b 
24 months e
N/A per Amendment 16
1 d 
30 
Ad26.COV2.S  
5×1010 vp
Placebo 
Placebo 
Placebo
2 
30 
Ad26.COV2.S  
5×1010 vp 
Ad26.COV2.S  
5×1010 vp
Placebo 
Placebo
3 
30 
Ad26.COV2.S  
5×1010 vp 
Placebo 
Ad26.COV2.S  
5×1010 vp
Placebo
4 d 
30 
Ad26.COV2.S  
5×1010 vp 
Placebo 
Placebo 
Ad26.COV2.S
5×1010 vp
5 c 
15 
Placebo 
Placebo c 
Placebo c 
Placebo c
Total 
135
a. Study vaccine will be administered as a single-dose primary regimen.
b. Study vaccine (Ad26.COV2.S or a placebo) will be administered at 6 months and 12 months after completion of
the single-dose primary regimen.
c. At the time of unblinding, after EUA or approval in any country and local approval of Protocol Amendment 10,
only the Group 5 (placebo only) participants not willing to receive a single dose of5×1010 vp Ad26.COV2.S or
another authorized/licensed COVID-19 vaccine will continue Group 5 booster vaccinations in Cohort 2a (refer to
Section 8.6).
d. Applicable to the US only; Following local approval of Protocol Amendment 15, all participants of Groups 1
and 4 not willing to receive a single ad hoc booster dose of 5×1010 vp Ad26.COV2.S will continue booster
vaccinations in Cohort 2a according to their current schedule.
e. Following local approval of Protocol Amendment 16, booster vaccinations (either placebo or Ad26.COV2.S
5x1010 vp) will not be administered at 24 months after completion of the primary regimen.
EUA = Emergency Use Authorization; N = number of participants; N/A = not applicable; vac = vaccination; vp = virus
particles.
Table 3: 
Cohort 2b Vaccination Schedule –Primary Regimen and Single Booster Vaccination
Primary Regimen 
Booster Vaccination
Group  
N 
Day 1 a 
(Vac 1) 
Day 57 a 
(Vac 2) 
8 months b 
14 months b 
26 months e
N/A per
Amendment 16
1 d 
30 
Ad26.COV2.S  
5×1010 vp 
Ad26.COV2.S  
5×1010 vp
Placebo 
Placebo 
Placebo
2 
30 
Ad26.COV2.S  
5×1010 vp 
Ad26.COV2.S  
5×1010 vp 
Ad26.COV2.S  
5×1010 vp
Placebo 
Placebo
3 
30 
Ad26.COV2.S  
5×1010 vp 
Ad26.COV2.S  
5×1010 vp 
Placebo 
Ad26.COV2.S  
5×1010 vp
Placebo
4 d 
30 
Ad26.COV2.S  
5×1010 vp 
Ad26.COV2.S  
5×1010 vp 
Placebo 
Placebo 
Ad26.COV2.S
5×1010 vp
5 c 
15 
Placebo 
Placebo 
Placebo c 
Placebo c 
Placebo c
Total 
135
a. Study vaccine will be administered as a 2-dose (Day 1 and Day 57) primary regimen.
b. Study vaccine (Ad26.COV2.S or a placebo) will be administered at 6 months and 12 months after completion of
the 2-dose primary regimen. If the 2nd vaccination at Day 57 is not provided, then participants will discontinue
the study (refer to Section 7.2).
c. At the time of unblinding, after EUA or approval in any country and local approval of Protocol Amendment 10,
only the Group 5 (placebo only) participants not willing to receive a single dose of 5×1010 vp Ad26.COV2.S or

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another authorized/licensed COVID-19 vaccine will continue Group 5 booster vaccinations in Cohort 2b (refer
to Section 8.6).
d. Applicable to the US only: Following local approval of Protocol Amendment 15, all participants of Groups 1 and
4 not willing to receive a single ad hoc booster dose of 5×1010 vp Ad26.COV2.S will continue booster
vaccinations in Cohort 2b according to their current schedule.
e. Following local approval of Protocol Amendment 16, booster vaccinations (either placebo or Ad26.COV2.S
5x1010 vp) will not be administered at 26 months after completion of the primary regimen.
EUA = Emergency Use Authorization; N = number of participants; N/A = not applicable; vac = vaccination; vp = virus
particles.
Study Duration
For Cohorts 1 and 3, the study duration from screening until the last follow-up visit will be
approximately 15 months per participant. For these participants, the study consists of a screening
period of up to 28 days, vaccinations on Day 1 and Day 57, and follow-up visits up to 12 months
after the second vaccination (Target Visit Day 422±21 days). In case participants consent for the
additional follow-up (see SoA in Section 1.3.9), the study duration from screening until the last
follow-up visit will be approximately 27 months per participant. For these participants, the study
consists of a screening period of up to 28 days, vaccinations on Day 1 and Day 57, and follow-up
visits up to 24 months after the second vaccination (Target Visit Day 787±21 days).
For Cohort 2a, the study duration from screening until the last follow-up visit will be
approximately 24 months per participant. In this case, the study would consist of a screening period
of up to 28 days, vaccination on Day 1, a single booster vaccination at 6 months or 12 months after
completion of the single-dose primary regimen on Day 1 and follow-up visits up to 24 months
after completion of the primary regimen on Day 1 (Target Visit Day 731±21 days).
For Cohort 2b, the study duration from screening until the last follow-up visit will be
approximately 24 months per participant. In this case, the study would consist of a screening period
of up to 28 days, vaccinations on Day 1 and Day 57, a single booster vaccination at 6 months or
12 months after completion of the 2-dose primary regimen on Day 57, and follow-up visits up to
24 months after completion of the primary regimen on Day 57(Target Visit Day 787±21 days). If
the 2nd vaccination at Day 57 is not provided, then participants will discontinue the study (refer to
Section 7.2).
Group 5 (placebo only) participants who wish to receive a single dose of 5×1010 vp Ad26.COV2.S
(ie, at the time of unblinding, after EUA or approval in any country and local approval of protocol
Amendment 10), will discontinue from participation in the placebo groups (refer to Sections 7.4
and 8.6). This will reduce study duration for all Cohort 2 and for some of the Cohort 1 and 3
participants. For Cohorts 1a, 1b, and 3, the safety follow-up will end at Day 422 (ie, the initially
planned study completion date) or 6 months after vaccination, whichever comes first. For
Cohorts 2a and 2b, the safety follow-up will end 6 months after vaccination.
All eligible participants who wish to receive a single ad hoc booster dose of 5×1010 vp
Ad26.COV2.S (ie, at the time of local approval of protocol Amendment 15), will discontinue from
participation in their current schedules (refer to Sections 7.5 and 8.7). In this case, the safety and
immunogenicity follow-up will end 6 months after the ad hoc booster vaccination.

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For each cohort, if a participant is unable to complete the study, but has not withdrawn consent, is
not lost to follow-up, or has not died, an early exit visit will be conducted.
Enrollment of Seropositive Participants
For all participants, a serological test will be performed at screening to detect
SARS-CoV-2-specific antibodies.
In Cohort 1a and 3, the first 15 participants to be randomized will be seronegative participants.
A maximum of 25 seropositive participants will be enrolled among the remaining participants in
Cohorts 1a and 3. No seropositive participants will be enrolled in Cohort 1b. A maximum of
25 seropositive participants will be enrolled in Cohort 2.
Enrollment of seropositive participants in the present study will allow an evaluation of vaccine
safety in this participant group.
Study Procedures
For each cohort, safety will be assessed by collection of solicited local (at injection site) and
systemic AEs, unsolicited AEs, SAEs, and AESIs. Other safety assessments include vital signs
measurements (heart rate, supine systolic and diastolic blood pressure, respiratory rate, and body
temperature) and physical examinations at the time points indicated in Section 1.3, Schedule of
Activities.
After each vaccination, participants will remain under observation at the study site for at least
15 minutes to 1 hour depending on the vaccination being administered (see SoAs for details) for
the presence of any acute reactions and solicited events. Any solicited local or systemic AEs,
unsolicited AEs, SAEs, concomitant medications, and vital signs will be documented by study-site
personnel following this observation period. In addition, participants will record solicited events
signs and symptoms in a diary for 7 days post-vaccination.
Participants will be provided with a booklet including a daily question on whether they are
experiencing COVID-19-like symptoms. Following local approval of protocol Amendment 15,
participants will not be required to complete the booklet but will be contacted by the site regularly
to check whether they experienced COVID-19 like symptoms. See Section 8.1.2.3 for the
prespecified criteria for suspected COVID-19. Prior to the local approval of Protocol
Amendment 16, if a participant experiences COVID-19-like symptoms, the following should take
place:
 
Participants should contact the study site at the time of symptom onset.
 
A nasal swab should be collected by a health care professional from the participant at home
(using available material for home swabs) or at the study site as soon as possible and
preferably no longer than 2 to 3 days after the onset of symptoms and stored appropriately.
The sample should be transferred to the study site by an appropriate method as soon as
possible after being collected. A second nasal swab will be obtained 2 to 4 days after the first
swab following the same procedures as the first nasal swab. The presence of SARS-CoV-2

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infection and influenza infection will be assessed at the study site by molecular testing using
the nasal swab sample.
 
Participants should complete the Symptoms of Infection with Coronavirus-19 (SIC  [see
Section 10.7, Appendix 7, Symptoms of Infection with Coronavirus-19 (SIC)]) and record
their highest body temperature daily starting on the first day they experience symptoms. If
either nasal swab is positive for SARS-CoV-2 or influenza, collection of data will continue
until sign and symptom resolution. If the first nasal swab is negative, collection of data will
continue until the negative test is confirmed by the second nasal swab  or until sign and
symptom resolution, whichever comes first. Long-term sequelae of COVID-19 (eg, anosmia,
headache, fatigue, and other symptoms at the investigator's judgement) will not be followed
until their resolution if not resolved within a month.
 
For participants with a positive test result for SARS-CoV-2 infection, a study visit will be
conducted 28 days after symptom onset to assess the clinical course of the infection, record
concomitant medications since symptom onset, and obtain a blood sample for evaluation of
the immune response and other biomarkers. The sponsor recommends to follow these
participants until 2 consecutive negative nasal swabs could be obtained.
Further details are provided in Section 8.1.2, Procedures in Case of COVID-19-like Signs and
Symptoms.
As of local approval of Protocol Amendment 16, participants will continue to be required to report
safety events, such as SAEs, AEs, and AESIs. The active follow-up of new suspected COVID-19
episodes will be replaced by passive follow-up at scheduled study visits to document COVID-19
events as SAEs or AEs, if applicable (See Section 1.3.6.1).
For enrolled participants who received placebo only during primary regimen and who are
accepting a single dose of 5×1010 vp Ad26.COV2.S offered at the time of unblinding, after EUA
or approval in any country and local approval of protocol Amendment 10, procedures outlined in
Section 8.6 apply. A single dose of 5×1010 vp Ad26.COV2.S will be administered during an ad hoc
crossover visit and participants will remain under observation at the study site for at least
15 minutes following vaccination. SAEs, special reporting situations (whether serious or
non-serious, that are related to study procedures or that are related to non-investigational sponsor
products), and COVID-19-like signs and symptoms will be reported from the time of unblinding
until the end-of-safety-follow-up phone call. In addition, suspected AESIs will be reported from
the time of vaccination until the end-of-safety-follow-up phone call after local approval of protocol
Amendment 11 is obtained.
4.2. 
Scientific Rationale for Study Design
Vector Selection
The rationale behind the selection of the Ad26 vector is described in Section 2, Introduction.
Dose Selection
The rationale behind the selection of the doses is described in Section 4.3, Justification for Dose.

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Blinding, Control, Study Phase/Periods, Vaccine Groups
A placebo control will be used to establish the frequency and magnitude of changes in clinical and
immunological endpoints that may occur in the absence of active vaccine. Randomization will be
used to minimize bias in the assignment of participants to vaccine groups, to increase the likelihood
that known and unknown participant attributes (eg, 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 of study endpoints.
Blinding will be guaranteed by the preparation of the study vaccine by an unblinded pharmacist or
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 will be randomly assigned to 1 of the groups based on a
computer-generated randomization schedule prepared before the study by or under the supervision
of the sponsor.
Following EUA, conditional licensure, or approval in any country for the single-dose regimen of
5×1010 vp Ad26.COV2.S, all participants from countries where Amendment 10 is locally approved
by the Health Authority and IEC/IRB, will be unblinded to disclose who received placebo only
during primary regimen. After unblinding, enrolled participants who initially received placebo
only will be offered a single dose of 5×1010 vp Ad26.COV2.S. If willing to receive, they will
discontinue from participation in the placebo groups (refer to Section 7.4). For more details
regarding procedures after EUA, refer to Section 8.6. Statistical analysis of data obtained from the
point of unblinding is outlined in Section 9.7.
Biomarker Collection
For all participants, biomarker analysis (PAXgene, RNA-seq) will be performed to explore
potentially informative biomarkers related to vaccine immunogenicity and SARS-CoV-2 infection
(including relations with COVID-19 disease severity). 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 compensation for the time and
inconveniences that may arise from participation in the study. See Section 2.3, Benefit-Risk

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Assessment for details on potential and known benefits and risks, and for the safety measures taken
to minimize risk to participants.
The total blood volume to be collected is considered to be an acceptable amount of blood to be
collected over this time period from the population in this study based upon the 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,47,48 as wellas the Belgian Red
Cross guidelines of 450-470 mL up to 4 times a year with at least 2 months between each
donation.7
4.3. 
Justification for Dose
The dose levels ofAd26.COV2.S to be assessed in the present study (5×1010 vp and 1×1011 vp)
are based on experience with other Ad26-vectored vaccines administered to adults in clinical
studies including Ad26.ZEBOV (Ebola virus program); Ad26.ENVA.01, Ad26.Mos.HIV, and
Ad26.Mos4.HIV (HIV program); Ad26.CS.01 (malaria program); Ad26.RSV.FA2 and
Ad26.RSV.preF (RSV program); and Ad26.ZIKV.001 (Zika virus program). These 2 dose levels
have shown to be well tolerated and immunogenic in these vaccine programs. Safety data from
studies with other Ad26-based vaccines are summarized in Section 2.3.1, Risks Related to Study
Participation.
Dose-ranging studies in immunologically naïve participants in the sponsor’s HIV and Ebola
programs have shown lower humoral immune responses below 5×1010 vp after a single
vaccination. The dose level of1×1011 vp is the highest dose level tested in clinical studies to date.
Therefore, both the 5×1010 vp and 1×1011 vp dose levels will be assessed to provide a safety margin
and to determine whether Ad26.COV2.S has a similar immunogenicity profile to that observed
with other Ad26-based vaccines.
The Ad26.COV2.S dose level for Cohort 2a has been adjusted to mimic the dosing regimen to be
evaluated in study VAC31518COV3001. As a result, Cohort 2 will assess the 5×1010 vp dose level
in a 1- and 2- dose regimen. Based on the current platform data with Ad26-based vaccines, these
two regimens provide the best possibility of having an efficacious 1-dose vaccine with longevity
for at least 6 months, or a 2-dose vaccine with protection after one dose if the virus is quite sensitive
to neutralizing antibody and a potential increased induction of immunologic memory following
the second immunization that might yield protection independent of the level of antibody at the
time of encounter of the virus.
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.

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Study Completion Definition
For Cohorts 1 and 3, a participant will be considered to have completed the study if he or she has
completed assessments at Day 422. In case participants consent for the additional follow-up (see
SoA in Section 1.3.9), they  will be considered to have completed the study if he or she has
completed assessments at Day 787. Participants who prematurely discontinue study vaccine for
any reason before completion of the last study visit will not be considered to have completed the
study.
For Cohort 2, a participant will be considered to have completed the study if he or she has
completed assessments at 12 months after completion of the last booster vaccination for any group.
Participants who prematurely discontinue study vaccine for any reason before that time will not
be considered to have completed the study.
Group 5 (placebo only) participants who wish to receive a single dose of 5×1010 vp Ad26.COV2.S
(ie, at the time of unblinding, after EUA or approval in any country and approval of protocol
Amendment 10), will discontinue from participation in the placebo groups (refer to Sections 7.4
and 8.6). This will reduce study duration for all Cohort 2 and for some of the Cohort 1 and 3
participants. For Cohorts 1a, 1b, and 3, the safety follow-up will end at Day 422 (ie, the initially
planned study completion date) or 6 months after vaccination, whichever comes first. For
Cohorts 2a and 2b, the safety follow-up will end 6 months after vaccination. At that time, the
participant will be contacted (phone call) by the site with regards to SAE and AESI collection,
after which the participant will be considered to have completed the study.
All eligible participants who wish to receive a single ad hoc booster dose of 5×1010 vp
Ad26.COV2.S (ie, at the time of local approval of protocol Amendment 15), will discontinue from
participation in their current schedules (refer to Sections 7.5 and 8.7). In this case, the safety and
immunogenicity follow-up will end 6 months after the ad hoc booster vaccination.
5. 
STUDY POPULATION
Screening for eligible participants will be performed within 28 days before the first study
vaccination. Eligibility will be reassessed pre-vaccination on Day 1.
The inclusion and exclusion criteria for enrolling participants in this study are described below. If
there is a question about the inclusion or exclusion criteria below, the investigator must consult
with the appropriate sponsor representative and resolve any issues before enrolling a participant in
the study. Waivers are not allowed.
Following local approval of protocol Amendment 10, after unblinding, participants who initially
received placebo only are offered to receive a single dose of 5×1010 vp Ad26.COV2.S at the study
site (ie, placebo crossover vaccination). Eligibility criteria to receive the placebo crossover
vaccination are described in Section 8.6.
Following local approval of protocol Amendment 15, a single ad hoc booster vaccination with
Ad26.COV2.S at the 5x1010 vp dose level will be offered to all eligible participants who have
previously received 1 or more doses of any COVID-19 vaccine (ie, the Ad26.COV2.S vaccine, an

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mRNA vaccine and/or another COVID 19 vaccine authorized for primary vaccination including
protein, inactivated, and adenovector-based vaccines) if the last vaccination was ≥6 months ago.
Eligibility criteria to receive the ad hoc booster vaccination are described in Section 8.7.
The following ongoing participants will not be eligible to receive this ad hoc booster vaccination:
 Group 5 participants (all cohorts) who crossed over from placebo to receive Ad26.COV2.S at
the 5x1010 vp dose level (ie, placebo crossover vaccination) (see Section 1.3.7).
 Group 5 participants (all cohorts) who did not opt for the placebo crossover vaccination and
therefore have not received any vaccination with the Ad26.COV2.S vaccine.
 Cohort 2 participants who will receive a booster vaccination according to their initial schedule
at 6 and 12 months after the primary regimen (Groups 2 and 3, respectively) (see Section 4.1).
 Applicable to Belgium only: Per the Belgian-specific protocol Amendment 15, participants
aged <65 years enrolled at Belgian sites.
5.1. 
Inclusion Criteria
Each potential participant must satisfy all of the following criteriaa to be enrolled in the study:
1. Participant must sign an ICF 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.
2. Participant is willing and able to adhere to the prohibitions and restrictions specified in this
protocol.
3. Criterion modified per Amendment 2:
3.1. Applicable to Cohorts 1 and 2 only: Participant is male or female and 18 to 55 years of
age, inclusive, on the day of signing the ICF.
Applicable to Cohort 3 only: Participant is male or female and 65 years of age or older
on the day of signing the ICF. For study sites in Belgium, participant is 65 to 75 years of
age, inclusive, on the day of signing the ICF.
4. Criterion modified per Amendment 1:
4.1 Criterion modified per Amendment 3:
4.2 Criterion modified per Amendment 4:
4.3 Participant must have a body mass index (BMI) 30.0 kg/m2.
5. Criterion modified per Amendment 1:
5.1 Criterion modified per Amendment 3:
5.2 Criterion modified per Amendment 4:
5.3 Criterion modified per Amendment 5:
a See also criteria for participants receiving a single ad hoc booster dose of 5x1010 vp Ad26.COV2.S described in
Section 8.7.

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5.4 Criterion modified per Amendment 6:
5.5 Applicable to Cohorts 1 and 2 only: Participant must be healthy, in the investigator’s
clinical judgment, as confirmed by medical history, physical examination, clinical
laboratory assessments, and vital signs performed at screening, and must not have
comorbidities related to an increased risk of severe COVID-19.11
Applicable to Cohort 3 only: In the investigator’s clinical judgment, participant must be
either in good or stable health. Participants may have underlying illnesses such as
hyperlipoproteinemia or hypothyroidism, as long as their symptoms and signs are
medically controlled and not considered to be comorbidities related to an increased risk
of severe COVID-19a.11 If they are on medication for a condition, the medication dose
must have been stable for at least 12 weeks preceding vaccination and expected to remain
stable for the duration of the study. Participants will be included on the basis of physical
examination, clinical laboratory assessments, medical history, and vital signsb.
6. Applicable to Cohorts 1 and 2 only: Contraceptive (birth control) use by women should be
consistent with local regulations regarding the acceptable methods of contraception for those
participating in clinical studies.
Before randomization, participants who were born female must be either (as defined in
Section 10.5, Appendix 5, Contraceptive Guidance and Collection of Pregnancy Information):
a. Not of childbearing potential
b. Of childbearing potential and practicing a highly effective method of contraception and
agrees to remain on such a method of contraception from signing the informed consent
until 3 months after the last dose of study vaccine. Use of hormonal contraception should
start at least 28 days before the first administration of study vaccine. The investigator
should evaluate the potential for contraceptive method failure (eg, noncompliance,
recently initiated) in relationship to the first vaccination. Highly effective methods for
this study include:
1) hormonal contraception:
i. combined (estrogen and progestogen containing) hormonal contraception
associated with inhibition of ovulation (oral, intravaginal, or transdermal)
ii. progestogen-only hormonal contraception associated with inhibition of ovulation
(oral, injectable, or implantable);
2) intrauterine device (IUD);
a Participants may have hypertension of mild severity (according to the Toxicity Grading Scale in Section 10.6,
Appendix 6), as long as it is stable and medically controlled as defined by no change in medication over the past
6 months (except for issues of tolerability or use of similar drug with same mechanism of action, eg, thiazides,
Beta blockers, Alpha blockers at the same effective dose).
b Participants can be enrolled with Grade 1 or Grade 2 values for vital signs measurements except for high blood
pressure which is only allowed at Grade 1.

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3) intrauterine hormone-releasing system (IUS);
4) bilateral tubal occlusion/ligation procedure;
5) vasectomized partner (the vasectomized partner should be the sole partner for that
participant);
6) sexual abstinence*.
*Sexual abstinence is considered an effective method only if defined as refraining from
heterosexual intercourse from signing the informed consent until 3months after the last dose
of study vaccine. The reliability of sexual abstinence needs to be evaluated in relation to the
duration of the study and the preferred and usual lifestyle of the participant.
Applicable to Cohort 3 only: Before randomization, a woman must be (as defined in
Section 10.5, Appendix 5, Contraceptive Guidance and Collection of Pregnancy Information):
a. postmenopausal (postmenopausal state is defined as no menses for 12 months without an
alternative medical cause)or permanently sterile; and
b. not intending to conceive by any methods.
7. All female participants of childbearing potential must:
a. Have a negative highly sensitive urine pregnancy test at screening
b. Have a negative highly sensitive urine pregnancy test immediately prior to each study
vaccine administration.
8. Participant agrees to not donate bone marrow, blood, and blood products from the first study
vaccine administration until 3 months after receiving the last dose of study vaccine.
9. Participant must be willing to provide verifiable identification, has means to be contacted and
to contact the investigator during the study.
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 first dose of study vaccine; randomization at a later date is
permitted at the discretion of the investigator and after consultation with the sponsor.
2. Participant has a history of malignancy within 5 years before screening (exceptions are
squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or
malignancy, which is considered cured with minimal risk of recurrence).
3. Criterion modified per Amendment 3:
3.1 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).

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4. Criterion modified per Amendment 3:
4.1 Criterion modified per Amendment 8:
4.2 Participant has abnormal function of the immune system resulting from:
a. Clinical conditions (eg, autoimmune disease, other immune-mediated inflammatory
disorders, or known or suspected immunodeficiency) expected to have an impact on the
immune response ofthe 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 substantial 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.
5. Criterion modified per Amendment 3:
5.1 Participant has a history of any neurological disorders or seizures including Guillain-Barré
syndrome (GBS), with the exception of febrile seizures during childhood.
6. Participant has a history of chronic urticaria (recurrent hives), eczema or adult atopic
dermatitis.
7. Criterion modified per Amendment 3:
7.1 Participant received treatment with immunoglobulins (Ig) in the 3 months or blood
products in the 4 months before the planned administration of the first dose of study
vaccine or has any plans to receive such treatment during the study.
8. Participant received or plans to receive:
a. Licensed live attenuated vaccines - within 28 days before or after planned administration
of the first or subsequent study vaccinations
b. Other licensed (not live) vaccines - within 14 days before or after planned administration
of the first or subsequent study vaccinations.
9. Criterion modified per Amendment 1:
9.1 Criterion modified per Amendment 7:
9.2 Criterion modified per Amendment 8:
9.3 Participant received an investigational drug (including investigational drugs for
prophylaxis of COVID-19) or used an invasive investigational medical device within
30 days or received investigational Ig or monoclonal antibodies within 3 months, or

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received convalescent serum for COVID-19 treatment within 4 months or received an
investigational vaccine (including investigational Adenoviral-vectored vaccines) within 6
months before the planned administration of the first dose of study vaccine or is currently
enrolled or plans to participate in another investigational study during the course of this
study.
Note: Participation in an observational clinical study is allowed at the investigator’s
discretion; please notify the sponsor (or medical monitor) of this decision.
Efforts will be made to ensure inclusion of participants who have not been previously
enrolled in coronavirus studies and to prevent participants from subsequently enrolling
in other coronavirus studies during their participation in this study.
The use of any coronavirus vaccine (licensed or investigational) other than Ad26.COV2.S
is disallowed at any time prior to vaccination (see also Exclusion Criterion 20) and during
the study except under the conditions described in Section 6.6  .
10. Criterion modified per Amendment 15:
10.1Criterion modified as per Amendment 16:
10.2Participant is a woman who is pregnant, breast-feeding, or planning to become pregnant
while enrolled in this study or within 3 months after the last dose of study vaccine. Note
(Applicable to the US only): Following local approval of Protocol Amendment 15,
participants who are pregnant may receive ad hoc booster vaccination with
Ad26.COV2.S, if allowed by local regulations and if the investigator considers that the
potential benefits outweigh the potential risks to the mother and fetus (see Section 8.7).
11. Criterion modified per Amendment 3:
11.1Participant has a history of an underlying clinically significant acute or chronic medical
condition, laboratory finding 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.
12. Participant had major surgery, per the investigator’s judgment, within  12 weeks before
vaccination, or will not have fully recovered from surgery, or has major surgery planned
during the time the participant is expected to participate in the study or within 6 months after
the last dose of study vaccine administration.
13. Participant has a contraindication to IM injections and blood draws eg, bleeding disorders.
14. Participant is an employee of the investigator or study site, with direct involvement in the
proposed study or other studies under the direction of that investigator or study site, as well
as family members of the employees or the investigator, or an employee of the sponsor.
15. Participant has chronic active hepatitis B or hepatitis C infection per medical history.
16. Participant has HIV infection per medical history.

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17. Participant has had major psychiatric illness or drug or alcohol abuse which in the
investigator’s opinion would compromise the participant’s safety or compliance with the
study procedures.
18. Participant cannot communicate reliably with the investigator.
19. 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.
20. Participant previously received a coronavirus vaccine.
21. Criterion modified per Amendment 3:
21.1Participant has a positive diagnostic test result for SARS-CoV-2 infection, confirmed by
PCR, at screening.
22. Criterion modified per Amendment 3:
22.1Criterion modified per Amendment 8:
22.2Based on a serological test for SARS-CoV-2-specific antibodies at screening:
Applicable to Cohorts 1a, 2, and 3 only: after a limited number of seropositive participants
have been enrolled, further seropositive participants will be excluded (see Section 4.1,
Overall Design).
Applicable to Cohort 1a and 3 (first 15 participants of each cohort) and Cohort 1b only:
seropositive participants will be excluded.
23. Criterion added per Amendment 1:
23.1Criterion modified per Amendment 3:
23.2Criterion modified per Amendment 4:
23.3Criterion modified per Amendment 5:
23.4Criterion modified per Amendment 6:
23.5Criterion modified per Amendment 8:
Participants with comorbidities that are or might be associated with an increased risk of
progression to severe COVID-19a, ie, participants with moderate-to-severe asthma;
chronic lung diseases such as chronic obstructive pulmonary disease (COPD) (including
emphysema and chronic bronchitis), idiopathic pulmonary fibrosis and cystic fibrosis;
diabetes (including type 1 or type 2); serious heart conditions, including heart failure,
coronary artery disease, congenital heart disease, cardiomyopathies, and (pulmonary)
hypertension or high blood pressure; obesity (BMI ≥30 kg/m2); chronic liver disease,
including cirrhosis; sickle cell disease; thalassemia; cerebrovascular disease; neurologic
aPer US CDC (See Section 10.10, Appendix 10). Gestational diabetes was deleted from the list since it is not applicable
as pregnant women are not allowed to participate in the study.

