A Randomized, Double-blind, Placebo-controlled Phase 2a Study to Evaluate a Range of Dose Levels and Vaccination Intervals of Ad26.COV2.S in Healthy Adults Aged 18 to 55 Years Inclusive and Adults Aged 65 Years and Older and to Evaluate 2 Dose Levels of Ad26.COV2.S in Healthy Adolescents Aged 12 to 17 Years Inclusive
Phase: PHASE2
Conditions: Healthy
Sponsor: Janssen Vaccines & Prevention B.V.

CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
1
Status: Approved,  Date: 21 July 2021
Janssen Vaccines & Prevention B.V.*
Clinical Protocol
Protocol Title
A Randomized, Double-blind, Placebo-controlled Phase 2a Study to Evaluate a Range of
Dose Levels and Vaccination Intervals of Ad26.COV2.S in Healthy Adults Aged 18 to 55
Years Inclusive and Adults Aged 65 Years and Older and to Evaluate 2 Dose Levels of
Ad26.COV2.S in Healthy Adolescents Aged 12 to 17 Years Inclusive
Protocol VAC31518COV2001; Phase 2a
AMENDMENT 6
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.
IND:22657
EudraCT NUMBER:2020-002584-63
Status: 
Approved
Date: 
21 July 2021
EDMS number: 
EDMS-RIM-58022, 9.0
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.
NCT04535453

VAC31518 (JNJ-78436735) 
Clinical Protocol VAC31518COV2001 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
2
Status: Approved,  Date: 21 July 2021
PROTOCOL AMENDMENT SUMMARYOF CHANGES TABLE
DOCUMENT HISTORY
Document 
Date
Amendment 6 
This document
Amendment 5 
18 May 2021
Amendment 4 
04 March 2021
Amendment 3 
22 December2020
Amendment 2 
29 October 2020
Amendment 1 
21 August 2020
Original Protocol 
23 July 2020
Amendment 6 (This document)
Overall Rationale for the Amendment: The purpose of the amendment is to cease recruitment of
adolescents in this study.
Following the initial vaccination of the first 33 adolescent participants (sentinels + safety cohort) enrolled
in the study in the 16-17 year old age group at a dose of 2.5x1010 vp enrolled in this study, the entire
Ad26.COV2.S COVID-19 vaccine program was paused to evaluate a safety concern of thrombosis with
thrombocytopenia (TTS) in adults. During this pause, the safety and immunogenicity data for these 33
adolescent participants was evaluated (see current version of Investigator’s Brochure0). While the
Independent Data Monitoring Committee (IDMC) endorsed further enrollment of adolescents that would
receive Ad26.COV2.S at a 5x1010 vp dose level, the sponsor made the decision not to evaluate the 5x1010
vp dose level in pediatric participants based on the immunogenicity data from the 2.5x1010 vp dose in Study
VAC31518COV2001 and has decided to redesign the pediatric studies. Study VAC31518COV3006 will
focus on adolescent participants 12-17 years of age, and no further enrollment of this age group will take
place in this study. The 33 adolescents already enrolled at the time of Amendment 6 will continue to be
followed in this study in accordance with the planned Schedule of Activities, but no further vaccination
with Ad26.COV2.S will occur in Groups A and B. Participants in Group C will receive a single dose of
Ad26.COV2.S at 2.5 x1010 vp.

VAC31518 (JNJ-78436735) 
Clinical Protocol VAC31518COV2001 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
3
Status: Approved,  Date: 21 July 2021
Section Number 
and Name
Description of Change 
Brief Rationale
1.1 Synopsis 
1.2 Schema 
1.3.5 Groups A to C –Adolescents 
1.3.6 Active Vaccine Regimen: 
Placebo Group C –Adolescents 
2.1 Study Rationale 
3 OBJECTIVES AND 
ENDPOINTS  
4.1 Overall Design  
4.3 Justification for Dose 
6.3 Measures to Minimize Bias: 
Randomization and Blinding 
6.6 Dose Modification  
8. STUDY ASSESSMENTS AND 
PROCEDURES  
9.2 Sample Size Determination  
9.4.1 General Considerations 
Text was modified to indicate that 
total enrollment for the adolescent 
groups will be 33 (11 sentinels and 
22 participants in the safety cohort 
for the 16-17 year old age group). 
Text regarding enrollment of 
adolescent participants in Groups 
D-F, and the 2-dose regimen and 
booster for Groups A and B was 
deleted. Visit days were 
renumbered accordingly. 
Text was modified to indicate that 
participants in Group C who 
initially received placebo will 
receive a single dose of active
Ad26.COV2.S vaccine at a dose
level of 2.5x1010 vp, rather than a
2-dose regimen.
All enrolled adolescent participants
will be followed for 12 months post
vaccination 1.
Due to the reactogenicity observed
at the 2.5x1010 vp dose level, it was
decided not to proceed to the
5x1010 vp dose level in adolescents.
The immunogenicity in the 33
enrolled adolescents with
2.5x1010 vp was similar to that of
young adults who received
5x1010 vp in other studies with
Ad26.COV2.S, the sponsor has
decided to cease enrollment of
adolescents in these study and to
study the safety, reactogenicity and
immunogenicity of Ad26.COV2.S
with a dose selection component
under separate study protocols.
1.1 Synopsis 
2.1 Study Rationale 
3 OBJECTIVES AND 
ENDPOINTS  
9.1 Statistical Hypotheses 
9.2.1 Immunogenicity  
9.4.2 Primary/Secondary Endpoints 
9.5 Planned Analysis 
Text was modified to indicate that 
no formal hypothesis testing will 
occur in this study. Non-inferiority  
testing ofadolescents vs adults was 
removed from the study objectives. 
Text regarding the interim and 
primary analyses for adolescent
participants was deleted. 
The 33 participants (sentinels and
Safety Cohort in the 16-17 year old
age group) will be followed for
safety and immunogenicity.. No
non-inferiority statistical analysis
with data from adult participants
will be performed.
Safety and immunogenicity data
will be summarized for the 33
enrolled adolescent participants.
1.3.8 Participants with a Suspected 
AESI –Adults and Adolescents 
8. STUDY ASSESSMENTS AND 
PROCEDURES  
The total blood volume to be drawn 
at Day 1 and Day 29 of a suspected 
adverse event of special interest 
(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 a
suspected AESI.
1.3.5 Groups A to C –Adolescents 
1.3.6 Active Vaccine Regimen: 
Placebo Group C –Adolescents 
8. STUDY ASSESSMENTS AND 
PROCEDURES  
Total blood volumes to be drawn in 
adolescents were updated after
vaccination 2 and booster-related
assessments were deleted. The 6-
months post-vaccination 1 visit was
changed from a safety phone call to
an on-site safety and
immunogenicity visit.
Corresponding updates
1.1 Synopsis 
3 OBJECTIVES AND 
ENDPOINTS  
8.2.4 Hematology Clinical
Laboratory Assessments
Anti-PF4 was added as an 
exploratory endpoint for adolescent 
participants.
This was added to more fully
evaluate coagulation parameters.

VAC31518 (JNJ-78436735) 
Clinical Protocol VAC31518COV2001 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
4
Status: Approved,  Date: 21 July 2021
Section Number 
and Name
Description of Change 
Brief Rationale
10.2 Appendix 2: Hematology
Clinical Laboratory Tests
1.1 Synopsis
3 OBJECTIVES AND
ENDPOINTS
Adenovirus neutralization as
measured by VNA was added as an
exploratory endpoint for adults and
adolescents.
To align with other study protocols
1.1 Synopsis 
3 OBJECTIVES AND 
ENDPOINTS  
1.3.5 Groups A to C –Adolescents
1.3.6 Active Vaccine Regimen:
Placebo Group C –Adolescents
8. STUDY ASSESSMENTS AND
PROCEDURES
8.1.1 Immunogenicity Assessments
Text related to assessment of
cellular immunogenicity (PBMC)
in adolescents was removed.
Per existing protocol text,
adolescent participants who were
sentinels or in the safety cohorts
were not to be included in the
PBMC subset. Therefore, none of
the 33 enrolled adolescents have
had or will have these blood draws.
9.5 Planned Analysis 
Text was modified to indicate that
participants, clinical staff, and
study-site personnel will remain
blinded to the study vaccine
allocation until the implementation
of protocol Amendment 5 (adults)
or Amendment 6 (adolescents).
Alignment with other protocol
sections
1.3.1 Groups 1 to 6 (56-day interval 
schedule [2-dose and single dose 
regimens]) –Adults 
1.3.2 Groups 7 and 8 (28-day 
interval schedule)- Adults 
1.3.3 Groups 9 and 10 (84-day 
interval schedule) –Adults 
8 STUDY ASSESSMENTS AND 
PROCEDURES  
Hematology blood sample, plasma,
5 mL, was deleted from Groups 1-6
study visit 11 and 12,
Groups 7-8 study visit 9 and 10,
Groups 9-10 study visit 10 and 11.
Total blood to be drawn
(approximate per day and
approximate cumulative total) was
updated accordingly.
All adult participants received
Injection 3 prior to implementation
of protocol Amendment 4, so these
draws were not collected from any
participants.
7.1 Discontinuation of Study 
Vaccination  
Text was added that participants
who have a history of capillary leak
syndrome or experienced this event
after the first study vaccination
should not be given further study
vaccine.
Based on emerging post-marketing
safety data
Throughout the protocol 
Footnote was modified to reflect
that adolescent sections of this
protocol are not applicable to sites
in the Netherlands and Germany.
Minor grammatical, formatting, or
spelling changes were made.
Clarification
Minor errors were noted

VAC31518 (JNJ-78436735) 
Clinical Protocol VAC31518COV2001 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
5
Status: Approved,  Date: 21 July 2021
TABLE OF CONTENTS
TABLE OF CONTENTS ............................................................................................................................... 5
LIST OF IN-TEXT TABLES AND FIGURES................................................................................................ 8
1. 
PROTOCOL SUMMARY..................................................................................................................... 9
1.1. 
Synopsis........................................................................................................................................... 9
1.2. 
Schema.......................................................................................................................................... 23
1.3. 
Schedule of Activities (SoA)........................................................................................................... 29
1.3.1. 
Groups 1 to 6 (56-day interval schedule [2-dose and single dose regimens]) –Adults$............ 29
1.3.2. 
Groups 7 and 8(28-day interval schedule)- Adults$ ................................................................... 33
1.3.3. 
Groups 9 and 10 (84-day interval schedule) –Adults$............................................................... 36
1.3.4. 
Active Vaccine Regimen: Placebo Groups 6, 8 and 10 (28-day interval schedule [2-
dose and single dose regimens]) –Adults.................................................................................. 39
1.3.5. 
Groups A to C Adolescents ........................................................................................................ 42
1.3.6. 
Active Vaccine Regimen: Placebo Group C –Adolescents ....................................................... 45
1.3.7. 
Procedures for Participants With (Suspected) COVID-19 –Adults and Adolescents................ 48
1.3.8. 
Participants with a Suspected AESI –Adults and Adolescents ................................................. 50
2. 
INTRODUCTION................................................................................................................................ 51
2.1. 
Study Rationale.............................................................................................................................. 55
2.2. 
Background .................................................................................................................................... 56
2.3. 
Benefit-Risk Assessment............................................................................................................... 60
2.3.1 
Risks Related to Study Participation .......................................................................................... 60
2.3.2 
Benefits of Study Participation.................................................................................................... 65
2.3.3 
Benefit-Risk Assessment of Study Participation ........................................................................ 65
3. 
OBJECTIVES AND ENDPOINTS ..................................................................................................... 66
4. 
STUDY DESIGN ................................................................................................................................ 71
4.1. 
Overall Design................................................................................................................................ 71
4.2. 
Scientific Rationale for Study Design............................................................................................. 80
4.2.1. 
Study-Specific Ethical Design Considerations ........................................................................... 81
4.3. 
Justification for Dose...................................................................................................................... 82
4.4. 
End of Study Definition................................................................................................................... 83
5. 
STUDY POPULATION ...................................................................................................................... 84
5.1. 
Inclusion Criteria............................................................................................................................ 84
5.1.1. 
Inclusion Criteria for Adults (18-55 Years, Inclusive and 65 Years or Older)............................. 84
5.1.2. 
Inclusion Criteria for Adolescents (12-17 Years, Inclusive)........................................................ 86
5.2. 
Exclusion Criteria........................................................................................................................... 87
5.2.1. 
Exclusion Criteria for Adults (18-55 years, Inclusive and 65 Years or Older)............................ 87
5.2.2. 
Exclusion Criteria for Adolescents (12-17 Years, Inclusive)....................................................... 91
5.3. 
Lifestyle Considerations................................................................................................................. 93
5.4. 
Screen Failures.............................................................................................................................. 93
5.5. 
Criteria for Temporarily Delaying Administration of Study Vaccination ......................................... 93
6. 
STUDY VACCINATION AND CONCOMITANT THERAPY............................................................. 94
6.1. 
Study Vaccinations Administered .................................................................................................. 94
6.2. 
Preparation/Handling/Storage/Accountability ................................................................................ 95
6.3. 
Measures to Minimize Bias: Randomization and Blinding............................................................. 96
6.4. 
Unblinding and Open-label Phase ................................................................................................. 99
6.5. 
Study Vaccination Compliance ...................................................................................................... 99
6.6. 
Dose Modification........................................................................................................................... 99
6.7. 
Continued Access to Study Vaccine After the End of the Study ................................................. 100
6.8. 
Treatment of Overdose ................................................................................................................ 100
6.9. 
Prestudy and Concomitant Therapy ............................................................................................ 101

VAC31518 (JNJ-78436735) 
Clinical Protocol VAC31518COV2001 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved,  Date: 21 July 2021
6.10. 
Study Vaccination Pausing Rules................................................................................................ 102
7. 
DISCONTINUATION OF STUDY VACCINATION AND PARTICIPANT
DISCONTINUATION/WITHDRAWAL............................................................................................. 104
7.1. 
Discontinuation of Study Vaccination........................................................................................... 104
7.2. 
Participant Discontinuation/Withdrawal From the Study.............................................................. 105
7.2.1. 
Withdrawal From the Use of Research Samples ..................................................................... 105
7.3. 
Lost to Follow-up.......................................................................................................................... 105
8. 
STUDY ASSESSMENTS AND PROCEDURES ............................................................................. 106
8.1. 
Immunogenicity Assessments ..................................................................................................... 112
8.1.1. 
Immunogenicity Assessments .................................................................................................. 112
8.1.2. 
Procedures in Case of (Suspected) COVID-19........................................................................ 114
8.1.2.1. 
Prespecified Criteria for (Suspected) COVID-19................................................................... 115
8.1.3. 
Asymptomatic SARS-CoV-2 Infection ...................................................................................... 117
8.2. 
Safety Assessments..................................................................................................................... 117
8.2.1. 
Physical Examinations.............................................................................................................. 117
8.2.2. 
Vital Signs................................................................................................................................. 118
8.2.3. 
Pregnancy Testing.................................................................................................................... 118
8.2.4. 
Hematology Clinical Laboratory Assessments ......................................................................... 118
8.3. 
Adverse Events, Serious Adverse Events, Adverse Events of Special Interest, and Other
Safety Reporting .......................................................................................................................... 119
8.3.1. 
Time Period and Frequency for Collecting Adverse Event, Adverse Event of Special
Interest, and Serious Adverse Event Information..................................................................... 119
8.3.2. 
Method of Detecting Adverse Events, Adverse Events of Special Interest, and Serious
Adverse Events......................................................................................................................... 120
8.3.3. 
Follow-up of Adverse Events, Adverse Events of Special Interest, and Serious Adverse
Events....................................................................................................................................... 122
8.3.4. 
Regulatory Reporting Requirements for Serious Adverse Events ........................................... 122
8.3.5. 
Pregnancy................................................................................................................................. 122
8.3.6. 
Adverse Events of Special Interest........................................................................................... 122
8.3.6.1. 
Thrombosis with Thrombocytopenia Syndrome (TTS).......................................................... 123
8.4. 
Virology Assessments.................................................................................................................. 124
8.5. 
Biomarkers................................................................................................................................... 124
8.6. 
Medical Resource Utilization and Health Economics .................................................................. 124
9. 
STATISTICAL CONSIDERATIONS................................................................................................ 124
9.1. 
Statistical Hypotheses.................................................................................................................. 124
9.2. 
Sample Size Determination ......................................................................................................... 124
9.2.1. 
Immunogenicity......................................................................................................................... 124
9.2.2. 
Safety........................................................................................................................................ 125
9.3. 
Populations for Analysis Sets ...................................................................................................... 126
9.4. 
Statistical Analyses ...................................................................................................................... 126
9.4.1. 
General Considerations............................................................................................................ 126
9.4.2. 
Primary/Secondary Endpoints.................................................................................................. 127
9.4.3. 
Tertiary/Exploratory Endpoints ................................................................................................. 128
9.4.4. 
Other Analyses ......................................................................................................................... 128
9.5. 
Planned Analysis.......................................................................................................................... 129
10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS .......................... 131
10.1. 
Appendix 1: Abbreviations ........................................................................................................... 131
10.2. 
Appendix 2: Hematology Clinical Laboratory Tests..................................................................... 133
10.3. 
Appendix 3: Regulatory, Ethical, and Study Oversight Considerations....................................... 134
10.3.1. 
Regulatory and Ethical Considerations .................................................................................... 134
10.3.2. 
Financial Disclosure.................................................................................................................. 137
10.3.3. 
Informed Consent Process and Assent Form .......................................................................... 137
10.3.4. 
Data Protection......................................................................................................................... 139
10.3.5. 
Long-Term Retention of Samples for Additional Future Research .......................................... 139

VAC31518 (JNJ-78436735) 
Clinical Protocol VAC31518COV2001 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
7
Status: Approved,  Date: 21 July 2021
10.3.6. 
Safety Monitoring Committees Structure.................................................................................. 140
10.3.7. 
Publication Policy/Dissemination of Clinical Study Data.......................................................... 141
10.3.8. 
Data Quality Assurance............................................................................................................ 142
10.3.9. 
Case Report Form Completion................................................................................................. 143
10.3.10. Source Documents ................................................................................................................... 143
10.3.11. Monitoring ................................................................................................................................. 144
10.3.12. On-Site Audits........................................................................................................................... 145
10.3.13. Record Retention...................................................................................................................... 145
10.3.14. Study and Site Start and Closure ............................................................................................. 146
10.4. 
Appendix 4: Adverse Events, Serious Adverse Events, Adverse Events of Special
Interest, Product Quality Complaints, and Other Safety Reporting: Definitions and
Procedures for Recording, Evaluating, Follow-up, and Reporting............................................... 147
10.4.1. 
Adverse Event Definitions and Classifications ......................................................................... 147
10.4.2. 
Attribution Definitions................................................................................................................ 148
10.4.3. 
Severity Criteria........................................................................................................................ 149
10.4.4. 
Special Reporting Situations .................................................................................................... 149
10.4.5. 
Procedures ............................................................................................................................... 150
10.4.6. 
Product Quality Complaint Handling......................................................................................... 151
10.4.7. 
Contacting Sponsor Regarding Safety, Including Product Quality........................................... 152
10.5. 
Appendix 5: Contraceptive Guidance and Collection of Pregnancy Information......................... 153
10.6. 
Appendix 6: Toxicity Grading Scale............................................................................................. 154
10.7. 
Appendix 7: Symptoms of Infection with Coronavirus-19 (SIC)................................................... 158
10.8. 
Appendix 8: Case Definitions for COVID-19................................................................................ 163
10.8.1. 
Case Definition for Moderate to Severe/Critical COVID-19...................................................... 163
10.8.2. 
Case Definition for Mild COVID-19........................................................................................... 164
10.8.3. 
US FDA Harmonized Case Definition for COVID-19................................................................ 165
10.8.4. 
Case Definition for Asymptomatic or Undetected COVID-19................................................... 165
10.9. 
Appendix 9: Summary of Guidance from CDC Website on Underlying Medical Conditions
That Lead or Might Lead to Increased Risk for Severe Illness From COVID-19 –Used for
Adult Cohort ................................................................................................................................. 166
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
–Used for Adolescent Cohort...................................................................................................... 168
10.11. Appendix 11: Symptoms of Coronavirus (US Centers for Disease Control and Prevention)...... 169
10.12. Appendix 12: Multisystem Inflammatory Syndrome in Children .................................................. 170
10.13. Appendix 13: TTS AESI Form...................................................................................................... 172
10.14. Appendix 14: Thrombotic Events to be Reported as Suspected AESIs...................................... 176
10.15. Appendix 15: Protocol Amendment History................................................................................. 177
11. REFERENCES................................................................................................................................. 196
INVESTIGATOR AGREEMENT............................................................................................................... 201