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conditions (dementia); smoking; end stage renal disease; organ transplantation; cancer;
HIV infection and other immunodeficiencies; hepatitis B infection; and sleep apnea.
Applicable to Cohort 3 only: Participants may have hypertension of mild severity
(according to the Toxicity Grading Scale in Section 10.6, Appendix 6), as long as it is
stable and medically controlled as defined by no change in medication over the past
6 months (except for issues of tolerability or use of similar drug with same mechanism of
action, eg, thiazides, Beta blockers, Alpha blockers at the same effective dose).
24. Criterion added per Amendment 1:
24.1Criterion modified per Amendment 3:
Applicable to Cohorts 1 and 3 only: Participant currently working in an occupation with
a high risk of exposure to SARS-CoV-2 (eg, health care worker or emergency response
personnel) or considered at the investigator’s discretion to be at increased risk to acquire
COVID-19 for any other reason.
25. Criterion added per Amendment 3:
History of confirmed COVID-19 or known exposure to an individual with confirmed
COVID-19 or SARS-CoV-2 infection within the past 2 weeks (Not applicable for the
seropositive participants).
26. Criterion added per Amendment 3:
History of confirmed SARS or MERS.
NOTE: Investigators should ensure that all study enrollment criteria have been met prior to the
first dose. If a participant's clinical status changes (including any available laboratory results or
receipt of additional medical records) after screening but before the first dose of study vaccination
is given such that he or she no longer meets all eligibility criteria, then the participant should be
excluded from participation in the study. The required source documentation to support meeting
the enrollment criteria are noted in Section 10.3, Appendix 3, Regulatory, Ethical, and Study
Oversight Considerations.
5.3. 
Lifestyle Considerations
Potential participants must be willing and able to adhere to the following lifestyle restrictions
during the course of the study to be eligible for participation:
1. 
Refer to Section  6.8, Prestudy and Concomitant Therapy  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.

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5.4. 
Screen Failures
Participant Identification, Enrollment, and Screening Logs
The investigator agrees to complete a participant identification and enrollment log to permit easy
identification of each participant during and after the study. This document will be reviewed by
the sponsor study-site contact for completeness.
The participant identification and enrollment log will be treated as confidential and will be filed
by the investigator in the study file. To ensure participant confidentiality, no copy will be made.
All reports and communications relating to the study will identify participants by participant
identification and age at initial informed consent. In cases where the participant is not randomized
into the study, the date seen and age at initial informed consent will be used.
An individual who does not meet the criteria for participation in this study (screen failure)may be
rescreened on one occasion only. Participants who are rescreened will be assigned a new
participant number, undergo the informed consent process, and then restart a new screening phase.
5.5. 
Criteria for Temporarily Delaying Administration of Study Vaccination
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 the first 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. If any of these events occur at the scheduled time for one of the subsequent
vaccinations, the vaccination can be rescheduled, as long as this is in agreement with the allowed
windows (see Visit Windows in Section 8, Study Assessments and Procedures).
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.
At the time of unblinding (ie, after EUA or approval in any  country  and local protocol
Amendment 10 approval), a single dose of 5×1010 vp Ad26.COV2.S will be offered to Group 5
(placebo only) participants during an ad hoc crossover visit (refer to Section 8.6). If any of the
above listed events occur at the time of the planned ad hoc visit, the visit can be postponed till
symptoms have resolved.
Following local approval of protocol Amendment 15, all eligible participants (see Section 8.7) will
be offered a single ad hoc booster dose of 5×1010 vp Ad26.COV2.S. The ad hoc booster
vaccination will be provided to participants who have previously received 1 or more doses of any
COVID-19 vaccine (ie, the Ad26.COV2.S vaccine, an mRNA vaccine and/or another COVID-19

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vaccine authorized for primary vaccination including protein, inactivated, and adenovector-based
vaccines) if the last vaccination was ≥6 months ago. If any of the above listed events occur at the
scheduled time for the ad hoc booster vaccination, the booster vaccination visit with active vaccine
can be delayed within the preferred visit window (see Section 8.7).
6. 
STUDY VACCINATION AND CONCOMITANT THERAPY
6.1. 
Study Vaccinations Administered
Ad26.COV2.S will be supplied at a concentration of 1x1011  vp/mL as a suspension in single-use
vials and dosed at 5x1010 vp and 1x1011 vp. Formulation buffer 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 and placebo is 0.9% NaCl.
Study vaccine will be administered by IM injection into the deltoid muscle, preferably of the
non-dominant arm:
 
Ad26.COV2.S:
 
5x1010 vp: 0.75 mL of formulation buffer is withdrawn from one vial and added to a vial
containing 0.75 mL 1×1011  vp/mL, providing 5x1010 vp/mL in a vial with an extractable
volume of more than 1 mL. Then 1 mL will be withdrawn from this vial.
 
1x1011 vp: 2 single-use vials (0.5 mL will be withdrawn from 1 vial and added to a second
vial, which will then have an extractable volume of more than 1 mL. Then, 1 mL will be
withdrawn from the second vial).
 
Placebo: 0.9% NaCl solution: 1 mL
For blinding purposes, the same volume (1 mL) will be administered to all participants in a cohort.
For participants who received placebo only during primary regimen and who are offered a single
dose of 5×1010 vp Ad26.COV2.S at the time of unblinding (ie, after EUA or approval in any
country and local Amendment 10 approval), a dose level of 5×1010 vp in a volume of0.5 mL will
be administered.
Following local approval of protocol Amendment 15, for all eligible participants who are offered
a single ad hoc booster dose of 5×1010 vp Ad26.COV2.S, a dose level of 5×1010 vp in a volume of
0.5 mL will be administered.
Study vaccine administration must be captured in the source documents and the electronic case
report form (eCRF).
Ad26.COV2.S will be manufactured and provided under the responsibility of the sponsor. Refer
to the IB for a list of excipients.

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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 study site investigational product and procedures manual (SIPPM) and the
Investigational Product Preparation Instructions (IPPI) for additional guidance on study vaccine
preparation, handling, and storage.
An unblinded pharmacist or other qualified individual who will have no other study function will
prepare the appropriate vial and syringe, labeled with the participant’s identification number, and
provide the syringe to the blinded vaccine administrator who will perform the injection.
Accountability
The investigator is responsible for ensuring that all study vaccine received at the site is inventoried
and accounted for throughout the study. The study vaccine administered to the participant must be
documented on the vaccine accountability form. All study vaccine will be stored and disposed of
according to the sponsor's instructions. Study-site personnel must not combine contents of the
study vaccine containers.
Study vaccine must be handled in strict accordance with the protocol and the container label, and
must be stored at the study site in a limited-access area or in a locked cabinet under appropriate
environmental conditions. Unused study vaccine must be available for verification by the sponsor's
study site monitor during on-site monitoring visits. The return to the sponsor of unused study
vaccine will be documented on the 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.
Potentially hazardous materials containing hazardous liquids should be disposed of immediately
in a safe manner and therefore will not be retained for vaccine accountability purposes.
Study vaccine should be dispensed under the supervision of the investigator or a qualified member
of the study-site personnel, or by a hospital/clinic pharmacist. Study vaccine will be administered
only to participants participating in the study. Returned study vaccine must not be dispensed again,
even to the same participant. Study vaccine may not be relabeled or reassigned for use by other
participants. The investigator agrees neither to dispense the study vaccine from, nor store it at, any
site other than the study sites agreed upon with the sponsor. Further guidance and information for
the final disposition of unused study vaccines are provided in the SIPPM.

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6.3. 
Measures to Minimize Bias: Randomization and Blinding
Vaccine Allocation
Procedures for Randomization and Stratification
Central randomization will be implemented in this study. Within each cohort, participants will be
randomly assigned to 1 of the vaccine groups based on a computer-generated randomization
schedule prepared before the study by or under the supervision of the sponsor. For Cohort 2,
participants will be first randomly assigned to either Cohort 2a or 2b, and subsequently randomly
assigned to 1 of the 5 vaccine groups in each of Cohort 2a and 2b (see Table 2 and Table 3).
Randomization will be balanced by using randomly permuted blocks. For Cohorts 1 and 3,
randomization will be stratified by study site and seropositivity status at screening. For Cohort 2,
randomization will be stratified study site, seropositivity status at screening, and age group (60%
of participants ≥18 to ≤40 years and 40% of participants aged >40 to ≤55 years).
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. In addition, if IWRS cannot be
updated to allow dispensing of investigational product to Cohort 2 participants who have
previously been unblinded but did not receive and authorized/licensed COVID-19 vaccine, manual
assignment of kits may be performed.
Blinding Before EUA or Approval in any Country and Local Protocol Amendment 10
Approval
The investigator will not be provided with randomization codes. The codes will be maintained
within the IWRS, which has the functionality to allow the investigator to break the blind for an
individual participant.
Data that may potentially unblind the intervention  assignment (ie, immunogenicity data, study
vaccine accountability data, study vaccine allocation, biomarker or other specific laboratory data)
will be handled with special care to ensure that the integrity of the blind is maintained and the
potential for bias is minimized. This can include making special provisions, such as segregating
the data in question from view by the investigators, clinical team, or others as appropriate until the
time of database lock (DBL)and unblinding.
Under normal circumstances, the blind should not be broken until the database is finalized. 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 contact the sponsor or its

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designee if possible, to discuss the particular situation, before breaking the blind. Telephone
contact with the sponsor or its designee will be available 24 hours per day, 7days per week. In the
event the blind is broken, the sponsor must be informed as soon as possible. The date, time, and
reason for the unblinding must be documented in the IWRS and in the source document.
In general, randomization codes will be disclosed fully only if the study is completed, and the
clinical database is closed. However, if an interim 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 interim analysis.
Refer to Section 9.5, Planned Analysis, for details of the analyses.
If randomized participants are withdrawn from vaccination before the first dose of study vaccine
is administered, additional participants may be recruited to replace these participants at the
discretion of the sponsor. Any replacement participant will be assigned to the same group as the
original (discontinued) participant. If randomized participants are withdrawn after the first dose of
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.
Investigators may receive requests to unblind study participants who become eligible to receive an
authorized/licensed COVID-19 vaccine if/when these become available. In these cases, the
investigator will discuss with the participant available options and ramifications. If the participant
is eligible for an authorized/licensed vaccine according to local immunization guidelines or
recommendations and if the participant wishes to proceed with the unblinding, the investigator
will follow the unblinding procedures described above. The reason for the unblinding request
should be documented. The name and date(s) of administration of the other COVID-19 vaccine
should be recorded (see Section 6.8).
When unblinding, if it is determined that the participant received the Ad26.COV2.S vaccine (and
not placebo), the participant will be informed that there are no clinical data on the safety of
receiving a different COVID-19 vaccine after receiving Ad26.COV2.S.
In the event of a participant unblinding to receive an authorized/licensed COVID-19 vaccine and
the participant received an authorized/licensed COVID-19 vaccine outside of the study, no further

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study vaccination will be permitteda. Unblinded participants, that did not receive an
authorized/licensed COVID-19 vaccine outside of the study, will be asked to continue to be
followed in this study in line with the SoAto the extent that they permit, including Cohort 2 booster
vaccinations.
Safety and immunogenicity evaluations will be identical for all participants, including participants
that are unblinded to obtain an authorized/licensed COVID-19 vaccine and who remain in the
study, if applicable and feasible. Procedures installed at the time of unblinding all participants after
EUA or approval in any  country and local approval of protocol Amendment 10 (refer to
Section 8.6), will also apply to participants who were unblinded at their own request prior to
Amendment 10. For details regarding statistical analysis of these evaluations, refer to Sections 9.6
and 9.7.
Unblinding after EUA  or Approval in any  Country and Local Protocol Amendment 10
Approval
Following EUA, conditional licensure, or approval in any country for the single-dose regimen of
5×1010 vp Ad26.COV2.S, all participants from countries where Amendment 10 is approved locally
by the Health Authority and IEC/IRB will be unblinded to disclose who received placebo only
during primary regimen. After unblinding, enrolled participants who initially received placebo
only will be offered a single dose of 5×1010 vp Ad26.COV2.S. If willing to receive, they will
discontinue from participation in the placebo groups. Refer to Sections 7.4 and 8.6 for more details.
Statistical analysis of data obtained from the point of unblinding is outlined in Section 9.7.
Unblinding after Protocol Amendment 15 Approval (Ad Hoc Booster Vaccination)
Following local approval of Amendment 15 by the Health Authority and IEC/IRB, participants in
Group 1 and 4 of Cohort 2 will be partially unblinded. After unblinding, enrolled eligible
participants from Groups 1 and 4 of Cohort 2 will be offered a single ad hoc booster dose of
5×1010 vp Ad26.COV2.S. If willing to receive, they will discontinue from participation in their
current booster schedule. Refer to Sections 7.5 and 8.7for more details.
Statistical analysis of data obtained from the point of unblinding is outlined in Section 9.8.
6.4. 
Study Vaccine Compliance
Study vaccines will be administered IM by blinded qualified study-site personnel at the study site.
Details of each administration will be recorded in the eCRF (including date and time of injection
and deltoid used for injection). For blinding procedures, see Section 6.3, Measures to Minimize
Bias: Randomization and Blinding.
a Following local approval of protocol Amendment 15, eligible participants who received an authorized/licensed
COVID-19 vaccine outside of the study are allowed to receive a single ad hoc booster dose of Ad26.COV2.S
vaccine (5×1010 vp) if the last vaccination was ≥6 months ago.

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6.5. 
Dose Modification
Dose modification is not applicable in this study.
6.6. 
Continued Access to Study Vaccine After the End of the Study
At the end of the study, participants who received placebo may be offered the Ad26.COV2.S study
vaccine at no cost when the vaccine has been shown to be safe and efficacious, and preferably also
after the duration of protection has been determined. This will occur in accordance with local and
national regulations and in consultation with the responsible national authorities. The consent form
will inform all potential volunteers that this is our intent, if feasible.
If the Ad26.COV2.S study vaccine is determined to be efficacious during the course of this study,
the country-specific conditions (eg, registration status and local recommendations/regulations)
ethical considerations, requirements for duration of protection, and long term safety will determine
whether the study vaccine can be made available to vaccinate the placebo group, at the time of this
occurrence. This will be done by an amendment to the protocol, which will further outline study
conditions and options for each participant.
At the time when a COVID-19 vaccine is determined to be efficacious and authorized/licensed for
use, some participants maybecome eligible to receive such vaccine, depending on country-specific
conditions (eg, registration status, local recommendations/regulations, vaccine availability or the
specific target group for vaccination). The investigator will discuss with the participants the
available information and options to allow the participant to make an informed choice as to
whether they qualify to receive the authorized/licensed vaccine and whether they should request
individual unblinding to take up the offer of an authorized/licensed COVID-19 vaccine. In the
event of a participant unblinding to receive an authorized/licensed COVID-19 vaccine, and the
participant received an authorized/licensed COVID-19 vaccine outside of the study, no further
study vaccination will be permitteda. Unblinded participants, whether in the vaccine or control
group that did not did not receive an authorized/licensed COVID-19 vaccine outside of the study,
will be asked to continue to be followed in this study in line with the schedule of activities to the
extent that they permit, including Cohort 2 booster vaccinations. Safety and immunogenicity
evaluations will be identical for all participants, including participants that are unblinded to obtain
an authorized/licensed COVID-19 vaccine and who remain in the study, if applicable and feasible.
All data will be analyzed separately from the point of unblinding under the conditions outlined in
Sections 6.3 and 9.6.
Following EUA, conditional licensure, or approval in any country for the single-dose regimen of
5×1010 vp Ad26.COV2.S, all participants from countries where Amendment 10 is locally approved
by the Health Authority and IEC/IRB will be unblinded to disclose who received placebo only
during primary regimen. After unblinding, enrolled participants who initially received placebo
a Following local approval of protocol Amendment 15, eligible participants who received an authorized/licensed
COVID-19 vaccine outside of the study are allowed to receive a single ad hoc booster dose of Ad26.COV2.S
vaccine (5×1010 vp) if the last vaccination was ≥6 months ago.

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only will be offered a single dose of 5×1010 vp Ad26.COV2.S. If willing to receive, they will
discontinue from participation in the placebo groups. Refer to Sections 7.4 and 8.6 for more details.
Following local approval of protocol Amendment 15, all eligible participants will be offered a
single ad hoc booster dose of 5×1010 vp Ad26.COV2.S at no cost, as described in Section 8.7. The
ad hoc booster vaccination will be provided to participants who have previously received 1 or more
doses of any COVID-19 vaccine (ie, the Ad26.COV2.S vaccine, an mRNA vaccine and/or another
COVID-19 vaccine authorized for primary vaccination including protein, inactivated, and
adenovector-based vaccines) if the last vaccination was ≥6 months ago. Analyses and procedures
installed at the time of unblinding all participants after EUA or approval in any country and local
approval of protocol Amendment 10 (refer to Section 8.6), will also apply to participants who were
unblinded at their own request prior to Amendment 10.
6.7. 
Treatment of Overdose
For this study, any dose ofAd26.COV2.S greater than the highest dose tested in the study will be
considered an overdose. The sponsor does not recommend specific treatment for an overdose.
In the event of an overdose, the investigator should:
 
Contact the medical monitor immediately.
 
Closely monitor the participant for AEs/SAEs: (ie, the participant will remain at the study site
for at least 15 minutes or 1 hour depending on the vaccination being administered (see SoAs
for details) 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.
6.8. 
Prestudy and 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 first dose of study vaccine 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 from
the first dose of study vaccine until 28 days after administration of study vaccine, and thereafter,
pre-dose on the day of vaccination and for 28 days after the subsequent dose of study vaccine.
Concomitant therapies associated with a suspected AESI meeting the criteria outlined in
Section 8.3.6, will be recorded.
Receipt of a licensed/authorized COVID-19 vaccine by a study participant at any timepoint during
the study must be recorded. The name and date(s) of administration of the COVID-19 vaccine
should be recorded. 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

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requirements outline in Section 8.3.1, Time Period and Frequency for Collecting Adverse Event
and Serious Adverse Event Information. Participants from Cohorts 1a, 1b and 3, who received
additional/booster COVID-19 vaccines outside of the study during the additional follow-up of the
study, should be allowed to stay in the study, however these vaccines should be recorded in the
Concomitant Medications section of the eCRF.
Use of any experimental medication (including experimental vaccines other than the study
vaccine) will lead to discontinuation of administration of any subsequent study vaccination. Any
participant who has received a COVID-19 vaccine outside of the study, or treatment, will not
receive further study vaccinationa. 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 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) within 6 months before the
planned administration of the first dose of study vaccine.
Vaccination with licensed live attenuated vaccines within 28 days of a study vaccination (ie, before
or after) is prohibited. 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. If a vaccine is indicated in a post-exposure setting (eg, rabies or tetanus), it must take
priority over the study vaccine.
Analgesic medications and nonsteroidal anti-inflammatory drugs may be used post-vaccination at
the first signs of symptoms or in case of medical need. Use of these medications as routine
prophylaxis prior to study vaccine administration is prohibited.
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 corticosteroidsb 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 first dose of 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, Exclusion Criteria, for further details of prohibited therapy.
a Following local approval of protocol Amendment 15, eligible participants who received an authorized/licensed
COVID-19 vaccine outside of the study are allowed to receive a single ad hoc booster dose of Ad26.COV2.S
vaccine (5×1010 vp) if the last vaccination was ≥6 months ago.
b Note: Ocular, topical or inhaled steroids are allowed.

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The sponsor must be notified in advance (or as soon as possible thereafter) of any instances in
which prohibited therapies are administered. The participant should remain in the study but receive
no further study vaccination. Depending on the time of the occurrence, any participant who
receives a prohibited concomitant medication will not be included in the immunogenicity analyses.
6.9. 
Study Vaccination Pausing Rules
Upon completion of all Day 57 vaccinations in all cohorts, the study pausing criteria as outlined
below are no longer applicable.
For Cohorts 1a and 3, randomization and vaccination of participants will be suspended during
review of the 24-hour data following the first administration of study vaccine to 5 sentinel
participants and, if applicable, during the review of safety data after the first 15 participants have
received the first vaccination (see Section 4.1, Overall Design).
For each cohort, the PI and the SRP will monitor safety in a blinded manner, including the study
vaccination pausing rules. If a study vaccination is considered to raise significant safety concerns
(and a specific set of pausing criteria have been met), further vaccination of participants will be
paused. The concerned data will be reviewed by the DRC, after which the DRC will recommend
whether the pause can be lifted or not, or whether other steps are needed.
The DRC will review blinded data first but has the right to request the randomization codes and
review unblinded data if deemed necessary. The DRC will make recommendations regarding the
continuation of the study to the sponsor study team. The sponsor study team will communicate
conclusions regarding study continuation to the investigator, the Independent Ethics Committee
(IEC) / Institutional Review Board (IRB), and applicable health authorities as appropriate.
After the first DRC meeting triggered by the occurrence of a given pausing rule, the DRC will
convene thereafter for each additional participant meeting that pausing rule.
The occurrence of any of the following events will lead to a pause in further study vaccination.
1. Death of a participant, considered related to study vaccine or if the causal relationship to the
study vaccine cannot be excluded; OR
Note: All cases of death will be sent for DRC information. Upon their review, the DRC
may then decide whether a study pause is required.
2. One or more participants experience an SAE or a Grade 4 (solicited or unsolicited) AE or a
persistent (upon repeat testing) Grade 4 laboratory abnormality 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; OR
4. Three or more participants experience a Grade 3 unsolicited AE of the same type (as per
medical judgment of the sponsor), that is determined to be related to study vaccine; OR

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5. Three or more participants experience a persistent (upon repeat testing) Grade 3 laboratory
abnormality related to the same laboratory parameter and considered related to study vaccine;
OR
6. Three or more participants experience a Grade 3 solicited AE of the same type, determined to
be related to study vaccine, and persisting as Grade 3 for longer than 3 consecutive daysa.
7. A study pause is triggered in Studies VAC31518COV1002, VAC31518COV2001, or
VAC31518COV3001.
For number 2 and number 5: to assess abnormal laboratory values, the test must be repeated at
least once, within 48 hours of the site becoming aware of the abnormal value.
For number 4, number 5, and number 6: after each DRC review of similar AEs, the Committee
will indicate the conditions under which it requires further notification and review of the
subsequent similar AEs.
To enable prompt response to a situation that could trigger pausing rules, the investigator should
notify the sponsor’s medical monitor or designee (AND fax or email SAE form to Global Medical
Safety Operations, if applicable), immediately and no later than 24 hours after becoming aware of
any related AE of Grade 3 or above AND update the eCRF with relevant information on the same
day the AE information is collected. A thorough analysis of all Grade 3 (or above) cases will be
carried out by the sponsor’s medical monitor or designee, irrespective of whether the criteria for
pausing the study are met. Based on the pausing criteria, the sponsor’s medical monitor or designee
then decides whether a study pause is warranted. 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 DRC members and coordination of a DRC meeting in case of a study pause.
Vaccinations for an individual participant may be suspended for safety concerns other than those
described in the pausing criteria, at the discretion of the investigator if he/she feels the participant’s
safety may be threatened. The sponsor’s medical monitor or designee or the investigator(s) (upon
consultation with the sponsor’s medical monitor or designee) may initiate DRC 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 DRC, participant safety may be
threatened.
Resumption of vaccinations paused by the DRC will start only upon receipt of written
recommendations by the DRC. The clinical site(s) will be allowed to resume activities upon receipt
of a written notification from the sponsor. The decision from the DRC will be forwarded by the
a The day of occurrence of the AE is counted as Day 1.

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investigator to the IRB/IEC and by the sponsor to the relevant health authorities, according to local
standards and regulations.
7. 
DISCONTINUATION OF STUDY VACCINATION AND PARTICIPANT
DISCONTINUATION/WITHDRAWAL
7.1. 
Discontinuation of Study Vaccination
Study vaccinations will be withheld for the reasons listed below. These participants must not
receive any further doses of study vaccine but should remain on study for follow-up with
assessments of safety and immunogenicity. Additional unscheduled visits may be performed for
safety/reactogenicity reasons, if needed. In case of questions, the investigator is encouraged to
contact the sponsor.
 
Any related AE, worsening of health status or intercurrent illnesses that, in the opinion of the
investigator, requires discontinuation from study vaccine
 
The participant becomes pregnant
 
Note: Applicable to the US only: Following local approval of Protocol Amendment 15,
participants who are pregnant may receive booster vaccination with Ad26.COV2.S, if
allowed by local regulations and if the investigator considers that the potential benefits
outweigh the potential risks to the mother and fetus (see Section 8.7).
 
Unblinding on the participant level that, in the opinion of the sponsor, would compromise the
integrity of the data
 
The participant received an authorized/licensed COVID-19 vaccine outside of the study.
 
Note: following local approval of protocol Amendment 15, eligible participants (see
Section 8.7) are allowed to receive a single ad hoc booster dose of Ad26.COV2.S vaccine
(5×1010 vp) if the last vaccination was ≥6 months ago.
 
Anaphylactic reaction following vaccination, not attributable to causes other than vaccination
 
SAE or other potentially life-threatening (Grade 4) event that is determined to be related to
study vaccine
 
Chronic or recurrent use of systemic corticosteroids and administration of antineoplastic and
immunomodulating agents or radiotherapy
 
Withdrawal from further study vaccination
 
Participant has a positive test result for SARS-CoV-2 infection during the study  (see
Section 8.1.2). Note: participants may receive a placebo crossover vaccination or ad hoc
booster vaccination with the Ad26.COV2.S vaccine after they have recovered from the acute
illness and at least 3 months have passed as specified in Sections 8.6 and 8.7.
 
Participant receives any experimental medication (including experimental vaccines other than
the study vaccine) or receives a COVID-19 treatment
 
Participant previously experienced TTS, or heparin-induced thrombocytopenia (HIT)or GBS.

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 
Participant experiences capillary leak syndrome (CLS)after the first dose.
 
Applicable to Belgium only: Per the Belgian-specific protocol Amendment 15, participants
aged <65 years enrolled at Belgian sites.
7.2. 
Participant Discontinuation/Withdrawal From the Study
A participant will be withdrawn from the study for any of the following reasons:
 
Lost to follow-up
 
Withdrawal of consent from the study
 
Death
 
Repeated failure to comply with protocol requirements
 
Participant in Cohort 2b does not have the second study vaccination on Day 57 (-3/+7 days),
except for when the vaccination was missed due to a confirmed SARS-CoV-2 infection (refer
to Sections 7.1 and 8.1.2)
 
Participants who received placebo only during primary regimen and who cho(o)se to receive
an authorized/licensed vaccine outside of the study (applies to participants unblinded before
and after EUA  or approval in any country), once protocol Amendment 10 has been
implemented locally
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 required,
but an optional safety visit will still be offered.
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, Appendix 3, Regulatory,
Ethical, and Study Oversight Considerations). In such a case, samples will be destroyed after they
are no longer needed for the clinical study. Details of the sample retention for research are
presented in the main ICF.
7.3. 
Lost to Follow-up
A participant will be considered lost to follow-up if he or she repeatedly fails to return for
scheduled visits and is unable to be contacted by the study site. A participant cannot be deemed
lost to follow-up until all reasonable efforts made by the study-site personnel to contact the

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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,
e-mails, 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.
7.4. 
Discontinue from Placebo Group Participation
Following EUA, conditional licensure, or approval in any country for the single-dose regimen of
5×1010 vp Ad26.COV2.S, all participants from countries where Amendment 10 is locally approved
by the Health Authority and IEC/IRB will be unblinded to disclose who received placebo only
during primary regimen. After unblinding, enrolled participants who initially received placebo
only will be offered a single dose of 5×1010 vp Ad26.COV2.S (ie, placebo crossover vaccination).
If willing to receive, they will discontinue from participation in the placebo groups. They will be
redirected to SoA "Procedures for Group 5 (Placebo Only) Participants Receiving a Single Dose
of 5x1010 vp Ad26.COV2.S (Placebo Crossover Vaccination) after EUA or Approval in any
Country" (see Section 1.3.7). Refer to Section 8.6 for more details regarding assessments and
procedures after EUA approval.
7.5. 
Discontinue from Cohort Vaccination
Following local approval of protocol Amendment 15, all eligible participants (see Section 8.7) will
be offered a single ad hoc booster dose of Ad26.COV2.S vaccine (5×1010 vp). The ad hoc booster
vaccination will be provided to participants who have previously received 1 or more doses of any
COVID-19 vaccine (ie, the Ad26.COV2.S vaccine, an mRNA vaccine and/or another COVID 19
vaccine authorized for primary vaccination including protein, inactivated, and adenovector-based
vaccines) if the last vaccination was ≥6 months ago. If willing to receive, they will discontinue
from participation in their current schedules (SoAs in Sections 1.3.1, 1.3.2, 1.3.3.2, 1.3.4.2, 1.3.5,
and 1.3.9) and will be redirected to SoA “Procedures for Participants Receiving an Ad Hoc Booster
Vaccination of 5x1010 vp Ad26.COV2.S” (see Section 1.3.10).

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8. 
STUDY ASSESSMENTS AND PROCEDURES
Overview
The Schedule of Activities summarizes the frequency and timing of safety, reactogenicity,
immunogenicity and other measurements applicable to each cohort in this study. See Section 1.3
for details.
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. Actual dates and times of
assessments will be recorded in the source document and in the eCRF.
Participants will be provided a thermometer (to measure body temperature), ruler (to measure local
injection site reactions), and participant diary to record body temperature and solicited local (at
injection site) and systemic signs and symptoms. The 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 diary will be reviewed by the study personnel at visits
indicated in the Section 1.3, Schedule of Activities. If the diary review is missed, the diary will be
reviewed during the following visit. If a participant misses a vaccination, the diary covering the
period after the missed vaccination does not have to be completed.
Participants will also be provided with a booklet (to answer a daily signs and symptoms
surveillance question, and including the SIC) and a kit to collect nasal swabs if they experience
COVID-19-like symptoms during the study (see Section 8.1.2, Procedures in Case of
COVID-19-like Signs and Symptoms and Section 8.1.2.3, Prespecified Criteria for Suspected
COVID-19).
For participants who do not undergo additional procedures due to COVID-19-like signs and
symptoms, the maximum amount of blood drawn in this study will not exceed approximately
965 mL for Cohorts 1a or 3, 1,225 mL for Cohort 1b, 514.5 mL for Cohort 2a and 752.5 mL for
Cohort 2b. For participants who undergo additional procedures due to COVID-19-like signs and
symptoms, an additional approximately 17.5 mL of blood will be collected. For participants who
experience a suspected AESI, an additional approximately 30 mL of blood will be collected. Refer
to Section 1.3, Schedule of Activities for the total blood volume (serum and, as applicable, PBMCs
and whole blood samples) to be collected at each visit and over the complete course of the study
for each cohortand in case of COVID-19-like signs and symptoms. Repeat or unscheduled samples
may be taken for safety reasons or for technical issues with the samples.
For participants who receive an ad hoc booster vaccination of 5x1010 vp Ad26.COV2.S, up to a
maximum of 284 mL of blood will be collected additionally.
Study visits, other than screening and visits at which study vaccination is scheduled, may take
place at the participant’s home if there are travel restrictions in case of an ongoing pandemic.

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Visit Windows
Visit windows that will be allowed are summarized below. The participant should be encouraged
to come on the exact day planned and use the visit window only if absolutely necessary.
The timings of the post-vaccination visits will be determined relative to the actual day of the
corresponding vaccination. If a participant misses a vaccination, the post-vaccination visits will be
scheduled using the date that the vaccination was scheduled to take place.
If a vaccination window is missed due to a study pause (see Section 6.9), efforts will be made to
still vaccinate the participant as soon as possible. Visit windows for vaccination visits will not
apply for study pauses or vaccination pauses. The timings of the post vaccination visits will be
determined relative to the actual day of the vaccination, unless they overlap with other scheduled
visits, in which case the sponsor should be contacted to discuss optimal scheduling for these visits.
Table 4: 
Visit Windows Cohort 1a
Visitc 
Target Visit Day  
Allowed Window  Primary Purpose
5 a 
8 
±2 days 
7 days post-vaccination 1 safety visit
6 
15 
±3 days 
14 days post-vaccination 1 safety and immunogenicity visit
7 
29 
±3 days 
28 days post-vaccination 1 safety and immunogenicity visit
8 
57 
-3/+7 days 
Vaccination 2
10 a 
64 b 
±2 days 
7 days post-vaccination 2 safety visit
11 
71 b 
±3 days 
14 days post-vaccination 2 safety and immunogenicity visit
12 
85 b 
±3 days 
28 days post-vaccination 2 safety and immunogenicity visit
13 
239 b 
±21 days 
6 months post-vaccination 2 safety and immunogenicity visit
14 
422 
±21 days 
12 months post-vaccination 2 safety and immunogenicity visit
FU1 
513b 
±21 days 
15 months post-vaccination 2 safety telephone call (visit if
necessary)
FU2 
604b 
±21 days 
18 months post-vaccination 2 safety and immunogenicity visit
FU3 
696b 
±21 days 
21 months post-vaccination 2 safety telephone call (visit if
necessary)
FU4 
787b 
±21 days 
24 months post-vaccination 2 safety and immunogenicity visit
a. If a participant comes in early for Visit 5 or 10, ie, 1 or 2 days prior to the Target Visit Day per the allowed visit
window, a subsequent phone call will be made at the end of the diary period to collect diary information recorded
between the actual visit and the end of the diary period. The diary will then be returned by the participant at the
next visit. If an event is still ongoing on the Target Visit Day, the participant should keep the diary after the review
and collect information until resolution. The diary should be reviewed again at the next visit.
b. The timings of visits after the second vaccination will be determined relative to the actual day of that vaccination.
c. Following local approval of Protocol Amendment 15, all eligible participants willing to receive a single ad hoc
booster dose of 5×1010 vp Ad26.COV2.S will discontinue their cohort schedule and follow the procedures in
Table 9.

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Table 5: 
Visit Windows Cohort 1b
Visite 
Target Visit Day  Allowed 
Window
Primary Purpose
4 a 
8 
±2 days 
7 days post-vaccination 1 safety and immunogenicity visit
5 
15 
±3 days 
14 days post-vaccination 1 safety and immunogenicity visit
6 
29 
±3 days 
28 days post-vaccination 1 safety and immunogenicity visit
7 
57 
-3/+7 days 
Vaccination 2
9 a 
64 b 
±2 days 
7 days post-vaccination 2 safety and immunogenicity visit
10 
71 b 
±3 days 
14 days post-vaccination 2 safety and immunogenicity visit
11 
85 b 
±3 days 
28 days post-vaccination 2 safety and immunogenicity visit
12 
239 b 
±21 days 
6 months post-vaccination 2 safety and immunogenicity visit
13 
422 
±21 days 
12 months post-vaccination 2 safety and immunogenicity visit
13ab, c 
422d 
-21/+60 days 
LNA safety and immunogenicity visit
13bb, c 
425 
±1 day  
72 hours post-LNA safety follow-up telephone call
13cb, c 
429 
±1 day  
1 week post-LNA safety visit
FU1 
513b 
±21 days 
15 months post-vaccination 2 safety telephone call (visit if
necessary)
FU2 
604b 
±21 days 
18 months post-vaccination 2 safety and immunogenicity visit
FU3 
696b 
±21 days 
21 months post-vaccination 2 safety telephone call (visit if
necessary)
FU4 
787b 
±21 days 
24 months post-vaccination 2 safety and immunogenicity visit
a. If a participant comes in early for Visit 4 or 9, ie, 1 or 2 days prior to the Target Visit Day per the allowed
visit window, a subsequent phone call will be made at the end of the diary period to collect diary information
recorded between the actual visit and the end of the diary period. The diary will then be returned by the
participant at the next visit. If an event is still ongoing on the Target Visit Day, the participant should keep
the diary after the review and collect information until resolution. The diary should be reviewed again at the
next visit.
b. The timings of visits after the second vaccination will be determined relative to the actual day of that
vaccination.
c. Visit 13a, 13b, and 13c are visits for Cohort 1b participants that provided consent for the optional LNAs.
d. The LNA may occur at Day 422 (in this case Visit 13 and optional Visit 13a will coincide) or will be
performed at a later timepoint within the specified window (Day 422 -21/+60).
e. 
Following local approval of Protocol Amendment 15, all eligible participants willing to receive a single ad
hoc booster dose of 5×1010 vp Ad26.COV2.S will discontinue their cohort schedule and follow the
procedures in Table 9.

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Table 6: 
Visit Windows Cohort 2a
Visitd 
Target Visit Day  Allowed 
Window
Primary Purpose
3 a 
8 
±2 days 
Safety and immunogenicity visit 7 days after primary regimen
4 
29 
±3 days 
Safety and immunogenicity visit 28 days after primary regimen
5 
183 
±21 days 
Safety and immunogenicity visit / single booster vaccination
6 months after primary regimen c
6 a 
190 b 
±2 days 
Safety and immunogenicity visit 7 days post-booster vaccination
7 
211 b 
±3 days 
Safety and immunogenicity visit 28 days post-booster vaccination
8 
366 
±21 days 
Safety and immunogenicity visit / single booster vaccination
12 months after primary regimen c
9 a 
373 b 
±2 days 
Safety and immunogenicity visit 7 days post-booster vaccination
10 
394 b 
±3 days 
Safety and immunogenicity visit 28 days post-booster vaccination
11 e 
731 
±21 days 
Safety
a. If a participant comes in early for Visit 3, 6, or 9, ie, 1 or 2 days prior to the Target Visit Day per the allowed
visit window, a subsequent phone call will be made at the end of the diary period to collect diary information
recorded between the actual visit and the end of the diary period. The diary will be returned by the participant
at the next visit. If an event is still ongoing on the Target Visit Day, the participant should keep the diary after
the review and collect information until resolution. The diary should be reviewed again at the next visit.
b. The timings of visits after a booster vaccination will be determined relative to the actual day of that vaccination.
c. Participants designated to receive a single booster vaccination will receive Ad26.COV2.S  at 6 months or
12 months after completion of the single-dose primary regimen and will receive placebo at the other indicated
time point. Participants not designated to receive a booster vaccination will receive placebo at each indicated
time point. See Table 2 for further details.
d. Following local approval of Protocol Amendment 15, all eligible participants of Groups 1 and 4 willing to
receive a single ad hoc booster dose of 5×1010 vp Ad26.COV2.S will discontinue their cohort schedule and
follow the procedures in Table 9
e. Visit 11 is the last visit.

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Table 7: 
Visit Windows Cohort 2b
Visit c 
Target Visit Day  Allowed 
Window
Primary Purpose
3 a 
8 
±2 days 
Safety and immunogenicity visit 7 days post-vaccination 1
4 
29 
±3 days 
Safety and immunogenicity visit 28 days post-vaccination 1
5 
57 
-3/+7 days 
Vaccination 2
6 a 
64 b 
±2 days 
Safety and immunogenicity visit 7 after primary regimen
7 
85 b 
±3 days 
Safety and immunogenicity visit 28 after primary regimen
8 
239 b 
±21 days 
Safety and immunogenicity visit / single booster vaccination
6 months after primary regimen c
9 a 
246 b 
±2 days 
Safety and immunogenicity visit 7 days post-booster vaccination
10 
267 b 
±3 days 
Safety and immunogenicity visit 28 days post-booster vaccination
11 
422 b 
±21 days 
Safety and immunogenicity visit / single booster vaccination
12 months after primary regimen c
12 a 
429 b 
±2 days 
Safety and immunogenicity visit 7 days post-booster vaccination
13 
450 b 
±3 days 
Safety and immunogenicity visit 28 days post-booster vaccination
14 e 
787 b 
±21 days 
Safety
a. If a participant comes in early for Visit 3, 6, 9, or 12, ie, 1 or 2 days prior to the Target Visit Day per the
allowed visit window, a subsequent phone call will be made at the end of the diary period to collect diary
information recorded between the actual visit and the end of the diary period. The diary will be returned by the
participant at the next visit. If an event is still ongoing on the Target Visit Day, the participant should keep the
diary after the review and collect information until resolution. The diary should be reviewed again at the next
visit.
b. The timings of visits after the second vaccination or a booster vaccination will be determined relative to the
actual day of that vaccination.
c. Participants designated to receive a single booster vaccination will receive Ad26.COV2.S  at 6 months or
12 months after completion of the 2-dose primary regimen and will receive placebo at the other indicated time
point. If the 2nd vaccination at Day 57 is not provided, then participants will discontinue the study (refer to
Section 7.2). Participants not designated to receive a booster vaccination will receive placebo at each indicated
time point. See Table 3 for further details.
d. Following local approval of Protocol Amendment 15, all eligible participants of Groups 1 and 4 willing to
receive a single ad hoc booster dose of 5×1010 vp Ad26.COV2.S will discontinue their cohort schedule and
follow the procedures in Table 9.
e. Visit 14 is the last visit.

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Table 8: 
Visit Windows Cohort 3
Visitc 
Target Visit Day  
Allowed Window  Primary Purpose
4 a 
8 
±2 days 
7 days post-vaccination 1 safety visit
5 
15 
±3 days 
14 days post-vaccination 1 safety and immunogenicity visit
6 
29 
±3 days 
28 days post-vaccination 1 safety and immunogenicity visit
7 
57 
-3/+7 days 
Vaccination 2
9 a 
64 b 
±2 days 
7 days post-vaccination 2 safety visit
10 
71 b 
±3 days 
14 days post-vaccination 2 safety and immunogenicity visit
11 
85 b 
±3 days 
28 days post-vaccination 2 safety and immunogenicity visit
12 
239 b 
±21 days 
6 months post-vaccination 2 safety and immunogenicity visit
13 
422 
±21 days 
12 months post-vaccination 2 safety and immunogenicity visit
FU1 
513b 
±21 days 
15 months post-vaccination 2 safety visit
FU2 
604b 
±21 days 
18 months post-vaccination 2 safety and immunogenicity visit
FU3 
696b 
±21 days 
21 months post-vaccination 2 safety visit
FU4 
787b 
±21 days 
24 months post-vaccination 2 safety and immunogenicity visit
a. If a participant comes in early for Visit 4 or 9, ie, 1 or 2 days prior to the Target Visit Day per the allowed visit
window, a subsequent phone call will be made at the end of the diary period to collect diary information
recorded between the actual visit and the end of the diary period. The diary will then be returned by the
participant at the next visit. If an event is still ongoing on the Target Visit Day, the participant should keep the
diary after the review and collect information until resolution. The diary should be reviewed again at the next
visit.
b. The timings of visits after the second vaccination will be determined relative to the actual day of that
vaccination.
c. Following local approval of Protocol Amendment 15, all eligible participants willing to receive a single ad hoc
booster dose of 5×1010 vp Ad26.COV2.S will discontinue their cohort schedule and follow the procedures in
Table 9.
Table 9: 
Visit Windows Ad Hoc Booster Vaccination
Visit 
Target Visit Day  
Allowed Window  
Primary Purpose
Ad hoc booster 
visit (AHBV) 
≥6 mo after last 
COVID-19 vaccination a 
As soon as possible, but 
no later than 120 days
post local approval of
protocol amendment 15
Ad hoc booster vaccination
Booster FU1 
AHBV + 28 days b 
±3 days 
Safety and immunogenicity visit
28 days post-booster vaccination
Booster FU2 c 
AHBV + 182 days b 
±21 days 
Safety and immunogenicity visit
6 months post-booster vaccination
a. Following local approval of protocol amendment 15, a single ad hoc booster vaccination with Ad26.COV2.S
at the 5x1010 vp dose level will be offered to all eligible participants. The ad hoc booster vaccination will be
provided to participants who have previously received 1 or more doses of any COVID-19 vaccine (ie, the
Ad26.COV2.S vaccine, an mRNA vaccine and/or another COVID-19 vaccine authorized for primary
vaccination including protein, inactivated, and adenovector-based vaccines) if the last vaccination was
≥6 months ago.
b. The timings of visits after the booster vaccination will be determined relative to the actual day of that
vaccination.
c. Changes following local approval of Protocol Amendment 16 for participants who are attending ad hoc booster
visit are provided in the Schedule of activities in Section 1.3.10.

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Screening
Screening will be performed within 28 days prior to the first 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. Screening must be completed and all eligibility criteria must be fulfilled prior to
randomization and vaccination.
Screening may be conducted in part via a sponsor- and IRB/IEC-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 4 weeks prior to first 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 molecular test for the
presence of SARS-CoV-2 infection must be done within 4 days before vaccinationa. Participants
who test positive for SARS-CoV-2 infection will be informed of the result by the study staff. The
study-specific ICF date will be entered into the eCRF. The non-study-specific ICF will be
considered source data.
Sample Collection and Handling
The actual dates and times of sample collection must be recorded in the eCRF or laboratory
requisition form. Refer to Section 1.3, 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.
Study-Specific Materials
The investigator will be provided with the following supplies:
 
IB for Ad26.COV2.S
 
Thermometer
 
Ruler (to measure diameter of any erythema and swelling)
 
Pharmacy manual/SIPPM
 
IWRS Manual
 
Sample ICF
 
Laboratory manual
a Vaccination with Ad26.COV2.S may interfere with some serologic assays utilized at local community health
clinics/commercial laboratories, by seeking and identifying the spike protein in the vaccine and rendering a false
positive result. For this reason, participants will be encouraged to not seek serologic testing outside the study. If a
participant requests serologic testing outside of the protocol-mandated testing schedule, this will be offered at the
next scheduled on-site blood draw visit.

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 
Participant diaries
 
Nasal swab kits
 
Participant instructions and booklet: COVID-19-like signs and symptoms daily surveillance,
nasal swab instructions, and SIC (for daily completion, if symptomatic)
 
Contact information page(s)
 
eCRF completion guidelines
8.1. 
Immunogenicity and Efficacy Assessments
8.1.1. 
Immunogenicity Assessments
Venous blood samples will be collected for assessment of humoral or cellular immune responses.
Sample volumes and time points are detailed in the Schedule of Activities for Cohort 1a
(Section 1.3.1), Cohort 1b (Section 1.3.2), Cohort 2a (Section 1.3.3), Cohort 2b (Section 1.3.4)
and Cohort 3 (Section 1.3.5), for participants with a positive test result for SARS-CoV-2 infection
(Section 1.3.6), for additional follow-up for Cohorts 1a, 1b and 3 (Section 1.3.9), and for
participants receiving an ad hoc booster vaccination (Section 1.3.10).
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, Schedule of Activities for further details.
Humoral and cellular immunogenicity assays may include, but are not limited to, the assays
summarized in Table 10 and Table 11 respectively.
Exploratory assessments on lymph node samples for Cohort 1b (Beth Israel Deaconess Medical
Center [BIDMC])may include, but are not limited to characterization of resident immune cells by
flow cytometry, gene expression, and cytokine release (see Section 8.1.1.1).

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Assays used for the double-blind phase and post unblinding of the study:
Table 10: Summary of Humoral Immunogenicity Assays
Assay 
Purpose
Secondary endpoints
SARS-CoV-2 neutralization 
(VNA) 
Analysis of neutralizing antibodies to the wild-type virus and/or
pseudovirion expressing S protein
SARS-CoV-2 binding 
antibodies (ELISA)
Analysis of antibodies binding to the SARS-CoV-2 S protein
Exploratory endpoints
SARS-CoV-2 binding 
antibodies to S protein (MSD) 
Analysis of antibodies binding to SARS-CoV-2 S protein and the
RBD of SARS-CoV-2 S protein
SARS-CoV-2 neutralization 
(neutralization assay) 
Analysis of neutralizing antibodies to the vaccine strain (or other
lineage), as measured by an alternative neutralization assay (different
from the VNA used for the secondary endpoint)
SARS-CoV-2 binding 
antibodies (ELISA) 
Analysis of antibodies binding to the SARS-CoV-2 N protein, if such
an assay can be developed
Adenovirus neutralization 
(neutralization assay)
Analysis of neutralizing antibodies to adenovirus
Functional and molecular 
antibody characterization  
Analysis of antibody characteristics including Fc-mediated viral
clearance, avidity, Fc characteristics, Ig subclass and IgG isotype
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; SARS-CoV-2 = severe acute respiratory syndrome coronavirus-2; VNA = virus
neutralization assay

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Table 11: Summary of Cellular Immunogenicity Assays
Assay 
Purpose
Secondary endpoints
Flow cytometry (ICS) 
Analysis of T-cell responses to SARS-CoV-2 S protein, and/or other protein
peptides by ICS including CD4+/CD8+, IFNγ, IL-2, TNFα, IL-4, IL-5,
IL-13, and/or other Th1/Th2 markers
Exploratory endpoints
ELISpot 
IFNγ and IL-4 responses to SARS-CoV-2 S protein peptides by PBMCs,
based on single 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-2 S
protein peptides or in unstimulated cells or whole blood (ex vivo)
Cytokine profiling 
(ELISA or multiplexed 
arrays) 
Analysis of cytokines, chemokines, and other proteins of the innate or
adaptive immune response in cells or whole blood stimulated with
SARS-CoV-2 S protein peptides, or in unstimulated cells or whole blood,
by ELISA or multiplexed arrays and confirmation by functional in vitro
assays
T and B cell phenotyping Analysis of the phenotype of antigen-specific T and B cells, assessed by
single cell analysis (on frozen or Smart tube isolated PBMCs)
Evaluation of germinal 
centers in lymph nodes
(see Section 8.1.1.1)
Analysis of the immune responses in lymph nodes
ELISA = enzyme-linked immunosorbent assay; ELISpot = enzyme-linked immunospot (assay); ICS = intracellular
cytokine staining; IFNγ = interferon gamma; IL = interleukin; PBMC = peripheral blood mononuclear cell;
RNA = ribonucleic acid; S = spike; SARS-CoV-2 = severe acute respiratory syndrome coronavirus-2;
TNFα = tumor necrosis factor alpha
Assays used for the ad hoc booster vaccination:
Table 12: Summary of Humoral Immunogenicity Assays
Assay 
Purpose
Exploratoryendpoints
SARS-CoV-2 neutralization
(VNA)
Analysis of neutralizing antibodies to the wild-type virus and/or
pseudovirion expressing S protein from the original strain and/or
emerging variants
SARS-CoV-2 binding 
antibodies (ELISA) 
Analysis of antibodies binding to the SARS-CoV-2 S and RBD
protein from the original strain and/or emerging variants
SARS-CoV-2 binding 
antibodies (ELISA)
Analysis of antibodies binding to the SARS-CoV-2 N protein
Adenovirus neutralization 
(neutralization assay)
Analysis of neutralizing antibodies to adenovirus
Functional and molecular 
antibody characterization  
Analysis of antibody characteristics including Fc-mediated viral
clearance, avidity, Fc characteristics, Ig subclass and IgG isotype
Epitope-specificity 
characterization
Analysis of site-specificity, epitope mapping
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; RBD = receptor-binding domain; SARS-CoV-2 = severe acute
respiratory syndrome coronavirus-2; VNA = virus neutralization assay

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Table 13: Summary of Cellular Immunogenicity Assays
Assay 
Purpose
Exploratoryendpoints
Flow cytometry (ICS) 
Analysis of T-cell responses to SARS-CoV-2 S protein, and/or other
protein peptides by ICS including CD4+/CD8+, IFNγ, IL-2, TNFα, IL-4,
IL-5, IL-13, and/or other Th1/Th2 markers
ICS = intracellular cytokine staining; IFNγ = interferon gamma; IL = interleukin; S = spike; SARS-CoV-2 = severe
acute respiratory syndrome coronavirus-2; TNFα = tumor necrosis factor alpha
8.1.1.1. 
Optional Lymph Node Aspiration
Late increases in neutralizing antibody  responses to COVID-19 variants have been observed,
suggesting ongoing B cell maturation. In this regard, there is an interest to study the immune
responses in lymph nodes to better understand the increase in neutralizing activities of the
antibodies against variants, generated by Ad26.COV2.S.
Fine-needle aspirates will be collected for Cohort 1b (Beth Israel Deaconess Medical Center
[BIDMC]), preferably  from the axillary lymph nodes draining the injection site (left or right
deltoid), corresponding to the side where the participant received the vaccination, in those
participants who consent to this optional procedure. For study participants who received open-label
ad hoc Ad26.COV2.S vaccination, the side of that vaccination should be preferably used. A
possible correlation between T-follicular helper cells, B-cell activation/specificity and the quality
of antibody response will be evaluated (eg, by flow cytometry). Fine needle aspiration is a
minimally invasive procedure routinely used by interventional radiologists and in cytopathology
laboratories to access lymphoid tissues for clinical evaluation of various malignancies, infections
and autoimmune diseases. Interventional radiologists are chosen to perform this procedure as
ultrasound-guidance will be necessary to locate non-palpable lymph nodes; these are the type of
lymph nodes most often encountered in healthy participants. If the interventional radiologist
determines that obtaining an axillary sample would pose an increased risk to the participants, or it
may be difficult to obtain adequate cell yield, sampling from axillary lymph nodes on the opposite
body side, or cervical/inguinal lymph nodes may be considered. Prior to the LNA an anesthetic
will be injected into the site of the procedure. At most, serial sampling of 1-2 lymph nodes will be
performed (each lymph node will be sampled 4 times). If sampling of the first lymph node is very
small, then there may be a need to sample a second lymph node.
The procedure will be performed at approximately 12 months after the 2nd vaccination (active or
placebo) orapproximately6 months after the ad hoc vaccination (for participants who crossed over
from placebo to receive active Ad26.COV2.S 5x1010 vp vaccination) in Cohort 1b participants that
have provided consent.
A study coordinator or study clinician will contact the participant by phone within 72 hours after
the procedure to further follow-up on the safety. Study staff will coordinate if the participant
prefers to schedule an in person visit for the follow-up contact. The participant will be asked
questions regarding any ongoing bleeding, pain control, and signs or symptoms of infection.
Participants contacted by a study coordinator will be asked if they would like to speak with a study
clinician to review their health status. Findings need to be collected as AEs related to the optional

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LNA procedure. In addition, AEs related to the optional LNA procedure will be collected 1 week
after the LNA.
8.1.2. 
Procedures in Case of COVID-19-like Signs and Symptoms
8.1.2.1. 
Passive Follow-up (As of Local Approval of Protocol Amendment 16)
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 1.3.6.1.
As of Amendment 16, active follow-up of suspected COVID-19 episodes will be replaced by a
passive follow-up approach. For COVID-19 events that are ongoing at the time oflocal approval
of Protocol Amendment 16:
a. Participant will no longer complete the SIC.
b. Any outstanding activities planned for the follow-up of COVID-19 events will end.
c. No further sampling for participants and no Day 1-4, Day 3-8, and Day 29 visit will be
performed.
For new suspected COVID-19 episodes no samples will be collected in the context of the study.
Site staff will collect information on new COVID-19 episodes at scheduled visits and report these
as SAEs or AEs, as applicable. Participants may also contact the site at any time in between
scheduled visits to report a safety concern (eg, hospitalization) or COVID-19 episodes.
Concomitant medications for each COVID-19 episode are to be reported into the eCRF as well as
any laboratory confirmation of COVID-19, if available.
8.1.2.2. 
Active Follow-up (Prior to Local Approval of Protocol Amendment 16)
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 1.3.6.2.
Participants will be provided with a booklet including a daily question on whether they are
experiencing COVID-19-like symptoms. Following local approval of protocol Amendment 15,
participants will not be required to complete the booklet but will be contacted by the site regularly
to check whether they experienced COVID-19 like symptoms. See Section 8.1.2.3 for the
prespecified criteria for suspected COVID-19. Participants will also be contacted regularly by
study-site personnel during the study to remind them to complete the SIC in the event ofany signs
and symptoms and to contact the site at the time of symptom onset.
For each cohort, if participants experience COVID-19-like symptoms, the following should take
place:
 
Participants should contact the study site at the time of symptom onset.
 
A nasal swab should be collected by a health care professional from the participant at home
(using available material for home swabs) or at the study site as soon as possible and
preferably no longer than 2 to 3 days after the onset of symptoms and stored appropriately.

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The sample should be transferred to the study site by an appropriate method as soon as
possible after being collected. A second nasal swab will be obtained 2 to 4 days after the first
swab following the same procedures as the first nasal swab. The presence of SARS-CoV-2
infection and influenza infection will be assessed at the study site by molecular testing using
the nasal swab sample. Leftover nasal swab samples will be stored and might be used for
central laboratory confirmation and/or quantification of SARS-CoV-2 and for detection of
other respiratory pathogens.
 