VAC31518 (JNJ-78436735) 
Clinical Protocol VAC31518COV2001 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
8
Status: Approved,  Date: 21 July 2021
LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1: 
Adverse Reactions Reported in Children 1 to 17 Years of Age Following Vaccination
with ZABDENO ......................................................................................................................... 59
Table 2: 
Vaccination Schedules Adults .................................................................................................. 74
Table 3: 
Vaccination Schedules –Adolescents...................................................................................... 76
Table 4: 
Visit Windows Groups 1 to 6 (56-day interval schedule [2- and single-dose regimens])
–Adults ................................................................................................................................... 108
Table 5: 
Visit Windows Groups 7 and 8 (28-day interval schedule) –Adults....................................... 109
Table 6: 
Visit Windows Groups 9 and 10 (84-day interval schedule) –Adults..................................... 110
Table 7: 
Visit Windows Groups A-C –Adolescents.............................................................................. 111
Table 8: 
Summary of Humoral and Cellular Immunogenicity Assays................................................... 113
Table 9 : Upper Limit of the 95% One-sided Confidence Interval if no Cases are Observed for
Different Sample Sizes ........................................................................................................... 125
Table 10: Probability of Observing at Least One AE in a Group of the Considered Sample Size
Given Several True AE Rates................................................................................................. 126
FIGURES
Figure 1: Schematic Overview of Groups 1-6 –Adults............................................................................ 23
Figure 2: Schematic Overview of Groups 7-8 –Adults............................................................................ 24
Figure 3: Schematic Overview of Groups 9-10 -Adults............................................................................ 25
Figure 4: Schematic Overview of Active Vaccine Regimen for Adult Placebo Groups 6, 8 and 10 ........ 26
Figure 5: Schematic Overview of Groups A -C –Adolescents ................................................................ 27
Figure 6: Schematic Overview of Active Vaccine Regimen for Adolescent Placebo Group C................ 28
Figure 7: Sentinel Decision Tree for Staggered Enrollment in Groups A-F –Adolescents ..................... 77

VAC31518 (JNJ-78436735) 
Clinical Protocol VAC31518COV2001 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
9
Status: Approved,  Date: 21 July 2021
1. 
PROTOCOL SUMMARY
1.1. 
Synopsis
A Randomized, Double-blind, Placebo-controlled Phase 2a Study to Evaluate a Range of Dose Levels and
Vaccination Intervals of Ad26.COV2.S in Healthy Adults Aged 18 to 55 Years Inclusive and Adults Aged
65 Years and Older and to Evaluate 2 Dose Levels of Ad26.COV2.S in Healthy Adolescents Aged 12 to
17 Years Inclusive.
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) spike (S) protein, which will be assessed in this study.
OBJECTIVES AND ENDPOINTS
ADULTS
Objectives 
Endpoints
Primary
 
To assess the humoral immune response to 
3 dose levels (5x1010 virus particle (vp), 
2.5x1010 vp, 1.25x1010 vp) of Ad26.COV2.S, 
administered intramuscularly (IM) as a 
2-dose schedule at a 56-day interval, 28 days 
after Vaccination 2.
 
Serological response to vaccination as
measured by virus neutralization assay (VNA)
titers and enzyme-linked immunosorbent
assay (S-ELISA, ELISA Units/mL [EU/mL]),
28 days after Vaccination 2.
 
Antibody geometric mean titers (GMTs)
(VNA) and geometric mean concentrations
(GMCs) 
(S-ELISA), 
28 days 
after
Vaccination 2.
 
To assess the humoral immune response to 
2 dose levels (1 x1011 vp and 5x1010 vp) of 
Ad26.COV2.S, administered IM as a single 
vaccination, 28 days after Vaccination 1. 
 
Serological response to vaccination as
measured by VNA titers and ELISA
(S-ELISA, 
EU/mL), 
28 days 
after
Vaccination 1.
 
Antibody 
GMTs 
(VNA) 
and 
GMCs
(S-ELISA), 28 days after Vaccination 1.
 
To assess the humoral immune response to 
Ad26.COV2.S  at the 5x1010 vp dose level, 
administered IM as a 2-dose schedule at a 
28-day and at an 84-day interval, 28 days 
after Vaccination 2.
 
Serological response to vaccination as
measured by VNA titers and ELISA
(S-ELISA, 
EU/mL), 
28 days 
after
Vaccination 2.
 
Antibody 
GMTs 
(VNA) 
and 
GMCs
(S-ELISA), 28 days after Vaccination 2.
 
To assess the safety and reactogenicity of 
Ad26.COV2.S, administered IM at several 
dose levels, as a 2-dose or a single-dose
schedule.
 
Solicited local and systemic adverse events
(AEs) for 7 days after each vaccination.
 
Unsolicited AEs for 28 days after each
vaccination.
 
Serious adverse events (SAEs) and adverse
events of special interest  (AESIs) throughout
the study (from first vaccination until end of
the study).

VAC31518 (JNJ-78436735) 
Clinical Protocol VAC31518COV2001 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
10
Status: Approved,  Date: 21 July 2021
Objectives 
Endpoints
Secondary
 
To assess the anamnestic response to antigen
presentation of Ad26.COV2.S  at the
1.25x1010 vp dose level, administered
4 months after Vaccination 2 (2-dose
schedule) or 6 months after a Vaccination 1
(single-dose schedule), 7days after antigen
presentation (Groups 1-5, 7 and 9).
 
Serological response to vaccination as
measured by VNA titers and ELISA
(S-ELISA, EU/mL), 7 days after antigen
presentation.
 
Antibody 
GMTs 
(VNA) 
and 
GMCs
(S-ELISA), 7 days after antigen presentation.
 
To assess the safety and reactogenicity of
antigen presentation of Ad26.COV2.S at the
1.25x1010 vp dose level, administered
4 months after Vaccination 2 (2-dose
schedule) or 6 months after a Vaccination 1
(single-dose schedule)(Groups 1-5, 7 and 9).
 
Solicited local and systemic AEs for 7 days
after antigen presentation.
 
Unsolicited AEs for 28 days after antigen
presentation.
 
SAEs and AESIs throughout the study (from
antigen presentation until end of the study).
 
To assess the humoral immune response to
Ad26.COV2.S across all groups, at all blood
collection timepoints.
 
Neutralizing antibody titers to the wild-type
SARS-CoV-2 virus expressing S protein as
measured by VNA, at all blood collection
timepoints.
 
Binding antibody titers to SARS-CoV-2 or
individual 
SARS-CoV-2 
proteins 
(eg,
S protein) as measured by ELISA, at all blood
collection timepoints.
Exploratory
 
To assess the cellular immune response to
Ad26.COV2.S at different dose levels in a
subset of participants (Groups 1 to 6) at
selected blood collection timepoints.
 
T helper (Th) 1 and Th2 immune responses as
assessed by Flow cytometry after SARS-CoV-
2 S protein peptide stimulation of peripheral
blood mononuclear cells (PBMC) and
intracellular staining (ICS) including cluster
of differentiation (CD) 4+/CD8+, interferon
gamma (IFNγ), interleukin (IL)-2, tumor
necrosis factor alpha (TNFα), IL-4, IL-5, IL-
13, and/or other Th1/Th2 markers.
 
To further assess the humoral immune
response to Ad26.COV2.S.
 
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).
 
Functional 
and 
molecular 
antibody
characterization including Fc-mediated viral
clearance, avidity, Fc characteristics, Ig
subclass and IgG isotype.
 
Passive 
transfer: 
analysis 
of 
immune
mediators correlating with protection against
experimental SARS-CoV-2 challenge in a
suitable animal model.

VAC31518 (JNJ-78436735) 
Clinical Protocol VAC31518COV2001 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
11
Status: Approved,  Date: 21 July 2021
Objectives 
Endpoints
 
Analysis of neutralizing antibodies against
emerging SARS-CoV-2 variants.
 
Adenovirus neutralization as measured by
VNA.
 
To assess the occurrence of symptomatic
molecularly confirmed COVID-19 and
severity of COVID-19 signs and symptoms.
 
The number of participants with molecularly
confirmed COVID-19.
 
Presence and severity of COVID-19 signs and
symptoms as measured by Symptoms of
Infection with Coronavirus-19 (SIC).
 
To examine the immune response in
vaccinated individuals after natural SARS-
CoV-2 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
pseudovirions expressing S protein).
 
SARS-CoV-2-binding antibodies measured
by ELISA: Analysis of antibodies binding to
the SARS-CoV-2 S protein.
 
Analysis of gene expression by ribonucleic
acid (RNA) transcript profiling.
 
To assess for the occurrence of
asymptomatic SARS-CoV-2 infection.
 
The number of asymptomatic participants
with positive non-S protein ELISA (eg,
nucleocapsid [N] protein ELISA), as feasible.
 
The number of asymptomatic participants
with a SARS-CoV-2 positive RT-PCR test.
 
To assess hematology laboratory parameters
after Ad26.COV2.S administration.
 
Lupus anticoagulants, anti-β2 glycoprotein,
anti-cardiolipin, D-dimers; anti-PF4.
 
To assess the correlation between the
binding antibody (ELISA) titers and
neutralizing antibody (VNA) titers to
SARS-CoV-2, in a subset of participants at
selected timepoints.
 
Correlation between ELISA (S-ELISA;
EU/mL) and VNA (wild-type virus [wt]VNA
and/or pseudovirion [ps]VNA) titers at
selected timepoints.
ADOLESCENTSa
Objectives 
Endpoints
Primary
 To assess the safety and reactogenicity of a 
single dose of Ad26.COV2.S, administered 
IM at the 2.5x1010vp dose level.
 
Solicited local and systemic AEs for 7 days
after vaccination.
 
Unsolicited AEs for 28 days after
vaccination.
a Not applicable in Germany and the Netherlands

VAC31518 (JNJ-78436735) 
Clinical Protocol VAC31518COV2001 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
12
Status: Approved,  Date: 21 July 2021
Objectives 
Endpoints
 
SAEs (incl. Multisystem Inflammatory
Syndrome in Children [MIS-C]) and AESIs
throughout the study (from first vaccination
until end of the study).
Secondary
 
To assess the humoral immune response to a
single dose of Ad26.COV2.S at the 2.5x1010
vp dose level, administered IM.
 
Serological response to vaccination as
measured by VNA titers and ELISA (S-ELISA,
EU/mL), 28 days after vaccination.
 
Antibody 
GMTs 
(VNA) 
and 
GMCs
(S-ELISA), 28 days after vaccination.
 
To assess the humoral immune response to
Ad26.COV2.S at the 2.5x1010 vp dose level,
at all blood collection timepoints.
 
Neutralizing antibody titers to the wild-type
SARS-CoV-2 virus expressing S protein as
measured by VNA, at all blood collection
timepoints.
 
Binding antibody titers to SARS-CoV-2 or
individual 
SARS-CoV-2 
proteins 
(eg,
S protein) as measured by ELISA, at all blood
collection timepoints.
Exploratory
 
To further assess the humoral immune
response to Ad26.COV2.S.
 
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).
 
Functional 
and 
molecular 
antibody
characterization including Fc-mediated viral
clearance, avidity, Fc characteristics, Ig
subclass and IgG isotype.
 
Passive transfer: analysis of immune mediators
correlating 
with 
protection 
against
experimental SARS-CoV-2 challenge in a
suitable animal model.
 
Analysis of neutralizing antibodies against
emerging SARS-CoV-2 variants.
 
Adenovirus neutralization as measured by
VNA.
 
To assess the occurrence of symptomatic
molecularly confirmed COVID-19 and
severity of COVID-19 signs and symptoms.
 
The number of participants with molecularly
confirmed COVID-19.
 
Presence and severity of COVID-19 signs and
symptoms as measured by Symptoms of
Infection with Coronavirus-19 (SIC).
 
To examine the immune response in
vaccinated individuals after natural SARS-
CoV-2 infection  and to explore other
 
Confirmation of SARS-CoV-2 infection by
molecular testing.

VAC31518 (JNJ-78436735) 
Clinical Protocol VAC31518COV2001 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
13
Status: Approved,  Date: 21 July 2021
Objectives 
Endpoints
potentially informative biomarkers (eg,
those associated with more severe disease).
 
SARS-CoV-2 neutralizing titers in serum
measured by a VNA (wild-type virus and/or
pseudovirions expressing S protein).
 
SARS-CoV-2-binding antibodies measured by
ELISA: Analysis of antibodies binding to the
SARS-CoV-2 S protein.
 
Analysis of gene expression by ribonucleic acid
(RNA) transcript profiling.
 
To 
assess 
for 
the 
occurrence 
of
asymptomatic SARS-CoV-2 infection.
 
The number of asymptomatic participants with
positive 
non-S 
protein 
ELISA 
(eg,
nucleocapsid [N] protein ELISA), as feasible.
 
The number of asymptomatic participants with
a SARS-CoV-2 positive RT-PCR test.
 
To assess coagulation-related parameters at
selected blood sample collection timepoints.
 
platelet factor 4-heparin complex (anti-PF4)
antibodies.
HYPOTHESIS
No formal hypothesis testing will be performed in this study.
OVERALL DESIGN
This is a randomized, double-blind, placebo-controlled, multicenter, Phase 2a study in healthy adolescents
aged 12 to 17years inclusive, adults aged 18 to 55 years inclusive and adults in good or stable health aged
65 years and older. Countries may participate in the adult and adolescent portions of the study or they may
participate in either the adult or adolescent portion.
In adults, the safety, reactogenicity, and immunogenicity of Ad26.COV2.S in 1- and 2-dose vaccination
regimens followed by antigen presentation  after 4 months (2-dose regimen) or 6 months (single-dose
regimen), will be evaluated across a range of dose levels and vaccination intervals.
In adolescents, the safety, reactogenicity, and immunogenicity of a single dose of Ad26.COV2.S will be
evaluated.
Participants will receive Ad26.COV2.S  or a placebo. In adults, 4  dose levels of Ad26.COV2.S  will be
administered IM: 1x1011 vp, 5x1010 vp, 2.5x1010 vp, and 1.25x1010 vp. Adolescents will be administered
2.5x1010 vp.
ADULTS
A target of approximately 550 adult participants will initially be enrolled in this study in a blinded manner
and randomly assigned to 1 of 10 groups to receive 1- or 2-doses of active Ad26.COV2.S vaccine or placebo
at a dose of 1x1011 vp, 5x1010 vp, 2.5x1010 vp, or 1.25x1010 vp and at a 28-day, 56-day or 84-day interval.
A single antigen presentation injection with 1.25x1010 vp Ad26.COV2.S (Groups 1-5, 7, 9) will be
administered 4 months after the second vaccination (ie, 4 months post vaccination 2 in the 2-dose regimens
and 6 months after Vaccination 1 in the 1-dose regimens) to all participants who received active vaccine in
the primary vaccine regimen.
After each vaccination, all participants will remain under observation at the study site for at least 1 hour to
monitor for the presence of any acute reactions and solicited events.

VAC31518 (JNJ-78436735) 
Clinical Protocol VAC31518COV2001 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
14
Status: Approved,  Date: 21 July 2021
Participants who were initially enrolled to receive placebo (Groups 6, 8 and 10), will be offered a 2-dose
(28-day interval) Ad26.COV2.S vaccination regimen at the 5x1010 vp dose level. In October 2020, the study
was temporarily paused because one of the pausing rules was met in study COV3001. When the pause was
lifted, most of the participants in Groups 7-8 had missed their visit window for Vaccination 2 (Visit 4),
rendering the intent of the 28-day vaccination interval in these groups futile. The goal in offering 2 doses
of study vaccine to those participants who initially received placebo in this study is to recreate this 28-day
vaccination interval, and to restore the objectives associated with this interval. The original 28-day interval
target group was 75 participants. Hence the total number of placebo recipients from Groups 6, 8 and 10
(target n=75) is intended to fulfill the original target enrollment for Group 7.
With the implementation of Amendment 5, all adult participants will be unblinded to the primary
vaccination regimen, and adults who received placebo in the primary vaccine regimen will receive a 2-dose
active Ad26.COV2.S vaccine regimen at a 28-day interval and at a dose level of 5x1010 vp, in an open-label
manner. Per group, approximately one third of participants will be 65 years and older.
Adult participants who received the active vaccine in the primary vaccine regimen will be followed up for
12 months after vaccination 2; adult participants who received placebo in the primary vaccine regimen will
be followed up for 6 months after receipt of the unblinded vaccination 1 (ie, receipt of the first active
vaccine following unblinding).
Groups 1-6
400 participants (75 participants per active vaccine group, 25 in the placebo group) will be randomized in
parallel in a 3:3:3:3:3:1 ratio to 1 of 6 vaccination groups. Participants will receive a 2-dose (56-day interval,
Groups 1-3) vaccination regimen at different dose levels (5×1010 vp,, 2.5x1010 vp, and 1.25x1010 vp) or
single-dose vaccination regimen (Groups 4-5) at different dose levels (1×1011 vp, 5x1010 vp), or placebo
(Group 6). For blinding purposes, participants in the single-dose groups (Groups 4-5) will receive a placebo
vaccination on Day 57. Additional exploratory cellular immunogenicity evaluations (PBMC) will be
performed in a subset of participants (21/group in Groups 1-5, 7 in Group 6; at selected sites). Participants
in Group 6 who received 2-doses of placebo in the primary vaccine regimen will receive 2 doses of active
vaccine at a single dose level of 5x1010 vp, at a 28-day interval.
Groups 7-8
75 participants (50 participants in the active vaccine group, 25 in the placebo group) will be randomized in
parallel in a 2:1 ratio, to 1 of 2 vaccination groups. Participants will receive a 2 dose (28-day interval,
Groups 7) vaccination regimen at a 5×1010 vp dose level or placebo (Group 8). Participants in Group 8 who
received 2-doses of placebo in the primary vaccine regimen will receive 2 doses of active vaccine at a single
dose level of 5x1010 vp, at a 28-day interval.
Groups 9-10
75 participants (50 participants in the active vaccine group, 25 in the placebo group) will be randomized in
parallel in a 2:1 ratio, to 1 of 2 vaccination groups. Participants will receive a 2 dose (84-day interval,
Group 9) vaccination regimen at a 5×1010 vp dose level or placebo (Group 10). Participants in Group 10
who received 2-doses of placebo in the primary vaccine regimen will receive 2 doses of active vaccine at a
single dose level of 5x1010 vp, at a 28-day interval.