Participants should complete the SIC (see Section 10.7, Appendix 7, Symptoms of Infection
with Coronavirus-19 [SIC]) and record their highest body temperature daily starting on the
first day they experience symptoms. If either nasal swab is positive for SARS-CoV-2 or
influenza, collection of data will continue until sign and symptom resolution. If the first nasal
swab is negative, collection of data will continue until the negative test is confirmed by the
second nasal swab or until sign and symptom resolution, whichever comes first. Long-term
sequelae of COVID-19 (eg, anosmia, headache, fatigue, and other symptoms at the
investigator's judgement) will not be followed until their resolution if not resolved within a
month.
 
For participants with a positive test result for SARS-CoV-2 infection, a study visit will be
conducted 28 days after symptom onset to assess the clinical course of the infection, record
concomitant medications since symptom onset, and obtain a blood sample for assessment of
the humoral immune response (VNA, ELISA, and Fc functionality) and other biomarkers
(RNA-seq).
If a participant has a positive test result for SARS-CoV-2 infection, the participant may  be
requested to remain at home and not visit the study site. If necessary, study-site personnel will visit
the participant at home. 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. The participant
will not receive further study vaccinations but should remain on study for follow-up with
assessments of safety and immunogenicity (see section 7.1), unless they withdraw consent from
the study (see section 7.2). The participant will be followed until resolution of clinical symptoms
(except for long-term sequelae of COVID-19).
The sponsor recommends to follow these participants until 2 consecutive negative nasal swabs
could be obtained.
If a participant has a positive test result for influenza infection, study visits will continue per the
Schedule of Activities (SoA).
8.1.2.3. 
Prespecified Criteria for Suspected COVID-19
The criteria for suspected COVID-19 (ie, the triggers to proceed with contacting the study site and
collection of the nasal swab) are prespecified as follows:
 
Headache
 
Malaise (appetite loss, generally unwell, fatigue, physical weakness)
 
Myalgia (muscle pain)
 
Chest congestion

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 
Cough
 
Runny nose
 
Shortness of breath or difficulty breathing (resting or on exertion)
 
Sore throat
 
Wheezing
 
Eye irritation or discharge
 
Chills
 
Fever (≥38.0°C or ≥100.4°F)
 
Gastrointestinal symptoms (diarrhea, vomiting, nausea, abdominal pain)
 
Neurologic symptoms (numbness, difficulty forming or understanding speech)
 
Red or bruised looking toes
 
Skin rash
 
New loss of taste or smell
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.
8.1.3. 
Procedures in Case of Asymptomatic COVID-19 RT-PCR Confirmed
Infection
Passive Follow-up (As of local approval of Protocol Amendment 16)
 
Participants will report any positive RT-PCR SARS-CoV-2 test results during their scheduled
visit.
Active Follow-up (Prior to local approval of Protocol Amendment 16)
For each cohort, if participants receive a positive RT-PCR SARS-CoV-2 result from a
private/off-study test, without experiencing any COVID-19 symptoms, the following should take
place:
 
Participants should contact the study site at the time the positive RT-PCR SARS-CoV-2 test
result is obtained.
 
The study staff should ensure the participant’s medical care provider has been/will be
informed. The sponsor recommends to contact the participant at least once per week, and
recommends to follow these participants until 2 consecutive negative nasal swabs could be
obtained.
The above must be done in accordance with local country and site level recommendations for
COVID-19, and these participants will not be permitted to receive further study vaccination
administrations (see Section 7.1). The participant can continue in the study for safety and
immunogenicity assessments, unless they withdraw consent from the study (see Section 7.2).
In the event a participant experiences COVID-19-like signs or symptoms after obtaining a positive
RT-PCR SARS-CoV-2 test result, procedures as described in Section 8.1.2 should be followed

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with the exception of nasal swab collection to assess the presence of SARS-CoV-2 infection or
influenza infection.
8.1.4. 
Efficacy Assessments
As an exploratory objective, a preliminary analysis of vaccine efficacy in the prevention of
molecularly confirmed COVID-19 will be performed. Identification and molecular confirmation
of SARS-CoV-2 infection will be performed as described in Section 8.1.2, Procedures in Case of
COVID-19-like Signs and Symptoms.
As an additional exploratory objective, a preliminary analysis of vaccine efficacy in the prevention
of asymptomatic SARS-CoV-2 infection will be performed. A non-S protein ELISA (eg,
SARS-CoV-2 N ELISA), if such an assay can be developed, will be performed to identify cases
of asymptomatic infection. This assay will be performed on samples obtained at:
 
Cohorts 1a, 1b, and 3: on Day 1 (pre-vaccination), at 6 months post-vaccination 2, and at
12-, 18- and 24-months post-vaccination 2.
 
Cohorts 2a and 2b: on Day 1 (pre-vaccination), and at 6 months and 12 months after
completion of the primary regimen.
8.2. 
Safety Assessments
Details regarding the DRC are provided in Committees Structure in Section 10.3, Appendix 3,
Regulatory, Ethical, and Study Oversight Considerations.
AEs will be reported and followed by the investigator as specified in Section 8.3, Adverse Events,
Serious Adverse Events, and Other Safety Reporting, and Section 10.4, Appendix 4, Adverse
Events, Serious Adverse Events, Product Quality Complaints, and Other Safety Reporting:
Definitions and Procedures for Recording, Evaluating, Follow-Up, and Reporting.
Any clinically relevant changes occurring during the study must be recorded on the Adverse Event
section of the eCRF.
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.
The study will include the following evaluations of safety and reactogenicity according to the time
points provided in the Schedule of Activities (SoA).
8.2.1. 
Physical Examinations
A full 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. This
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warranted. Symptom-directed physical examination may be repeated if deemed necessary by the
investigator.
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.
8.2.2. 
Vital Signs
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. Confirmatory vital signs
measurement can be performed if inconsistent with a prior measurement.
Participants will utilize a diary to record body temperature measurements post-vaccination.
Blood pressure and pulse/heart rate measurements will be assessed supine 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.
8.2.3. 
Pregnancy Testing
For Cohorts 1 and 2 only, a urine pregnancy test for women of childbearing potential will be
performed at screening and before each vaccination.
Additional pregnancy tests may be performed, as determined necessary by the investigator or
required by local regulation, to establish the absence of pregnancy at any time during the
participation in the study.
8.2.4. 
Clinical Laboratory Assessments
Blood samples for clinical laboratory assessments (as detailed in Section 10.2, Appendix 2) will
be collected as described in the Schedules of Activities in Section 1.3. In case of a suspected AESI,
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
TTS AESI form (see Section 10.11, 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 and
Section 10.2, Appendix 2). The Investigator will review the laboratory test results to assist the
investigation of the AESI.
See Section 8.3.6 for details on laboratory test details to be reported for an AE of
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8.3. 
Adverse Events, Adverse Events of Special Interest, Serious Adverse
Events, and Other Safety Reporting
Timely, accurate, and complete reporting and analysis of safety information, including AEs,
suspected AESIs, SAEs, 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.
AEs 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, suspected AESIs, SAEs, and PQC  can be found in  Section 10.4,
Appendix 4, Adverse Events, Serious Adverse Events, Product Quality Complaints, and Other
Safety Reporting: Definitions and Procedures for Recording, Evaluating, Follow-Up, and
Reporting.
For enrolled participants who received placebo only during primary regimen and who are
accepting a single dose of 5×1010 vp Ad26.COV2.S offered at the time of unblinding, after EUA
or approval in any country and local approval of protocol Amendment 10, procedures outlined in
Section 8.6 apply. A single dose of 5×1010 vp Ad26.COV2.S will be administered during an ad
crossover hoc visit and participants will remain under observation at the study site for at least
15 minutes following vaccination. SAEs, special reporting situations (whether serious or
non-serious, that are related to study procedures or that are related to non-investigational sponsor
products), and COVID-19-like signs and symptoms will be reported from the time of unblinding
until the end-of-safety-follow-up phone call. In addition, suspected AESIs will be reported after
local approval of protocol Amendment 11 is obtained.
8.3.1. 
Time Period and Frequency for Collecting Adverse Event, Adverse
Events of Special Interest, and Serious Adverse Event Information
All Adverse Events
For all cohorts, AEs and special reporting situations, whether serious or non-serious, that are
related to study procedures or that are related to non-investigational sponsor products will be
reported for all participants 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 the
signing of the ICF and moment of first vaccination will be collected on the Medical History eCRF
page as pre-existing conditions.
Solicited AEs, collected through a diary, will be recorded for each vaccination from the time of
vaccination until 7 days post-vaccination.

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All other unsolicited AEs and special reporting situations, whether serious or non-serious, will be
reported for each vaccination from the time of vaccination until 28 days post-vaccination.
Unsolicited AEs with the onset date outside the timeframe defined above (>28 days after previous
study vaccination), which are ongoing on the day of the subsequent vaccination, should be
recorded as such.
All SAEs and AEs leading to discontinuation from the study/vaccination (regardless of the causal
relationship) are to be reported for all participants from the moment of first 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. Suspected AESIs will be reported
once local approval of protocol Amendment 11 is obtained until the end of the study/early
withdrawal.
All AEs will be followed until resolution or until clinically stable.
As of protocol Amendment 16, for all participants:
 
A passive follow-up approach is adopted, defined as on-site study visits to document new
COVID-19 events as SAEs or AEs, as applicable. Participants may also contact the site at any
time in between scheduled visits to report a safety concern (eg, hospitalization) or COVID-19
episodes.
 
Concomitant medications for these events should be reported.
 
If a COVID-19 confirmatory laboratory or assay read-out is available, this should be reported
in the eCRF together with the method of the test if known.
Adverse Events of Special Interest
From the time of local approval of protocol Amendment 11 onwards, TTS is considered an AESI.
Suspected AESIs (thrombotic events and/or thrombocytopenia [defined as platelet count below
150,000/µL9]) will be reported 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 8.3.6).
Serious Adverse Events
All SAEs, as well as PQC, occurring during the study must be reported to the appropriate sponsor
contact person by study-site personnel within 24 hours of their knowledge of the event.
SAEs, including those spontaneously reported to the investigator, must be reported using an SAE
form. 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 Serious Adverse Event
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

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reports of a 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.
8.3.2. 
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, suspected 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 the injection site) and systemic events for which the participant is specifically questioned and
which are noted by participants in their diary.
After each vaccination, participants will remain under observation at the study site for at least
15 minutes to 1 hour depending on the vaccination being administered (see SoAs for details) for
the presence of any acute reactions and solicited events.
In addition, participants will record solicited signs and symptoms in a diary for 7 days post-
vaccination. All participants will be provided with a diary and instructions on how to complete the
diary (see Overview in Section 8, Study Assessments and Procedures). Diary information will be
transferred to the sponsor. After review and verbal discussion of the initial diary entries with the
participant, the investigator will complete his/her own assessment in the relevant sections of the
eCRF. Once a solicited sign or symptom from a diary is considered to be of severity Grade 1 or
above, it will be recorded as a solicited AE.
Solicited Injection Site (Local) Adverse Events
Participants will be asked to note in the 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.28,36
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 diary in the evening of the day of
vaccination, and then daily for the next 7days approximately at the same time each day. If more
than one measurement is made on any given day, the highest temperature of that day will be used
in the eCRF.
Fever is defined as endogenous elevation of body temperature ≥38° C, as recorded in at least one
measurement.41

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Participants will also be instructed on how to note signs and symptoms in the 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.
For details about AESIs, refer to Section 8.3.6.
8.3.3. 
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 laboratory tests or investigations, histopathological
examinations, or consultation with other health care professionals.
AEs, including pregnancy, will be followed by the investigator as specified in Section 10.4,
Appendix 4, Adverse Events, Serious Adverse Events, Product Quality Complaints, and Other
Safety Reporting: Definitions and Procedures for Recording, Evaluating, Follow-up, and
Reporting.
8.3.4. 
Regulatory Reporting Requirements for Serious Adverse Events
The sponsor assumes responsibility for appropriate reporting of AEs to the regulatory authorities.
The sponsor will also report to the investigator (and the head of the investigational institute where
required) all suspected unexpected serious adverse reactions (SUSARs). The investigator (or
sponsor where required) must report SUSARs to the appropriate IEC/IRB that approved the
protocol unless otherwise required and documented by the IEC/IRB. A SUSAR will be reported to
regulatory authorities unblinded. Participating investigators and IEC/IRB will receive a blinded
SUSAR summary, unless otherwise specified.
8.3.5. 
Pregnancy
All initial reports of pregnancy in female participants or partners of male participants must be
reported to the sponsor by the study-site personnel within 24 hours of their knowledge of the event
using the appropriate pregnancy notification form. Abnormal pregnancy outcomes
(eg, spontaneous abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy) are
considered SAEs and must be reported using anSAE reporting form. Any participant who becomes
pregnant during the study must discontinue further study vaccination.
Applicable to the US only: Following local approval of protocol Amendment 15, participants who
are pregnant may receive ad hoc booster vaccination with Ad26.COV2.S, if allowed by local
regulations and if the investigator considers that the potential benefits outweigh the potential risks
to the mother and fetus (see Section 8.7).

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Follow-up information regarding the outcome of the pregnancy and any postnatal sequelae in the
infant will be required.
8.3.6. 
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 or suspected 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.
8.3.6.1. 
Thrombosis with Thrombocytopenia Syndrome
As described in Section 2.3.1, Risks Related to Study Participation, 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.3,9
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
Section 10.11, Appendix 11. A suspected TTS case is defined as:
 
Thrombotic events: suspected deep vessel venous or arterial thrombotic events as detailed in
Section 10.12, Appendix 12
 
Thrombocytopenia, defined as platelet count below 150,000/µL9
Symptoms, signs, or conditions suggestive of a thrombotic event 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.
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.

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Suspected AESIs will require enhanced data collection and evaluation (see Section 1.3.8). 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 Section 10.11, 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.
The 
sponsor 
will 
also 
attempt 
to 
collect 
information 
from 
any 
thrombotic
event/thrombocytopenia/TTS reported prior to protocol Amendment 11.
8.4. 
Medical Resource Utilization and Health Economics
Medical resource utilization and health economics parameters are not evaluated in this study.
8.5. 
Biomarkers
For all participants, biomarker analysis (PAXgene, RNA-seq) will be performed to explore
potentially informative biomarkers related to vaccine immunogenicity and SARS-CoV-2 infection
(including relations with COVID-19 disease severity). For participants with a positive test result
for SARS-CoV-2 infection, a blood sample for evaluation of biomarkers (eg, those associated with
severe COVID-19) will be collected 28 days after symptom onset (see Section 1.3.6, Procedures
for Participants with COVID-19-like Signs and Symptoms).
8.6. 
Assessments and Procedures after EUA or Approval in any Country
Following EUA, conditional licensure, or approval in any country for the single-dose regimen of
5×1010 vp Ad26.COV2.S, all participants from countries where Amendment 10 is approved locally
by the Health Authority and IEC/IRB, will be unblinded to disclose who received placebo only
during primary regimen.
The Procedures detailed in this section also apply to participants who were unblinded at their own
request prior to Amendment 10.
In general, after unblinding, participants who initially received placebo only, can elect to receive
a single dose of 5×1010 vp Ad26.COV2.S  offered at the study site (ie, placebo crossover
vaccination), can opt to receive an authorized/licensed COVID-19 vaccine outside of the study, or
may choose not to receive any additional vaccinations. Participants who received active vaccine
will be asked to continue in the study or can opt to receive an authorized/licensed COVID-19
vaccine outside of the study.
All currently enrolled participants will be contacted by the study site to inform them whether they
received active vaccine or placebo only. Participants will be counseled regarding the importance
to continue practicing preventative measures to limit the spread of the disease including social

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distancing, wearing face masks, and frequent hand washing, in compliance with local and national
guidelines. This contact will be documented in the source documents.
Participants in the active vaccine groups will be informed they received at a minimum the dose
level approved for Emergency Use (single-dose regimen of 5x1010 vp Ad26.COV2.S) and will be
asked to continue to be followed in this study in line with the Schedule of Activities (SoA). For
participants who were unblinded (at any time) and did not receive an authorized/licensed
COVID-19 vaccine outside of the study, they will be permitted to receive the Cohort 2 booster
vaccinations. Ifthey opt to receive an authorized/licensed COVID-19 vaccine outside of the study,
they will be discontinued from further study vaccination (see Section 7.1).
Participants who received placebo only during primary regimen, will be offered a single dose of
5×1010 vp Ad26.COV2.S  (ie, placebo crossover vaccination). If willing to receive, they will
discontinue from participation in the placebo groups (see Section 7.4). If they opt to receive an
authorized/licensed COVID-19 vaccine outside of the study, they will discontinue the study (see
Section 7.2). If they choose not to receive an authorized/licensed COVID-19 vaccine outside of
the study, they will be asked to continue to be followed in this study in line with the Schedule of
Activities (SoA), including Cohort 2 booster vaccinations.
Criteria for Group 5 (Placebo Only) Participants to Receive a Single Dose of 5x1010 vp
Ad26.COV2.S after EUA or Approval in any Country
 
Participants have to be actively enrolled in the study.
 
Participants have not received an authorized/licensed COVID-19 vaccine outside of the study.
 
Participants, who were already unblinded for any reason, might receive a single dose of
5x1010 vp Ad26.COV2.S vaccine at the investigator’s discretion, provided they did not receive
another licensed/authorized COVID-19 vaccine.
 
Participants who have become infected with SARS-CoV-2 during the double-blind phase of
the study may receive a single dose of 5x1010 vp Ad26.COV2.S vaccine after being made
aware that the safety and efficacy data on vaccinating a previously infected individual is
limited.
 
Participants should not have previously experienced TTS, HIT, or GBS.
 
Participant should not have previously experienced CLS
Procedures for Group 5 (Placebo Only) Participants Receiving a Single Dose of 5x1010 vp
Ad26.COV2.S after EUA or Approval in any Country
Participants who received placebo only during primary regimen accepting a single dose of
5×1010 vp Ad26.COV2.S, will discontinue from participation in the placebo groups (see
Section 7.4). They will be redirected to SoA 'Procedures for Group 5 (Placebo Only) Participants
Receiving a Single Dose of 5x1010 vp Ad26.COV2.S (Placebo Crossover Vaccination)after EUA
or Approval in any Country' (see Section 1.3.7).

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Vaccination will be planned during an ad hoc crossover visit as soon as the site is operationally
ready. A urine pregnancy test will be collected from all women of childbearing potential
(Cohorts 1 and 2) and a blood sample for a platelet count (as part of a complete blood count if
applicable) will be collected from all participants prior to vaccination. Vaccination will be
performed by a trained and qualified study nurse, medical doctor, or otherwise qualified HCP.
Participants will remain under observation at the study site for at least 15 minutes for the presence
of any acute reactions. SAEs, special reporting situations (whether serious or non-serious, that are
related to study procedures or that are related to non-investigational sponsor products), and
COVID-19-like signs and symptoms (refer to Section 8.1.2) will be reported from the time of
unblinding until the end ofsafety follow-up/early withdrawal. In addition, AESIs will be reported
after local approval of protocol Amendment 11 is obtained until the end of safety follow-up/early
withdrawal. For Cohorts 1a, 1b, and 3, the safety follow-up will end at Day 422 (ie, the initially
planned study completion date) or 6 months after vaccination, whichever comes first. For
Cohorts 2a and 2b, the safety follow-up will end 6 months after vaccination. At that time, the
participant will be contacted (phone call) by the site with regards to AESI and SAE collection,
after which the participant will be considered to have completed the study.
8.7. 
Assessments and Procedures after Protocol Amendment 15 Approval (Ad
Hoc Booster Vaccination)
Ad Hoc Booster Vaccination
Following local approval of protocol Amendment 15, all eligible participants will be offered a
single ad hoc booster dose of 5×1010 vp Ad26.COV2.S.
As soon as possible, but no later than 120 days post local approval of protocol amendment 15, the
ad hoc booster vaccination will be provided to participants who have previously received 1 or more
doses of any COVID-19 vaccine (ie, the Ad26.COV2.S vaccine, an mRNA vaccine and/or another
COVID-19 vaccine authorized for primary vaccination including protein, inactivated, and
adenovector-based vaccines) if the last vaccination was ≥6 months ago. Participants are free to
choose to delay the booster vaccination within the window of the booster vaccination visit, to
receive booster vaccination outside the study, or not to receive booster vaccination. Participants
who choose to receive an outside of the study booster vaccination with the Ad26.COV2.S vaccine
(if recommended by local authorities and available) or another authorized COVID-19 vaccine,
choose not to receive an ad hoc booster vaccination, or are not eligible to receive the ad hoc booster
vaccination, will not be withdrawn from the study and will be encouraged to remain in the study.
Participants in Group 1 and 4 of Cohort 2 will be partially unblinded. See Section 6.3 for more
details.
Participants will be counseled regarding the importance to continue practicing preventative
measures to limit the spread of the disease including social distancing, wearing face masks, and
frequent hand washing, in compliance with local and national guidelines. This contact will be
documented in the source documents.

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Criteria for Participants Receiving a Single Ad Hoc Booster Dose of 5x1010 vp Ad26.COV2.S:
 
Participants have to be actively enrolled in the study.
 
Participants have not received anyCOVID-19-related experimental medication (including any
experimental vaccine other than the study vaccine).
 
Participants who have become infected with SARS-CoV-2 during the study may receive
booster vaccination with the Ad26.COV2.S vaccine after they have recovered from the acute
illness and at least 3 months have passed. Such participants should be made aware that the
safety and efficacy data on vaccinating a previously infected individual is limited.
 
Participants should not have previously experienced TTS, HIT, or GBS.
 
Participant should not have previously experienced CLS.
 
Applicable to the US only: Participants who are pregnant may receive ad hoc booster
vaccination with Ad26.COV2.S, if allowed by local regulations and if the investigator
considers that the potential benefits outweigh the potential risks to the mother and fetus (see
Section 8.7).
Following ongoing participants will not be eligible to receive the ad hoc booster vaccination:
 Group 5 participants (all cohorts) who crossed over from placebo to receive Ad26.COV2.S at
the 5x1010 vp dose level (ie, placebo crossover vaccination) (see Section 1.3.7).
 Group 5 participants (all cohorts) who did not opt for the placebo crossover vaccination and
therefore have not received any vaccination with the Ad26.COV2.S vaccine.
 Cohort 2 participants who will receive a booster vaccination according to their initial schedule
at 6 and 12 months after the primary regimen (Groups 2 and 3, respectively) (see Section 4.1).
 Applicable to Belgium only: Per the Belgian-specific protocol Amendment 15, participants
aged <65 years enrolled at Belgian sites.
Procedures for Participants Receiving a Single Ad Hoc Booster Dose of 5x1010 vp
Ad26.COV2.S
Vaccination will be planned during the ad hoc booster vaccination  visit as soon as the site is
operationally ready  and the participant has met the length of time requirements from last
vaccination (see details above). During this visit, the investigator should ask the participant if
he/she received any other COVID-19 vaccine and record type and date of administration.
A urine pregnancy test will be collected from all women of childbearing potential (Cohort 1 and 2
only) and a blood sample for a platelet count (as part of a complete blood count if applicable) will
be collected from all participants prior to and 28 days post ad hoc booster vaccination. Vaccination
will be performed by a trained and qualified blinded study nurse, medical doctor, or otherwise
qualified HCP. Participants will remain under observation at the study site for at least 15 minutes
for the presence of any acute reactions. Solicited AEs, collected through a diary, will be recorded
from the time of ad hoc booster vaccination until 7 days post-vaccination. All other unsolicited
AEs and special reporting situations, whether serious or non-serious, will be reported from the

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time ofad hoc booster vaccination until 28 days post-vaccination. Unsolicited AEs with the onset
date outside the timeframe of >28 days after previous study vaccination, which are ongoing on the
day of the subsequent visit, should be recorded as such. SAEs and COVID-19-like signs and
symptoms (refer to Section 8.1.2) will be reported from the time of booster vaccination till the end
of booster follow-up/early withdrawal. In addition, AESIs will be reported until the end of booster
follow-up/early withdrawal. At that time, the participant will visit the site with regards to AESI
and SAE collection, after which the participant will be considered to have completed the study.
Venous blood samples will be collected for assessment of humoral or cellular immune responses
from a subset of participants prior to and 28 days, and 6 months post ad hoc booster vaccination
(see SoA in Section 1.3.10 for details).
9. 
STATISTICAL CONSIDERATIONS
Statistical analysis will be done by the sponsor or under the authority of the sponsor. A general
description of the statistical methods to be used to analyze the efficacy and safety data is outlined
below. Specific details will be provided in the Statistical Analysis Plan.
9.1. 
Statistical Hypotheses
No formal statistical hypothesis for safety or immunogenicity will be tested.
9.2. 
Sample Size Determination
The number of participants chosen for this study will provide a preliminary safety and
immunogenicity assessment. Placebo recipients are included for blinding and safety purposes and
will provide additional control specimens for immunogenicity assays.
While mild-to-moderate vaccine reactions (local site and systemic responses) are expected, AEs
that preclude further dose administration or more serious ones that would limit product
development are not anticipated. When 75 and 120 participants are vaccinated, the observation
of0 such reactions would be associated with a 95% confidence that the true rate is less than 3.9%
and <2.5% respectively. Table 14 provides the probabilities of observing at least one AE at given
true AE rates.
Table 14: 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=75 
N=120
1% 
53%  
70%
2.5% 
85% 
95%
5% 
98% 
>99%
10% 
>99%  
>99%
20%  
>99%  
>99%
N: number of participants receiving study vaccine (Ad26.COV2.S or a placebo).

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9.3. 
Populations for Analysis Sets
For purposes of analysis, the following populations are defined:
FAS: The full analysis set will include all participants with at least one vaccine administration
documented.
PPIa: The per protocol immunogenicity population will include all randomized and vaccinated
participants for whom immunogenicity data are available excluding participants with major
protocol deviations expecting to impact the immunogenicity outcomes. In addition, samples
obtained after missed vaccinations or from participants with  natural infection occurring after
screening (if applicable) will be excluded from the analysis.
PPE: The per protocol efficacy population will include all randomized participants having received
at least 1 vaccination for whom efficacy data concerning endpoint measures are available. All
efficacy analyses will be done according to the as treated principle (ie, actually received
vaccinations).
9.4. 
Statistical Analyses
The Statistical Analysis Plan will be finalized prior to interim DBL and it will include a more
technical and detailed description of the statistical analyses described in this section. This section
is a summary of the planned statistical analyses of the most important endpoints including primary
and key secondary endpoints.
9.4.1. 
General Considerations
Analysis populations are defined in Section 9.3, Populations for Analysis Sets. Planned analyses
are defined in Section 9.5, Planned Analysis.
For safety and immunogenicity analyses, results will be analyzed by vaccine group. In addition,
safety and immunogenicity analyses will be repeated by vaccine group and participant
seropositivity status at screening. Immunogenicity subanalyses will also be performed by BMI,
ethnicity, and other factors as will be described in the Statistical Analysis Plan.
9.4.2. 
Primary Endpoints
Safety Endpoints
No formal statistical testing of safety data is planned. Safety data will be analyzed descriptively
by vaccine group. In addition, for selected tables, tabulations pooled by vaccine dose will also be
provided. All safety analyses will be made on the FAS.
a If a participant would be vaccinated out of window due to a study pause (per Section 6.9), this will not by default be
a reason for excluding this participant from the PPI. A sensitivity analysis might also be performed. Further details
will be described in the Statistical Analysis Plan.

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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 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 vaccine 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. A listing ofthe abnormalities will
be made.
9.4.3. 
Secondary Endpoints
Immunogenicity Endpoints
No formal hypothesis on immunogenicity will be tested. Descriptive statistics (geometric mean
and 95% confidence interval, or median and interquartile range Q1-Q3, as appropriate) will be
calculated for continuous immunologic parameters at all available time points. 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 protein ELISA, respectively, will be calculated.

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The immunogenicity analyses will be performed on the PPI population. Immunogenicity analyses
will also be done on the FAS (participants who became infected during the study will be analyzed
as a subgroup and shown in the graphs using different colors and symbols).
9.4.4. 
Tertiary/Exploratory Endpoint(s)
Detailed statistical methodology for analysis of exploratory endpoints will be described in the
Statistical Analysis Plan.
9.4.5. 
Other Analyses
Descriptive analysis will be performed for the results of the SIC and results of diagnostic tests for
SARS-CoV-2 infection after screening. Further details will be provided in the Statistical Analysis
Plan.
Statistical analysis of biomarker responses (eg, RNA-seq responses) and LNA immune responses
will be detailed in a separate Statistical Analysis Plan.
9.5. 
Planned Analysis
Interim and primary analyses for each cohort are presented in Figure 9. Additional interim analyses
may be conducted by the sponsor as needed.
Interim and Primary Analyses for Cohort 1a
A first interim analysis post-dose 1 for Cohort 1a is planned when approximately 375 participants
have completed Day 29 (ie, 28 days after the first study vaccination) or discontinued the study
earlier. This interim analysis will include all available safety data for approximately
375 participants through Day  29 and may include immunogenicity data (VNA, ELISA, and
Th1/Th2 assay) for at least 25 seronegative participants (ie, participants who were seronegative at
screening) per group through Day 15 (ie, 14 days after the first study vaccination)a. A second
interim analysis for Cohort 1a will include immunogenicity data through Day 29 (all available
VNA  and ELISA  data for seronegative participants; Th1/Th2 assay  data for approximately
40 seronegative participants per group). For logistical reasons, aspects of the first and second
interim analyses may be combined.
The first primary analysis post-dose 2 for Cohort 1a will be performed when approximately
375 participants have completed Day 85 (ie, 28 days after the second study vaccination) or
discontinued the study earlier. The primary analysis will include all available safety data for all
participants through Day 85. It may also include immunogenicity data through Day 71, ie, 14 days
after the second study vaccination (all available VNA and ELISA data for seronegative
participants; Th1/Th2 assay data for approximately 40 seronegative participants per group)a. A
second primary analysis for Cohort 1a will include immunogenicity data through Day 85 (all
available VNA and ELISA data for seronegative participants; Th1/Th2 assay  data for
a May be performed based on operational availability of data.

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approximately 40 seronegative participants per group). For logistical reasons, aspects ofthe first
and second primary analyses may be combined.
Interim and Primary Analyses for Cohort 2
An interim analysis for Cohort 2 will be performed when 28-day safety data is collected for
approximately  270 participants after the first study vaccination. This safety analysis may be
required as the basis for enrollment of adults aged ≥18 to ≤55 years in subsequent larger studies.
It will also include available immunogenicity data for seronegative participants (VNA and
ELISA).
The primary analysis for Cohort 2 will include all available safety data for approximately
270 participants through 28 days after completion of the second study vaccination in the 2-dose
primary regimen. It will also include available immunogenicity data for seronegative participants
(VNA and ELISA).
Interim analyses of the data from each booster vaccination will be performed after the last
participant receives their respective booster vaccination and will include all available safety and
immunogenicity data up to 28 days after the vaccination. These interim analyses will present the
data in a group-level unblinded fashion, as follows:
 
The interim analysis of the first booster vaccination (at 6 months for Cohort 2a or at 8 months
for Cohort 2b), will keep the groups 1, 3, and 4 pooled.
 
The interim analysis of the second booster vaccination (at 12 months for Cohort 2a or at
14 months for Cohort 2b), will keep the groups 1 and 4 pooled.
This stepwise group-level unblinding approach avoids indirect unblinding of individual
participants who have yet to receive the active (or last) booster (eg, due to rare or unique events).
Interim and Primary Analyses for Cohort 3
The analysis strategy for Cohort 3 is the same as for Cohort 1a.
A first interim analysis post-dose 1 for Cohort 3 is planned when approximately 375 participants
have completed Day 29 (ie, 28 days after the first study vaccination) or discontinued the study
earlier. This interim analysis will include all available safety  data for approximately
375 participants through Day 29 and may include immunogenicity data (VNA, ELISA, and
Th1/Th2 assay) for at least 25 seronegative participants per group through Day 15 (ie, 14 days
after the first study vaccination)a. A second interim analysis for Cohort 3 will include
immunogenicity data through Day 29 (all available VNA  and ELISA  data for seronegative
participants; Th1/Th2 assay data for approximately 40 seronegative participants per group). For
logistical reasons, aspects ofthe first and second interim analyses may be combined.
The first primary analysis post-dose 2 for Cohort 3 will be performed when approximately
375 participants have completed Day 85 (ie, 28 days after the second study vaccination) or
a May be performed based on operational availability of data.

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discontinued the study earlier. The primary analysis will include all available safety data for all
participants through Day 85. It may also include immunogenicity data through Day 71, ie, 14 days
after the second study vaccination (all available VNA and ELISA data for seronegative
participants; Th1/Th2 assay data for approximately 40 seronegative participants per group)a. A
second primary analysis for Cohort 3 will include immunogenicity data through Day 85 (all
available VNA and ELISA data for seronegative participants; Th1/Th2 assay  data for
approximately 40 seronegative participants per group). For logistical reasons, aspects ofthe first
and second primary analyses may be combined.
End-of-study Analysis
The end-of-study analysis will be performed when all included participants have completed the
last visit or last booster vaccination follow-up visit or discontinued the study earlier.
Planned Analyses: General Considerations
For all analyses, all data available at the time of the analysis will be included. If any of the
above-mentioned analyses coincide, the analyses will be combined. Additional interim analyses
may be performed for safety and/or immunogenicity to facilitate decision making with regards to
the planning of future studies.
The Statistical Analysis Plan will describe the planned analyses in greater detail.
Analysis and Reporting of Unblinded Data
Selected available group unblinded immunogenicity data and blinded safety data from the interim
analysis of Cohorts 1a, 1b, and 3 will be published. Following the 7-day post-vaccination 2 safety
data being available in Cohorts 1a, 1b, and 3, the sponsor will be unblinded for these cohorts,
except for sponsor personnel directly involved with the study site for assessment of safety.
Participants, clinical staff, and study-site personnel will remain blinded to the study vaccine
allocation.
Selected members of the statistical programming and the statistics group will receive individual
level unblinded data pertaining to study VAC31518COV1001 when unblinding at the participant
level is required. In addition, they will monitor the number and severity of molecularly confirmed
COVID-19 cases in the Ad26.COV2.S  and placebo groups to identify an imbalance between
groups if it occurs (see Statistical Analysis Plan). They  will inform the DRC as soon as an
imbalance between groups is detected. A prespecified threshold (imbalance above a certain
percentage and/or number of cases) that will trigger notification of the DRC will be described in
the Statistical Analysis Plan.
Following Emergency Use Authorization (EUA), conditional licensure, or approval in anycountry
for the single-dose regimen of 5×1010 vp Ad26.COV2.S and local approval of protocol
Amendment 10 by both Health Authority (HA) and Independent Ethics Committees
(IEC)/Institutional Review Board (IRB), a single dose of 5×1010 vp Ad26.COV2.S will be offered
to enrolled participants who initially received placebo only, resulting in de facto unblinding of

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participants and investigators. A stepwise group-level unblinding approach will be used for
Cohort 2 to avoid indirect unblinding of individual participants.
Figure 9: 
Interim and Primary Analyses
*May be performed based on operational availability of data.
**Analysis of VNA/ELISA may be performed before availability of Th1/Th2 data, which may not be available at the
time of this analysis.
ELISA = enzyme-linked immunosorbent assay; Th = T-helper; VNA = virus neutralization assay

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9.6. 
Analyses for Participants Requesting Unblinding to Receive an
Authorized/Licensed COVID-19 Vaccine
Investigators may receive requests to unblind study participants who become eligible to receive an
authorized/licensed COVID-19 vaccine if/when these become available. In these cases, the
investigator will discuss with the participant available options and ramifications. If the participant
is eligible for an authorized/licensed vaccine according to local immunization guidelines or
recommendations and if the participant wishes to proceed with the unblinding, the investigator
will follow the unblinding procedures. The reason for the unblinding request should be
documented.
When unblinding, if it is determined that the participant received the Ad26.COV2.S vaccine (and
not placebo), the participant will be informed that there are no clinical data on the safety of
receiving a different COVID-19 vaccine after receiving Ad26.COV2.S. In the event of a
participant unblinding to receive an authorized/licensed COVID-19 vaccine and the participant
received an authorized/licensed COVID-19 vaccine outside of the study, no further study
vaccination will be permitteda. Unblinded participants, whether in the vaccine or control group
that did not receive an authorized/licensed COVID-19 vaccine outside of the study, will be asked
to continue to be followed in this study in line with the SoAto the extent that they permit, including
Cohort 2 booster vaccinations. Safety and immunogenicity evaluations will be identical for all
participants, including participants that are unblinded to obtain an authorized/licensed COVID-19
vaccine and who remain in the study, if applicable and feasible.
Procedures installed at the time of unblinding all participants after EUA or approval in any country
and local approval of protocol Amendment 10 (refer to Section 8.6), will also apply to participants
who were unblinded at their own request prior to Amendment 10. The statistical analyses will
follow the same approach as outlined in Section 9.7. The only exception is for Cohorts 2a and 2b
participants: if unblinding occurs at their request, they are likely to be completely unblinded,
implying they would know in advance whether they would receive active vaccine or placebo at
each of the booster time points. These participants will therefore not be included in any of the
post-booster safety or efficacy analyses of Cohorts 2a and 2b. If they continue with the booster
vaccinations and all study procedures as described in the SoA, they will be included in the
immunogenicity analysis.
9.7. 
Analyses after Unblinding all Participants Following EUA or Approval in
any Country
9.7.1. 
Cohorts 1a, 1b, and 3
The participants in these cohorts have completed the planned study vaccination regimen by the
time of unblinding (or have discontinued earlier). In general, after unblinding, participants who
received placebo only  during primary regimen, can elect to receive a single dose of
a Following local approval of protocol Amendment 15, participants who received an authorized/licensed COVID-19
vaccine outside of the study are allowed to receive a single ad hoc booster dose of Ad26.COV2.S vaccine
(5×1010 vp) if the last vaccination was ≥6 months ago.

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5x1010 vp Ad26.COV2.S offered at the study site, can opt to receive an authorized/licensed
COVID-19 vaccine outside of the study, or may choose not to receive any additional vaccinations.
Participants who already received active vaccine will be asked to continue the study or can opt to
receive an authorized/licensed COVID-19 vaccine outside of the study.
The safety analyses will be censored at the date of unblinding or the receipt of an unscheduled
vaccinea, whichever event occurs first. SAEs and AESIs reported after unblinding or receipt of an
unscheduled vaccine, whichever comes first, will be listed.
The immunogenicity analyses will be censored at the date of the receipt of an unscheduled vaccine.
Immunogenicity samples taken after the receipt of an unscheduled vaccine will be included in the
listings and flagged. Samples obtained from unblinded participants who do not get any further
vaccination, will not be censored from the analyses.
Efficacy analyses will be censored at the date of unblinding or the receipt of an unscheduled
vaccine, whichever comes first.
9.7.2. 
Cohorts 2a and 2b
The participants in Cohorts 2a and 2b will not have completed the planned vaccination schedule
by the time of unblinding, because the booster vaccinations will not yet have occurred.
For safety, efficacy, and immunogenicity, the same analysis strategy will be applied as for
Cohorts 1a, 1b, and 3.
Analyses pertaining to the booster vaccinations will be produced as planned. The analyses will
include all available participants who have followed the vaccination schedules as per the study
design (ie, did not receive an unscheduled vaccination). Note that the post-booster safety or
efficacy analyses will not include participants who were unblinded at their own request, since they
are likely to be completely unblinded (implying they would know in advance whether they would
receive active vaccine or placebo at each of the booster time points). Participants who continue
with the booster vaccinations and all study procedures as described in the SoA, will be included in
the immunogenicity analysis.
The analysis strategy is depicted graphically in Figure 10.
a Unscheduled vaccination: for placebo participants: a single dose of 5x1010 vp Ad26.COV2.S offered at the study site
or an authorized/licensed COVID-19 vaccine offered outside of the study; for participants in the active vaccine
groups: an authorized/licensed COVID-19 vaccine offered outside of the study.

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Figure 10: 
Analysis strategy after unblinding, depicted by scenario
AESI  adverse event of special interest; C  cohort; SAE  serious adverse event

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9.8. 
Analysis After Receipt of the Ad Hoc Booster Vaccination
Amendment 15 of this protocol offers eligible study participants (see Section 5) a single ad hoc
booster vaccination with the Ad26.COV2.S vaccine at the 5×1010 vp dose level. The main analyses
will be conducted as described in Section 9.7, in which censoring is applied for the various
statistical analyses depending on the date of unblinding or receipt of an unscheduled vaccine. In
addition, receipt of the ad hoc booster vaccination will also be a reason for censoring data from
the main analyses.
For safety and reactogenicity, additional analyses will be conducted on study participants who
received the ad hoc booster vaccination. Safety and reactogenicity analyses will be presented from
the start of the ad hoc booster vaccination until 7 days post vaccination for reactogenicity, until
28 days post vaccination for unsolicited AEs, and until the end of the study for SAEs and AESIs.
For immunogenicity, an additional analysis will be conducted on study participants who received
the ad hoc booster vaccination. Immunogenicity analyses will be presented from the start of the ad
hoc booster vaccination and will show their immune responses at each subsequent time point, as
available.
The analyses will be descriptive, presenting study participants according to their original
vaccination regimen. In addition, the analyses may also be conducted separately by subgroups of
study participants who received a COVID-19 vaccine outside of the study versus study participants
who did not receive a COVID-19 vaccine outside of the study. Additional exploratory analyses
may be conducted.
Details for the analysis of the ad hoc booster vaccination will be provided in an amendment to the
study Statistical Analysis Plan.

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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Abbreviations
Ad26 
adenovirus type 26
ADCC  
antibody-dependent cellular cytotoxicity
ADCP  
antibody-dependent cellular phagocytosis
AdVac® 
adenoviral vaccine
AE 
adverse event
AESI 
adverse event of special interest
BIDMC  
Beth Israel Deaconess Medical Center
BMI 
body mass index
CLS  
capillary leak syndrome
Cont 
continuous
COPD  
chronic obstructive pulmonary disease
COVID-19 
coronavirus disease-2019
CRF  
case report form(s) (paper or electronic as appropriate for this study)
CT  
computed tomographic
d 
day(s)
DBL  
database lock
DNA  
deoxyribonucleic acid
DRC  
Data Review Committee
eDC  
electronic data capture
ELISA  
enzyme-linked immunosorbent assay
ELISpot 
enzyme-linked immunospot
ERD  
eCRF  
enhanced respiratory disease
electronic case report form
EUA  
emergency use authorization
FAMHP  
Federal Agency for Medicines and Health Products
FAS  
full analysis set
FDA  
Food and Drug Administration
FI 
formalin-inactivated
FIH  
first-in-human
FOIA  
Freedom of Information Act
FU 
follow-up
GBS  
Guillain-Barre Syndrome
GCP  
Good Clinical Practice
GLP  
Good Laboratory Practice
HIV  
human immunodeficiency virus
HIT  
heparin-induced thrombocytopenia
IB  
Investigator's Brochure
ICF  
informed consent form
ICH  
International Conference on Harmonisation
ICMJE 
International Committee of Medical Journal Editors
ICS  
intracellular staining
IEC  
Independent Ethics Committee
IFNγ 
interferon gamma
Ig 
immunoglobulin
IL 
interleukin
IM  
intramuscular(ly)
IPPI 
Investigational Product Preparation Instructions
IRB  
Institutional Review Board
IUD  
intrauterine device
IUS  
intrauterine hormone-releasing system
IWRS  
interactive web response system
LNA  
lymph node aspirate
mRNA  
messenger ribonucleic acid
MedDRA  
Medical Dictionary for Regulatory Activities

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MERS  
Middle East respiratory syndrome
MERS-CoV  
Middle East respiratory syndrome coronavirus
mo 
month(s)
MSD  
Meso Scale Discovery
PBMC  
peripheral blood mononuclear cell
PF4 
platelet factor 4
PI 
PPE 
principal investigator
per protocol efficacy
PPI 
per protocol immunogenicity
PQC  
product quality complaint
RBD  
receptor-binding domain
RNA  
ribonucleic acid
RSV  
respiratory syncytial virus
RT-PCR  
reverse-transcriptase polymerase chain reaction
S 
spike
SAE 
serious adverse event
SARS  
severe acute respiratory syndrome
SARS-CoV  
severe acute respiratory syndrome coronavirus
SARS-CoV-2 
severe acute respiratory syndrome coronavirus-2
SIC  
Symptoms of Infection with Coronavirus-19
SIPPM  
site investigational product and procedures manual
SoA  
Schedule of Activities
SRP  
study responsible physician
SUSAR  
tel 
suspected unexpected serious adverse reaction
telephone contact
Th 
T-helper
TNFα 
tumor necrosis factor alpha
TTS  
thrombosis with thrombocytopenia syndrome
vac 
vaccination
VNA  
virus neutralization assay
vp 
virus particles
WHO  
World Health Organization

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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 Conference on Harmonisation (ICH) guidelines on Good Clinical
Practice (GCP), and applicable regulatory and country-specific requirements.
GCPis an international ethical and scientific quality standard for designing, conducting, recording,
and reporting studies that involve the participation of human participants. Compliance with this
standard provides public assurance that the rights, safety, and well-being of study participants are
protected, consistent with the principles that originated in the Declaration of Helsinki, and that the
study data are credible.
Protocol Amendments
Neither the investigator nor the sponsor will modify this protocol without a formal amendment by
the sponsor. All protocol amendments must be issued by the sponsor, and signed and dated by the
investigator. Protocol amendments must not be implemented without prior IEC/IRB approval, or
when the relevant competent authority has raised any grounds for non-acceptance, except when
necessary to eliminate immediate hazards to the participants, in which case the amendment must
be promptly submitted to the IEC/IRB and relevant competent authority. Documentation of
amendment approval by the investigator and IEC/IRB must be provided to the sponsor. When the
change(s) involve only logistic or administrative aspects of the study, the IEC/IRB (where
required) only needs to be notified.
During the course of the study, in situations where a departure from the protocol is unavoidable,
the investigator or other physician in attendance will contact the appropriate sponsor representative
listed in the Contact Information page(s), which will be provided as a separate document. Except
in emergency situations, this contact should be made before implementing any departure from the
protocol. In all cases, contact with the sponsor must be made as soon as possible to discuss the
situation and agree on an appropriate course of action. The data recorded in the eCRF and source
documents will reflect any departure from the protocol, and the source documents will describe
this departure and the circumstances requiring it.
Regulatory Approval/Notification
This protocol and any amendment(s) must be submitted to the appropriate regulatory authorities
in each respective country, if applicable. A study may not be initiated until all local regulatory
requirements are met.

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Required Prestudy Documentation
The following documents must be provided to the sponsor before shipment of study vaccine to the
study site:
 
Protocol and amendment(s), if any, signed and dated by the PI
 
A copy of the dated and signed (or sealed, where appropriate per local regulations), written
IEC/IRB approval of the protocol, amendments, ICF, any recruiting materials, and if
applicable, participant compensation programs. This approval must clearly identify the
specific protocol by title and number and must be signed (or sealed, where appropriate per
local regulations) by the chairman or authorized designee.
 
Name and address of the IEC/IRB, including a current list of the IEC/IRB members and their
function, with a statement that it is organized and operates according to GCP and the
applicable laws and regulations. If accompanied by a letter of explanation, or equivalent, from
the IEC/IRB, a general statement may be substituted for this list. If an investigator or a
member of the study-site personnel is a member of the IEC/IRB, documentation must be
obtained to state that this person did not participate in the deliberations or in the vote/opinion
of the study.
 
Regulatory authority approval or notification, if applicable
 
Signed and dated statement of investigator (eg, Form FDA 1572), if applicable
 
Documentation of investigator qualifications (eg, curriculum vitae)
 
Completed investigator financial disclosure form from the PI, 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
Independent Ethics Committee or Institutional Review Board
Before the start of the study, the investigator (or sponsor where required) will provide the IEC/IRB
with current and complete copies of the following documents (as required by local regulations):
 
Final protocol and, if applicable, amendments
 
Sponsor-approved ICF (and any other written materials to be provided to the participants)
 
IB (or equivalent information) and amendments/addenda

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

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must be submitted promptly to the IEC/IRB for review and approval before implementation of the
change(s).
At least once a year, the IEC/IRB will be asked to review and reapprove this study, where required.
At the end of the study, the investigator (or sponsor where required) will notify the IEC/IRB about
the study completion.
Country 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, Study-Specific Ethical Design
Considerations.
Other Ethical Considerations
For study-specific ethical design considerations, refer to Section 4.2.1.
10.3.2. 
Financial Disclosure
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial
information in accordance with local regulations to allow the sponsor to submit complete and
accurate financial certification or disclosure statements to the appropriate regulatory authorities.
Investigators are responsible for providing information on financial interests during the course of
the study and for 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
IEC/IRB and be in a language that the participant can read and understand. The informed consent
should be in accordance with principles that originated in the Declaration of Helsinki, current ICH
and GCP guidelines, applicable regulatory requirements, and sponsor policy.
Before enrollment in the study, the investigator or an authorized member of the study-site
personnel must explain to potential participants the aims, methods, reasonably anticipated benefits,
and potential hazards of the study, and any discomfort participation in the study may entail.
Participants will be informed that their participation is voluntary and that they may withdraw
consent to participate at any time. They will be informed that choosing not to participate will not
affect the care the participant will receive. Finally, they will be told that the investigator will
maintain a participant identification register for the purposes of long-term follow-up if needed and
that their records may be accessed by health authorities and authorized sponsor personnel without
violating the confidentiality of the participant, to the extent permitted by the applicable law(s) or
regulations. By signing the ICF the participant is authorizing such access. It also denotes that the

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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. Participants will be reconsented,
including, but not limited to the following cases:
 Group 5 placebo participants receiving a single dose of 5x1010 vp Ad26.COV2.S after EUA
or approval in any country.
 Participants from Cohort 1a, 1b, and 3 who wish to participate in the additional follow-up
after local approval of protocol amendment 14.
 Participants receiving a single ad hoc booster dose of 5x1010 vp Ad26.COV2.S after local
approval of protocol amendment 15.
All Cohort 1b participants will be offered participation in an optional fine needle LNA procedure,
for which they will have to sign an additional ICF. The participant will be asked to sign and
personally date an ICF indicating agreement to participate in the LNA procedure. Refusal to
participate in the optional procedure will not result in ineligibility for the study. A copy of this
signed ICF will be given to the participant.
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
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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.
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 Ad26.COV2.S, to understand
SARS-CoV-2 infection, to understand differential vaccine responders, and to develop tests/assays
related to Ad26.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, Withdrawal From the Use of Research Samples).
10.3.6. 
Committees Structure
Data Review Committee
An internal DRC, consisting of members that are not directly involved in the study conduct, data
management, or statistical analysis, will be established and will monitor data to ensure the
continuing safety of the participants enrolled in this study. The DRC will review data as indicated
in Section 4.1, Overall Design. When appropriate, the conclusions of the DRC will be
communicated to the investigators, the IRB/IEC, and the national regulatory authorities.
In addition, ad hoc review may be performed further to the occurrence of any AE/SAE leading to
a study pausing situation as outlined in Section 6.9, Study Vaccination Pausing Rules, or at request
of the sponsor’s medical monitor or designee. The PI(s) and SRP will inform the DRC of any AE
of concern.
The DRC will review blinded data first, but is entitled to and has the right to require submission
of unblinded data if deemed necessary.
It will also be possible for the DRC to review unblinded immunogenicity data during the course
of the study if this is deemed necessary for future vaccine development-related decisions. If this is

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the case, a biomarker representative (not involved in the conduct of the study) will be part of the
DRC.
This committee will consist of at least one medical expert in the relevant therapeutic area and at
least one statistician. The DRC responsibilities, authorities, and procedures will be documented in
its 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 8.3.6). A Charter will be
developed to describe the roles and responsibilities of the Committee.
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 biomarker 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
biomarker 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

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publish information from the study, a copy of the manuscript must be provided to the sponsor for
review at least 60 days before submission for publication or presentation. Expedited reviews will
be arranged for abstracts, poster presentations, or other materials. If requested by the sponsor in
writing, the investigator will withhold such publication for up to an additional 60 days to allow for
filing of a patent application. In the event that issues arise regarding scientific integrity or
regulatory compliance, the sponsor will review these issues with the investigator. The sponsor will
not mandate modifications to scientific content and does not have the right to suppress information.
For multicenter study designs and sub-study approaches, secondary results generally should not
be published before the primary endpoints of a study have been published. Similarly, investigators
will recognize the integrity of a multicenter study by not submitting for publication data derived
from the individual study site until the combined results from the completed study have been
submitted for publication, within 18 months after the study end date, or the sponsor confirms there
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 will 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
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10.3.9. 
Case Report Form Completion
Case report forms (CRFs) are prepared and provided by the sponsor for each participant in
electronic format. All data relating to the study must be recorded in 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.
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; vaccine
receipt/dispensing/return records; study vaccine administration information; and date of study
completion and reason for early discontinuation of study vaccine or withdrawal from the study, if
applicable.
The author of an entry in the source documents should be identifiable.
Participant- and investigator-completed scales and assessments designated by the sponsor
(ie, diary to record solicited AEs, daily signs and symptoms surveillance question, and SIC) will
be recorded and will be considered source data. The participant’s diary used to collect information
regarding solicited signs and symptoms after vaccination will be considered source data.
Documentation of recommended procedures for (a)symptomatic COVID-19 participants with
RT-PCR confirmed SARS-CoV-2 infection (refer to Sections 8.1.2 and 8.1.3), will be added to
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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, 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 will compare the data entered into the eCRF with the source documents
(eg, hospital/clinic/physician’s office medical records). The nature and location  of all source
documents will be identified to ensure that all sources of original data required to complete the
eCRF are known to the sponsor and study-site personnel and are accessible for verification by the
sponsor study-site contact. If electronic records are maintained at the study site, the method of
verification must be discussed with the study-site personnel.
Direct access to source documents (medical records) must be allowed for the purpose of verifying
that the recorded data are consistent with the original source data. Findings from this review will
be discussed with the study-site personnel. The sponsor expects that during monitoring visits, the
relevant study-site personnel will be available, the source documents will be accessible, and a
suitable environment will be provided for review of study-related documents. The monitor will
meet with the investigator on a regular basis during the study to provide feedback on the study
conduct.
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
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

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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
study site is considered closed when all required documents and study supplies have been collected
and a study-site closure visit has been performed.

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The investigator may initiate study-site closure at any time, provided there is reasonable cause and
sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a study site by the sponsor or investigator may include but are not
limited to:
 Failure of the investigator to comply with the protocol, the requirements of the IEC/IRB or
local health authorities, the sponsor's procedures, or GCP guidelines
 Inadequate recruitment of participants by the investigator
 Discontinuation of further study vaccine development

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10.4. Appendix 4: Adverse Events, Adverse Events of Special Interest, Serious
Adverse Events, 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 vaccine. An AE can therefore be any unfavorable and unintended
sign (including an abnormal finding), symptom, or disease temporally associated with the use of a
medicinal (investigational or non-investigational) product, whether or not related to that medicinal
(investigational or non-investigational) product. (Definition per 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  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,
(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: For time period of sponsor’s AE collection, see All Adverse Events under Section 8.3.1,
Time Period and Frequency for Collecting Adverse Event and Serious Adverse Event Information.
Serious Adverse Event
An SAE based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for
Human Use is any untoward medical occurrence that at any dose:
 
Results in death
 
Is life-threatening
(The participant was at risk of death at the time of the event. It does not refer to an event that
hypothetically might have caused death if it were more severe.)
 
Requires inpatient hospitalization or prolongation of existing hospitalization
 
Results in persistent or significant disability/incapacity
 
Is a congenital anomaly/birth defect
 
Is a suspected transmission of any infectious agent via a medicinal product
 
Is Medically Important*

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*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).
Any respiratory tract infection fulfilling the criteria of an SAE will be reported as such during the
entire study. If the molecular test is positive for SARS-CoV-2, the SAE will be excluded from the
SAE analysis in the Clinical Study Report and will be tabulated separately.
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.
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.
AEs Related to the Optional Lymph Node Aspiration Procedure
AEs and relevant concomitant therapies occurring during the optional LNA study period will be
collected in the eCRF if related to study procedures or if serious or AESI be reported to the sponsor
according to SAE/AESI requirements.
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.