VAC31518 (JNJ-78436735) 
Clinical Protocol VAC31518COV2001 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
15
Status: Approved,  Date: 21 July 2021
Vaccination Schedule –Adults
Adults ≥18 to ≤55 Years and ≥65 Years
Group  N 
Day 1 
(Vaccination 1) 
Ad26.COV2.S dose 
level / placebo 
Day 29 
(Vaccination 2) 
Ad26.COV2.S dose 
level / placebo 
Day 57 
(Vaccination 2) 
Ad26.COV2.S dose 
level / placebo 
Day 85 
(Vaccination 2) 
Ad26.COV2.S dose 
level / placebo 
4 Months Post Vaccination 2 
(Injection 3)1 
Ad26.COV2.S dose 
level/ placebo 
Unblinded Vaccination 1 
Ad26.COV2.S  
dose level 
Day 29 Post Unblinded
Vaccination 1
(Unblinded Vaccination 2)
Ad26.COV2.S
dose level
1 
75 
5x1010 vp 
5x1010 vp 
1.25x1010 vp 
- 
-
2 
75 
2.5x1010 vp 
2.5x1010 vp 
1.25x1010 vp 
- 
-
3 
75 
1.25x1010 vp 
1.25x1010 vp 
1.25x1010 vp 
- 
-
4 
75 
1x1011 vp 
Placebo 
1.25x1010 vp2 
- 
-
5 
75 
5x1010 vp 
Placebo 
1.25x1010 vp2 
- 
-
6 
25 
Placebo 
Placebo 
Placebo 
5x1010 vp 
5x1010 vp
7 
50 
5x1010 vp 
5x1010 vp 
1.25x1010 vp 
- 
-
8 
25 
Placebo 
Placebo 
Placebo 
5x1010 vp 
5x1010 vp
9 
50 
5x1010 vp 
5x1010 vp 
1.25x1010 vp 
- 
-
10 
25 
Placebo 
Placebo 
Placebo 
5x1010 vp 
5x1010 vp
N  number of participants; vp  virus particles.
1. Antigen presentation
2. 6 Months after Vaccination 1 in the single dose regimens (Groups 4 and 5).

VAC31518 (JNJ-78436735) 
Clinical Protocol VAC31518COV2001 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
16
Status: Approved,  Date: 21 July 2021
ADOLESCENTSa
From the time of protocol Amendment 2, adolescent participants (12 to 17 years of age, inclusive) were to
be enrolled in a randomized and staggered manner.
The safety profile of Ad26.COV2.S in adolescents was planned to be assessed separately by age group and
by escalating dose, with the 2 adolescent age groups (12 to 15 years and 16 to 17 years) assessed
independently and enrollment progressing in a sequential manner. The safety and tolerability of the
Ad26.COV2.S vaccine was to be assessed in the first instance in a group of sentinels at Day 4
post-vaccination, and if acceptable, in the larger safety cohort at Day 8 post-vaccination. The Day 4 and
Day 8 post-vaccination safety profiles of the Ad26.COV2.S vaccine at the 2.5x1010 vp dose level in the
sentinel and safety cohorts was to be assessed in participants at 16 to 17 years of age, by the Safety
Monitoring Committee (SMC) before progressing to enrollment of the sentinel group of participants at 12
to 15 years of age.
The first doses of Ad26.COV2.S study vaccine at 2.5x1010 vp were to be administered to a sentinel group
of 11 participants in Groups A-C (randomly assigned at a ratio of 5:5:1 to Ad26.COV2.S, with 5 each from
Groups A and B, and 1 participant in Group C to receive placebo), to monitor for any unexpected severe
adverse reactions. The sentinel participants were to be vaccinated at least 1 hour apart even if enrolled at
different study sites. A telephone call was to be made to each of these 11 sentinel participants on Day 4
post-vaccination to collect safety data, which was to include solicited and unsolicited AEs and SAEs. The
collected data were to be reviewed in a blinded manner by the principal investigator and the sponsor's study
responsible physician/scientist (SRP/S). Randomization and vaccination of additional participants was to
be halted until the review was completed. The SMC was to review the unblinded Day 4 post-vaccination
safety data, including solicited and unsolicited AEs and SAEs, and if the safety profile was found to be
acceptable, a safety cohort of 22 participants in Groups A-C (randomly assigned at a ratio of 5:5:1 to
Ad26.COV2.S, with 10 each from Groups A and B, and 2 participants in Group C to receive placebo) was
to be enrolled. The Day 8 post-vaccination safety data from both sentinel groups, including solicited and
unsolicited AEs and SAEs, was also to be reviewed by the SMC, and in the absence of any safety concerns,
the enrollment and vaccination of the remainder of the participants for Groups A-C (49 participants) in this
age group was to proceed, and simultaneously, sentinel enrollment in Groups D-F (to receive Ad26.COV2.S
study vaccine at 5x1010 vp) was to start. In addition, enrollment of the younger age group of adolescents
(12-15 years, inclusive) was to proceed for Groups A-C.
After vaccination, all participants were to remain under observation at the study site for at least 1 hour
(including participants in the Sentinel and Safety Cohort) to monitor for the presence of any acute reactions
and solicited events.
Following the initial vaccination ofthe first 33 adolescent participants (sentinels + safety cohort) in the 16-
17 year old age group at a dose of 2.5x1010 vp enrolled in this study, the entire Ad26.COV2.S COVID-19
vaccine program was paused to evaluate the a safety concern of thrombosis with thrombocytopenia (TTS)
in adults. During this pause, the safety and immunogenicity data for these 33 adolescent participants was
evaluated (see current version of Investigator’s Brochure0). While the IDMC endorsed further enrollment
of adolescents that would receive Ad26.COV2.S at a 5x1010 vp dose level, the sponsor has decided not to
evaluate the 5x1010 vp dose level in pediatric participants based on the immunogenicity data from the
2.5x1010 vp dose in Study VAC31518COV2001 and has decided to redesign the pediatric studies. Study
VAC31518COV3006 will focus on adolescent participants 12-17 years of age, and no further enrollment
of this age group will take place in this study.
a Not applicable in Germany and the Netherlands

VAC31518 (JNJ-78436735) 
Clinical Protocol VAC31518COV2001 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
17
Status: Approved,  Date: 21 July 2021
Therefore, per protocol Amendment 6, the 33 adolescents already enrolled will continue to be followed in
this study in accordance with the planned Schedule of Activities (Sections 1.3.5 and 1.3.6), but no further
vaccination with Ad26.COV2.S will occur in Groups A and B. Participants in Group C will receive a single
dose of Ad26.COV2.S at 2.5 x1010 vp.
With the implementation of Amendment 6, the 33 adolescent participants will be unblinded to the primary
vaccination regimen. Participants who were initially randomized to receive placebo (Group C), will receive
a single dose of Ad26.COV2.S at the 2.5 x1010 vp dose level in an open-label manner.
Vaccination Schedules –Adolescents
Adolescents: 12 to 17 Years of Age, Inclusive
Group  
Day 1 
(Vaccination 1) 
Ad26.COV2.S dose level/placebo 
Implementation of Amendment 6 (At approximately
6 Months of Study Participation)
(Unblinded Vaccination 1)
Ad26.COV2.S
dose level
A 
2.5x1010 vp 
-
B 
2.5x1010 vp 
-
C 
Placebo 
2.5x1010 vp
vp  virus particles.
ADULTS AND ADOLESCENTS
Initially, an internal Data Review Committee (DRC) was commissioned for this study. However, an IDMC
was installed for the different studies throughout the COVID-19 vaccine program. The charter was updated
to include VAC31518COV2001 on 29 October 2020, and the IDMC kickoff for review was held on 15
December 2020, after which the IDMC took over the responsibilities of the DRC in this study.
Participants will be provided with a booklet including a daily question on whether they are experiencing
COVID-19-like symptoms, and for documentation of body temperature and pulse oximetry results.
Baseline pulse oximetry will be conducted at Visit 1. If participants meet one of the prespecified criteria
for (suspected) COVID-19a, the following should take place:
 
Participants should contact the study site at the time of symptom onset/at time of becoming aware of
the positive RT-PCR test.
 
If the trigger was a sign or symptom: a nasal swab should be collected by 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 ofsymptoms, and stored appropriately. It is preferred that the swab is
taken by a caregiver (spouse, partner, relative, friend, or health care professional). If that is not
possible, the participant can collect the swab himselfor herself. The site should arrange transfer of the
sample to the study site as soon as possible after sample collection. If the trigger was a positive
RT-PCR test, then this first nasal swab is not needed.
 
A second nasal swab will be obtained on COVID-19 Day 3-8 following the same procedures as the
first nasal swab. The second nasal swab may also be collected at home, at the hospital, or at another
location, if needed, by a study site staff, if appropriate procedures are in place. The presence of SARS-
CoV-2 infection will be assessed at the study site by molecular testing using the nasal swab samples.
The nasal swabs may be tested at the central laboratory for the presence of SARS-CoV-2 and other
respiratory pathogens using a broad respiratory pathogens panel. A physical examination, vital signs
a 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.

VAC31518 (JNJ-78436735) 
Clinical Protocol VAC31518COV2001 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
18
Status: Approved,  Date: 21 July 2021
measurements and pulse oximetry will be performed and a blood sample for assessment of the humoral
immune response and other biomarkers will be taken. The sponsor recommends to follow these
participants until 2 consecutive negative nasal swabs could be obtained.
 
From COVID-19 Day 3-8 onwards: Once a first negative swab is obtained, a second swab should be
taken as soon as possible, but with a minimum of 1 day between the 2 swabs. This should be repeated
until 2 consecutive negative swabs are obtained. These precautionary measures are to ensure that site
staff who come into physical contact with a participant deemed to be a COVID-19 case undertake the
proper safety procedures such as wearing of personal protective equipment.
 
Participants should complete the SIC and record their highest body temperature daily starting on the
first day of trigger onset. Blood oxygen saturation and pulse rate should be measured using a pulse
oximeter 3 times a day, preferably in the morning, at lunch time, and in the evening.
 
Collection of data will continue until resolution  of the COVID-19 episode, defined as having 2
consecutive days with no COVID-19-related signs or symptoms and 2 consecutive SARS-CoV-2
negative nasal swabs.
 
For participants with a positive test result for SARS-CoV-2 infection, a study visit will be conducted
28 days after trigger onset to assess the clinical course of the infection, record concomitant medications
since trigger onset, and obtain a blood sample for assessment of the humoral immune response and
other biomarkers.
The occurrence of asymptomatic SARS-CoV-2 infection will also be assessed, if feasible.
End of Study Definition
The end of study is considered as the last visit for the last participant in the study.
NUMBER OF PARTICIPANTS
Overall, a target of 550 adult participants aged 18 to 55 years, inclusive, and 65 years and older, and 33
adolescent participants, aged 12 to 17 years, inclusive, will be enrolled in this study.
DOSAGE AND ADMINISTRATION
Participants will be vaccinated at the study site according to the schedule detailed above:
 
Ad26.COV2.S will be supplied at a concentration of 1x1011 vp/mL and 2x1011 vp/mL, as a suspension
in single-use vials, with an extractable volume of 0.5 mL. Formulation buffer will be supplied as
diluent. Dose levels throughout the different groups will be 1x1011 vp, 5x1010 vp, 2.5x1010 vp and
1.25x1010 vp.
 
Placebo will be supplied as a 0.9% NaCl solution.
A volume of 0.5 mL will be administered to all participants.
IMMUNOGENICITY EVALUATIONS
Venous blood samples will be collected for assessment of humoral immune responses and cellular
immunogenicity (RNA sequencing) in all participants. Blood for evaluation of humoral andcellular (PBMC
in subset only) immune responses will be drawn from adult participants at the time points specified in the
Schedule of Activities. Cellular immune responses (PBMC) will only be assessed in a subset of adult
participants in Groups 1-6 (approximately 112; 21 participants per group in Groups 1-5, 7 participants in
Group 6; at selected sites).Immunogenicity assessments may include, but are not limited to, the humoral
and cellular immunogenicity assays (as available and feasible) summarized in the below table.

VAC31518 (JNJ-78436735) 
Clinical Protocol VAC31518COV2001 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
19
Status: Approved,  Date: 21 July 2021
Table: Summary of Humoral and Cellular Immunogenicity Assays
Assay 
Purpose
Humoral Immunogenicity
Primary/Secondary/Exploratory
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 SARS-CoV-2 or individual SARS-CoV-2
proteins (eg, S protein)
Exploratory endpoints
SARS-CoV-2 binding antibodies 
(ELISA) 
Analysis of antibodies binding to the SARS-CoV-2 N protein, if such an
assay is available
SARS-CoV-2 binding antibodies 
(MSD) 
Analysis of antibodies binding to the SARS-CoV-2 S protein (different than
the assays supportive of the secondary objectives) and the RBD of the
SARS-CoV-2 S protein
Functional and molecular antibody 
characterization  
Analysis of antibody characteristics including Fc-mediated viral clearance,
avidity, Fc characteristics, Ig subclass and IgG isotype
Passive transfer 
Analysis of immune mediators correlating with protection against
experimental SARS-CoV-2 challenge in a suitable animal model
SARS-CoV-2 neutralizing 
antibodies
Analysis of neutralizing antibodies against emerging SARS-CoV-2 variants
Adenovirus neutralization 
(neutralization assays)
Analysis of neutralizing antibodies to adenovirus
Cellular Immunogenicity
Exploratory endpoint
Flow cytometry (ICS) 
Analysis of T-cell responses to SARS-CoV-2 S protein, and/or other protein
peptides by intracellular cytokine staining (ICS) including CD4+/CD8+,
IFNγ, IL-2, TNFα, IL-4, IL-5, IL-13, and/or other Th1/Th2 markers
Gene expression analysis 
Analysis of gene expression by RNA transcript profiling
CD = cluster of differentiation; ELISA = enzyme-linked immunosorbent assay; IFNγ = interferon gamma;
IL = interleukin; MSD = meso scale discovery; PBMC = peripheral blood mononuclear cell; RBD = receptor-
binding domain; RNA = ribonucleic acid; S = Spike protein; SARS-CoV-2 = severe acute respiratory syndrome
coronavirus-2; Th = T helper; TNFα = tumor necrosis factor alpha; VNA = virus neutralization assay
BIOMARKER EVALUATIONS
For participants with a positive test result for SARS-CoV-2 infection, blood will be drawn for evaluation
of biomarkers (eg, those associated with severe COVID-19), 28 days after symptom onset.
SAFETY EVALUATIONS
After each vaccination, participants will remain under observation at the study site for at least 1 hour to
monitor 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.

VAC31518 (JNJ-78436735) 
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CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
20
Status: Approved,  Date: 21 July 2021
 
AEs and special reporting situations, whether serious or non-serious, that are related to study
procedures or that are related to non-investigational sponsor products will be reported from the time a
signed and dated ICF is obtained until the end of the study/early withdrawal. All other unsolicited AEs
will be reported for each vaccination from the time of vaccination until 28 days post vaccination. All
SAEs and AEs leading to discontinuation from the study/vaccination (regardless of the causal
relationship) will be reported from the moment of first vaccinationuntil completion of the participant’s
last study-related procedure.
 
From the time of local approval of protocol Amendment 5 onwards, TTS is considered to be an AESI.
Suspected AESIs (thrombotic events and thrombocytopenia [defined as platelet count below
150,000/µLa]) will be reported from the moment of vaccination until the end of the study/early
withdrawal for adjudication. 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 adult participants chosen for this study will provide a preliminary safety and
immunogenicity assessment. The number of adolescent participants has been chosen to provide sufficient
power for the non-inferiority comparisons versus the adult population.
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 25, 50, 75 and 150 participants are vaccinated, the observation of 0 events (eg, SAEs) is
associated with 95% confidence that the true event rate is below 11.3%, 5.8%, 3.9% and 2.0%, respectively,
for the considered number of participants.
Sample size for the adolescent participants was originally calculated based on assessment of non-inferiority
of immune responses with adults; however, following enrollment of the first 33 participants, further
enrollment of adolescents will cease with this Protocol Amendment 6. (Refer to Overall Design -
Adolescents for further details.)
Populations for Analysis Set
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.
PPIb: The per protocol immunogenicity population will include all randomized and vaccinated participants
for whom immunogenicity data are available excluding participants with major protocol deviations
expected to impact the immunogenicity outcomes. In addition, samples obtained after missed vaccinations
or participants with natural SARS-CoV-2 infection occurring after screening (if applicable) will be
excluded from the analysis set.
a Reference for definition of thrombocytopenia: Brighton Collaboration. Interim Case Definition of Thrombosis with
Thrombocytopenia 
Syndrome 
(TTS). 
21 
April 
2021. 
https://brightoncollaboration.us/thrombosis-with-
thrombocytopenia-syndrome-interim-case-definition/. Accessed: 29 April 2021.
b If a participant would be vaccinated out of window due to a study pause, 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 SAP

VAC31518 (JNJ-78436735) 
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21
Status: Approved,  Date: 21 July 2021
Primary/Secondary Endpoints
Immunogenicity
Descriptive statistics (geometric mean and confidence intervals, or median and interquartile range Q1-Q3,
as appropriate) will be calculated for continuous immunologic parameters. Several definitions of serological
response will be applied (fold increases in GMT [VNA] or GMC [ELISA]). 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 together with confidence intervals.
The immunogenicity analyses will be performed on the PPI population. Immunogenicity analyses will also
be done on the full analysis set (FAS; participants who became infected during the study will be analyzed
as a subgroup and shown in the graphs using different colors and symbols).
For adults, all data will be analyzed separately from the point of unblinding for safety and immunogenicity.
Details will be described in the Statistical Analysis Plan (SAP).
For adolescents, limited pooled safety and reactogenicity data (planned for IDMC review) and group
unblinded immunogenicity data (summary of S-ELISA, including GMC, and seroresponse rates for all
participants and seronegative at baseline participants, in Ad26.COV2.S 2.5x1010 vp only) were reviewed
by the sponsor prior to Amendment 6 (see Overall Design).
Safety
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 done on the FAS.
Planned Analyses
Interim and Primary Analyses for Adult Participants
An interim analysis of safety and immunogenicity will be performed, including all available
immunogenicity data up to Day 29 (if applicable) and all available safety data post vaccination 1 of all
groups in the adult cohort. Unblinded data at the vaccination group level will be available to the sponsor
and might be used for regulatory submissions.
The primary analysis of safety and immunogenicity post-vaccination 2 will be performed when all adult
participants have completed the visit that takes place 28 days after the second study vaccination in all groups
or discontinued earlier. The analysis will include safety and immunogenicity data (VNA and ELISA) for
all participants through Day 85 (Groups 1-6), Day 57 (Groups 7-8) or Day 113 (Groups 9-10). It will also
include Th1-Th2 responses assessed only in Groups 1-6 (as available and feasible) through Day 85 (ie,
28 days after the second study vaccination). Unblinded data at the vaccination group level will be available
to the sponsor and might be used for regulatory submissions.
A second interim analysis of safety and immunogenicity will be performed, including 28-day
immunogenicity and 28-day safety data post antigen presentation (Groups 1-5, 7 and 9).
The final analysis ofthe adult cohort will be performed when all included adult participants have completed
the last visit, or discontinued earlier.
Additional interim analyses may be performed for safety and/or immunogenicity to facilitate decision
making with regards to the planning of future studies.

VAC31518 (JNJ-78436735) 
Clinical Protocol VAC31518COV2001 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
22
Status: Approved,  Date: 21 July 2021
Unblinding due to availability of 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 recommendation 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. 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 data on the safety of receiving 2 different
COVID-19 vaccines. Participants who were already unblinded for any reason may receive Ad26.COV2.S
vaccine upon discussion with the investigator, provided that they  did not receive another COVID-19
vaccine. Unblinded participants, whether in the vaccine or control group, will be asked to continue to be
followed in this study in line with the Schedule of Activities to the extent that the participant is amenable.
All data will be analyzed separately from the point of unblinding, for safety and immunogenicity analysis,
as described in the SAP.

VAC31518 (JNJ-78436735) 
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CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
26
Status: Approved,  Date: 21 July 2021
Figure 4: 
Schematic Overview of Active Vaccine Regimen for Adult Placebo Groups 6, 8 and 10
VISIT
101 
Unblinded Vaccination 1
102 
Safety and Immunogenicity: 7 days post unblinded Vaccination 1
103
Unblinded Vaccination 2:
28 days post Vaccination 1
104 
Safety: 7 days post unblinded Vaccination 2
105 
Safety and Immunogenicity: 14 days post unblinded Vaccination 2
106 
Safety and Immunogenicity: 28 days post unblinded Vaccination 2
107 
Safety and Immunogenicity: 6 months post unblinded Vaccination 1 follow up

VAC31518 (JNJ-78436735) 
Clinical Protocol VAC31518COV2001 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
27
Status: Approved,  Date: 21 July 2021
Figure 5: 
Schematic Overview of Groups A -C –Adolescentsa
VISIT
Screening:
Days -28 to 1
1
2 
Vaccination 1: Day 1
3 
Safety phone call: 3 days post Vaccination 1
4 
Safety: 7 days post Vaccination 1
5 
Safety and Immunogenicity: 28 days post Vaccination 1
6 
Safety and Immunogenicity: 56 days post Vaccination 1
7 
Safety and Immunogenicity: 84 days post Vaccination 1
8 
Safety and Immunogenicity: 6 months post Vaccination 1
9 
Safety phone call: 9 months post Vaccination 1
10 
Safety and Immunogenicity: 12 months post Vaccination 1
a Not applicable in Germany and the Netherlands

VAC31518 (JNJ-78436735) 
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CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
28
Status: Approved,  Date: 21 July 2021
Figure 6: 
Schematic Overview of Active Vaccine Regimen for Adolescenta Placebo Group C
VISIT
101
At approximately 6 months of study participation
Unblinded Vaccination
102 
Safety: 7 days post Unblinded Vaccination
103 
Safety and Immunogenicity: 28 days post Unblinded Vaccination
104 
Safety and Immunogenicity: 56 days post Unblinded Vaccination
105 
Safety and Immunogenicity: 84 days post Unblinded Vaccination
106 
Safety and Immunogenicity: 6 months post Unblinded Vaccination
a Not applicable in Germany and the Netherlands

VAC31518 (JNJ-78436735) 
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CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
31
Status: Approved,  Date: 21 July 2021
1 pre vaccination; 2 pre and post vaccination; 3 blood samples for immunogenicity will only be taken if the early exit visit is at least 10 days after the previous immunogenicity blood
draw; 4 if within 7days of the previous vaccination; 5 if within 28 days of the last vaccination; 6 Screening diagnostic test for SARS CoV 2 past or current infection will be performed.
7 to be repeated pre vaccination if the screening test was done more than 4 days before Day 1. 8 No extra blood required. The anti β2 glycoprotein, anti PF4, and anti cardiolipin tests will
be performed retrospectively or prospectively with blood from samples collected for the humoral immunogenicity assessment.
$As soon as Group 6 (placebo) participants are unblinded they should follow the procedures as outlined in the Schedule of Activities Section 1.3.4.
*The timings of visits after the second or third (ie, antigen presentation) vaccination will be determined relative to the actual day of that vaccination.
**Upon implementation of Amendment 5.
a. 
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.
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 to continue with safety and immunogenicity follow-up visits. 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 3, 7or 11, ie, 1 or 2 days prior to the 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. 
Antigen presentation administered as 1.25x1010 vp of Ad26.COV2.S (Groups 1-5) or placebo (Group 6).
e. 
Signing of the ICF should be done before any study-related activity.
f. 
A history-directed 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. 
All participants will be provided a pulse oximeter at baseline to measure blood oxygen saturation and pulse rate during a COVID-19 episode (see Section 1.3.7)
h. 
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.
i. 
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. If the vaccination visit cannot be rescheduled within the
allowed window or the contraindications to vaccination persist, the sponsor should be contacted for further guidance. The investigator should also check if any
other reasons, as listed in Section 7.1, Discontinuation of Study Vaccination, have been met and would prevent further study vaccination.
j. 
For women of childbearing potential only. Only women who are postmenopausal as defined in Section 5.1.1 (see Inclusion Criterium 6a) or who have had their
uterus removed are of non-childbearing potential. All other women are considered of childbearing potential.
k. 
In a subset of participants in Groups 1-6.
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. Applicable from the time of local approval of protocol Amendment 5 onwards: Suspected AESIs are to be reported from
the moment of vaccination until completion of the participant’s last study-related procedure (see Section 8.3.1).

VAC31518 (JNJ-78436735) 
Clinical Protocol VAC31518COV2001 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
32
Status: Approved,  Date: 21 July 2021
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. 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, Day 64, or Day 176 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 meets the prespecified criteria for (suspected) COVID-19 (see Section 8.1.2.1), refer to Section 1.3.7.
s. 
In case the screening serological test was done more than 4 days before Day 1 an additional 8 mL of blood will need to be taken (repeat of pre-vaccination test).
t. 
With the implementation of protocol Amendment 5, all adult participants will be unblinded, and participants who received placebo (Group 6) will start following
the Schedule of Activities for the active vaccine regimen in Section 1.3.4.
u. 
Once protocol Amendment 4/5 is approved and implemented, hematology serum samples will be collected for all participants (see Section 10.2, Appendix 2).
v. 
Hematology plasma samples to be collected up to protocol Amendment 2.
AE = adverse event; AESI = adverse event of special interest; COVID-19 = coronavirus disease-2019; d = day(s); ICF = informed consent form; meds = medication; mo
= months; PBMC = peripheral blood mononuclear cell; SAE = serious adverse event; SARS-CoV-2 = severe acute respiratory syndrome coronavirus-2; UB =
unblinding visit; vac = vaccination; vp = virus particles.

VAC31518 (JNJ-78436735) 
Clinical Protocol VAC31518COV2001 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
35
Status: Approved,  Date: 21 July 2021
i. 
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. If the vaccination visit cannot be rescheduled within the
allowed window or the contraindications to vaccination persist, the sponsor should be contacted for further guidance. The investigator should also check if any
other reasons, as listed in Section 7.1, Discontinuation of Study Vaccination, have been met and would prevent further study vaccination.
j. 
For women of childbearing potential only. Only women who are postmenopausal as defined in Section 5.1.1 (see Inclusion Criterium 6a) or who have had their
uterus removed are of non-childbearing potential. All other women are considered of childbearing potential.
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. Applicable from the time of local approval of protocol Amendment 5 onwards: Suspected AESIs are to be reported from
the moment of vaccination until completion of the participant’s last study-related procedure (see Section 8.3.1).
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. 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, Day 36, or Day 148 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 meets the prespecified criteria for (suspected) COVID-19 (see Section 8.1.2.1), refer to Section 1.3.7
r. 
In case the screening serological test was done more than 4 days before Day 1 an additional 8 mL of blood will need to be taken (repeat of pre-vaccination test).
s. 
With the implementation of protocol Amendment 5, all adult participants will be unblinded, and participants who received placebo (Group 8) will start following
the Schedule of Activities for the active vaccine regimen in Section 1.3.4.
t. 
Once protocol Amendment 4/5 is approved and implemented, hematology serum samples will be collected for all participants (see Section 10.2, Appendix 2).
u. 
Hematology plasma samples to be collected up to protocol Amendment 2.
AE = adverse event; AESI = adverse event of special interest; COVID-19 = coronavirus disease-2019; d = day(s); EUA = Emergency Use Authorization; ICF =
informed consent form; meds = medication; mo = months; PBMC = peripheral blood mononuclear cell; SAE = serious adverse event; SARS-CoV-2 = severe acute
respiratory syndrome coronavirus-2; UB = unblinding visit; vac = vaccination; vp = virus particles.

VAC31518 (JNJ-78436735) 
Clinical Protocol VAC31518COV2001 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
38
Status: Approved,  Date: 21 July 2021
d. 
Antigen presentation administered as 1.25x1010 vp of Ad26.COV2.S (Group 9) or placebo (Group 10).
e. 
Signing of the ICF should be done before any study-related activity.
f. 
A history-directed 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. 
All participants will be provided a pulse oximeter at baseline to measure blood oxygen saturation and pulse rate during a COVID-19 episode (see Section 1.3.7)
h. 
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.
i. 
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. If the vaccination visit cannot be rescheduled within the
allowed window or the contraindications to vaccination persist, the sponsor should be contacted for further guidance. The investigator should also check if any
other reasons, as listed in Section 7.1, Discontinuation of Study Vaccination, have been met and would prevent further study vaccination.
j. 
For women of childbearing potential only. Only women who are postmenopausal as defined in Section 5.1.1 (see Inclusion Criterium 6a) or who have had their
uterus removed are of non-childbearing potential. All other women are considered of childbearing potential.
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. Applicable from the time of local approval of protocol Amendment 5 onwards: Suspected AESIs are to be reported from
the moment of vaccination until completion of the participant’s last study-related procedure (see Section 8.3.1).
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. 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, Day 92, or Day 204 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 meets the prespecified criteria for (suspected) COVID-19 (see Section 8.1.2.1), refer to Section 1.3.7.
r. 
In case the screening serological test was done more than 4 days before Day 1 an additional 8 mL of blood will need to be taken (repeat of pre-vaccination test).
s. 
With the implementation of protocol Amendment 5, all adult participants will be unblinded, and participants who received placebo (Group 10) will start following
the Schedule of Activities for the active vaccine regimen in Section 1.3.4.
t. 
Once protocol Amendment 4/5 is approved and implemented, hematology serum samples will be collected for all participants (see Section 10.2, Appendix 2).
u. 
Hematology plasma samples to be collected up to protocol Amendment 2.
AE = adverse event; AESI = adverse event of special interest; COVID-19 = coronavirus disease-2019; d = day(s); EUA = Emergency Use Authorization; ICF =
informed consent form; meds = medication; mo = months; PBMC = peripheral blood mononuclear cell; SAE = serious adverse event; SARS-CoV-2 = severe acute
respiratory syndrome coronavirus-2; UB = unblinding visit; vac = vaccination; vp = virus particles.

VAC31518 (JNJ-78436735) 
Clinical Protocol VAC31518COV2001 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
40
Status: Approved,  Date: 21 July 2021
a. 
If a participant shows COVID-19 like symptoms, the participant should contact the site for guidance and must follow their local country and site level
recommendations for COVID-19.
b. 
For those participants who are unable to continue participation in the study up to Visit 15 or 19 (depending on the vaccination regimen), but for whom consent is
not withdrawn, an early exit visit will be conducted as soon as possible. Participants who no longer wish to receive study vaccination (see Section 7.1) will be
offered all safety and immunogenicity follow-up visits according to the current Schedule of Activities. 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 14 or 16, 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.
d. 
An abbreviated, symptom-directed examination may be performed if determined necessary by the investigator.
e. 
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.
f. 
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. If the vaccination visit cannot be rescheduled within the
allowed window or the contraindications to vaccination persist, the sponsor should be contacted for further guidance. The investigator should also check if any
other reasons, as listed in Section 7.1, have been met and would prevent further study vaccination.
g. 
For women of childbearing potential only. Only women who are postmenopausal as defined in Section 5.1.1 (see Inclusion Criterium 6a) or who have had their
uterus removed are of non-childbearing potential. All other women are considered ofchildbearing potential.
h. 
Participants will be closely observed for a at least 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.
i. 
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.
j. 
All SAEs related to study procedures or 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 SAEs are to be reported from the moment of first vaccination until completion of the participant’s last study-related procedure.
Applicable from the time of local approval of protocol Amendment 5 onwards: Suspected AESIs are to be reported from the moment of vaccination until
completion of the participant’s last study-related procedure (see Section 8.3.1).
k. 
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. All other concomitant therapies should also be recorded if administered in conjunction with new or worsening
AEs reported per protocol requirements outlined in Section 8.3.1. Concomitant therapies associated with an SAE meeting the criteria outlined in Section 10.3.1
will be collected and recorded in the eCRF from the moment of 1st vaccination through the end of the study.
l. 
Participants should keep the diary after the review and collect information until resolution. The diary should be reviewed again at the next visit.
m. If an event is still ongoing on UB8 or Day UB36 the participant should continue to collect information in the reactogenicity diary until resolution. The
reactogenicity diary should be reviewed again at the next visit.
n. 
Once protocol Amendment 4/5 is approved and implemented, serum samples will be collected for all participants (see Section 10.2, Appendix 2).
o. 
Starting at 460.5 and 155.5 mL at the time of the Unblinding visit in the PBMC and non-PBMC subsets, respectively, per Schedule 1.3.1.
p. 
Starting at 140.5 mL at the time of the Unblinding visit per Schedule 1.3.2 and 1.3.3.

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AE = adverse event; AESI = adverse event of special interest; COVID-19 = coronavirus disease-2019; d = day(s); meds = medication; m = months; SAE = serious
adverse event; SARS-CoV-2 = severe acute respiratory syndrome coronavirus-2; UB = unblinding; Vac = vaccination.

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allowed window or the contraindications to vaccination persist, the sponsor should be contacted for further guidance. The investigator should also check if any
other reasons, as listed in Section 7.1, Discontinuation of Study Vaccination, have been met and would prevent further study vaccination.
i. 
For participants of childbearing potential only. Only women who are postmenopausal as defined in Section 5.1.2 (see Inclusion Criterium 6a) or who have had
their uterus removed are of non-childbearing potential. All other women are considered of childbearing potential.
j. 
In a subset of participants.
k. 
Participants will be closely observed for a minimum of1 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 moment of vaccination until completion of the participant’s last study-related
procedure.
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. 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 7 days after vaccination, 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 meets the prespecified criteria for (suspected) COVID-19 (see Section 8.1.2.1), refer to Section 1.3.7.
r. 
In case the screening serological test was done more than 4 days before Day 1 an additional 8 mL of blood will need to be taken (repeat of pre-vaccination test).
s. 
With the implementation of Amendment 6 (at approximately 6 months of study participation), all adolescent participants and investigators will be unblinded (ie,
informed whether they received placebo or Ad26.COV2.S) and the study will continue as an open-label study. The site staff may be unblinded up to 7 days before
the scheduled Unblinded visit date to allow for appropriate planning and preparations to take place. Participants who received active vaccine (Groups A and B) will
continue to follow this schedule. Participants who received placebo (Group C) will complete Visit 8 activities, including a coagulopathy blood draw to take place
at the same time as the blood draw for humoral immunity, after which they will start following the Schedule of Activities for the active vaccine regimen in
Section 1.3.6. Note that assessments on Visit 8 are to be performed for all participants, irrespective of the unblinding outcome.
t. 
Telephone contact on Day 4 post vaccination for the 11 sentinel participants, with diary review during phone call.
AE = adverse event; COVID-19 = coronavirus disease-2019; d = day(s); EUA = Emergency Use Authorization; ICF = informed consent form; meds = medication; mo =
months; PBMC = peripheral blood mononuclear cell; SAE = serious adverse event; SARS-CoV-2 = severe acute respiratory syndrome coronavirus-2; vac = vaccination;
vp = virus particles.

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a. 
If a participant shows COVID-19 like symptoms, the participant should contact the site for guidance and must follow their local country and site level
recommendations for COVID-19.
b. 
For those participants who are unable to continue participation in the study up to Visit 106, but for whom consent is not withdrawn, an early exit visit will be
conducted as soon as possible. Participants who no longer wish to receive study vaccination (see Section 7.1) will be offered all safety and immunogenicity follow-
up visits according to the current Schedule of Activities. 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 102, 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.
d. 
An abbreviated, symptom-directed examination may be performed if determined necessary by the investigator.
e. 
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.
f. 
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. If the vaccination visit cannot be rescheduled within the
allowed window or the contraindications to vaccination persist, the sponsor should be contacted for further guidance. The investigator should also check if any
other reasons, as listed in Section 7.1, have been met and would prevent further study vaccination.
g. 
For women of childbearing potential only. Only women who are postmenopausal as defined in Section 5.1.2 (see Inclusion Criterium 6a) or who have had their
uterus removed are of non-childbearing potential. All other women are considered of childbearing potential.
h. 
Participants will be closely observed for a at least 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.
i. 
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.
j. 
All SAEs related to study procedures or 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 SAEs are to be reported from the moment of first vaccination until completion of the participant’s last study-related procedure.
Suspected AESIs are to be reported from the moment of vaccination until completion of the participant’s last study-related procedure
k. 
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. All other concomitant therapies should also be recorded if administered in conjunction with new or worsening
AEs reported per protocol requirements outlined in Section 8.3.1. Concomitant therapies associated with an SAE meeting the criteria outlined in Section 10.3.1
will be collected and recorded in the eCRF from the moment of 1st vaccination through the end of the study.
l. 
Participants should keep the diary after the review and continue to collect information until resolution. The diary should be reviewed again at the next visit.
m. If an event is still ongoing at Visit 102, the participant should continue to collect information in the diary until resolution. The diary should be reviewed again at
the next visit.
n. 
Whole blood samples will be used for complete blood cell count, including platelet count, in a local laboratory or substitute for local laboratory, depending on local
feasibility towards turnaround time of sample processing. Results should be available within 72 hours. The division of volumes between whole blood, plasma and
serum is described in the laboratory manual. Serum and plasma are to be stored for future testing to evaluate the impact of any potential thromboembolic events.
Samples can also be tested for anti-PF4 antibodies and platelet activation assay (if HIT/PF4 is positive). Unused samples may be used for immunogenicity testing.
o. 
Starting at 58 mL at the time of the Unblinding visit per Schedule 1.3.5.

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AE = adverse event; COVID-19 = coronavirus disease-2019; d = day(s); meds = medication; m = months; SAE = serious adverse event; SARS-CoV-2 = severe acute
respiratory syndrome coronavirus-2; Vac = vaccination.

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f. 
Participant should measure body temperature daily and record the highest temperature each day.
g. Participants should complete the SIC starting on the first day of trigger onset See Section 10.7for an example of the SIC.
h. If a participant has a positive test result for SARS-CoV-2 infection, the participant will be notified and 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 SIC will be reviewed by study staff during these contacts (phone call or visit).
i. 
15 mL for adults. 7.5 mL for adolescents. The sponsor recommends to follow these participants until 2 consecutive negative nasal swabs could be obtained.
COVID-19 = coronavirus disease-2019; RNA = ribonucleic acid; SARS-CoV-2 = severe acute respiratory syndrome coronavirus-2; SIC = Symptom of Infection with
COVID-19.