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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 2007,46 included in Section 10.6, Appendix 6, Toxicity
Grading Scale.
The AESI definition includes thrombocytopenia, defined as platelet count <150,000/µL as per the
Brighton Collaboration (Section 8.3.6.1).
For the purpose of severity grading, an AE of thrombocytopenia based on platelet counts
>140,000/µL and <150,000 µL should be considered Grade 1.
For AEs not identified in the grading table, the following guidelines will be applied:
Grade 1 
Mild 
Symptoms causing no or minimal interference with usual social
and functional activities
Grade 2 
Moderate 
Symptoms causing greater than minimal interference with usual
social and functional activities
Grade 3 
Severe 
Symptoms causing inability to perform usual social and
functional activities and requires medical intervention
Grade 4 
Potentially 
life- 
threatening 
Symptoms causing inability to perform basic self-care functions
OR medical or operative intervention indicated to prevent
permanent impairment, persistent disability OR ER visit or
hospitalization
The severity of solicited signs and symptoms will be graded in the diary by the participant based
on the severity assessment provided in the diary and then verified by the investigator using the
toxicity grading scale in Section 10.6, Appendix 6. (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 intervention in an interventional studythat may require
expedited reporting or safety evaluation include, but are not limited to:
 
Overdose of a sponsor study intervention
 
Suspected abuse/misuse of a sponsor study intervention
 
Accidental or occupational exposure to a sponsor study intervention
 
Medication error, intercepted medication error, or potential medication error involving a
Johnson & Johnson medicinal product (with or without patient exposure to the Johnson &

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Johnson medicinal product, eg, product name confusion, product label confusion, intercepted
prescribing or dispensing errors)
 
Exposure to a sponsor study intervention from breast-feeding
Special reporting situations should be recorded in the eCRF. Any special reporting situation that
meets the criteria of a 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
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 24-hour 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
For participants who provided consent for the optional LNA procedure, AEs related to this
procedure will be collected as indicated in Section 8.1.1.1.
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

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 
It becomes unlikely that any additional information can be obtained (participant or health care
practitioner refusal to provide additional information, lost to follow-up after demonstration of
due diligence with follow-up efforts)
Suspected transmission of an infectious agent by a medicinal product will be reported as an SAE.
Any event requiring hospitalization (or prolongation of hospitalization) that occurs during
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.
Adverse Events of Special Interest
Adverse events of special interest will be carefully monitored during the study by the sponsor.
These events 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 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.

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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.

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10.5. Appendix 5: Contraceptive Guidance and Collection of Pregnancy
Information
Participants must follow contraceptive measures as outlined in Section 5.1, Inclusion Criteria.
Pregnancy information will be collected and reported as noted in Section 8.3.5, Pregnancy and
Section 10.4, Appendix 4, Adverse Events, Serious Adverse Events, Product Quality Complaints,
and Other Safety Reporting: Definitions and Procedures for Recording, Evaluating, Follow-up,
and Reporting.
Definition of Woman of Childbearing Potential
Woman of Childbearing Potential
A woman is considered fertile following menarche and until becoming postmenopausal unless
permanently sterile (see below).
Woman Not of Childbearing Potential
 
premenarchal
A premenarchal state is one in which menarche has not yet occurred.
 
postmenopausal
A postmenopausal state is defined as no menses for 12 months without an alternative medical
cause.
 
permanently sterile (for the purpose of this study)
Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral
oophorectomy.
Note: If the childbearing potential changes after start of the study (eg, a premenarchal woman
experiences menarche) or the risk of pregnancy changes (eg, a woman who is not heterosexually
active becomes active), a woman must begin a highly effective method of contraception, as
described throughout the inclusion criteria.

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10.6. Appendix 6: Toxicity Grading Scale
Adapted from the FDA Guidance document “Toxicity Grading Scale for Healthy Adult and
Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials” (September 2007).
A: Tables for Clinical Abnormalities
Local Reaction to 
Injectable Product 
Mild (Grade 1) 
Moderate (Grade 2) Severe (Grade 3) 
Potentially Life
Threatening
(Grade 4)
Pain/Tenderness# 
Aware of symptoms 
but easily tolerated; 
Does not interfere 
with activity; 
Discomfort only to 
touch  
Notable symptoms; 
Requires modification 
in activity or use of 
medications; 
Discomfort with 
movement 
Incapacitating 
symptoms; 
Inability to do work, 
school, or usual 
activities; Use of 
narcotic pain reliever
Hospitalization;
Pain/tenderness
causing inability to
perform basic self-
care function
Erythema# 
25 –50 mm  
51 –100 mm  
> 100 mm  
Hospitalization;
Necrosis or
exfoliative dermatitis
Swelling# 
25 –50 mm  
51 –100 mm  
> 100 mm  
Hospitalization;
Necrosis
# Revised by the sponsor.
Vital Signs * 
Mild (Grade 1) 
Moderate (Grade 2) Severe (Grade 3) 
Potentially Life
Threatening
(Grade 4)
Fever (°C) ** 
           (°F)** 
38.0 - 38.4 
100.4 - 101.1 
38.5 - 38.9 
101.2 - 102.0 
39.0 - 40.0 
102.1 - 104.0 
> 40
> 104.0
Tachycardia - beats 
per 
minute
101 –115 
116 –130 
> 130 
Hospitalization for
arrhythmia#
Bradycardia - beats 
per 
minute***
50 –54 
45 –49 
< 45 
Hospitalization for
arrhythmia#
Hypertension 
(systolic) - mm Hg 
141 –150 
151 –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.

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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.

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Systemic Illness 
Mild (Grade 1) 
Moderate (Grade 2) Severe (Grade 3) 
Potentially Life
Threatening
(Grade 4)
Illness or clinical 
adverse 
event (as defined 
according to 
applicable
regulations)
No interference with  
activity  
Some interference 
with activity not 
requiring medical 
intervention 
Prevents daily  
activity and
requires medical
intervention
Hospitalization#
# Revised by the sponsor.
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
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

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Bilirubin –when Liver Function Test 
is normal; increase by factor
1.1 –1.5 x ULN  1.6 –2.0 x ULN  2.0 –3.0 x ULN  > 3.0 x ULN
Cholesterol 
201 –210 
211 –225 
> 226 
---
Pancreatic enzymes –amylase, lipase 
1.1 –1.5 x ULN 1.6 –2.0 x ULN 2.1 –5.0 x ULN > 5.0 x ULN
* The laboratory values provided in the tables serve as guidelines and are dependent upon institutional normal
parameters. Institutional normal reference ranges should be provided to demonstrate that they are appropriate.
** The clinical signs or symptoms associated with laboratory abnormalities might result in characterization of the
laboratory abnormalities as potentially life-threatening (Grade 4). For example. a low sodium value that falls
within a Grade 3 parameter (125-129 mEq/L)should be recorded as a Grade 4 hyponatremia event ifthe
participant had a new seizure associated with the low sodium value.
***ULN is the upper limit ofthe 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 ofthe normal range.
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

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* 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.
10.7. Appendix 7: Symptoms of Infection with Coronavirus-19 (SIC)
Note: An example SIC is provided below. Participants will be provided with the most recent
version of the 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 this 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

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In the last 24 hours,
have you
experienced…
Please rate the severity of each symptom you experienced.
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
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

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In the last 24 hours,
have you
experienced…
Please rate the severity of each symptom you experienced.
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
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

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In the last 24 hours,
have you
experienced…
Please rate the severity of each symptom you experienced.
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
What was your highest temperature in the last 24 hours? ____  °C/°F
What method did you use to take your temperature?
oral   armpit   ear    other
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

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10.8. Appendix 8: Case Definitions for COVID-19
10.8.1. 
Case Definition for Moderate to Severe COVID-19
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 observationa:
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 judgement.
** 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.
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
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 8.1.1.1).

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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 ³ 30 breaths/minute,
heart rate ³ 125 beats/minute, oxygen saturation (SpO2) 93% on room air at sea level*, or
partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2)<300 mmHg)
* SpO2 criteria will be adjusted according to altitude per the investigator judgement.
 
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 mmHg, diastolic blood pressure
<60 mmHg, or requiring vasopressors)
 
Significant acute renal, hepatic, or neurologic dysfunction
 
Admission to the ICU
 
Death
10.8.2. 
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 in Section 10.8.1.
10.8.3. 
US FDA Harmonized Case Definition for COVID-19
The following case definition is recommended by the FDA as a primary or secondary endpoint for
all efficacy studies against COVID-19:
If a participant presents with symptoms as those listed by the US FDA harmonized case definition13
(see Section 10.9, Appendix 9), the investigator (or designated medically trained clinician) should
assess if these are suggestive of 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
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 8.1.1.1).

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 
COVID-19 symptoms consistent with those defined by the US FDA harmonized case
definition13 at the time of finalization of this protocol: fever or chills, cough, shortness of
breath or difficulty breathing, fatigue, muscle or body aches, headache, new loss of taste or
smell, sore throat, congestion or runny nose, nausea or vomiting, diarrhea.
10.8.4. 
Case Definition for Asymptomatic or Undetected COVID-19
If a participant does not fulfil the criteria for suspected COVID-19 based on signs and symptoms
(see Section 8.1.2.3),
AND
 
has 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
OR
 
develops a positive serology (non-S protein) test
Then, the participant will be considered to have experienced asymptomatic or undetected
COVID-19.
The recommended procedure for participants with asymptomatic COVID-19 RT-PCR confirmed
infection is detailed in Section 8.1.3.

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10.9. Appendix 9: Symptoms of Coronavirus (US Centers for Disease Control
and Prevention)
The following extract shows symptoms of coronavirus infection as listed on the US CDC website
(https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html) dated 13 May
2020:

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10.10. Appendix 10: Summary of Guidance from CDC Website on Underlying
Medical Conditions That Lead or Might Lead to Increased Risk for Severe
Illness From COVID-19
People of any age with certain underlying medical conditions are at increased risk for severe
illness from COVID-19:
People of any age with the following conditions are at increased risk of severe illness from
COVID-19:
 Cancer
 Chronic kidney disease
 COPD (chronic obstructive pulmonary disease)
 Immunocompromised state (weakened immune system) from solid organ transplant
 Obesity (body mass index [BMI] of 30 or higher)
 Serious heart conditions, such as heart failure, coronary artery disease, or cardiomyopathies
 Sickle cell disease
 Type 2 diabetes mellitus
COVID-19 is a new disease. Currently there are limited data and information about the impact of
underlying medical conditions and whether they increase the risk for severe illness from
COVID-19. Based on what we know at this time, people with the following conditions might be
at an increased risk for severe illness from COVID-19:
 Asthma (moderate to severe)
 Cerebrovascular disease (affects blood vessels and blood supply to the brain)
 Cystic fibrosis
 Hypertension or high blood pressure
 Immunocompromised state (weakened immune system) from blood or bone marrow
transplant, immune deficiencies, HIV, use of corticosteroids, or use of other immune
weakening medicines
 Neurologic conditions, such as dementia
 Liver disease
 Pregnancy
 Pulmonary fibrosis (having damaged or scarred lung tissues)
 Smoking
 Thalassemia (a type of blood disorder)
 Type 1 diabetes mellitus
Source: 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. Accessed: 13 July 2020.

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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 to help adjudicate whether the event is a case of TTS. Additional data may be requested by
the sponsor for investigation of the event.
Adverse Event of Special Interest Questionnaire (AESIQ) for Thromboembolism with
Thrombocytopenia Syndrome
Date of Report: 
[dd-MMM-yyyy]
1. Adverse Event Description
Participant’s clinical signs and symptoms
Leg/Calf Oedema 
Pain in Leg/Calf 
Haemoptysis
Dyspnoea 
Chest Pain/Discomfort 
Syncope
Tachypnoea 
Tachycardia 
Cough
Loss of consciousness 
Headache  
Seizure
Visual impairment 
Weakness 
Impaired speech
Confusional state 
Paresthesia 
Gait disturbance
Other symptoms:
Was patient on VTE prophylaxis? 
No 
Yes, details:
2. Medical History and Concurrent Conditions
Provide details:
Is the participant overweight or have obesity? 
No 
Yes
    If available, please provide: 
    
       Height 
Weight 
BMI
Does the participant have a sedentary lifestylea? 
No 
Yes –details:
Has the participant been in a sitting position for long 
periods of time prior to the event?
No 
Yes –details:
Is there a current history of smoking (active or passive)? 
No 
Yes –details:
Is there a prior history of smoking (active or passive)? 
No 
Yes –details:
Does the participant have a prior history of:
Cancer 
No 
Yes –details:
Autoimmune disease (i.e., collagen-vascular disease, 
inflammatory bowel disease) or myeloproliferative
disease?
No 
Yes –details:
Clotting disorder or a hypercoagulable state 
No 
Yes –details:
Varicose veins 
No 
Yes –details:
Trauma to the involved leg or pelvis 
No 
Yes –details:
DVT/PE or other VTE  
No 
Yes –details:
Blood transfusion  
No 
Yes –details:
Cardiovascular disease 
No 
Yes –details:
a Any waking behavior characterized by an energy expenditure less than or equal to 1.5 metabolic equivalents (METs),
while in a sitting, reclining or lying posture

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If the participant has experienced a previous thrombotic
event, address the following:
    1.  Date (or estimate) 2.  Provide brief description of the
nature of the event  3.  Provide brief description of the
treatment of the event  4.  Note any residual
manifestations of the event.
 
If the patient has experienced more than one previous
thrombotic event, please list other events.
Was the (female) participant pregnant at the time of 
event?
No 
Yes –details:
Does the participant has any of genetic risk factors:
Dysfibrinogenemia 
Antiphospholipid syndrome 
Factor V Leiden mutation
Protein C or S deficiency  
Elevated factor VIII levels 
Anti-thrombin deficiency
Hyperhomocysteinemia 
Prothrombin gene mutation  
Blood-clotting disorder
Thrombophilia
Does the participant have any acquired risk factors:
Reduced mobility (paralysis, paresis, travel etc.) 
Recent surgery
Indwelling central venous catheters                       
Recent trauma
Recent discontinuation of anticoagulants (e.g., heparin, warfarin, DOACs)
Hormone replacement therapy (including contraceptives)
Phlebitis 
Lupus
Inflammatory bowel disease 
Myeloproliferative disorders
Diabetes mellitus 
Hyperlipidemia
Hypertension                                                                       
Dehydration
Other significant medical co-morbidities or risk factors for DVT, specify:
If yes to any of the above, provide details:
Provide Well’s score, if calculated:
3. Relevant results of diagnostic tests including laboratory tests, imaging, biopsies, etc. (Note
the levels/conclusion, date performed, normal ranges as well as any other details. Alternatively,
attach full reports of the diagnostic tests.)
Diagnostic Test 
Results at baseline or prior 
to use of product (Include 
date and value/details) 
Test results after use of
product (Include date
and value/details)
CBC with smear (microscopic
evaluation)
ESR
Platelet count
Antibodies to platelet factor 4
(PF4)
Fibrinogen levels
Clauss fibrinogen assay

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Diagnostic Test 
Results at baseline or prior 
to use of product (Include 
date and value/details) 
Test results after use of
product (Include date
and value/details)
D-Dimer
Clotting Profile (PT, aPTT- prior
to an anticoagulation treatment)
Thrombin time (Bovine) Plasma
Prothrombin
Antithrombin activity
Factor V Leiden
Protein C activity
Protein S activity
C-reactive protein
Homocystein levels
Dilute Russells Viper Venom
Time (DRVVT), Plasma
Activated Protein C Resistance
V (APCRV), Plasma
Thrombophilia interpretation
Anticardiolipin antibodies (IgG
and IgM) or beta-2
glycoproteins antibodies
Antiphospholipid antibodies
(IgG and IgM)
Lupus anticoagulant
Heparin antibodies
ANA and ANCA
IL6 levels
ADAMTS13 Activity Assay
Ceruloplasmin
Direct Coombs test
Complement C3, C4
MethylenetetraHydrofolate
reductase gene mutation
Prothrombin gene mutation
(G20210A)
Occult blood in stool
COVID-19 test
Troponins
Brain Natriuretic Peptide
Arterial Blood Gases

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Diagnostic Test 
Results at baseline or prior 
to use of product (Include 
date and value/details) 
Test results after use of
product (Include date
and value/details)
Chest X-Ray
Electrocardiography
Echocardiography
Duplex Ultrasonography
MRI scan
CT scan
Contrast Venography
Pulmonary Angiography
Ventilation-Perfusion Scanning
Provide details of any additional diagnostic results:

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10.12. Appendix 12: Thrombotic Events to be Reported as AESIs
At the time of protocol Amendment 11 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

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10.13. Appendix 13: Protocol Amendment History
The Protocol Amendment Summary of Changes Table for the current amendment is located
directly before the Table of Contents (TOC).
Amendment 1 (20 May 2020)
Overall Rationale for the Amendment: To address regulatory feedback on the study design and
eligibility criteria.
Section Number 
and Name
Description of Change 
Brief Rationale
1.1 Synopsis Objectives and
Endpoints, Overall Design;
1.3 Schedule of Activities; 3
Objectives and Endpoints;
4.1 Overall Design; 4.2
Scientific Rationale for Study
Design; 6.3 Measures to
Minimize Bias; 8.1.1
Immunogenicity
Assessments; 8.1.2
Procedures in Case of
COVID-19-like Signs and
Symptoms; 8.5 Biomarkers;
9.4.5 Other Analyses; 10.2.7
Publication Policy
Study visit added at 28 days after onset of
symptoms for participants with SARS-CoV-2
infection, with clinical examination and
collection of blood samples to assess the
humoral immune response and other
biomarkers (RNA-seq). For comparison with
biomarkers at baseline, a whole blood sample
will be collected in PAXgene tubes for all
participants instead of a subset. An exploratory
objective and endpoint was added for
evaluation of the immune response in
vaccinated individuals after natural infection
and to explore other potentially informative
biomarkers.
Based on regulatory feedback
to examine the clinical course,
and immune response and
other biomarkers, after
SARS-CoV-2 infection.
1.2 Schema; 1.3.3 and 1.3.4
Schedule of Activities
Cohorts 2a and 2b; 8 Study
Assessments and Procedures
Added safety and immunogenicity visit at 
7days after each study vaccination in Cohorts 
2a and 2b. 
To allow additional
comparisons of the immune
response to vaccination in the
1-dose and 2-dose primary
regimens with single booster
vaccination.
1.1 Synopsis Overall Design,
Statistical Methods; 4.1
Overall Design; 9.5 Planned
Analysis
It was clarified that all participants in Cohort 1 
could be randomized and vaccinated in the 
absence of safety concerns from the review of 
24-hour safety data from the first 5 sentinel 
participants in Cohort 1a. It was also clarified 
that randomization and vaccination of
participants in Cohort 3 could begin in the
absence of safety concerns from review of 7-
day safety data from the first 15 participants in
Cohort 1a.
Based on regulatory feedback
on the safety data required to
fully enroll Cohort 1 and
initiate enrollment of
Cohort 3.
1.1 Synopsis Objectives and
Endpoints, Overall Design;
3 Objectives and Endpoints;
4.1 Overall Design; 4.3
Justification for Dose; 6.1
Study Vaccinations
Administered
The Ad26.COV2.S dose level for vaccination 
in Cohort 2a was revised to 1×1011 vp. It was 
also clarified that the volume administered to 
participants in Cohort 2 would be 1 mL. 
To allow assessment in Cohort
2 of a 1-dose primary regimen
and booster vaccination with
each vaccination at a dose
level 1×1011 vp, and
comparison with a 2-dose
primary regimen and booster
vaccination with each
vaccination at a dose level of
5×1010 vp.
5.1 Inclusion Criteria; 5.2
Exclusion Criteria; 10.1
Abbreviations; 11 References
Eligibility criteria were revised to clarify that 
participants will not have underlying 
comorbidities that increased the risk of severe 
COVID-19. 
Based on regulatory feedback
to exclude participants who
would be at higher risk of
severe COVID-19.

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Section Number 
and Name
Description of Change 
Brief Rationale
5.2 Exclusion Criteria; 6.8 
Prestudy and Concomitant 
Therapy; 7.1 Discontinuation 
of Study Vaccination 
Exclusion criterion 9 was clarified to specify 
that participants on current treatment with 
investigational agents for prophylaxis of
COVID-19 will be excluded. Text was revised
to clarify that any participant who received
anti-COVID-19 vaccine or treatment will not
receive further study vaccination.
Based on regulatory feedback
to exclude such participants.
5.2 Exclusion Criteria 
Exclusion criterion added to exclude 
participants currently working in occupation 
with high risk of exposure to SARS-CoV-2 
from Cohorts 1 and 3.
Based on regulatory feedback
to exclude such participants
from Cohorts 1 and 3.
1.1 Synopsis Overall Design; 
1.3.6 Procedures for 
Participants with COVID-19- 
like Signs and Symptoms; 
4.1 Overall Design; 8 Study 
Assessments and Procedures; 
8.1.2 Procedures in Case of 
COVID-19-like Signs and
Symptoms; 9.4.5 Other
Analyses; 10.1
Abbreviations; 10.2.10
Source Documents
The Global Impression of Severity and Global 
Impression of Change were removed from the 
procedures in case ofCOVID-19-like
symptoms. The name of the COVID-19 Signs
and Symptoms Instrument (CSSI) was updated
to the Symptoms of Infection with COVID-19
(SIC).
To reflect changes made to the
PRO assessments in the study.
6.9 Study Vaccination 
Pausing Rules 
Study vaccination pausing rules were revised to 
remove temporal requirements. 
Based on regulatory feedback
that temporal requirements
should be included in the
assessment of causality.
1.1 Synopsis Statistical 
Methods; 9.2 Sample Size 
Determination  
The probability of observing an AE based on 
possible true AE incidences was revised to 
reflect the number of active vaccine recipients 
in Cohorts 2a and 2b. 
To reflect the number of
active vaccine recipients in
Cohorts 2a and 2b in the
description of the safety
assessment provided by the
study sample size.
4.1 Overall Design  
Details were added on the estimation of an 
over-enrollment rate for seronegative 
participants in the absence of a serological test 
at screening. 
To provide more details on the
over-enrollment of
seronegative participants, if
needed.
2.3.1 Risks Study 
Participation; 9.5 Planned 
Analysis 
Clarification added that a prespecified 
threshold for the imbalance in molecularly 
confirmed COVID-19 cases to trigger DRC 
notification will be described in the Statistical 
Analysis Plan.
Based on regulatory feedback
to clarify that this threshold
will be described in the
Statistical Analysis Plan.
4.2 Scientific Rationale for 
Study Design; 6.3 Measures 
to Minimize Bias 
Details were added on the possible initial use of 
a paper randomization list if the IWRS is not 
live at the planned time of randomization of the 
first participant.
A paper randomization list
could initially be used until
IWRS is live.
8 Study Assessments and 
Procedures 
Added eCRF guidelines to list of study-specific 
materials. 
To provide more information
on material for investigator.
General 
Minor errors and inconsistencies were 
corrected throughout the protocol. 
Correction of minor errors and
inconsistencies.

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Amendment 2 (5 June 2020)
Overall Rationale for the Amendment: To address regulatory agency feedback on the study
design.
Section Number 
and Name
Description of Change 
Brief Rationale
1.1 Synopsis, Overall Design, 
Number of Participants, 
Statistical Methods; 1.3 
Schedule of Activities; 4.1 
Overall Design; 9.2 Sample 
Size Determination; 9.5
Planned Analysis
The number of participants in Cohorts 1a and 3
was increased. In addition, the number of
participants for whom peripheral blood
mononuclear cells (PBMCs) will be collected
was increased in Cohorts 1a and 3.
To generate additional
immunogenicity data in
Cohorts 1a and 3 based on
regulatory agency feedback.
5.1 Inclusion Criteria 
The age for participants to be enrolled in
Cohort 3 was revised to 65 to 75 years
inclusive for study sites in Belgium.
Based on regulatory agency
feedback.
1.1 Synopsis, Overall 
Design; 1.3 Schedule of 
Activities; 4.1 Overall 
Design; 6.8 Prestudy and 
Concomitant Therapy; 8.1.2 
Procedures in Case of 
COVID-19-like Signs and
Symptoms
The recording of concomitant medications was
added to the procedures for the study visit
conducted 28 days after symptom onset for
participants with a positive test result for severe
acute respiratory syndrome coronavirus-2
(SARS-CoV-2) infection.
To obtain additional
information on coronavirus
disease-2019 (COVID-19)
cases.
1.3 Schedule of Activities; 8 
Study Assessments and 
Procedures 
The time period from screening after which the
nasal swab sample and, if available, serological
test for SARS-CoV-2-specific antibodies are to
be repeated on Day 1 was increased from 2
days to 3 days.
To allow more flexibility in
the screening process.
8 Study Assessments and 
Procedures 
The maximum blood volume to be collected
was clarified.
To account for the possibility
of blood samples being
collected in case of
COVID-19-like signs and
symptoms.
1.1 Synopsis, Dosage and 
Administration; 6.1 Study 
Vaccinations Administered 
Clarification was added that Ad26.COV2.S
will be supplied as a suspension in single-use
vials.
To provide more information
on Ad26.COV2.S vaccine.
4.3 Justification for Dose 
Text was revised to clarify the highest dose
level of adenovirus type 26 (Ad26)-based
vaccines previously evaluated in clinical
studies.
To clarify the reasons for dose
level selection.
10.1 Abbreviations; 10.2.8 
Data Quality Assurance 
Text describing data quality assurance was
revised.
To clarify the processes to be
followed for data quality
assurance / quality control.
1.1 Synopsis, Statistical 
Methods; 9.5 Planned 
Analysis 
Although the assay will still be conducted,
references to the antibody-dependent cellular
phagocytosis (ADCP) assay were removed
from the description of the interim and primary
analyses.
To focus the description of
immunogenicity data in the
interim and primary analyses
on virus neutralization assay
(VNA), enzyme-linked
immunosorbent assay
(ELISA), and T-helper
(Th)1/Th2 assays.

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Section Number 
and Name
Description of Change 
Brief Rationale
2.2 Background 
Revisions were made to the text describing 
clinical safety experience with Ad26-based 
vaccines. 
To align text to standard
wording used for documents
in the Ad26.COV2.S clinical
development program.
Amendment 3 (8 July 2020)
Overall Rationale for the Amendment: To address regulatory agency feedback on the study
design and eligibility criteria.
Section Number 
and Name
Description of Change 
Brief Rationale
1.1 Synopsis, 1.3 Schedule of
Activities (SoA), 1.2
Schema, 4.1 Overall Design,
4.4 End of Study Definition,
8 Study Assessments and
Procedures, 8.1.3 Efficacy
Assessments, 9.5 Planned
Analysis
Extension of follow up to at least 1 year after
the last vaccine dose in all participants to
further evaluate safety (including the risk of
vaccine-enhanced disease), to assess the
durability of immune response, and to
maximize the opportunity of obtaining
preliminary data on possible efficacy after
SARS-CoV-2 exposure.
Based on regulatory agency
feedback.
1.1 Synopsis, 1.3 Schedule of
Activities (SoA), 2.3.1 Risks
related to Study Participation,
2.3.3 Benefit-Risk
Assessment of Study
Participation, 4.1 Overall
Design, 8.3.2 Method of
Detecting Adverse Events
and Serious Adverse Events
After each vaccination, participants should
remain under observation at the study site for at
least 1 hour (instead of 30 minutes) for the
presence of any acute reactions and solicited
events.
Based on regulatory agency
feedback.
1.1 Synopsis; 4.1 Overall
Design,
It has been clarified in the protocol that, if the
immunogenicity results obtained after the 1st
vaccination in Cohort 1a are not adequately
supporting initiation of Cohort 2, then results
obtained after the 2nd vaccination in the 2-dose
regimens in Cohort 1a will be used to select the
vaccine regimens to be evaluated in Cohort 2 of
this study. If the immunogenicity results
obtained after the 2nd vaccination in the 2-dose
regimens in Cohort 1a do not demonstrate an
adequately increased immune response, the
sponsor will not provide the 2nd vaccination at
Day 57 in Cohort 2 of this study.
Based on regulatory agency
feedback.
1.3 Schedule of Activities
(SoA), 2.3.3 Benefit-Risk
Assessment of Study
Participation, 5 Study
Population
Eligibility will be reassessed pre-vaccination
on Day 1.
Based on regulatory agency
feedback.