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1.3.8. 
Participants with aSuspected AESI –Adults and Adolescents
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 Hematology0, British Society of Haematology Expert Haematology Panel0, and the CDC0). 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 Janssen Adjudication Committee.
In the event of a suspected thrombotic event or TTS, laboratory assessments are required to facilitate diagnosis and determine treatment
options, including but not limited to platelet count and anti-PF4 tests. Additional blood samples should be collected for central laboratory
testing as detailed below. However, results of central laboratory testing may not be available to guide immediate treatment decisions.
a. Day 1 refers to first awareness of the event, which might be later than the date of onset. Every effort should be made to report as much information as possible about
the event to the sponsor in a reasonable timeframe. The investigator should contact the sponsor for input on the feasibility of collecting blood samples, including the
need for additional samples based on the nature of the event.
b. Day 29 is to be calculated relative to the actual day of onset of the event. If the event is not resolved on Day 29, subsequent follow-up assessments can be performed
at unscheduled visits as needed until resolution of the event.
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. Whole blood samples will be used for a platelet count (as part of a complete blood count, if applicable) in a local laboratory or substitute for local laboratory, depending
on local feasibility towards turnaround time of sample processing. Serum and plasma samples will be derived from the whole blood sample for coagulation-related
testing in a central laboratory (see Section 10.2, Appendix 2). For the follow-up visit, the volume of blood to be collected may vary depending on the clinical evaluation
of the case.
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 10.13, Appendix 13 for further details.
f. Refer to Section 6.9 for collection and recording of concomitant therapies associated with a suspected AESI.
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 29b
Visit Window  
 
±7 d
Site to report suspected AESIc
 
Clinical lab blood sample (whole blood), mLd
15 
15
TTS AESI forme
Continuous
Concomitant therapiesf
 


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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) spike (S) protein, which will be assessed in
this study.
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.0
The term “study vaccine” throughout the protocol refers to Ad26.COV2.S or placebo as defined
in Section  6.1, Study Vaccinations Administered. Scientifically, the administration of the
Ad26.COV2.S  1.25x1010 virus particles (vp) or placebo dose 4 months after the primary
vaccination regimen is considered as presentation of antigen. Nevertheless, for the sake of
simplicity, the terms “study vaccine” and “vaccination” throughout the protocol encompass
administration of the antigen presentation dose. 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.”
The term “legal guardian” used throughout the document refers to the parent(s) (preferably both if
available or as per local requirements), legally appointed guardian(s), or legally acceptable
representative(s), as defined by national and local laws and regulations, who consent(s) on behalf
of the minor child (participant). For the purposes of this study, all references to participants refers
to the participants (child) and his or her legal guardian(s) (as defined above) who have provided
consent (and assent as applicable) according to the Informed Consent Process and Assent Form
described in Section 10.3.3.
Study VAC31518COV2001 is being conducted under the sponsorship of Janssen (Janssen
Vaccines & Prevention B.V.) in collaboration with the United States (US) government and the
COVID-19 Response Team (formerly Operation Warp Speed), which also encompasses the
Biomedical Advanced Research and Development Authority, the National Institutes of Health, and
the COVID-19 Prevention Trials Network.
COVID-19 Vaccine and Considerations
Currently, there is only limited availability ofauthorized/licensed vaccines for the prevention
of coronavirus disease-2019 (COVID-19). The continued development of safe and effective
vaccines 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.0,0 Recent studies suggest that SARS-CoV-2 has several
similarities to SARS-CoV based on the full-length genome phylogenetic analysis and the

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putatively similar cell entry mechanism and human cell receptor usage.0,0,0 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).
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 1 dose, in both naïve and pre-immune individuals (RSV). These antibodies may
persist for a year or more (RSV) after a single vaccination in pre-immune participants. They have
functional properties of neutralization (RSV, Zika), crystallizable fragment (Fc)-mediated
antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis
(HIV, malaria). Furthermore, these data support an immunogenicity profile with emphasis on
T-helper cell type 1 (Th)1 responses and demonstrate predominantly interferon gamma (IFN-γ)
and tumor necrosis factor alpha (TNF-α) production in cluster of differentiation (CD) 4+ and CD8+
T cells.0,0,0
Ad26.COV2.S Candidate Vaccine
The aim of the COVID-19 vaccine clinical development program is to develop a safe and effective
vaccine for the prevention of COVID-19. The candidate vaccine to be assessed in this study is
Ad26.COV2.S, which is a recombinant, replication-incompetent Ad26 encoding a prefusion
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.0,0,0 The S 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.0 In this study, different vaccination intervals and multiple

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lower dose levels compared to the dose levels in the first-in-human study (VAC31518COV1001)
will be assessed.
SARS-CoV-2 Virology and COVID-19 Disease Burden
SARS-CoV-2 is an enveloped, positive-sense, single-stranded ribonucleic acid (RNA)
betacoronavirus.0,0 It was first identified following reports of a cluster of acute respiratory illness
cases in Wuhan, Hubei Province, China in December 2019.0 Early epidemiological investigations
suggested 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.0 However, there is some controversy about
the initial origin of the virus.0 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.0,0 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.0
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
on January 30, 2020, and declared the outbreak to be a pandemic on March 11, 2020.0,0 As of
October 21, 2020, approximately 40,792,599 cases of COVID-19 and approximately 1,124,918
COVID-19-related deaths have been reported.0
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.0 Severe clinical
presentations have been reported in as many as 20% to 25% of laboratory-confirmed cases.0 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%).0 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%).0
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 (ICU) because of complications, including acute respiratory distress
syndrome, arrhythmia, and shock. Subsequent US  Centers for Disease Control and Prevention
(CDC) descriptions of COVID-19 clinical case definitions0 and Janssen-sponsored interviews with
COVID-19-experienced clinicians have included signs and symptoms of respiratory distress such
as blue lips, extreme shortness of breath and dyspnea, persistent cough, deep vein thrombosis
(DVT), Kawasaki-like disease, discoloration of feet and toes, chills, shaking chills, loss of sense
of taste and smell, signs of stroke, disorientation, inability to respond or understand verbal
communication, among others.

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At present, it appears that individuals aged ≥65 years, especially those with comorbid diseases, are
subject to the highest incidence of morbidity and mortality.0 In 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.0 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). A study of 149,082 COVID-19 cases reported in the US was consistent with these
findings.0 Only 1.7% of these cases occurred in persons aged <18 years, although this age group
accounts for 22% of the US population. 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. Recent (April-May 2020) reports describe several cases of multisystem
inflammatory syndrome (MIS) in children with Kawasaki disease-like features (ie, fever,
laboratory markers of inflammation, severe illness requiring hospitalization, multisystem organ
involvement). Most of these children had tested positive for current or recent SARS-CoV-2
infection or were linked to a COVID-19 case. It is currently unknown if MIS is specific to children
or if it may also occur in adults.0,0
More recently, it has been observed that although the rate of hospitalizations due to COVID-19 is
lower in children than in adults, the burden of the hospitalizations is similar to that caused by other
diseases that can be prevented by vaccination.0 In addition, evidence points to Hispanic and Black
children likely being at increased risk for severity of COVID-19 infection.0,0,0
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.0 The first known cases of severe acute respiratory syndrome (SARS) occurred in
Southern China in November 2002.0 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 multiorgan  failure in June 2012.0 MERS-CoV is
considered to be a zoonotic virus capable of nonsustained 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.
Patients with SARS or MERS present with various clinical features, ranging from asymptomatic
or mild respiratory illness to fulminant severe acute respiratory disease with extrapulmonary
manifestations.0,0 
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.0,0 The case-fatality rate
of MERS-CoV infections is estimated to be 35%.0

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It is not known if SARS-CoV-2 will remain as a worldwide pandemic. It is also not known if
immunity is acquired after symptomatic or asymptomatic SARS-CoV-2 infection and how long it
might last. Currently, the only preventive measures that have been employed with some success
have been social distancing and quarantine after contact tracing and testing. Test and treat
approaches await an effective proven safe therapy that can be implemented on a mass scale. It is
generally believed that an effective vaccine will be 1 of the most important tools to help control
this highly contagious respiratory virus.
The sponsor is developing a COVID-19 vaccine based on a human replication-incompetent Ad26
vector encoding the SARS-CoV-2 S protein. The S protein is the major surface protein of
coronaviruses. Different animal models have been used for the evaluation of candidate coronavirus
vaccines against SARS-CoV (2002-2003 outbreak), and the common conclusion that has emerged
from the evaluation of several different vaccines is that the viral S protein is the only significant
target for neutralizing antibodies0,0,0,0 and the only viral protein that can elicit protective immunity
in animal models.0,0,0,0,0 Based on these findings, the S protein was selected as the sponsor’s
candidate vaccine antigen.
2.1. 
Study Rationale
Detailed information about the rationale for the selected doses can be found in Section 4.3
Justification for Dose.
Adults
In this study, safety and immunogenicity responses following 2-dose (5x1010 vp, 2.5x1010 vp,
1.25x1010 vp) and single-dose (5x1010 vp, 1x1011 vp) primary vaccination regimens will be
assessed in adults aged 18 to 55 years inclusive, and adults in good or stable health aged 65 years
and older, to investigate dose sparing measures resulting in an increase of the number of vaccine
doses available in a pandemic context. Safety and immunogenicity of 28-, 56-, and 84-day
vaccination intervals for the 2-dose regimen (5x1010 vp) will also be assessed to gather insight on
the possible compression and delay of the vaccination schedule, as this may be of interest in an
emergency use setting.
The 5x1010 vp dose level is administered in the Phase 3 efficacy studies VAC31518COV3001 (1-
dose regimen) and VAC31518COV3009 (2-dose regimen).
In addition, an assessment of the immunogenicity of the 1.25x1010 vp Ad26.COV2.S dose level
that is representative of the vaccine titer at the end of the foreseen shelf-life for the 5x1010 vp dose
level in the context of emergency use with storage at 2-8 °C will be done. By lowering the dose
level (ie, to 2.5x1010 vp and 1.25x1010 vp), there will also be a potential to immunobridge to a
lower dose level regimen, should the efficacy study (VAC31518COV3001) provide evidence of
an immune correlate of protection.
And finally, the anamnestic response after 7 days following a low-dose antigen presentation
(1.25x1010 vp Ad26.COV2.S) as a surrogate of antigen exposure upon SARS-CoV-2 infection,

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after the primary 2-dose or single-dose vaccination regimens, will be assessed in adult Groups 1-5,
7 and 9.
Adolescents
Available platform data, as well as safety data from the VAC31518COV1001 study, (see
Section 2.2 and Section 2.3.1) support initiating evaluation of Ad26.COV2.S in adolescents aged
12 to 17years, inclusive. In order to generate data in adolescents that will allow the use of a vaccine
to prevent COVID-19 in this age group, the safety and immunogenicity responses following
primary vaccination regimens will also be assessed in adolescents aged 12 to 17 years, inclusive.
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 development program. In addition, vaccine
efficacy of Ad26.COV2.S has been shown in Syrian hamsters and NHP. Details are provided in
the IB.0
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 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 dose levels up to 1.2×1011 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 signals detected

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in any of the available GLP toxicology studies with Ad26-based vaccines up to the highest dose
level tested (1.2×1011 vp). In a combined embryo-fetal and pre- and postnatal development GLP
study in female rabbits with another Ad26-based vaccine (Ad26.ZEBOV, encoding an Ebola virus
antigen), there was no maternal or developmental toxicity observed following maternal exposure
during the premating and gestation period. A repeated dose and local tolerance GLP study, and a
combined embryo-fetal and pre- and postnatal development GLP study with Ad26.COV2.S are
planned to run in parallel with study VAC31518COV1001.
Clinical Studies
At the time of initial protocol writing, no clinical data with the Ad26.COV2.S vaccine were
available. At this stage of protocol Amendment 2, initial immunogenicity and safety data (28 days
post-Dose 1 data from Cohort 1a (participants aged ≥18 to ≤55 years) and available data from
Cohort 3 (participants aged ≥65 years) from study VAC31518COV1001 have become available
and demonstrate that a single dose of Ad26.COV2.S at 5×1010 virus particles (vp) and 1×1011vp
induces an immune response that meets prespecified minimum criteria and has an acceptable safety
profile. Data from study VAC31518COV1001 supports the evaluation of Ad26.COV2.S vaccine
in younger age groups. A dose escalation approach will be used in the present study.
Refer to the latest IB0 and its addenda (if applicable) for a high level description of the additional
ongoing studies with Ad26.COV2.S.
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, Zika virus and
filovirus.
As of 04 September 2020, Ad26-based vaccines have been administered to approximately
114,000 participants in ongoing and completed studies, including more than 99,000 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, cut-off 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 04 September 2020, more than 109,000 participants were enrolled in ongoing studies and in
the ongoing immunization campaign in Rwanda (UMURINZI Ebola Vaccine Program campaign).
However, their safety data were not included in the AdVac® safety database report V5.0 because

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the studies were still blinded, the studies were unblinded but their analysis took place after the
AdVac® safety database report cut-off 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.
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
in 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 cut-off date of 24 April
2020, approximately 3,700 participants aged ≥60 years have received an Ad26.RSV.preF-based
regimen in completed and ongoing studies. An acceptable safety and reactogenicity 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.
Th1/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.0,0,0,0 Although the mechanisms for ERD are not fully understood, it is thought that the
FI-RSV vaccine 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 T helper cell (Th) type 2-skewed type T-cell response.0 Vaccine-
induced ERD has also been described for SARS-CoV and MERS-CoV in some animal models in
which candidate vaccines induced a Th2 biased immune response,0,0,0,0,0,0 but proof of human
SARS-CoV or MERS-CoV vaccine-associated enhanced disease does not exist as these candidate
vaccines were never tested for efficacy nor used in outbreak situations. For SARS and MERS, the
mechanism of enhanced disease observed in mice has been associated with a Th2-mediated
eosinophilic infiltration in the lung, which is reminiscent of ERD effects observed after RSV
infection of mice immunized with FI-RSV. Similar to RSV vaccines, enhanced disease has been
shown for whole-inactivated SARS-CoV vaccines, as well as subunit vaccines inducing a Th2-
type immune response, which can be rescued by formulating vaccines in Th1-skewing adjuvants.
In addition to a Th1-biased immune response, also induction of a high proportion of neutralizing
antibodies compared with virus binding antibodies is desirable to prevent predisposition to
enhanced disease as observed for RSV vaccines. While vaccine-associated enhanced disease was
observed in nonclinical studies with experimental SARS and MERS vaccines, it is not a given that
the same risk applies to COVID-19 vaccines. To the sponsor’s knowledge, antibody-related
COVID-19 disease enhancement has not been observed in nonclinical models yet. Antibodies
against the receptor-binding domain (RBD) of SARS-CoV-2 were shown not to enhance in vitro
infectivity. Repeated SARS-CoV-2 challenge of NHP or NHP studies with Th2 biasing COVID-

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19 vaccines that would be expected to predispose to enhanced disease did not show any signs of
enhanced disease. In addition, disease enhancement was not observed in NHP immunized with
ChAdOx1 encoding SARS-CoV-2 S protein prior to challenge with SARS-CoV-2.0 The Ad26
vector was chosen due to its ability to induce humoral and strong cellular responses with a Th1
immune phenotype.0,0,0,0,0,0,0,0,0,0 This type 1 polarity of the immune response minimizes the risk
of enhanced disease after SARS-CoV-2 infection.
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.0,0,0 In the RSV
vaccine clinical development program, Ad26.RSV.preF was 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
a favorable Th1 bias, was confirmed. In August 2020, the study had been completed and showed
that Ad26.RSV.preF had an acceptable safety and reactogenicity profile. 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
vaccination.
Ad26-based Vaccines in the Pediatric Population
Ad26.RSV.preF in Toddlers: see above under subheading of Th1/Th2 profile.
Ad26.ZEBOV in Children and Adolescents
ZABDENO® (Ad26.ZEBOV; suspension for injection) was recently approved in the EU, as part
of the ZABDENO, MVABEA® (MVA-BN-Filo; suspension for injection) vaccine regimen
indicated for active immunization for prevention of disease caused by Ebola virus (Zaire
ebolavirus species) in individuals ≥1 year of age(ZABDENO SmPC, 2020).
Adverse reactions following ZABDENO vaccination reported in children 1 to 17 years of age are
provided in Table 1.
Table 1: 
Adverse Reactions Reported in Children 1 to 17 Years of Age Following Vaccination with
ZABDENO
System Organ Class 
Frequency  
Adverse Reaction
Metabolism and nutrition disorders 
very common  
decreased appetite
Psychiatric disorders 
very common  
irritability
Gastrointestinal disorders 
common 
vomiting, nausea
Musculoskeletal and connective tissue 
disorders
common 
arthralgia, myalgia
General disorders and administration 
site conditions 
very common  
Fatigue, decreased activity, injection site pain
common 
Pyrexia, injection site pruritus, injection site
swelling, injection site erythema

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The approval of ZABDENO in pediatric individuals was based on pooled safety data from 2 Ebola
clinical studies (Phase 2 study VAC52150EBL2002 and Phase 3 study VAC52150EBL3001). A
total of 839 participants are included in this pooling of which 649 participants (253 aged 12 to 17
years, 252 aged 4 to 11 years and 144 aged 1 to 3 years) received the Ad26.ZEBOV (5x1010 vp)
vaccine as Dose 1 of the heterologous Ebola vaccine regimen, which also includes MVA-BN-Filo
(1x108 infectious units [Inf.U]) as Dose 2, with an interval of at least 28 days between the doses.
In these studies, 189 participants were enrolled to receive the control regimen (placebo [N 45] or
active control [MenACWY; N 144]).
No deaths, serious adverse events (SAEs) considered related to study vaccine or adverse events
(AEs) leading to discontinuation were reported in children or adolescents.
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.0
2.3.1 Risks Related to Study Participation
The following potential risks for Ad26.COV2.S  will be monitored during the study and are
specified in the protocol:
Risks Related to Ad26.COV2.S
Interim analyses after the first dose of blinded safety data from approximately 800 participants of
18-55 years of age and 65 years and older in study COV1001 showed that local AEs were observed
in 58% and 27% of participants, respectively. Solicited systemic AEs were reported in 64% and
36% of participants, respectively. Fevers occurred in both cohorts in 19% (5% Grade 3) and 4%
(0% Grade 3), respectively, were mostly mild or moderate, and resolved within 1 to 2 days after
vaccination. The most frequent local AE was injection site pain and the most frequent solicited
AEs were fatigue, headache and myalgia. The safety and reactogenicity profiles of 2 dose levels,
5x1010 vp and 1x1011 vp were considered acceptable.
For the most comprehensive nonclinical information regarding Ad26.COV2.S, refer to the latest
version of the IB.0
Sites should advise participants that side effects include fever as well as injection site pain,
headache, fatigue, myalgia, and nausea per the current ICF.
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

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thrombosis, in combination with thrombocytopenia. These cases occurred approximately
1-2 weeks following vaccination, mostly in women under 60 years of age. Thrombosis in
combination with thrombocytopenia can be fatal. The exact physiology of TTS is unclear. TTS is
considered an important identified risk for Ad26.COV2.S. Participants should be instructed to seek
immediate medical attention if they develop symptoms such as shortness of breath, chest pain, leg
swelling, persistent abdominal pain, severe or persistent headaches, blurred vision, 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 Hematology0, British Society of
Haematology - Expert Haematology Panel0, CDC0). 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 Janssen
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
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 and Section 8.3.6.1), which
may facilitate diagnosis and clinical management of the event.
Risks Related to Adenoviral-vectored Vaccines
The clinical AdVac® safety database (report version 5.0, dated 10 April 2020, cut-off 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
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-

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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 toward an increase in the frequency of some local AEs with an increase in Ad26
dose, ie, injection site pain (18.7% of participants at the 0.8×1010 vp dose level, 38.7% of
participants at the 2×1010 vp dose level, 52.0% of participants at the 5×1010 vp dose level, and
77.1% of participants at the 1×1011 vp dose level), and to a lesser extent injection site swelling
(6.7%, 2.7%, 9.3%, and 17.6%, respectively). Injection site warmth was not collected at the
0.8×1010 vp and the 2×1010 vp dose level. The frequency of injection site warmth at the 5×1010 vp
and the 1×1011 vp dose level was 19.5%, and 26.7%, respectively. This trend needs to be
interpreted with caution since the participants in the lower dose groups (0.8×1010 vp and 2×1010 vp
dose level) were all from a single study (VAC52150EBL3002), and the majority of the participants
in the highest dose group (1×1011 vp dose level) were also from a single study
(VAC18193RSV2003).
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).
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 toward 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

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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).
For Ad26, the most frequently reported unsolicited AE in children 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.
General Risks Related to Vaccination
In general, IM injection may cause local itching, warmth, pain, tenderness, erythema/redness,
induration, swelling, arm discomfort, or bruising of the skin. Participants may exhibit general signs
and symptoms associated with IM injection of a vaccine and/or placebo, including fever, chills,
rash, myalgia, nausea/vomiting, headache, dizziness, arthralgia, general itching, and fatigue. These
side effects will be monitored butare generally short-term. Instructions regarding use of antipyretic
medication can be found in Section 6.9.
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 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) will be excluded from the study.
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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After each vaccination, participants will remain at the study site for at least 1 hour and will be
closely observed by study staff. Necessary emergency equipment and medications must be
available in the clinic to treat severe allergic reactions.
Pregnancy and Birth Control
The effect of the study vaccine on a fetus or on a nursing baby is unknown.
Given the limited number of incident pregnancies in the clinical studies with Ad26-based vaccines
in the AdVac® safety database report (HIV vaccine: 20 pregnancies in participants and 10 in
partners of participants; Ebola vaccine: 32 pregnancies in participants and 13 in partners of
participants), it is not possible at present to draw firm conclusions on the safety of the vaccines
when administered around the time of conception or prior to the initiation of the pregnancies. There
is currently no concerning pattern of AEs in the pregnancies initiated around the time of
vaccination or after exposure to the Ad26-based vaccines in the Janssen vaccines clinical
development programs.
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 vaccination  (See Section 5.1, Inclusion Criteria).
Women who are pregnant or breastfeeding 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).
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.
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,0,0,0,0,0 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, Background). Participants in the present study will be informed
of the theoretical risk of disease enhancement in the ICF. Furthermore, 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). This active and passive
surveillance system for detection of COVID-19 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

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will receive individual level unblinded data pertaining to study VAC31518COV2001 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 immediately inform the SMC  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 SMC will be described in
the Statistical Analysis Plan (SAP).
Unknown Risks
There may be other risks that are not known. If any significant new risks are identified, the
investigators and participants will be informed.
2.3.2 Benefits of Study Participation
Participants may benefit from clinical testing and physical examination.
The clinical benefits of Ad26.COV2.S have yet to be established. Currently, there are no effective
vaccines for the prevention of COVID-19, and no efficacy can be concluded from current data.
The overall benefit and risk balance for individual participants thus cannot be ascertained.
Participants must be informed that this vaccine has not yet been proven to be effective, and it
should be assumed that it is not the case until clinical studies are conducted to demonstrate its
effectiveness.
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.
 After each vaccination, participants will remain at the study site for at least 1 hour 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.

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 From the time of local approval of protocol Amendment 5 onwards, TTS is considered to
be an AESI (Section 8.3.6). Suspected AESIs (thrombotic events and thrombocytopenia
[defined as platelet count below 150,000/µL0]) 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.
 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.
 
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 hematology laboratory assessments (see Section 10.2) will be performed for
adults as indicated in the SoA (see Section 1.3).
 
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
SMC reviews all safety data (see Section 10.3.6).
 
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.
 
For the adolescent cohort, an SMC will review safety data of sentinels before proceeding
to enrollment of the full cohort (as detailed in Section 4.1).
3. 
OBJECTIVES AND ENDPOINTS
ADULTS
Objectives 
Endpoints
Primary
 
To assess the humoral immune response to
3 dose levels (5x1010 virus particle (vp),
2.5x1010 vp, 1.25x1010 vp) of Ad26.COV2.S,
administered intramuscularly (IM) as a
2-dose schedule at a 56-day interval, 28 days
after Vaccination 2.
 
Serological response to vaccination as
measured by virus neutralization assay (VNA)
titers and enzyme-linked immunosorbent assay
(S-ELISA, 
ELISA 
Units/mL 
[EU/mL]),
28 days after Vaccination 2.
 
Antibody geometric mean titers (GMTs)
(VNA) and geometric mean concentrations
(GMCs) 
(S-ELISA), 
28 days 
after
Vaccination 2.
 
To assess the humoral immune response to
2 dose levels (1 x1011 vp and 5x1010 vp) of
Ad26.COV2.S, administered IM as a single
vaccination, 28 days after Vaccination 1.
 
Serological response to vaccination as
measured by VNA titers and ELISA (S-ELISA,
EU/mL), 28 days after Vaccination 1.
 
Antibody 
GMTs 
(VNA) 
and 
GMCs
(S-ELISA), 28 days after Vaccination 1.

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Objectives 
Endpoints
 
To assess the humoral immune response to
Ad26.COV2.S at the 5x1010 vp dose level,
administered IM as a 2-dose schedule at a
28-day and at an 84-day interval, 28 days
after Vaccination 2.
 
Serological response to vaccination as
measured by VNA titers and ELISA (S-ELISA,
EU/mL), 28 days after Vaccination 2.
 
Antibody 
GMTs 
(VNA) 
and 
GMCs
(S-ELISA), 28 days after Vaccination 2.
 
To assess the safety and reactogenicity of
Ad26.COV2.S, administered IM at several
dose levels, as a 2-dose or a single-dose
schedule.
 
Solicited local and systemic adverse events
(AEs) for 7 days after each vaccination.
 
Unsolicited AEs for 28 days after each
vaccination.
 
Serious adverse events (SAEs) and adverse
events of special interest (AESIs) throughout
the study (from first vaccination until end of the
study).
Secondary
 
To assess the anamnestic response to antigen
presentation of Ad26.COV2.S at the
1.25x1010 vp dose level, administered
4 months after Vaccination 2 (2-dose
schedule) or 6 months after a Vaccination 1
(single-dose schedule), 7days after antigen
presentation (Groups 1-5, 7and 9).
 
Serological response to vaccination as
measured by VNA titers and ELISA (S-ELISA,
EU/mL), 7 days after antigen presentation.
 
Antibody 
GMTs 
(VNA) 
and 
GMCs
(S-ELISA), 7 days after antigen presentation.
 
To assess the safety and reactogenicity of
antigen presentation of Ad26.COV2.S at the
1.25x1010 vp dose level, administered
4 months after Vaccination 2 (2-dose
schedule) or 6 months after a Vaccination 1
(single-dose schedule)(Groups 1-5, 7and 9).
 
Solicited local and systemic AEs for 7 days
after antigen presentation.
 
Unsolicited AEs for 28 days after antigen
presentation.
 
SAEs and AESIs throughout the study (from
antigen presentation until end of the study).
 
To assess the humoral immune response to
Ad26.COV2.S across all groups, at all blood
collection timepoints.
 
Neutralizing antibody titers to the wild-type
SARS-CoV-2 virus expressing S protein as
measured by VNA, at all blood collection
timepoints.
 
Binding antibody titers to SARS-CoV-2 or
individual 
SARS-CoV-2 
proteins 
(eg,
S protein) as measured by ELISA, at all blood
collection timepoints.

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Objectives 
Endpoints
Exploratory
 
To assess the cellular immune response to
Ad26.COV2.S at different dose levels in a
subset of participants (Groups 1 to 6) at
selected blood collection timepoints.
 
T helper (Th) 1 and Th2 immune responses as
assessed by Flow cytometry after SARS-CoV-
2 S protein peptide stimulation of peripheral
blood mononuclear cells (PBMC) and
intracellular staining (ICS) including cluster of
differentiation (CD) 
4+/CD8+, 
interferon
gamma (IFNγ), interleukin (IL)-2, tumor
necrosis factor alpha (TNFα), IL-4, IL-5, IL-13,
and/or other Th1/Th2 markers.
 
To further assess the humoral immune
response to Ad26.COV2.S.
 
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).
 
Functional 
and 
molecular 
antibody
characterization including Fc-mediated viral
clearance, avidity, Fc characteristics, Ig
subclass and IgG isotype.
 
Passive transfer: analysis of immune mediators
correlating 
with 
protection 
against
experimental SARS-CoV-2 challenge in a
suitable animal model.
 
Analysis of neutralizing antibodies against
emerging SARS-CoV-2 variants.
 
Adenovirus neutralization as measured by
VNA.
 
To assess the occurrence of symptomatic
molecularly confirmed COVID-19 and
severity of COVID-19 signs and symptoms.
 
The number of participants with molecularly
confirmed COVID-19.
 
Presence and severity of COVID-19 signs and
symptoms as measured by Symptoms of
Infection with Coronavirus-19 (SIC).
 
To examine the immune response in
vaccinated individuals after natural SARS-
CoV-2 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
pseudovirions expressing S protein).
 
SARS-CoV-2-binding antibodies measured by
ELISA: Analysis of antibodies binding to the
SARS-CoV-2 S protein.
 
Analysis of gene expression by ribonucleic acid
(RNA) transcript profiling.

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Objectives 
Endpoints
 
To assess for the occurrence of
asymptomatic SARS-CoV-2 infection.
 
The number of asymptomatic participants with
positive 
non-S 
protein 
ELISA 
(eg,
nucleocapsid [N] protein ELISA), as feasible.
 
The number of asymptomatic participants with
a SARS-CoV-2 positive RT-PCR test.
 
To assess hematology laboratory parameters
after Ad26.COV2.S administration.
 
Lupus anticoagulants, anti-β2 glycoprotein,
anti-cardiolipin, D-dimers, anti-PF4.
 
To assess the correlation between the
binding antibody (ELISA) titers and
neutralizing antibody (VNA) titers to
SARS-CoV-2, in a subset of participants at
selected timepoints.
 
Correlation 
between 
ELISA 
(S-ELISA;
EU/mL) and VNA (wild-type virus [wt]VNA
and/or pseudovirion [ps]VNA) titers at selected
timepoints.
ADOLESCENTSa
Objectives 
Endpoints
Primary
 To assess the safety and reactogenicity of a
single dose of Ad26.COV2.S, administered
IM at the 2.5x1010 vp dose level.
 
Solicited local and systemic AEs for 7 days
after vaccination.
 
Unsolicited AEs for 28 days after
vaccination.
 
SAEs (incl. Multisystem Inflammatory
Syndrome in Children [MIS-C]) and AESIs
throughout the study (from first vaccination
until end of the study).
Secondary
 
To assess the humoral immune response to a
single dose of Ad26.COV2.S at the 2.5x1010
vp dose level, administered IM.
 
Serological response to vaccination as
measured by VNA titers and ELISA (S-ELISA,
EU/mL), 28 days after vaccination.
 
Antibody GMTs (VNA) and GMCs (S-
ELISA), 28 days after vaccination.
 
To assess the humoral immune response to
Ad26.COV2.S at the 2.5x1010 vp dose level,
at all blood collection timepoints.
 
Neutralizing antibody titers to the wild-type
SARS-CoV-2 virus expressing S protein as
measured by VNA, at all blood collection
timepoints.
 
Binding antibody titers to SARS-CoV-2 or
individual 
SARS-CoV-2 
proteins 
(eg,
S protein) as measured by ELISA, at all blood
collection timepoints.
a Not applicable in Germany and the Netherlands

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Objectives 
Endpoints
Exploratory
 
To further assess the humoral immune 
response to Ad26.COV2.S. 
 
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).
 
Functional 
and 
molecular 
antibody
characterization including Fc-mediated viral
clearance, avidity, Fc characteristics, Ig
subclass and IgG isotype.
 
Passive transfer: analysis of immune mediators
correlating 
with 
protection 
against
experimental SARS-CoV-2 challenge in a
suitable animal model.
 
Analysis of neutralizing antibodies against
emerging SARS-CoV-2 variants.
 
Adenovirus neutralization as measured by
VNA.
 
To assess the occurrence of symptomatic 
molecularly confirmed COVID-19 and 
severity of COVID-19 signs and symptoms.
 
The number of participants with molecularly
confirmed COVID-19.
 
Presence and severity of COVID-19 signs and
symptoms as measured by Symptoms of
Infection with Coronavirus-19 (SIC).
 
To examine the immune response in 
vaccinated individuals after natural SARS- 
CoV-2 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
pseudovirions expressing S protein).
 
SARS-CoV-2-binding antibodies measured by
ELISA: Analysis of antibodies binding to the
SARS-CoV-2 S protein.
 
Analysis of gene expression by ribonucleic acid
(RNA) transcript profiling.
 
To 
assess 
for 
the 
occurrence 
of 
asymptomatic SARS-CoV-2 infection. 
 
The number of asymptomatic participants with
positive 
non-S 
protein 
ELISA 
(eg,
nucleocapsid [N] protein ELISA), as feasible.
 
The number of asymptomatic participants with
a SARS-CoV-2 positive RT-PCR test.
 
To assess coagulation-related parameters at 
selected blood sample collection timepoints. 
 
platelet factor 4-heparin complex (anti-PF4)
antibodies.
HYPOTHESIS
No formal hypothesis testing will be performed in this study.

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4. 
STUDY DESIGN
4.1. 
Overall Design
This is a randomized, double-blind, placebo-controlled, multicenter, Phase 2a study in healthy
adolescents aged 12 to 17 years, inclusive, adults aged 18 to 55 years inclusive, and adults in good
or stable health aged 65 years and older. Countries may participate in the adult and adolescent
portions of the study or they may participate in either the adult or adolescent portion.
In adults, the safety, reactogenicity, and immunogenicity of Ad26.COV2.S  in 1- and 2-dose
vaccination regimens followed by antigen presentation  after 4 months (2-dose regimen) or
6 months (single-dose regimen), will be evaluated across a range of dose levels and vaccination
intervals. At the start of this study for adults, interim safety data through Day 29 and interim
immunogenicity data, including VNA and ELISA through Day 29 and Day 15 Th1/Th2 response,
from Cohort 1a of the first-in-human study VAC31518COV1001 in adults will be available.
In adolescents, the safety, reactogenicity, and immunogenicity of a single dose of Ad26.COV2.S
will be evaluated.
Participants will receive Ad26.COV2.S or a placebo. In adults, 4 dose levels of Ad26.COV2.S will
be administered IM: 1x1011 vp, 5x1010 vp, 2.5x1010 vp, and 1.25x1010 vp. Adolescents will be
administered 2.5x1010 vp.
With the implementation of protocol Amendment 5, enrolled adult participants will be unblinded
and those who initially received placebo in the primary vaccine regimen will be offered 2 doses of
the Ad26.COV2.S vaccine at 5×1010 vp (adult Groups 6, 8 and 10).
ADULTS
A target of approximately 550 adult participants will initially be enrolled in this study in a blinded
manner and randomly assigned to 1 of 10 groups to receive 1- or 2-doses of active Ad26.COV2.S
vaccine or placebo at a dose of 1x1011 vp, 5x1010 vp, 2.5x1010 vp, or 1.25x1010 vp and at a 28-day,
56-day or 84-day interval.
A single antigen presentation injection with 1.25x1010 vp Ad26.COV2.S (Groups 1-5, 7, 9) or
placebo (Groups 6, 8, 10) will be administered 4 months after the second vaccination (ie, 4 months
post-vaccination 2 in the 2-dose regimens and 6 months after Vaccination 1 in the 1-dose
regimens).
After each vaccination, all participants will remain under observation at the study site for at least
1 hour to monitor for the presence of any acute reactions and solicited events.
With implementation of protocol Amendment 5, participants who were initially enrolled to receive
placebo (Groups 6, 8 and 10), will be offered a 2-dose (28-day interval) Ad26.COV2.S vaccination
regimen at the 5x1010 vp dose level. In October 2020, the study was temporarily paused because
one of the pausing rules was met in study COV3001. When the pause was lifted, most of the
participants in Groups 7-8 had missed their visit window for Vaccination 2 (Visit 4), rendering the

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intent of the 28-day vaccination interval in these groups futile. The goal in offering 2 doses of
study vaccine to those participants who initially received placebo in this study is to recreate this
28-day vaccination interval, and to restore the objectives associated with this interval. The original
28-day interval target group was 75 participants. Hence the total number of placebo recipients
from Groups 6, 8 and 10 (target n 75) is intended to fulfill the original target enrollment for
Group 7.
With implementation of protocol Amendment 5, all adult participants will be unblinded to the
primary vaccination regimen, and, adults who received placebo in the primary vaccine regimen,
will receive a 2 dose active Ad26.COV2.S vaccine regimen at a 28-day interval and at a dose level
of 5x1010 vp, in an open-label manner. Per group, approximately one third of participants will be
65 years and older.
Adult participants who received the active vaccine in the primary vaccine regimen will be followed
up for 12 months after vaccination 2; adult participants who received placebo in the primary
vaccine regimen will be followed up for 6 months after receipt of the unblinded vaccination 1 (ie,
receipt of the first active vaccine following unblinding).
Groups 1-6
400 participants (75 participants per active vaccine group, 25 in the placebo group) will be
randomized in parallel in a 3:3:3:3:3:1 ratio to 1 of 6 vaccination groups. Participants will receive
a 2-dose (56-day interval, Groups 1-3) vaccination regimen at different dose levels (5×1010 vp,,
2.5x1010 vp, and 1.25x1010 vp) or single-dose vaccination regimen (Groups 4-5) at different dose
levels (1×1011 vp, 5x1010 vp), or placebo (Group 6). For blinding purposes, participants in the
single-dose groups (Groups 4-5) will receive a placebo vaccination on Day  57. Additional
exploratory cellular immunogenicity evaluations (PBMC) will be performed in a subset of
participants (21/group in Groups 1-5, 7 in Group 6; at selected sites). Participants in Group 6 who
received 2-doses of placebo in the primary vaccine regimen will receive 2 doses of active vaccine
at a single dose level of 5x1010 vp, at a 28-day interval.
Groups 7-8
75 participants (50 participants in the active vaccine group, 25 in the placebo group) will be
randomized in parallel in a 2:1 ratio, to 1 of 2 vaccination groups. Participants will receive a 2 dose
(28-day interval, Groups 7a) vaccination regimen at a 5×1010 vp dose level or placebo (Group 8).
Participants in Group 8 who received 2-doses of placebo in the primary vaccine regimen will
receive 2 doses of active vaccine at a single dose level of 5x1010 vp, at a 28-day interval.
a Group 7 and 8: only 2 subjects (one in each group) are vaccinated at a 28-day interval, due to a study pause

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Groups 9-10
75 participants (50 participants in the active vaccine group, 25 in the placebo group) will be
randomized in parallel in a 2:1 ratio, to 1 of 2 vaccination groups. Participants will receive a 2 dose
(84-day interval, Group 9) vaccination regimen at a 5×1010 vp dose level or placebo (Group 10).
Participants in Group 10 who received 2-doses of placebo in the primary vaccine regimen will
receive 2 doses of active vaccine at a single dose level of 5x1010 vp, at a 28-day interval.
The vaccination schedules are presented in Table 2.