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Section Number 
and Name
Description of Change 
Brief Rationale
1.3 Schedule of Activities 
(SoA), 2.3.3 Benefit-Risk 
Assessment of Study 
Participation, 5.1 Inclusion 
Criteria, 8.2.4 Clinical 
Laboratory Assessments, 
9.4.2 Primary Endpoints,
10.2 Appendix 2: Clinical
Laboratory Tests
Addition of a clinical laboratory assessment 
(blood and urine) at screening, pre-vaccination 
at each day of vaccination (pre-dose 1 and
pre-dose 2), and at the Day 7 post vaccination
visit for the primary regimens (Day 8 and
Day 64).
Based on regulatory agency
feedback.
1.3 Schedule of Activities 
(SoA), 8.3.1 Time Period and 
Frequency for Collecting
Adverse Event and Serious
Adverse Event Information
Clarified that SAEs will be reported until the 
end of the study for all participants. 
Based on regulatory agency
feedback.
1.3.6 Procedures for 
Participants With COVID- 
19-like Signs and Symptoms;
4.1 Overall Design;
8 STUDY ASSESSMENTS
AND PROCEDURES;
8.1.2 Procedures in Case of
COVID-19-like Signs and
Symptoms;
8.1.2.1 Prespecified Criteria
for Suspected COVID-19
Prespecified criteria for suspected COVID-19 
are added and updated. 
Based on regulatory agency
feedback.
5.1 Inclusion Criteria 
Obesity is a risk factor of severe COVID-19. 
The criterion ‘Participant must have a body 
mass index (BMI) <40.0 kg/m2’ has been
updated to ≤30.0 kg/m2 as per CDC definition
of obesity.
Based on regulatory agency
feedback.
5.2 Exclusion Criteria 
4.1 Overall Design  
Several exclusion criteria were updated. Since 
a serological test to detect SARS-CoV-2 
specific antibodies will be available, the
paragraph on over-enrollment has been
removed from Section 4.1.
Based on regulatory agency
feedback.
10.7 Appendix 7: Symptoms 
of Infection with 
Coronavirus-19 (SIC)
Section 10.7, Appendix 7 has been added with 
an example SIC. 
For consistency across
protocols.
Throughout the protocol 
 Ad26.COV2.S will be used as primary 
compound ID instead of Ad26COVS1. 
 Minor errors and inconsistencies were 
corrected throughout the protocol. 
 Change of vaccine name in
the company development
program.
 Correction of minor errors
and inconsistencies.

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Amendment 4 (6 August 2020)
Overall Rationale for the Amendment: To address EC feedback on nasal swab sampling. In
addition, clarification to the eligibility criteria on blood pressure for the elderly population
(Cohort 3) was included. Furthermore, minor errors and inconsistencies were corrected throughout
the protocol.
Section Number 
and Name
Description of Change 
Brief Rationale
1.1 Synopsis, 1.3.6
Procedures for Participants
with COVID-19-like Signs
and Symptoms, 4.1 Overall
Design, 8.1.2 Procedures in
Case of COVID-19-like
Signs and Symptoms, 8.1.2.1
Prespecified Criteria for
Suspected COVID-19
It has been clarified in the protocol that the
nasal swab sample should be taken by a health
care professional for study sites in Belgium.
Based on Belgian EC
feedback.
5.1 Inclusion Criteria, 5.2
Exclusion Criteria
Clarification added to the eligibility criteria on
blood pressure for the elderly population
(Cohort 3).
Clarification.
1.1 Synopsis, 3 Objectives
and Endpoints, 8.1.1
Immunogenicity
Assessments
ELISpot has been moved from secondary to
exploratory endpoints.
At the time of protocol
amendment 3, the sponsor
intended to use ICS or
ELISpot for the determination
of Th1 and Th2 responses.
The sponsor has decided to
keep the ICS as the primary
cellular assay for assessment
of Th1 and Th2 responses. In
order to reinforce our Th1/Th2
response assessment, the
sponsor has now decided to
also include IFNγ and IL-4
ELISpot as an exploratory
endpoint to support the
secondary cellular endpoint
assessed by ICS.
1.3 Schedule of Activities,
8 Study Assessments and
Procedures
Add flexibility to allow a window up to 4 days
for availability of serology test for presence of
SARS-CoV-2-specific antibodies and
confirmatory PCR test for the presence of
SARS-CoV-2 infection before start of the first
vaccination. In addition, the same window will
apply to clinical laboratory testing and
urinalysis.
Operational request.
6.8 Prestudy and
Concomitant Therapy
It has been clarified in the protocol that
participants should be instructed to take
antipyretics at the first signs of symptoms post
vaccination
DRC recommendation.
1.1 Synopsis, 4.1 Overall
Design, 9.5 Planned Analysis
Added “approximately” to the target number of
participants to be enrolled in each cohort.
Operational request.

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Section Number 
and Name
Description of Change 
Brief Rationale
10.8 Appendix 8: Case 
Definitions for COVID-19, 
10.9 Appendix 9: Symptoms 
of Coronavirus (US Centers 
for Disease Control and 
Prevention)
Case definitions for COVID-19 have been 
aligned with the Phase 3 protocols. In addition,
"new loss of taste or smell" was added to the
case definition of mild disease at the
recommendation of the NIH
Alignment and NIH request.
Throughout the protocol 
Minor errors and inconsistencies were 
corrected throughout the protocol. 
Correction of minor errors and
inconsistencies.
Amendment 5 (13 August 2020)
Overall Rationale for the Amendment: To address HA feedback on the eligibility criteria on
blood pressure for the elderly population (Cohort 3).
Section Number 
and Name
Description of Change 
Brief Rationale
5.1 Inclusion Criteria, 5.2 
Exclusion Criteria 
Cohort 3 participants, ie, 65 year-olds or older,
with mild hypertension or high blood pressure
will only be included in the study, as long as
their symptoms and signs are stable and
medically controlled as defined by no change
in medication over the past 6 months (except
for issues of tolerability or use of similar drug
with same mechanism of action eg, thiazides,
Beta blockers, Alpha blockers at the same
effective dose).
Upon HA request.
5.2 Exclusion Criteria 
Numbering of exclusion criteria 23, 25 and 26
was corrected.
Correction.

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Amendment 6 (19 September 2020)
Overall Rationale for the Amendment: The Ad26.COV2.S dose level for Cohort 2a has been
changed from 1×1011 virus particles (vp) to 5×1010 vp based on emerging data from Cohorts 1a,
1b and 3. In addition, clarifications on several issues have been made to align the study design
with that of the proposed Phase 3 study VAC31518COV3001 and address health authority
requests.
Section Number 
and Name
Description of Change 
Brief Rationale
1.1 Synopsis
2.2 Background
3 Objectives and Endpoints
4.1 Overall Design
4.3 Justification for Dose
For Cohort 2a, the Ad26.COV2.S dose level
has been changed from 1×1011 vp to 5×1010 vp.
The Ad26.COV2.S dose level
for Cohort 2a has been
adjusted to mimic the dosing
regimen to be evaluated in
study VAC31518COV3001.
1.3.3.1 Cohort 2a: Primary
Regimen
1.3.4.1 Cohort 2b: Primary
Regimen
A footnote that randomization and vaccination
may occur on the same day has been added for
Cohorts 2a and 2b.
Clarification on performing
randomization and vaccination
has been made.
1.1 Synopsis
1.3.6 Procedures for
Participants with
COVID-19-like Signs and
Symptoms: footnote b
4.1 Overall Design
8.1.2 Procedures in Case of
COVID-19-like Signs and
Symptoms
It has been clarified in the protocol that the
nasal swab sample should be taken by a health
care professional, not only for study sites in
Belgium as requested by the Ethics Committee
(EC), but also for study sites in the US.
Based on regulatory agency
feedback to align with the
Belgian EC recommendation.
2.3.1 Risks Related to Study
Participation
6.8 Prestudy and
Concomitant Therapy
Guidance on the use of antipyretics during the
study has been added in the prestudy and
concomitant therapy section of the protocol.
To clarify that antipyretics are
recommended post-
vaccination for symptom
relief, as needed. Prophylactic
antipyretic use is not
encouraged.
5.1 Inclusion Criteria
5.2 Exclusion Criteria
Text was updated to clarify that participants
enrolled in Cohort 3 may have mild
hypertension, but not other comorbidities
associated with an increased risk of severe
COVID-19. Additionally, an inconsistency in
footnote for Inclusion Criterion 5 has been
corrected.
Based on regulatory agency
feedback.

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Section Number 
and Name
Description of Change 
Brief Rationale
1.3.1 Cohort 1a: footnote g 
1.3.2 Cohort 1b: footnote f 
1.3.3.1 Cohort 2a: Primary
Regimen: footnote f
1.3.3.2 Cohort 2a: Booster
Vaccination: footnote d
1.3.4.1 Cohort 2b: Primary
Regimen: footnote f
1.3.4.2 Cohort 2b: Booster
Vaccination: footnote d
1.3.5 Cohort 3: footnote g
1.3.6 Procedures for
Participants with COVID-
19-like Signs and Symptoms:
footnote d
8.2.2 Vital Signs
Text revised to align with wording in Section 8, 
Study Assessments and Procedures.
Alignment.
9.4.2 Primary Endpoints 
10.4.1 Adverse Event 
Definitions and 
Classifications 
It has been clarified that respiratory tract 
infections will be excluded from the (S)AE 
analyses if the molecular test is subsequently 
found to be positive for SARS-CoV-2.
Clarification on criteria and
analysis of (S)AEs have been
made.
9.5 Planned Analysis 
Text was revised to clarify that data will be 
made publicly available. 
The Sponsor plans to publish
selected available group
unblinded immunogenicity
and blinded safety data for
Cohorts 1a, 1b, and 3 for
reasons of transparency since
a large Phase 3 study will start
based on this data. The
Sponsor does however wish to
reduce the potential for
unblinding until the review of
safety data 7 days after Dose 2
in Cohorts 1a, 1b, and 3 is
completed at which time
selected available group
unblinded immunogenicity
and safety data will be
published. All participants and
investigators will remain
blinded to their treatment
regimen until the end of the
study.
10.6 Appendix 6: Toxicity 
Grading Scale 
A minor error was corrected in the footnote of 
the Laboratory Abnormalities table.
Correction of minor error.
10.8.1 Case Definition for 
Moderate to Severe 
COVID-19 
10.8.2 Case Definition for 
Mild COVID-19 
The case definitions ofboth mild and moderate 
COVID-19 have been modified and 
terminology has been aligned across case 
definitions. 
To incorporate additional key
conditions in the case
definition of mild disease and
to simplify the moderate case
definition based on feedback
from regulatory agencies and
partners.

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Amendment 7 (03 November 2020)
Overall Rationale for the Amendment: In this amendment, the mitigation strategy after a study
pause is clarified. Additional changes are listed below.
Section Number 
and Name
Description of Change 
Brief Rationale
1.1 Synopsis
8 STUDY ASSESSMENTS
AND PROCEDURES
9.3 Populations for
Analysis Sets
Clarified that efforts will be made to still
vaccinate a participant if the vaccination
window is missed due to a study pause.
Clarified that these participants will not be
excluded from the PPI by default for this
reason.
Mitigation in case of study pause:
clarification on out of window
vaccination.
6.9 Study Vaccination
Pausing Rules
Text added to state that this study will also
be paused if a pausing rule is met in studies
COV1002, COV2001, or COV3001.
Mitigation in case of study pause:
additional safety measure.
8.1.2.1 Prespecified Criteria
for Suspected COVID-19
It has been clarified that because several of
the prespecified criteria for suspected
COVID-19 overlap with vaccine-related
reactogenicity, investigators' clinical
judgement is required to exclude vaccine-
related events.
To ensure that vaccine-related
events do not trigger the
COVID-19 related follow-up
procedures for mild disease, to be
able to include cases of moderate
disease that were not classifiable
by the definition and for
simplification and clarification
purposes.
8 STUDY ASSESSMENTS
AND PROCEDURES
It has been added that serology testing
outside the study is discouraged and if
testing would be needed, the site will guide
the participant to an appropriate assay.
Vaccination with Ad26.COV2.S
may interfere with some serologic
assays utilized at local community
health clinics/commercial
laboratories and may result in
unblinding the participant.
8 STUDY ASSESSMENTS 
AND PROCEDURES  
It has been clarified that the participant will
be notified of a confirmed positive
SARS-CoV-2 infection and positive serology
test.
For clarification purposes. 
5.2 Exclusion Criteria 
A note regarding the use of any coronavirus 
vaccine (licensed or investigational) other
than Ad26.COV2.S, has been added to
Exclusion Criterion 9 for clarification
purposes.
For clarification purposes.
2.3.1 Risk Related to Study 
Participation
Inconsistencies were corrected. 
Correction of inconsistencies.
Title page 
Prepared by line removed. 
To align with internal guidelines
on legal entity to be mentioned on
title page.

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Amendment 8 (08 December 2020)
Overall Rationale for the Amendment: In this amendment, a recommendation to the protocol
was added regarding additional follow-up procedures for participants with (a)symptomatic
COVID-19 RT-PCR confirmed infection.
Section Number 
and Name
Description of Change 
Brief Rationale
1.1 Synopsis 
1.3.6 Procedures for 
Participants with COVID- 
19-like Signs and 
Symptoms 
4.1 Overall Design  
8.1.2 Procedures in Case of 
COVID-19-like Signs and
Symptoms
8.1.3 Procedures in Case of
Asymptomatic COVID-19
RT-PCR Confirmed
Infection
10.3.10 Source Documents
10.8.4 Case Definition for
Asymptomatic or
Undetected COVID-19
A recommendation was added to the
protocol regarding procedures in case of
(a)symptomatic COVID-19 RT-PCR
confirmed infection. These participants
are recommended to be followed until 2
consecutive negative nasal swabs can be
obtained.
To ensure the safety of people that
are in contact with these participants
and to be able to include the data
from participants with asymptomatic
COVID-19 RT-PCR confirmed
infection in efficacy evaluations.
9.5 Planned Analysis 
Text was revised to clarify that at the time
of the interim analysis, the sponsor will
be unblinded for cohorts 1a, 1b, and 3,
except for sponsor personnel directly
involved with the study site.
Clarification added regarding the
unblinding of the data at the time of
the interim analysis.
1.3 Schedule of Activities 
(SoA) (and subsections) 
7.1 Discontinuation of 
Study Vaccination 
7.2 Participant 
Discontinuation/Withdrawal 
From the Study  
Clarified that participants who no longer
wish to receive study vaccination will be
offered safety and immunogenicity
follow-up. Participants who wish to
withdraw consent from participation in
the study will be offered an optional visit
for safety follow-up.
Clarification added for participants
who do not wish to receive the
second vaccination or who wish to
withdraw consent.
8 Study Assessments and 
Procedures 
On-site serologic testing will be offered
upon participant's request at the next
scheduled blood draw visit.
To avoid participants being
unblinded by serologic testing
organized outside the study.
4.2 Scientific Rationale for 
Study Design  
8.5 Biomarkers 
For all participants, biomarker analysis
(PAXgene, RNA-seq) will be performed
to explore potentially informative
biomarkers related to vaccine
immunogenicity and SARS-CoV-2
infection (including relations with
COVID-19 disease severity).
Alignment with Phase 3 protocols.

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Section Number 
and Name
Description of Change 
Brief Rationale
5.2 Exclusion Criteria 
6.8 Prestudy and 
Concomitant Therapy  
7.1 Discontinuation of 
Study Vaccination 
 Clarified that non-immunomodulator 
treatment is allowed as well as steroids
at a non-immunosuppressive dose or
route of administration.
 Added that a substantial
immunosuppressive steroid dose is
defined as ≥2 weeks of daily receipt of
20 mg of prednisone or equivalent.
Therefore, the specification of
‘(>10 days)’ when referring to the
chronic use of systemic corticosteroids
has been removed from the exclusion
criterion 4 and aligned throughout.
Alignment with Phase 3 protocols.
5.2 Exclusion Criteria 
6.8 Prestudy and 
Concomitant Therapy  
Clarified that the use of investigational 
immunoglobulin (Ig) and monoclonal
antibodies or convalescent serum are not
allowed during the study.
Alignment with Phase 3 protocols.
5.2 Exclusion Criteria 
Clarified that a serological test for 
SARS-CoV-2-specific antibodies should
be performed at screening.
Clarification.
5.2 Exclusion Criteria 
Updated the list of conditions that 
increase the risk of progression to severe
COVID-19.
Alignment with Phase 3 protocols.
5.2 Exclusion Criteria 
Gestational diabetes has been removed 
from the list of comorbidities (or risk 
factors) that might be associated with 
increased risk of progression to severe
COVID-19 as pregnant women are not
allowed to participate.
Gestational diabetes is not applicable
in the current study as pregnant
women are not allowed to participate.
5.2 Exclusion Criteria 
6.6 Continued Access to 
Study Vaccine After the 
End of the Study  
It has been clarified that the sponsor will 
look into the possibility of offering
placebo recipients the study vaccine, if
this vaccine is determined to be
efficacious, considering country-specific
conditions and ethical considerations.
Alignment with Phase 3 protocols.
10.4.1 Adverse Event 
Definitions and 
Classifications 
Section updated to clarify that (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.
Alignment with Section 9.4.2.
4.1 Overall Design  
Sentence about the procedure for 
participants not receiving the second
vaccination was removed, because it was
explained more correctly in the footnote
underneath.
Alignment with footnote table 2.
6.7 Treatment of Overdose 
Definition of what can be regarded as an 
overdose was corrected.
Correction of inconsistency
10.8.1 Appendix 8: Case 
Definition for Moderate to 
Severe COVID-19 
It has been clarified that the adjustment 
according to altitude for the SpO2 criteria
is per the investigator judgement.
Clarification

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Section Number 
and Name
Description of Change 
Brief Rationale
6.3 Measures to Minimize 
Bias: Randomization and 
Blinding 
Immunogenicity follow-up was added to 
the allowed safety follow-up for
participants who had their intervention
assignment unblinded.
Clarification
9.3 Populations for Analysis 
Sets 
Though samples obtained after missed 
vaccinations or after natural infection will
not be analyzed, the participants remain
included in the PPI.
Clarification
Amendment 9 (18 December 2020)
Overall Rationale for the Amendment: In this amendment, language was included regarding
unblinding of study participants who may become eligible to receive an authorized/licensed
COVID-19 vaccine during the course of the study.
Section Number 
and Name
Description of Change 
Brief Rationale
1.1 Synopsis 
1.3 Schedule of Activities 
(SoA) 
6.3 Measures to Minimize 
Bias: Randomization and 
Blinding
6.6 Continued Access to
Study Vaccine After the
End of the Study
7.1 Discontinuation of
Study Vaccination
9.6 Analyses for
Participants Unblinded Due
to Administration of an
Authorized/Licensed
COVID-19 Vaccine
Clarification of procedures for unblinding
of study participants who may become
eligible to receive an authorized/licensed
COVID-19 vaccine during the course of
the study.
To ensure that if participants become
eligible to receive an
authorized/licensed COVID-19
vaccine, they are aware of the
potential options and ramifications,
including the lack of safety data on
receiving two different COVID-19
vaccines.
1.1 Synopsis 
3 OBJECTIVES AND 
ENDPOINTS  
8.1.1 Immunogenicity 
Assessments 
10.1 Appendix 1: 
Abbreviations
An exploratory humoral immunogenicity
endpoint was added: analysis of
antibodies binding to SARS-CoV-2 S
protein and the receptor-binding domain
(RBD) of the SARS-CoV-2 S protein by
Meso Scale Discovery (MSD) assay.
To allow for in-depth analysis of the
binding antibody generated by
Ad26.COV2.S.
9.5 Planned Analysis 
Separate headers were added to this
section to group information regarding
analysis and reporting of unblinded data
and general considerations.
To provide oversight and clarity.

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Amendment 10 (25 February 2021)
Overall Rationale for the Amendment: The main purpose of this amendment is to outline the
procedures to be followed after Emergency Use Authorization (EUA), conditional licensure, or
approval in any country for the single-dose regimen of 5×1010 vp Ad26.COV2.S and local
approval of protocol Amendment 10 by both Health Authority (HA) and Independent Ethics
Committees (IEC)/Institutional Review Board (IRB), when a single dose of 5×1010 vp
Ad26.COV2.S will be offered to enrolled participants who initially received placebo only,
resulting in de facto unblinding of participants and investigators.
Section Number 
and Name
Description of Change 
Brief Rationale
1.1 Synopsis
1.3.7 Procedures for
Group 5 (Placebo Only)
Participants Receiving a
Single Dose of 5x1010 vp
Ad26.COV2.S after EUA or
Approval in any Country
3 OBJECTIVES AND
ENDPOINTS
4.1 Overall Design
4.2 Scientific Rationale for
Study Design
5.5 Criteria for Temporarily
Delaying Administration of
Study Vaccination
6.3 Measures to Minimize
Bias: Randomization and
Blinding
6.1 Study Vaccinations
Administered
6.6 Continued Access to
Study Vaccine After the
End of the Study
7.1 Discontinuation of
Study Vaccination
7.2 Participant
Discontinuation/Withdrawal
from the Study
7.4 Discontinue from
Placebo Group Participation
8.3 Adverse Events, Serious
Adverse Events, and Other
Safety Reporting
8.6 Assessments and
Procedures after Emergency
Use Approval
Following Emergency Use Authorization,
conditional licensure, or approval in any
country for the single-dose regimen of
5×1010 vp Ad26.COV2.S, all participants from
countries where Amendment 10 is locally
approved by the Health Authority and
IEC/IRB will be unblinded to disclose who
received placebo only during primary regimen.
To avoid participants in the
active vaccine groups from
requesting unblinding in order
to receive an
authorized/licensed COVID-19
vaccine and to enable
participants in the placebo
groups to receive a single dose
of 5×1010 vp Ad26.COV2.S.
After unblinding, a single dose of 5×1010 vp
Ad26.COV2.S will be offered to enrolled
participants who received placebo only during
primary regimen. If willing to receive, they
will discontinue from participation in the
placebo groups.
Keeping participants on placebo
during a pandemic while
authorized vaccines have
become available is not
sustainable and cannot be
defended from an ethical point
of view.

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Section Number 
and Name
Description of Change 
Brief Rationale
1.1 Synopsis 
4.2 Scientific Rationale for 
Study Design  
6.3 Measures to Minimize
Bias: Randomization and
Blinding
9.5 Planned Analysis
9.6 Analyses for
Participants Requesting
Unblinding in order to
Receive an
Authorized/Licensed
COVID-19 Vaccine
9.7 Analyses after
Unblinding all Participants
Following EUA or
Approval in any Country
All data will be analyzed separately from the 
point of unblinding. 
Statistical analysis is impacted
by the unblinding and needs to
be updated.
1.1 Synopsis 
6.3 Measures to Minimize 
Bias: Randomization and 
Blinding 
6.6 Continued Access to 
Study Vaccine After the 
End of the Study  
7.1 Discontinuation of
Study Vaccination
9.6 Analyses for
Participants Requesting
Unblinding in order to
Receive an
Authorized/Licensed
COVID-19 Vaccine
Procedures and analyses installed at the time of 
unblinding all participants after Emergency
Use Authorization or approval in any country,
and local approval of protocol Amendment 10,
will also apply to participants who were
unblinded at their own request prior to
Amendment 10.
Clarification.
1.1 Synopsis 
3 OBJECTIVES AND 
ENDPOINTS  
Analysis of neutralizing and binding antibodies 
against emerging SARS-CoV-2 virus lineages 
has been added to exploratory endpoints. 
To accommodate for additional
research regarding the new
emerging SARS-CoV-2 virus
variants.
6.9 Study Vaccination 
Pausing Rules 
The prespecified pausing criteria will no longer 
be in place to trigger a study pause upon 
completion of all Day 57 vaccinations in all 
cohorts. 
This additional safety measure
is no longer applicable at the
stage of booster vaccination
administration.
1.3 Schedule of Activities 
(SoA) 
Footnotes with regards to the 1-hour post- 
vaccination observation were also added to
vital signs to emphasize that vital signs need to
be checked at the end of the observation
period.
Clarification.
1.1 Synopsis 
1.3.6 Procedures for 
Participants with COVID- 
19-like Signs and 
Symptoms 
4.1 Overall Design
8.1.2 Procedures in Case of
COVID-19-like Signs and
Symptoms
Long-term sequelae of COVID-19 (eg, 
anosmia, headache, fatigue, and other
symptoms at the investigator's judgement) will
not be followed until their resolution if not
resolved within a month.
Clarification and alignment.

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Section Number 
and Name
Description of Change 
Brief Rationale
1.1 Synopsis 
1.3.6 Procedures for 
Participants with COVID- 
19-like Signs and 
Symptoms 
4.1 Overall Design
8.1.2 Procedures in Case of
COVID-19-like Signs and
Symptoms
If the first nasal swab is negative, collection of 
data will continue until the negative test is
confirmed by the second nasal swab or until
sign and symptom resolution, whichever
comes first.
Clarification and alignment.
1.3 Schedule of Activities 
(SoA) 
6.8 Prestudy and 
Concomitant Therapy
It was added that receipt of a licensed 
COVID-19 vaccination should be recorded at
any timepoint during the study.
Clarification and alignment.
1.1 Synopsis 
8.1.2 Procedures in Case of 
COVID-19-like Signs and 
Symptoms
8.1.3 Procedures in Case of
Asymptomatic COVID-19
RT-PCR Confirmed
Infection
An additional paragraph from the protocol 
body was copied into the synopsis and some
additional minor clarifications were added.
Clarification.
1.1 Synopsis 
1.2 Schema 
1.3.4 Cohort 2b 
4.1 Overall Design  
8 STUDY ASSESSMENTS
AND PROCEDURES
Footnotes directing participants in Cohort 2b 
who missed the Day 57 vaccination have been
corrected to align with Section 7.2 of the
protocol.
Correction of inconsistency.
2.2 Background 
2.3.1 Risks Related to Study 
Participation  
2.3.2 Benefits of Study 
Participation
Ad26.COV2.S safety and efficacy data 
acquired from primary/interim analyses of
ongoing clinical studies have been updated in
line with the current IB.
To update information.
Throughout the protocol 
Minor errors and inconsistencies were 
corrected, and minor clarifications were added 
throughout the protocol. 
Correction of minor errors and
inconsistencies. Addition of
minor clarifications. Alignment
across sections in the protocol.

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Amendment 11 (6 May 2021)
Overall Rationale for the Amendment: This amendment has been created to include additional
safety measures due to reports of adverse events following use of the Ad26.COV2.S vaccine under
emergency use authorization in the US, suggesting an increased risk of thrombosis combined with
thrombocytopenia. Based on this, thrombosis with thrombocytopenia syndrome (TTS), which is a
very rare event, will be followed in this protocol as adverse event of special interest (AESI) that
needs to be reported to the sponsor within 24 hours of awareness. In addition, anaphylaxis has
been added as an important identified risk.
Section Number
and Name
Description of Change 
Brief Rationale
1.1 Synopsis
1.3.3.2 Booster Vaccination Cohort 2a
1.3.4.2 Booster Vaccination Cohort 2b
1.3.7Procedures for Group 5 (Placebo
Only) Participants Receiving a Single
Dose of 5x1010 vp Ad26.COV2.S after
EUA or Approval in any Country
1.3.8 Procedures for Participants with a
Suspected AESI
2.3.1 Risks Related to Study
Participation
2.3.3  Benefit-Risk Assessment of
Study Participation
3 OBJECTIVES AND ENDPOINTS
4.1 Overall Design
4.4 End of Study Definition
6.8 Prestudy and Concomitant Therapy
7.1 Discontinuation of Study
Vaccination
8 STUDY ASSESSMENTS AND
PROCEDURES
8.2.4 Clinical Laboratory Assessments
8.3 Adverse Events, Serious Adverse
Events, and Other Safety Reporting
8.3.1 Time Period and Frequency for
Collecting Adverse Event and Serious
Adverse Event Information
8.3.2 Method of Detecting Adverse
Events, and Serious Adverse Events,
and Adverse Events of Special Interest
8.3.3 Follow-up of Adverse Events,
and Serious Adverse Events, and
Adverse Events of Special Interest
8.3.6 Adverse Events of Special
Interest
8.6 Assessments and Procedures after
EUA or Approval in any Country
9.4.2 Primary Endpoints
10.1 Appendix 1: Abbreviations
10.2 Appendix 2: Clinical Laboratory
Tests
10.4.1 Adverse Event Definitions and
Classifications
10.4.5 Procedures
Thrombosis with thrombocytopenia
syndrome (TTS) will be considered
an adverse event of special interest
(AESI). Follow-up assessments will
be performed in the event of a
suspected AESI.
Emerging data following use of
the Ad26.COV2.S vaccine
under emergency use
authorization in the US suggest
an increased risk of thrombosis
combined with
thrombocytopenia, with onset of
symptoms approximately 1-2
weeks after vaccination.
Therefore, additional reporting
and data collection procedures
are implemented to detect and
follow-up thrombotic events and
thrombocytopenia and identify
cases of TTS.