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Table 2: 
Vaccination Schedules Adults
Adults ≥18 to ≤55 Years and ≥65 Years
Group  N 
Day 1 
(Vaccination 1) 
Ad26.COV2.S dose 
level / placebo 
Day 29 
(Vaccination 2) 
Ad26.COV2.S dose 
level / placebo 
Day 57 
(Vaccination 2) 
Ad26.COV2.S dose 
level / placebo 
Day 85 
(Vaccination 2) 
Ad26.COV2.S dose 
level / placebo 
4 Months Post-Vaccination 2
(Injection 3)1 
Ad26.COV2.S dose 
level/ placebo 
Unblinded Vaccination 1 
Ad26.COV2.S  
dose level 
Day 29 Post Unblinded Vaccination 1
(Unblinded Vaccination 2)
Ad26.COV2.S dose level
1 
75 
5x1010 vp 
5x1010 vp 
1.25x1010 vp 
- 
-
2 
75 
2.5x1010 vp 
2.5x1010 vp 
1.25x1010 vp 
- 
-
3 
75 
1.25x1010 vp 
1.25x1010 vp 
1.25x1010 vp 
- 
-
4 
75 
1x1011 vp 
Placebo 
1.25x1010 vp2 
- 
-
5 
75 
5x1010 vp 
Placebo 
1.25x1010 vp2 
- 
-
6 
25 
Placebo 
Placebo 
Placebo 
5x1010 vp 
5x1010 vp
7 
50 
5x1010 vp 
5x1010 vp 
1.25x1010 vp 
- 
-
8 
25 
Placebo 
Placebo 
Placebo 
5x1010 vp 
5x1010 vp
9 
50 
5x1010 vp 
5x1010 vp 
1.25x1010 vp 
- 
-
10 
25 
Placebo 
Placebo 
Placebo 
5x1010 vp 
5x1010 vp
N  number of participants; vp  virus particles.
1. Antigen presentation
2. 6 Months after Vaccination 1 in the single dose regimens (Groups 4 and 5).

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ADOLESCENTSa
From the time of protocol Amendment 2, adolescent participants (12 to 17 years of age, inclusive)
were to be enrolled in a randomized and staggered manner.
The safety profile of Ad26.COV2.S in adolescents was planned to be assessed separately by age
group and by escalating dose, with the 2 adolescent age groups (12 to 15 years and 16 to 17 years)
assessed independently and enrollment progressing in a sequential manner. The safety and
tolerability of the Ad26.COV2.S vaccine was to be assessed in the first instance in a group of
sentinels at Day 4 post-vaccination, and if acceptable, in the larger safety cohort at Day 8
post-vaccination. The Day 4 and Day 8 post-vaccination safety profiles of the Ad26.COV2.S
vaccine at the 2.5x1010 vp dose level in the sentinel and safety cohorts was to be assessed in
participants at 16 to 17 years of age, by the Safety Monitoring Committee (SMC) before
progressing to enrollment of the sentinel group of participants at 12 to 15 years of age (see
Figure 7).
The first doses of Ad26.COV2.S study vaccine at 2.5x1010 vp were to be administered to a sentinel
group of 11 participants in Groups A-C (randomly assigned at a ratio of 5:5:1 to Ad26.COV2.S,
with 5 each from Groups A and B, and 1 participant in Group C to receive placebo), to monitor
for any unexpected severe adverse reactions. The sentinel participants were to be vaccinated at
least 1 hour apart even if enrolled at different study sites. A telephone call was to be made to each
of these 11 sentinel participants on Day 4 post-vaccination to collect safety data, which was to
include solicited and unsolicited AEs and SAEs. The collected data were to be reviewed in a
blinded manner by the principal investigator (PI) and the sponsor's study responsible
physician/scientist (SRP/S). Randomization and vaccination of additional participants were to be
halted until the review is completed. The SMC was to review the unblinded Day 4 post-vaccination
safety data, including solicited and unsolicited AEs and SAEs, and if the safety profile was found
to be acceptable, a safety cohort of 22 participants in Groups A-C (randomly assigned at a ratio of
5:5:1 to Ad26.COV2.S, with 10 each from Groups A and B, and 2 participants in Group C to
receive placebo) was to be enrolled. The Day 8 post-vaccination safety data from both sentinel
groups, including solicited and unsolicited AEs and SAEs, was also to be reviewed by the SMC,
and in the absence of any safety concerns, the enrollment and vaccination of the remainder of the
participants for Groups A-C (49 participants) in this age group can proceed, and simultaneously,
sentinel enrollment in Groups D-F (to receive Ad26.COV2.S study vaccine at 5x1010 vp) was to
start. In addition, enrollment of the younger age group of adolescents (12-15 years, inclusive) was
to proceed for Groups A-C.
After vaccination, all participants were to remain under observation at the study site for at least 1
hour (including participants in the Sentinel and Safety Cohort) to monitor for the presence of any
acute reactions and solicited events.
Following the initial vaccination of the first 33 adolescent participants (sentinels + safety cohort)
in the 16-17 year old age group at a dose of 2.5x1010 vp enrolled in this study, the entire COVID-19
vaccine program was paused to evaluate a safety concern of TTS in adults. During this pause, the
a Not applicable in Germany and the Netherlands

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safety and immunogenicity data for these 33 adolescent participants was evaluated (see current
version of Investigator’s Brochure0). While the IDMC endorsed further enrollment of adolescents
that would receive Ad26.COV2.S at a 5x1010 vp dose level, the sponsor has decided not to evaluate
the 5x1010 vp dose level in pediatric participants based on the immunogenicity data from the
2.5x1010 vp dose in Study VAC31518COV2001 and has decided to redesign the pediatric studies.
Study VAC31518COV3006 will focus on adolescent participants 12-17 years of age, and no
further enrollment of this age group will take place in this study.
Therefore, per protocol Amendment 6, the 33 adolescents already enrolled at the time of
Amendment 6 will continue to be followed in this study in accordance with the planned Schedule
of Activities (Sections 1.3.5 and 1.3.6), but no further vaccination with Ad26.COV2.S will occur
in Groups A and B. Participants in Group C will receive a single dose of Ad26.COV2.S at
2.5x1010 vp.
With the implementation of Amendment 6, the 33 adolescent participants will be unblinded to the
primary vaccination regimen. At this time, adolescents who received placebo (Group C) will
receive a single dose of Ad26.COV2.S at the 2.5 x1010 vp dose level in an open-label manner.
Table 3: 
Vaccination Schedules –Adolescents
Adolescents: 12 to 17 Years of Age, Inclusive
Group  
Day 1 
(Vaccination 1) 
Ad26.COV2.S  
dose level 
or placebo 
With Implementation of Amendment 6
(At approximately 6 Months
of Study Participation)
(Unblinded Vaccination 1)
Ad26.COV2.S dose level
A 
2.5x1010 vp 
-
B 
2.5x1010 vp 
-
C 
Placebo 
2.5x1010 vp
vp  virus particles

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Figure 7: 
Sentinel Decision Tree for Staggered Enrollment in Groups A-F –Adolescents
*
For more information on the SMC, see Section 10.3.6.
Following the initial vaccination of the first 33 adolescent participants (sentinels + safety cohort) in the 16 17 year old age group at a dose of 2.5x1010 vp enrolled in this study,
the entire Ad26.COV2.S COVID 19 vaccine program was paused to evaluate a safety concern of TTS in adults. During this pause, the safety and immunogenicity data for these
33 adolescent participants was evaluated. While the IDMC endorsed further enrollment of adolescents that would receive Ad26.COV2.S at a 5x1010 vp dose level, the sponsor
has decided not to evaluate the 5x1010 vp dose level in pediatric participants based on the immunogenicity data from the 2.5x1010 vp dose and has decided to redesign the
pediatric studies. Study VAC31518COV3006 will focus on adolescent participants 12 17 years of age, and no further enrollment of this age group will take place in this study.

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Therefore, per protocol Amendment 6, the 33 adolescents already enrolled at the time of Amendment 6 will continue to be followed in this study in accordance with the planned
Schedule of Activities, but no further vaccination with Ad26.COV2.S will occur in Groups A and B. Participants in Group C will receive a single dose of Ad26.COV2.S at
2.5x1010 vp.

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Study Duration
The study duration from screening until the last follow-up visit will be approximately 15 months
for adult participants in Groups 1-5, approximately 14 months for adult participants in Group 7,
and approximately 16 months for adult participants in Group 9. The study duration for adult
participants in Groups 6, 8 and 10 is approximately 15 months. For the majority of participants in
Group 7, whose vaccination 2 was delayed due to the study pause, study duration will be
approximately 15 months. For adults, the study will consist of a 28-day screening phase, a 1 to
3-month vaccination phase depending on the vaccination interval and a 12-month follow-up
(which includes an antigen presentation 4 months after vaccination 2).
The study duration from screening until the last follow-up visit will be approximately 13 months
per adolescent participant in Groups A-C.
If a participant is unable to complete the study, but has not withdrawn consent, an early exit visit
will be conducted. The end of study is considered as the last visit for the last participant in the
study.
Study Procedures
For each group, safety will be assessed by collection of solicited local (at injection site) and
systemic AEs, unsolicited AEs, and SAEs. 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. For adults, also hematology laboratory samples will be taken.
After each vaccination, participants will remain under observation at the study site for at least 1
hour for 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 signs
and symptoms in a diary for 7 days post vaccination.
The reporting periods of AEs, SAEs, and special reporting situations are detailed in Section 8.3,
Adverse Events, Serious Adverse Events, and Other Safety Reporting. Reporting periods for
concomitant therapy are outlined in Section 6.9, Prestudy and Concomitant Therapy.
A final safety follow-up visit is foreseen 12 months after Vaccination 2 (adults) and 12 months
after Vaccination 1 (adolescents).
For the assessment of COVID-19, and to assess possible ERD, participants will be provided with
a booklet including a daily question on whether they are experiencing COVID-19-like symptoms,
and for documentation of body temperature and pulse oximetry results. Baseline pulse oximetry
will be conducted at Visit 1. If a participant meets the prespecified criteria for (suspected)

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COVID-1915 (as detailed in Section 8.1.2.1), procedures should be followed as detailed in
Section 8.1.2.
The occurrence of asymptomatic SARS-CoV-2 infection will be assessed by a non-S-protein
ELISA (eg, SARS-CoV-2 N-ELISA), as feasible (see Section 8.1.3, Asymptomatic SARS-CoV-2
Infection) and by collection of positive RT-PCR results for SARS-CoV-2, regardless where the
testing was performed (under the auspices of the study or through a private or public laboratory
independent of the study).
From all participants, blood samples will be collected at selected timepoints indicated in
Section 1.3, Schedule of Activities for humoral immunogenicity assessments, with an emphasis
on neutralizing and binding antibody responses. In a subset of adult participants (approximately
112; 21 participants per group in Groups 1-5, 7 participants in Group 6; at selected sites), cellular
immunogenicity (PBMC) will be assessed at selected timepoints. Further details about the
immunogenicity assessments are provided in Section 8.1.1.
Initially, an internal DRC was commissioned for this study. However, an independent IDMC was
installed to include VAC31518COV2001 on 29 October 2020, and the IDMC kickoff for review
was held on 15 December 2020. In light of the transition of DRC to IDMC, when the term SMC
is mentioned, it can refer to either. Refer to Section 10.3.6 for details.
The planned interim, primary, and final analyses are detailed in Section 9.5, Planned Analysis.
A diagram of the study design is provided in Section 1.2, Schema.
4.2. 
Scientific Rationale for Study Design
Dose Level Selection
The rationale behind the selection of the dose levels is described in Section 4.3, Justification for
Dose.
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.
15 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.

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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.
Biomarker Collection
For participants with a positive test result for SARS-CoV-2 infection, biomarker analysis
(PAXgene, RNA-seq) will be performed for evaluation of COVID-19 cases and to explore
potentially informative biomarkers, eg, those associated with severe COVID-19.
4.2.1. 
Study-Specific Ethical Design Considerations
Potential participants and their legal guardians (for adolescents as appropriate) will be fully informed
of the risks and requirements of the study and, during the study, they will be given any new
information that may affect their decision to continue participation. They will be told that their
consent/assent 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.
Potential participants will only be enrolled ifparticipants, and their legal guardians (as appropriate
for adolescents) are fully able to understand the risks, benefits, and potential AEs of the study, and
provide their consent/assent voluntarily.
The primary ethical concern is that this study will be performed in adult and adolescent 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. The potential risk to adolescent
participants in this study include study vaccine exposure, with the potential for AEs. See
Section 4.3 for the justification for dose level to be used in adolescents. See Section 2.3, Benefit-
Risk Assessment for details on potential and known benefits and risks, and for the safety measures
taken to minimize risk to participants.
When referring to the signing of the ICF, the terms legal guardian and legally acceptable
representative refer to the legally appointed guardian(s) of the child with authority to authorize
participation in research. For each participant, his or her parent(s) (preferably both parents, if
available) or legally acceptable representative(s), as required by local regulations, must give written
consent (permission) according to local requirements after the nature of the study has been fully
explained and before the performance of any study-related assessments. Assent should be obtained
from children (minors) capable of understanding the nature of the study, typically participants
7years of age and older, depending on the local regulations and practice. For the purposes of this
study, all references to participants who have provided consent (and assent as applicable) refers to
the participants and his or her parent(s) or the participant’s legal guardian(s) or legally acceptable
representative(s) who have provided consent according to this process. Minors who assent to a study
and later withdraw that assent should not be maintained in the study against their will, even if their
parents still want them to participate.

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The total blood volume to be collected from adults 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,0,0 as well as the European
Commission guidelines of 500 mL per donation and 3 L per consecutive 12 month period.0
The total blood volume to be collected from adolescents is considered acceptable according to
guidelines0,0,0 and will not exceed 40 mL per blood draw or 120 mL over a 30-day period.
4.3. 
Justification for Dose
Adults
The regimen and dose selection in this study are aimed at providing information on safety and
immunogenicity of multiple 2-dose and single-dose schedules of the Ad26.COV2.S  vaccine,
including lower dose levels (ie, 2.5x1010 vp, and 1.25x1010 vp) compared to the dose levels used
in the first-in-human study (VAC31518COV1001). In October 2020, the study was temporarily
paused because one of the pausing rules was met in study COV3001. When the pause was lifted,
most of the participants in Groups 7-8 had missed their visit window for Vaccination 2 (Visit 4),
rendering the intent of the 28-day vaccination interval in these groups futile. The goal in offering
2 doses of study vaccine to those participants who initially received placebo in this study is to
recreate this 28-day vaccination interval, and to restore the objectives associated with this interval.
The original 28-day interval target group was 75 participants. Hence the total number of placebo
recipients from Groups 6, 8 and 10 (target n 75) is intended to fulfill the original target enrollment
for Group 7.
Four dose levels will be evaluated: 1x1011 vp, 5x1010 vp, 2.5x1010 vp, and 1.25x1010 vp.
 The evaluation of the 2.5x1010 vp vaccine dose level will provide insight (immunogenicity)
in the possibility to use this dose level for dose sparing.
 The evaluation of the 1.25x1010 vp vaccine dose level will allow for the assessment of
immunogenicity of this dose level which is representative of the vaccine titer of the 5x1010
vp dose level at the end of the foreseen shelf-life in the context of emergency use with
storage at 2-8 °C.
By lowering the dose level (ie, to 2.5x1010 vp and 1.25x1010 vp), there will also be a potential to
immunobridge to a lower dose level regimen, should the efficacy study (VAC31518COV3001)
provide evidence of an immune correlate of protection.
The regimen is selected based on previous preclinical and clinical data from other Ad26-based
vaccines.

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Note that 2 clinical studies, VAC52150EBL3002 (Ebola) and IPCAVD001 (HIV), showed that
Ad26-based vaccines induce a potent humoral and cellular immune response at doses equivalent
or lower than 1.25x1010 vp.
Adolescents
Available platform data, as well as safety data from the VAC31518COV1001 study, (see
Section 2.2 and Section 2.3.1) supported initiating evaluation of Ad26.COV2.S in adolescents
aged 12 to 17 years, inclusive, with the dose levels as proposed. From the time of protocol
Amendment 2, in Groups A-F, 2 dose levels were to be evaluated: 2.5x1010 vp and 5x1010 vp.
Following the initial vaccination of the first 33 adolescent participants (sentinels + safety cohort)
in the 16 17 year old age group at a dose of 2.5x1010 vp enrolled in this study, the entire
Ad26.COV2.S COVID 19 vaccine program was paused to evaluate a safety concern of thrombosis
with TTS in adults. During this pause, the safety and immunogenicity data for these 33 adolescent
participants was evaluated. While the IDMC endorsed further enrollment of adolescents that would
receive Ad26.COV2.S at a 5x1010 vp dose level, the sponsor has decided not to evaluate the 5x1010
vp dose level in pediatric participants based on the immunogenicity data from the 2.5x1010 vp dose
and has decided to redesign the pediatric studies. Study VAC31518COV3006 will focus on
adolescent participants 12-17 years of age, and no further enrollment of this age group will take
place in this study.
Therefore, per protocol Amendment 6, the 33 adolescents already enrolled at the time of
Amendment 6 will continue to be followed in this study in accordance with the planned Schedule
of Activities, but no further vaccination with Ad26.COV2.S will occur in Groups A and B.
Participants in Group C will receive a single dose of Ad26.COV2.S at 2.5x1010 vp.
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 each participating study site will be sent to the sponsor (or designee) after completion of the
final participant visit at that study site, in the time frame specified in the Clinical Trial Agreement.
Study Completion Definition
An adult participant will be considered to have completed the study if he or she has completed
assessments at the 12-month post vaccination 2 visit (on Day 393 for Groups 1-5, Day 365 for
Group 7, and Day 421 for Group 9) or the 6-month post unblinded vaccination 1 visit for Groups
6, 8 and 10.
An adolescent participant will be considered to have completed the study if he or she has completed
assessments at the 12-month post vaccination 1 visit (Groups A and B) or 6 month post active
vaccination visit (Group C).