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Section Number 
and Name
Description of Change 
Brief Rationale
10.11 Appendix 11: TTS AESI form
10.12 Appendix 12: Thrombotic
Events to be Reported as AESIs
11 REFERENCES
2.3.1 Risks Related to Study 
Participation  
Side effects were updated to 
include injection site pain and 
nausea. It has been clarified that 
anaphylaxis is considered an
important identified risk.
To align with the vaccine’s risk
language. Added anaphylaxis as
identified risk.
1.3 Schedule of Activities (SoA) 
7.2 Participant 
Discontinuation/Withdrawal From the 
Study
Clarify that an early exit visit is not 
required for participants that are
lost to follow-up or have died.
Prevent protocol deviations.
Throughout the protocol 
Minor updates. 
Minor updates.
Amendment 12 (27 May 2021)
Overall Rationale for the Amendment:  This amendment was created to clarify that suspected
adverse events of special interest (AESIs) should be reported for all participants after local
approval of protocol Amendment 11. Additional changes are listed below.
Section Number 
and Name
Description of Change 
Brief Rationale
1.1 Synopsis
1.3.1 Cohort 1a
1.3.2 Cohort 1b
1.3.3.2 Booster Vaccination
Cohort 2a
1.3.4.2 Booster Vaccination
Cohort 2b
1.3.5 Cohort 3
1.3.7 Procedures for Group
5 (Placebo Only)
Participants Receiving a
Single Dose of 5x1010 vp
Ad26.COV2.S after EUA or
Approval in any Country
3 OBJECTIVES AND
ENDPOINTS
8.3.1 Time Period and
Frequency for Collecting
Adverse Event and Serious
Adverse Event Information
Clarified that suspected AESIs should be
reported for all participants after local approval
of protocol Amendment 11.
Clarification.
1.1 Synopsis
6.3 Measures to Minimize
Bias: Randomization and
Blinding
8.6 Assessments and
Procedures after EUA or
Approval in any Country
9.6 Analyses for
Participants Requesting
Unblinding to Receive an
It was clarified that unblinded participants
(active or placebo) who did not receive an
authorized/licensed COVID-19 vaccine outside
of the study will be asked to continue to be
followed in this study, including booster
vaccinations for Cohort 2 participants.
Clarification.

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Authorized/Licensed
COVID-19 Vaccine
6.6 Continued Access to 
Study Vaccine After the 
End of the Study  
6.8 Prestudy and 
Concomitant Therapy
7.1 Discontinuation of
Study Vaccination
9.6 Analyses for
Participants Requesting
Unblinding to Receive an
Authorized/Licensed
COVID-19 Vaccine
Participants who received an 
authorized/licensed COVID-19 vaccine outside
of the study will be discontinued from
vaccination.
Clarification.
1.1 Synopsis 
6.3 Measures to Minimize 
Bias: Randomization and 
Blinding
9.6 Analyses for
Participants Requesting
Unblinding to Receive an
Authorized/Licensed
COVID-19 Vaccine
Clarified that there are no clinical data on the 
safety of receiving a different COVID-19
vaccine after receiving Ad26.COV2.S.
Clarification.
6.3 Measures to Minimize 
Bias: Randomization and 
Blinding 
Clarified that manual kits may be used if IWRS 
cannot be updated to allow dispensing of
investigational product to Cohort 2 participants
who have previously been unblinded but did
not receive and authorized/licensed COVID-19
vaccine.
Clarification.
8 STUDY ASSESSMENTS 
AND PROCEDURES  
It was clarified that visit windows for 
vaccination visits will not apply for study
pauses or vaccination pauses.
Clarification.
2.3.1 Risks Related to Study 
Participation  
It was clarified that cases of thrombosis with 
thrombocytopenia syndrome occurred within 
the first 3 weeks following vaccination instead
of 1-2 weeks following vaccination.
Clarification requested by HA
to align with SmPC.
1.1 Synopsis 
9.6 Analyses for 
Participants Requesting 
Unblinding to Receive an 
Authorized/Licensed 
COVID-19 Vaccine 
9.7.2 
Clarified for that for Cohorts 2a and 2b, if 
unblinding occurs at the participants request,
these participants will not be included in any of
the post-booster safety or efficacy analyses of
Cohorts 2a and 2b. If they continue with the
booster vaccinations and all study procedures
as described in the SoA, they will be included
in the immunogenicity analysis.
Clarification.
Throughout the protocol 
Minor errors and inconsistencies were 
corrected throughout the protocol. 
Correction of minor errors and
inconsistencies.

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Amendment 13 (04 June 2021)
Overall Rationale for the Amendment:  This amendment was created to update the blood volume
to be drawn in the event of an adverse event of special interest (AESI).
Section Number
and Name
Description of Change 
Brief Rationale
1.3.8 Procedures for
Participants with a
Suspected AESI
8 STUDY ASSESSMENTS
AND PROCEDURES
10.2.2 Additional
Hematology and
Coagulation Testing
The total blood volume to be drawn at Day 1 
and Day 29 of a suspected AESI is 15 mL, for a 
total of 30 mL additional blood in the event 
that a participant experiences a suspected
AESI. 
Clarification on blood volume
collected in the event of an
AESI.
Appendix was clarified to
indicate that testing in the event
of a suspected AESI is
applicable to all Cohorts.
Amendment 14 (29 July 2021)
Overall Rationale for the Amendment:  This amendment was created to add another year of follow-up
and its related safety and immunogenicity assessments for Cohorts 1a, 1b and 3 participants in order to
collect additional long-term safety and immunogenicity data for more than one year after second
vaccination.
Section Number 
and Name
Description of Change 
Brief Rationale
1.1 Synopsis
1.2 Schema
1.3 Schedule of Activities
4.1 Overall Design
4.4 End of Study Definition
8 STUDY ASSESSMENTS
AND PROCEDURES
8.1.1 Immunogenicity
Assessments
8.1.4 Efficacy assessments
One additional year of follow-up and its related
safety and immunogenicity assessments for
Cohorts 1a, 1b and 3 participants were added.
Inclusion of four visits during the additional
year of follow-up.
Additional safety and
immunogenicity follow-up for
two years after second
vaccination.
To aid in participant retention
during the additional follow-up
period in the current study.
1.1 Synopsis
3 OBJECTIVES AND
ENDPOINTS
Updated the time-period of primary objective
for safety assessment from 12 months after
second vaccination to 24 months after second
vaccination.
Update in accordance with the
additional year of follow-up.
1.1 Synopsis
9.5 Planned Analysis
Added text regarding the follow-up analysis of
the study at 24 months after second vaccination
in Cohorts 1a, 1b and 3.
Update in accordance with the
additional year of follow-up.
1.3.9 Additional Follow-up
for Cohorts 1a, 1b and 3
8 STUDY ASSESSMENTS
AND PROCEDURES
The total blood volume to be drawn during the
study for Cohorts 1a, 1b and 3 was updated.
Update to the blood volume
collected during the additional
year of follow-up.
1.3.8 Procedures for
Participants with a
Suspected AESI
Clarification was added that if an AESI is
reported to the investigator, more than 28 days
after the onset of the event, AESI Day 29 visit
will therefore become redundant and does not
need to be performed.
Clarification

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1.3.9 Additional Follow-up 
for Cohorts 1a, 1b and 3 
6.8 Prestudy and 
Concomitant Therapy  
Text was added about participants from 
Cohorts 1a, 1b and 3, who received
additional/booster COVID-19 vaccines outside
of the study during the additional follow-up of
the study, should be allowed to stay in the
study (if willing), however these vaccines
should be recorded in the Concomitant
Medications section ofthe eCRF.
Clarification
2.3.1 Risks Related to Study 
Participation  
7.1 Discontinuation of 
Study Vaccination 
8.2.1 Physical Examinations 
8.6 Assessments and 
Procedures after EUA or 
Approval in any Country  
10.1 Abbreviations
Text has been added regarding the increased 
risk of Guillain-Barre Syndrome (GBS) 
following use of the Ad26.COV2.S vaccine. 
GBS has also been added to the list of reasons 
for the discontinuation of the Ad26.COV2.S 
vaccine. The symptom-directed physical 
examination will also include basic
neurological examination, if warranted.
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.
7.1 Discontinuation of 
Study Vaccination 
8.6 Assessments and 
Procedures after EUA or 
Approval in any Country  
10.1 Abbreviations 
Capillary Leak Syndrome (CLS) was added to 
the list of reasons for the discontinuation of the 
Ad26.COV2.S vaccine. 
Based on the emerging data
following use of the
Ad26.COV2.S vaccine, CLS
has been identified as a
contraindication for the use of
Ad26.COV2.S vaccine.
Throughout the protocol 
Minor errors and inconsistencies were 
corrected throughout the protocol. 
Correction of minor errors and
inconsistencies.
Amendment 15 (7 October 2021)
Overall Rationale for the Amendment: The main purpose of this amendment is to offer a single ad hoc
booster vaccination with Ad26.COV2.S at the 5x1010 vp dose level to all eligible participants  who have
previously received 1 or more doses of any COVID-19 vaccine (ie, the Ad26.COV2.S vaccine, a messenger
ribonucleic acid (mRNA) vaccine and/or another COVID 19 vaccine authorized for primary vaccination
including protein, inactivated, and adenovector-based vaccines) if the last vaccination was ≥6 months ago.
The following ongoing participants will not be eligible to receive this ad hoc booster vaccination:
− Group 5 participants (all cohorts) who crossed over from placebo to receive Ad26.COV2.S at the 5x1010
vp dose level (ie, placebo crossover vaccination) (see Section 1.3.7).
− Group 5 participants (all cohorts) who did not opt for the placebo crossover vaccination and therefore
have not received any vaccination with the Ad26.COV2.S vaccine.
− Cohort 2 participants who will receive a booster vaccination according to their initial schedule at 6 and
12 months after the primary regimen (Groups 2 and 3, respectively) (see Section 4.1).
Rationale: A single dose of Ad26.COV2.S vaccine is immunogenic and highly efficacious against severe
COVID-19 disease and COVID-19-related hospitalization and death. Furthermore, while protection against
variants of concern (such as the Beta and Mu variants in study VAC31518COV3001 and the Delta variant
in the Sisonke studya) remains high against severe disease, hospitalization, and death, this protection is
lower against, for example, the Gamma variant compared to the reference Wuhan strain. Protection against
a. Gray G, Bekker L-G. Sisonke Update on the Janssen®(JNJ) Ad26.COV2.S vaccine. https://sacoronavirus.co.za/wp-
content/uploads/2021/08/Sisonke-Provisional-Results-6-August-2021GG2.pdf (accessed September 21, 2021).

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severe/critical disease caused by different variants of concern (such as Gamma, Lambda and Mu variants)
was shown to be reduced in the final analysis of study VAC31518COV3001 compared to the reference
Wuhan strain and the Alpha variant, for example. Giving a second dose of Ad26.COV2.S results in marked
increases of immune responses and those higher immune responses correlate with better protection against
COVID-19, as shown in the primary analysis of study VAC31518COV3009a. Some national vaccination
recommendation bodies (eg, CDCb) have recently advised to give a booster vaccination. Therefore, based
on this recommendation for a booster vaccination and the availability of booster vaccinations outside the
study, this amendment will permit boosting of all eligible participants in this study who have previously
received 1 or more doses of any COVID-19 vaccine.
These and other changes made to the clinical protocol of study VAC31518COV1001 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 
1.2 Schema 
1.3 Schedule of Activities 
(SoA) 
3 OBJECTIVES AND  
ENDPOINTS  
4.1 Overall Design  
4.4 End of Study Definition  
5 STUDY POPULATION  
5.5 Criteria for Temporarily  
Delaying Administration of 
Study Vaccination  
6.1 Study Vaccinations
Administered 
6.3 Measures to Minimize 
Bias: Randomization and 
Blinding 
6.6 Continued Access to 
Study Vaccine After the 
End of the Study  
6.8 Prestudy and 
Concomitant Therapy
8 STUDY ASSESSMENTS  
AND PROCEDURES  
8.1.1 Immunogenicity  
Assessments
8.7Assessments and 
Procedures for Ad Hoc 
Booster Vaccination  
At the ad hoc booster vaccination visit, all 
eligible participants will be offered a single ad 
hoc booster dose of Ad26.COV2.S vaccine
(5×1010 vp). The ad hoc booster vaccination
will be provided to participants who have
previously received 1 or more doses of any
COVID-19 vaccine (ie, the Ad26.COV2.S
vaccine, an mRNA vaccine and/or another
COVID 19 vaccine authorized for primary
vaccination including protein, inactivated, and
adenovector-based vaccines) if the last
vaccination was ≥6 months ago.
Safety and immunogenicity follow-up visits
are scheduled at 28 days, 6 months, and 12
months after ad hoc booster vaccination.
Procedures and assessments for safety and
immunogenicity follow-up phase for the ad
hoc booster vaccination have been added. The
study duration and study completion definition
have been adapted accordingly.
Blood volumes to be collected in the study for
the ad hoc booster vaccination phase were
added.
Objectives & endpoints were added for the ad
hoc booster vaccination phase of the study.
Added that a dose level of 5×1010 vp in a
volume of 0.5 mL will be administered to
See overall rationale for
amendment.
a Johnson & Johnson News Release. Johnson & Johnson Announces Real-World Evidence and Phase 3 Data
Confirming Strong and Long-Lasting Protection of Single-Shot COVID-19 Vaccine in the U.S. Press Release,
New 
Brunswick, 
N.J., 
21 
September 
2021. 
Available 
at:
https://www.janssen.com/emea/sites/www janssen com emea/files/johnson johnson announces real-
world evidence and phase 3 data confirming strong and long-lasting prote.pdf. Accessed on 28 September
2021.
b Centers for Disease Control and Prevention. CDC Statement on ACIP Booster Recommendations. Press Release 24
September, 2021. Available at: https://www.cdc.gov/media/releases/2021/p0924-booster-recommendations-.html.
Accessed on: 30 September 2021.

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Section Number 
and Name
Description of Change 
Brief Rationale
9.6 Analyses for 
Participants Requesting 
Unblinding to Receive an 
Authorized/Licensed
COVID-19 Vaccine 
9.8 Analysis After Receipt 
of the Ad Hoc Booster 
Vaccination
10.2.2 Additional
Hematology and
Coagulation Testing
10.3.3 Informed Consent
Process
participants that are eligible for and have
consented to receive an ad hoc booster
vaccination.
Statistical considerations for the analysis of
the ad hoc booster vaccination phase were
added.
1.1 Synopsis 
4.1 Overall Design  
8.1.2 Procedures in Case of 
COVID 19-like Signs and 
Symptoms 
Following local approval of protocol 
Amendment 15, the participant will not be
required to complete the daily calendar
booklet but will be contacted by the site
regularly to check whether they experienced
COVID 19 like symptoms.
Update
1.1 Synopsis 
1.3.10 Procedures for 
Participants Receiving an 
Ad Hoc Booster 
Vaccination of 5x1010 vp 
Ad26.COV2.S  
2.3.1 Risks Related to Study
Participation
5.2 Exclusion Criteria
8.3.5 Pregnancy
8.7Assessments and
Procedures after Protocol
Amendment 15 Approval
(Ad Hoc Booster
Vaccination)
Participants who are pregnant may receive ad 
hoc booster vaccination with Ad26.COV2.S, if
allowed by local regulations and if the
investigator considers that the potential
benefits outweigh the potential risks to the
mother and fetus.
Update
2.3.1 Risks Related to Study 
Participation  
Updated that Guillain-Barré syndrome (GBS) 
is considered an important identified risk for
Ad26.COV2.S.
It was added that no clinical data are available
for Ad26.COV2.S administration after
previous vaccination with a COVID-19
vaccine other than Ad26.COV2.S. Available
clinical information on the administration of
an Ad26.COV2.S booster vaccination
following a single dose of Ad26.COV2.S was
added.
To update the potential risks.
2.3.1 Risks Related to Study 
Participation  
2.3.3 Benefit-Risk 
Assessment of Study 
Participation  
4.1 Overall Design  
6.7Treatment of Overdose 
8.3.2 Method of Detecting 
Adverse Events, Adverse 
Added that participants will remain under 
observation at the study site for at least 
15 minutes to 1 hour depending on the 
vaccination being administered. 
Participants who received
placebo only during primary
regimen and who accepted a
single dose of 5×1010 vp
Ad26.COV2.S after unblinding
and participants that receive an
ad hoc booster vaccination will
remain under observation at the
study site for at least 15 minutes.

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Section Number 
and Name
Description of Change 
Brief Rationale
Events of Special Interest,
and Serious Adverse Events
1.1 Synopsis 
1.2 Schema 
1.3.2 Cohort 1b 
1.3.2.1 Optional Lymph 
Node Aspirates for 
Cohort 1b Participants 
(Beth Israel Deaconess 
Medical Center [BIDMC]) 
1.3.7Procedures for 
Group 5 (Placebo Only)
Participants Receiving a
Single Dose of 5x1010 vp
Ad26.COV2.S (Placebo
Crossover Vaccination)
after EUA or Approval in
any Country
2.3.1 Risks Related to Study
Participation
2.3.3 Benefit-Risk
Assessment of Study
Participation
3 OBJECTIVES AND
ENDPOINTS
4.1 Overall Design
8 STUDY ASSESSMENTS
AND PROCEDURES
8.1.1 Immunogenicity
Assessments
8.1.1.1 Optional Lymph
Node Aspiration
9.4.5 Other Analyses
10.1 Abbreviations
10.3.3 Informed Consent
Process
10.4.1 Adverse Events and
Classification
10.4.5 Procedures
Addition of optional fine needle lymph node 
aspirates (LNAs) for Cohort 1b at 
approximately 12 months after the second 
vaccination. 
In addition, details on the method, risks related 
to study participation, analysis, informed 
consent process, and adverse events, are added 
in the respective sections. 
Additional analysis for
Cohort 1b (site BIDMC only) to
allow for further exploration of
immune responses in lymph
nodes to better understand the
increase in neutralizing activities
of the antibodies against
variants, generated by
Ad26.COV2.S.
1.3.8 Procedures for 
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.
It is clarified that all local laboratory results
need to be encoded in the eCRF, including
platelet counts. Low platelet counts are to be
recorded as a suspected AESI
(thrombocytopenia).
Clarification
10.2 Appendix 2: Clinical 
Laboratory Tests 
For the clinical evaluation of suspected AESIs, 
added that it is upon discretion of the sponsor
that all or some of the coagulation-related
assays may be conducted on the stored pre-
vaccination sample and on the AESI samples.
Clarification

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Section Number 
and Name
Description of Change 
Brief Rationale
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 could be
used for coagulation-related assays.
10.3.3 Informed Consent 
Process 
Added that a new ICF needs to be signed for 
− Participants from Cohort 1a, 1b, and 3 who
wish to participate in the additional follow-
up.
− Participants receiving a single ad hoc
booster dose of 5x1010 vp Ad26.COV2.S
after local approval of protocol amendment
15.
Update
1.1 Synopsis 
11 REFERENCES  
The reference to the Brighton Collaboration 
case definition of thrombotic events and
thrombocytopenia was updated.
Update
Throughout the protocol 
The term ‘placebo crossover vaccination’ was 
introduced to define the single vaccination
with Ad26.COV2.S in the open-label phase
that is offered to participants that were
randomized to the placebo arm in the double-
blind phase.
Clarification
Throughout the protocol 
Minor errors and inconsistencies were 
corrected, and minor clarifications were added 
throughout the protocol. 
Correction of minor errors and
inconsistencies. Addition of
minor clarifications.

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11. 
REFERENCES
1. 
Adenoviral Vaccine Safety Database V5.0. Janssen Vaccines & Prevention B.V. 10 April 2020.
2. 
Agrawal AS, 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.
3. 
American Society of Hematology. 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.
4. 
Anywaine Z, 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.
5. 
Barouch DH, Liu J, Peter L, et al. Characterization of humoral and cellular immune responses elicited by a
recombinant adenovirus serotype 26 HIV-1 Env vaccine in healthy adults (IPCAVD 001). J Infect Dis.
2013:207(2);248-256.
6. 
Barouch DH, Tomaka FL, Wegmann F, et al. Evaluation of a mosaic HIV-1 vaccine in a multicentre,
randomised, double-blind, placebo-controlled, phase 1/2a clinical trial (APPROACH) and in rhesus monkeys
(NHP 13-19). Lancet. 2018;392(10143):232-243.
7. 
Belgian Red Cross. https://www.rodekruis.be/. Accessed 12 April 2020.
8. 
Bolles M, 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.
9. 
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). 11 November 2021.
https://brightoncollaboration.us/wp-content/uploads/2021/05/TTS Updated-Brighton-Collaboration-Case-
Defintion-Draft-Nov-11-2021.pdf. Accessed: 225 February 2022.
10. British Society for Haematology. 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; 7April 2021. Accessed: 27 April 2021.
11. Centers for Disease Control and Prevention. Coronavirus disease 2019 (COVID-19). Groups at higher risk for
severe illness. https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/groups-athigher-risk.html.
Accessed 7 May 2020.
12. Center for Disease Control and Prevention. Coronavirus Disease 2019 (COVID-19) Symptoms and
Complications. https://www.cdc.gov/coronavirus/2019-ncov/about/symptoms.html. Accessed 15 February
2020.
13. Center for Disease Control and Prevention. Symptoms of Coronavirus. https://www.cdc.gov/coronavirus/2019-
ncov/symptoms-testing/symptoms.html. Accessed 8 July 2020.
14. Centers for Disease Control and Prevention (CDC). 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.
15. Center for Disease Control and Prevention COVID-19 Response Team. Coronavirus disease 2019 in children -
United States, February 12–April 2, 2020. Morb Mortal Wkly Rep 2020;69:422–426.
16. Chan JF, Lau SK, To KK, Cheng VC, Woo PC, Yuen KY. Middle East respiratory syndrome coronavirus:
another zoonotic betacoronavirus causing SARS-like disease. Clin. Microbiol. Rev. 2015; 28(2):465–522.
17. Chen N, 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.

VAC31518 JNJ-78436735 
Clinical Protocol VAC31518COV1001 Amendment 16
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Status: Approved, Date: 16 August 2022
18. Chen Z, Zhang L, Qin C, et al. Recombinant modified vaccinia virus Ankara expressing the spike glycoprotein
of severe acute respiratory syndrome coronavirus induces protective neutralizing antibodies primarily targeting
the receptor binding region. J Virol. 2005;79(5):2678-2688.
19. Cheng VC, Lau SK, Woo PC, Yuen KY. Severe acute respiratory syndrome coronavirus as an agent of
emerging and reemerging infection. Clin Microbiol Rev. 2007;20(4):660-694.
20. Chin J, Magoffin RL, Shearer LA, Schieble JH, Lennette EH. Field evaluation of a respiratory syncytial virus
vaccine and a trivalent parainfluenza virus vaccine in a pediatric population. Am J Epidemiol. 1969;89(4);449-
463.
21. Coronaviridae Study Group of the International Committee on Taxonomy of Viruses. The species Severe acute
respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol.
2020;5(4):536-544.
22. Deming D, 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.
23. Dong Y, Mo X, Hu Y, et al. Epidemiological Characteristics of 2143 Pediatric Patients With 2019 Coronavirus
Disease in China. Pediatrics. 2020 Mar 16. pii: e20200702. [Epub ahead of print]
24. European Centre for Disease Prevention and Control. Factsheet for health professionals on coronaviruses.
https://www.ecdc.europa.eu/en/factsheet-health-professionals-coronaviruses. Accessed 15 February 2020.
25. Faber M, Lamirande EW, Roberts A, et al. A single immunization with a rhabdovirus-based vector expressing
severe acute respiratory syndrome coronavirus (SARS-CoV) S protein results in the production of high levels
of SARS-CoV-neutralizing antibodies. J Gen Virol. 2005;86(Pt 5):1435-1440.
26. Fulginiti VA, Eller JJ, Sieber OF, Joyner JW, Minamitani M, Meiklejohn G. Respiratory virus immunization. I.
A field trial of two inactivated respiratory virus vaccines; an aqueous trivalent parainfluenza virus vaccine and
an alum-precipitated respiratory syncytial virus vaccine. Am J Epidemiol. 1969:89(4);435-448.
27. Garg S, 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;69:458–464.
28. Gidudu JK, Walco GA, Taddio A, et al./The Brighton Immunization Site Pain Working Group. Immunization
site pain: Case definition and guidelines for collection, analysis, and presentation of immunization safety data.
Vaccine. 2012:30(30);4558-4577.
29. Honda-okubo Y, 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.
30. Houser KV, 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.
31. Investigator's Brochure: Ad26COVS1 (VAC31518), Edition 6.0. (17May 2022) Janssen Vaccines &
Prevention B.V.
32. Janssen Vaccines & Prevention B.V. Data on file.
33. Johns Hopkins CSSE. Coronavirus COVID-19 Global Cases.
https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6.
Accessed 29 April 2020.
34. Kapikian AZ, Mitchell RH, Chanock RM, Shvedoff RA, Stewart CE. An epidemiologic study of altered
clinical reactivity to respiratory syncytial (RS) virus infection in children previously vaccinated with an
inactivated RS virus vaccine. Am J Epidemiol. 1969:89;405-421.
35. Kim HW, Canchola JG, Brandt CD, et al. Respiratory syncytial virus disease in infants despite prior
administration of antigenic inactivated vaccine. Am J Epidemiol. 1969:89(4);422-434.
36. Kohl KS, 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 2007:31;5858-5874.

VAC31518 JNJ-78436735 
Clinical Protocol VAC31518COV1001 Amendment 16
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225
Status: Approved, Date: 16 August 2022
37. Kohl KS, Walop W, Gidudu J, et al./The Brighton Collaboration Local Reaction Working Group for Induration
at or near Injection Site. Induration at or near injection site: Case definition and guidelines for collection,
analysis and presentation of immunization safety data. Vaccine 2007:31;5839-5857.
38. Letko M, Marzi A, Munster V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and
other lineage B betacoronaviruses. Nat Microbiol. 2020;5:562–569.
39. Li Q, 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.
40. Lu R, 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)30251-8.
41. Marcy SM, 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.
42. Milligan ID, Gibani MM, Sewell R, et al. Safety and immunogenicity of novel adenovirus type 26- and
modified vaccinia ankara-vectored ebola vaccines: a randomized clinical trial. JAMA. 2016:315;1610-1623.
43. Modjarrad K, Roberts CC, Mills KT, et al. Safety and immunogenicity of an anti-Middle East respiratory
syndrome coronavirus DNA vaccine: a phase 1, open-label, single-arm, dose-escalation trial. Lancet Infect Dis.
2019;19(9):1013-1022.
44. Moghaddam A, Olszewska W, Wang B, et al. A potential molecular mechanism for hypersensitivity caused by
formalin-inactivated vaccines. Nat Med. 2006:12(8);905-907.
45. Smatti MK, Al Thani AA, Yassine HM. Viral-Induced Enhanced Disease Illness. Front Microbiol.
2018;9:2991.
46. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Biologics
Evaluation and Research. September 2007. Guidance for Industry. Toxicity Grading Scale for Healthy Adult
and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials.
https://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidan
ces/Vaccines/ucm091977.pdf. Accessed 19 February 2020.
47. 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 24 February 2020.
48. 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 24 February 2020.
49. Wang D, Hu B, Hu C. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–
Infected Pneumonia in Wuhan, China. JAMA. 2020 Feb 7. doi: 10.1001/jama.2020.1585. [Epub ahead of
print].
50. World Health Organization. Statement on the second meeting of the International Health Regulations (2005)
Emergency Committee regarding the outbreak of novel coronavirus (2019-nCoV). https://www.who.int/news-
room/detail/30-01-2020-statement-on-the-second-meeting-of-the-international-health-regulations-(2005)-
emergency-committee-regarding-the-outbreak-of-novel-coronavirus-(2019-ncov). Accessed 15 February 2020.
51. World Health Organization. WHO Director-General's opening remarks at the media briefing on COVID-19 -
11 March 2020. https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-
media-briefing-on-covid-19---11-march-2020. Accessed 12 March 2020.
52. World Health Organization. WHO guidelines for the global surveillance of severe acute respiratory syndrome
(SARS). Updated recommendations, October 2004.
https://www.who.int/csr/resources/publications/WHO CDS CSR ARO 2004 1/en/. Accessed 15 February
2020.
53. Wu F, Zhao S, Yu B, et al. A new coronavirus associated with human respiratory disease in China. Nature.
2020;579(7798):265-269.

VAC31518 JNJ-78436735 
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54. Zhao J, Alshukairi AN, Baharoon SA, et al. Recovery from the Middle East respiratory syndrome is associated
with antibody and T-cell responses. Sci Immunol. 2017;2(14). pii: eaan5393.
55. Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat
origin. Nature. 2020;579(7798):270-273.
56. Zumla A, Chan JF, Azhar EI, Hui DS, Yuen KY. Coronaviruses - drug discovery and therapeutic options. Nat
Rev Drug Discov. 2016;15(5):327-347.

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

Signature
User 
Date 
Reason
 
18-Aug-2022
12:54:58
(GMT)
Document Approval
PPD