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Participants who prematurely discontinue study vaccination for any reason before that time will
not be considered to have completed the study.
5. 
STUDYPOPULATION
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.
NOTE: Investigators should ensure that all study enrollment criteria have been met prior to the
first vaccination. 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 described in Section 10.3.
5.1. 
Inclusion Criteria
5.1.1. 
Inclusion Criteria for Adults (18-55 Years, Inclusive and 65 Years or
Older)
Each potential participant must satisfy all of the following criteria 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 
Participant is 18 to 55 years of age, inclusive, or 65 years of age or older on the day of
signing the ICF.
4 
Participant must have a body mass index (BMI) <30.0 kg/m2.
5 
Criterion modified per Amendment 1:
5.1. Participant 18 to 55 years of age, inclusive: participant must be healthy, in the
investigator’s clinical judgment, as confirmed by medical history, physical
examination, and vital signs performed at screening, and must not have
comorbidities related to an increased risk of severe COVID-19, except for smoking,
which is allowed (see also exclusion criterion 21).
Participant 65 years of age and older: in the investigator’s clinical judgment,
participant must be either in good or stable health. Participant may have underlying

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illnesses, as long as the symptoms and signs are medically controlled and not
considered to be comorbidities related to an increased risk of severe COVID-1916,
except for smoking, which is allowed (see also exclusion criterion 21). If 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. Participant will be included on the basis of physical examination,
medical history, and vital signs17.
6 
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
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
a. combined (estrogen and progestogen containing) hormonal contraception
associated with inhibition of ovulation (oral, intravaginal, or transdermal)
b. progestogen-only hormonal contraception associated with inhibition of ovulation
(oral, injectable, or implantable)
2. intrauterine device (IUD)
3. intrauterine hormone-releasing system (IUS)
4. bilateral tubal occlusion/litigation 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 3 months after the
last dose of study vaccine. The reliability of sexual abstinence needs to be evaluated in
16 Participants may have hypertension of mild severity, 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).
17 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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relation to the duration of the study and the preferred and usual lifestyle of the
participant.
7 
All 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.
5.1.2. 
Inclusion Criteria for Adolescents (12-17 Years, Inclusive)
Each potential participant must satisfy all of the following criteria to be enrolled in the study:
1 Participants must have signed an ICF (or their legally acceptable representative or parent(s)
[preferably both parents if available or as per local requirements] must sign) indicating that
they understand the purpose of, and procedures required for, the study, are willing/able to
adhere to the prohibitions and restrictions specified in the protocol and study procedures, and
are willing (or the parents are willing for their adolescent) to participate in the study.
Informed assent must be obtained from adolescents, depending on local regulations and
practice.
2 Participants who have given written consent or assent as required by local regulations after
the nature of the study has been explained to them according to local regulatory requirements.
3 Participant is 12 to 17years of age, inclusive, on the day of signing the ICF
4 Participant must be healthy, in the investigator’s clinical judgment, as confirmed by medical
history, physical examination, and vital signs performed at screening, and must not have
comorbidities related to an increased risk of severe COVID-19, as listed in Section 10.10,
summarized from the CDC website available at the time of writing this protocol
amendment 2.
5 
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):
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

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for contraceptive method failure (eg, noncompliance, recently initiated) in
relationship to the first vaccination. Highly effective methods for this study
include:
1. hormonal contraception
a. combined (estrogen and progestogen containing) hormonal contraception
associated with inhibition of ovulation (oral, intravaginal, or transdermal)
b. progestogen-only hormonal contraception associated with inhibition of ovulation
(oral, injectable, or implantable)
2. intrauterine device (IUD)
3. intrauterine hormone-releasing system (IUS)
4. bilateral tubal occlusion/litigation 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 3 months 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.
6 
All 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.
Note: If the pregnancy test result is positive, in order to maintain participantconfidentiality,
the investigator will ensure adequate counseling and follow-up will be made available.
7 
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.
8 
Participant and, where required by local regulation, parent(s)/legal guardian(s)are available
and willing to participate for the duration of the study visits and follow-up.
9 
Participant and, where required by local regulation, parent(s)/legal guardian(s) must be
willing to provide verifiable identification, has means to be contacted and to contact the
investigator during the study.
5.2. 
Exclusion Criteria
5.2.1. 
Exclusion Criteria for Adults (18-55 years, Inclusive and 65 Years or
Older)
Any potential participant who meets any of the following criteria will be excluded from
participating in the study.

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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 
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 IB0).
4 
Criterion modified per Amendment 3
4.1 Participant has abnormal function of the immune system resulting from:
a. Clinical conditions (eg, autoimmune disease, potential immune mediated disease
or known or suspected immunodeficiency, chronic kidney disease [with dialysis])
expected to have an impact on the immune response of the study vaccine.
Participants with clinical conditions stable under non-immunomodulator treatment
(eg, autoimmune thyroiditis, autoimmune inflammatory rheumatic disease such as
rheumatoid arthritis) may be enrolled at the discretion of the investigator. Non-
immunomodulator treatment is allowed as well as steroids at a non-
immunosuppressive dose or route of administration.
b. Chronic or recurrent use of systemic corticosteroids within 6 months before
administration of study vaccine and during the study. A 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 
Participant has a history of any neurological disorders or seizures including Guillain-Barré
syndrome, with the exception of febrile seizures during childhood.
6 
Participant has a history of chronic urticaria (recurrent hives), eczema or adult atopic
dermatitis.
7 
Participant received treatment with immunoglobulins 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:
c. Licensed live attenuated vaccines
 within 28 days before or after planned
administration of the first or subsequent study vaccinations.
d. Other licensed (not live) vaccines 
 within 14 days before or after planned
administration of the first or subsequent study vaccinations.

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9 Criterion modified per Amendment 1:
9.1 Criterion modified per Amendment 2:
9.2 Criterion modified per Amendment 3:
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 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 19) and during the
study except under the conditions described in Section 6.7 .
10 Criterion modified per Amendment 1:
10.1 Participant is a woman who is pregnant, breastfeeding, or planning to become pregnant
within 3 months after the last dose of study vaccine.
11 Participant has a history of an underlying clinically significant acute or chronic medical
condition or physical examination findings for which, in the opinion of the investigator,
participation would not be in the best interest of the participant (eg, compromise the well-
being) or that could prevent, limit, or confound the protocol-specified assessments.
12 Participant had surgery requiring hospitalization (defined as inpatient stay for longer than
24 hours or overnight stay), within  12 weeks before vaccination, or will not have fully
recovered from surgery requiring hospitalization, or has surgery requiring hospitalization
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 Criterion Deleted per Amendment 4.
14.1 Criterion reinstated per Amendment 5:
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.

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16 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.
17 Participant cannot communicate reliably with the investigator.
18 
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.
19 Participant previously received a coronavirus vaccine.
20 Participant has a positive diagnostic test result for past (serological testing) or current (PCR
based viral RNA detection) SARS-CoV-2 infection at screening.
21 Criterion modified per Amendment 1:
21.1 Criterion modified per Amendment 3:
21.2 Participants with comorbidities that are or might be associated with an increased risk
of progression to severe COVID-19, 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 conditions (dementia); end stage
renal disease; organ transplantation; cancer; HIV infection and other
immunodeficiencies; hepatitis B infection; and sleep apnea. This list is consistent with
the list of conditions that increase the risk of progression to severe COVID-19
available at the CDC website at the time of writing of this protocol0, except for
smoking, which is allowed. The data from the CDC website is summarized in
Section 10.9.
Applicable only to participants 65 years of age and older: Participants may have
hypertension of mild severity 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).
22 Participant who is currently working in an occupation with a high risk of exposure to
SARS-CoV-2 infection (eg, health care worker or emergency response personnel who work
in close contact with SARS-CoV-2 infected patients) or considered at the investigator’s
discretion to be at increased risk to acquire COVID-19 for any other reason
23 Participant who has had a known exposure to an individual with confirmed COVID-19 or
SARS-CoV-2 infection within the past 2 weeks
24 History of confirmed SARS or MERS.

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5.2.2. 
Exclusion Criteria for Adolescents (12-17 Years, Inclusive)
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.
3 
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 IB0).
4 
Participants who required chronic administration (defined as more than 14 days) of
immunosuppressants or other immune-modifying drugs within 6 months prior to the study
vaccination. (For corticosteroids, this means prednisone, or equivalent, ≥ 20mg/day.
Inhaled and topical steroids are allowed). For participants below 45 kg, the dose is
1 mg/kg/day.
Participants in treatment with systemic corticosteroids given p.o., i.v., i.m. ≤ 1 month prior
to inclusion or during the study. Participants administered corticosteroid topically or by
asthma inhalators are eligible for inclusion
5 
Participants with a history of illness or with an ongoing illness that, in the opinion of the
investigator, may pose additional risk to the participant if he/she participates in the study
6 
Any serious, chronic, or progressive disease (eg, neoplasm, diabetes, cardiac disease,
hepatic disease, progressive neurological disease or seizure disorder; autoimmune disease,
HIV infection or AIDS, blood dyscrasias, bleeding diathesis, signs of cardiac or renal
failure, or severe malnutrition)
7 
Participant has obesity (as defined by the Growth Chart being used as appropriate in the
participant’s country, e.g. the CDC Growth Chart)0
8 
Participant received treatment with immunoglobulins 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.
9 
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.
10 
Criterion modified per Amendment 1:
10.1 Participant received an investigational drug (including investigational drugs for
prophylaxis of COVID-19) or used an invasive investigational medical device within 30

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days or received investigational Ig or monoclonal antibodies against SARS-CoV-2 within
3 months, or 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 17) and during
the study except under the conditions described in Section 6.7 .
11 
Participant is pregnant, breastfeeding, or planning to become pregnant within 3 months
after the last dose of study vaccine.
12 
Participant has a contraindication to IM injections and blood draws eg, bleeding disorders.
13 
Criterion Deleted per Amendment 4.
14 
Participant has chronic active hepatitis B or hepatitis C infection per medical history.
15 
Criterion Modified per Amendment 4:
15.1 Participant has had major psychiatric illness or drug abuse which in the investigator’s
opinion would compromise the participant’s safety or compliance with the study
procedures.
16 
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.
17 
Participant previously received a coronavirus vaccine.
18 
Participant has a positive diagnostic test result for past (serological testing) or current
(PCR based viral RNA detection) SARS-CoV-2 infection at screening.
19 
Participant who has had a known exposure to a person with confirmed COVID-19 or
SARS-CoV-2 infection within the past 2 weeks
20 
History of confirmed SARS or MERS.
21 
Criterion Added per Amendment 4
Participant has a history of Kawasaki disease.
22 
Criterion Added per Amendment 4
Participant has a history of an underlying clinically significant acute or chronic medical
condition or physical examination findings for which, in the opinion of the investigator,

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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.
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 6.9, 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.
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 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/assent 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

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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.
6. 
STUDY VACCINATION AND CONCOMITANT THERAPY
6.1. 
Study Vaccinations Administered
Ad26.COV2.S (also known as Ad26COVS1) will be supplied at a concentration of 1x1011 vp/mL
and 2x1011 vp/mL as a suspension in single-use vials, with an extractable volume of 0.5 mL.
Formulation buffer will be supplied as diluent 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
will be supplied as a 0.9% NaCl solution.
Adult participants in Groups 1-6 will be vaccinated on Day 1 and Day 57, in Groups 7-8 on Day 1
and Day 29, in Groups 9-10 on Day 1 and Day 85.
Adolescent participants in Groups A-B will be vaccinated with a single dose of Ad26.OV2.S at
2.5x1010 vp on Day 1. Adolescent participants in Group C who received placebo on Day 1 will
receive a single dose of Ad26.OV2.S at 2.5x1010 vp following unblinding at approximately 6
months of study participation.
A volume of 0.5 mL will be administered to all (adult and adolescent) participants.
 
Ad26.COV2.S:
 
1x1011 vp dose level (Adult Group 4): 0.5 mL is withdrawn from one vial containing
0.75mL 2x1011 vp/mL.
 
5x1010 vp dose level (Adult Groups 1, 5, 7, 9): 0.5 mL is withdrawn from one vial
containing 0.75 mL 1x1011 vp/mL.
 
2.5x1010 vp dose level (Adult Group 2, and Adolescent Groups A, B and C): 0.75 mL of
formulation buffer is added to a vial containing 0.75 mL 1x1011 vp/mL, providing
5x1010 vp/mL in a vial with an extractable volume of more than 1 mL. Then 0.5 mL will
be withdrawn from this vial.
 
1.25x1010 vp dose level (Adult Group 3 and antigen presentation in Groups 1-5, 7and 9):
0.4 mL is withdrawn from one vial containing 0.75 mL 1×1011 vp/mL and added to a vial
containing 1.2 mL formulation buffer, providing 2.5×1010 vp/mL in a vial with an
extractable volume of more than 1 mL. Then 0.5 mL will be withdrawn from this vial.
 
Placebo: 0.9% NaCl solution (Groups 6, 8, and 10): 0.5 mL
Study vaccine will be administered by IM injection into the deltoid muscle, preferably of the
non-dominant arm. Subsequent vaccinations are preferably administered in the opposite arm. If an
injection cannot be given in the deltoid muscle due to a medical or other contraindication (for

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example, tattooed upper arms rendering it difficult to assess site reactogenicity), use alternative
locations such as the hip, thigh or buttocks. If alternative locations are used for vaccine
administration, these locations should consistently be used for later vaccinations.
For information on vaccination windows, see Section 8, Study Assessments and Procedures.
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 IB0 for a list of excipients.
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.

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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 vaccine are provided in the SIPPM.
6.3. 
Measures to Minimize Bias: Randomization and Blinding
Vaccine Allocation
Procedures for Randomization and Stratification
Central randomization will be implemented in this study. 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 adults, the randomization will be balanced
by using randomly permuted blocks and will be stratified by study site and age group
(approximately two thirds of participants ≥18-≤55 years of age and one third of participants ≥65
years of age per group). For the adolescent cohort, the randomization will be balanced by using
randomly permuted blocks and will be stratified age group (half of participants 12 to 15 years of
age inclusive and half of participants 16 to 17 years of age inclusive per group).
From the time of protocol Amendment 2, for each of the age strata (16 to 17 years and 12 to 15
years) in the adolescent cohort, the safety of the Ad26.COV2.S vaccine at a dose level of 2.5x1010
vp (Group A-C) or 5x1010 vp (Group D-F) was planned to be evaluated by dose escalation in a
sequential manner initially in groups of sentinels (11 participants in each group) and subsequently
if the safety profile is favorable, in a group of 22 participants that will form the safety cohort
(randomization ratio of 5:5:1 for both sentinels and safety cohorts). Safety was to initially be
assessed in older adolescents (16 to 17 years of age) before proceeding with evaluation of safety
in cohorts of younger adolescents (12 to 15 years of age). If, the safety profile is found to be
acceptable, enrollment of study participants in Groups D-F was to start.
Following the initial vaccination of the first 33 adolescent participants (sentinels + safety cohort)
in the 16-17 year old age group at a dose of 2.5x1010 vp enrolled in this study, the entire COVID-19
vaccine program was paused to evaluate a safety concern of TTS in adults. During this pause, the
safety and immunogenicity data for these 33 adolescent participants was evaluated (see current
version of Investigator’s Brochure0). While the IDMC endorsed further enrollment of adolescents
that would receive Ad26.COV2.S at a 5x1010 vp dose level, the sponsor has decided not to evaluate
the 5x1010 vp dose level in pediatric participants based on the immunogenicity data from the
2.5x1010 vp dose in Study VAC31518COV2001 and has decided to redesign the pediatric studies.
Study VAC31518COV3006 will focus on adolescent participants 12-17 years of age, and no

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further enrollment of this age group will take place in this study. Therefore, per protocol
Amendment 6, the 33 adolescents already enrolled at the time of Amendment 6 will continue to
be followed in this study in accordance with the planned Schedule of Activities (Sections 1.3.5
and 1.3.6), but no further vaccination with Ad26.COV2.S will occur in Groups A and B.
Participants in Group C will receive a single dose of Ad26.COV2.S at 2.5x1010 vp.
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 adult participant and at the planned time
of randomization of the first adolescent participant, randomization may be started based on a paper
randomization list until the IWRS is live. 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.
Blinding
The investigator will not be provided with randomization codes. The codes will be maintained
within the IWRS, which has the functionality to allow the investigator to break the blind for an
individual participant.
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 and unblinding.
Under normal circumstances, the blind should not be broken until the database is finalized or until
unblinding to primary vaccination regimen (with the implementation of Amendment 5).
With implementation of protocol Amendment 5, adult participants who were initially enrolled to
receive placebo (Groups 6, 8 and 10), will be offered a 2-dose (28-day interval) Ad26.COV2.S
vaccination regimen at the 5x1010 vp dose level.
With the implementation of Amendment 5, all adult participants will be unblinded to the primary
vaccination regimen. Adults who received active vaccine in the primary vaccination regimen will
receive an antigen presentation injection with 1.25x1010 vp Ad26.COV2.S (Groups 1-5, 7, 9) in an
unblinded manner, and adults who received placebo in the primary vaccine regimen, will receive
a 2 dose active Ad26.COV2.S vaccine regimen at a 28-day interval and at a dose level of 5x1010 vp,

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in an open-label manner. Per group, approximately one third of participants will be 65 years and
older.
Similarly, all adolescents will initially be randomized and enrolled in a blinded manner to receive
either an active vaccine or placebo in a 1-dose or 2-dose primary vaccination regimen (56-day
interval). With implementation of Amendment 6 (at approximately 6 months of study
participation), the 33 enrolled adolescent participants will be unblinded to the primary vaccination
regimen. At this time, adolescent participants who were initially enrolled to receive placebo
(Group C), will receive a single dose of Ad26.COV2.S vaccination regimen at the 2.5 x1010 vp
dose level.
The investigator may in an emergency determine the identity of the intervention by contacting the
IWRS or by opening the sealed code (if IWRS is not available yet). The date, time, and reason for
the unblinding must be documented in the appropriate section of the eCRF, and in the source
document. 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
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.
Participants who have had their intervention assignment unblinded should continue to return for
scheduled evaluations. Participants should not be allowed to receive further study vaccinations and
are only to be followed for safety and immunogenicity evaluation visits.
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.
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
recommendation 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

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be documented. The name and date(s) of administration of the other COVID-19 vaccine should be
recorded (see Section 6.9).
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 data on the safety of receiving 2
different COVID-19 vaccines. Participants who were already unblinded for any reason may
receive Ad26.COV2.S vaccine upon discussion with the investigator, provided that they did not
receive another COVID-19 vaccine. Unblinded participants, whether in the vaccine or control
group, will be asked to continue to be followed in this study in line with the Schedule of Activities
to the extent that the participant is amenable. All data will be analyzed separately from the point
of unblinding for safety and immunogenicity, as described in the SAP.
6.4. 
Unblinding and Open-label Phase
With the implementation of protocol Amendment 5, all adult participants will be unblinded at the
on-site unblinding visit. Participants who received active vaccine will then resume the schedule in
Section 1.3.1, 1.3.2, or 1.3.3, as appropriate. Participants who received placebo will start following
the Schedule of Activities for the active vaccine regimen in Section 1.3.4. Participants who were
already unblinded for any reason may receive Ad26.COV2.S vaccine upon discussion with the
investigator, provided that they did not receive another COVID-19 vaccine.
With implementation of Amendment 6 (at approximately 6 months of study participation), the 33
enrolled adolescent participants will be unblinded to the primary vaccination regimen. At this time,
adolescent participants who were initially enrolled to receive placebo (Group C) will receive a
single dose of Ad26.COV2.S vaccination regimen at the 2.5 x1010 vp dose level and will continue
the schedule in Section 1.3.6.
Before the actual participant unblinding, all of the previously available data should be complete
and accurate in the participant’s eCRF.
6.5. 
Study Vaccination 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 the location used for injection [deltoid or alternative location]). For blinding procedures, see
Section 6.3, Measures to Minimize Bias: Randomization and Blinding.
6.6. 
Dose Modification
Dose modification is not applicable for adults.
Following the initial vaccination of the first 33 adolescent participants (sentinels + safety cohort)
in the 16-17 year old age group at a dose of 2.5x1010 vp enrolled in this study, the entire COVID-19
vaccine program was paused to evaluate a safety concern of TTS in adults. During this pause, the
safety and immunogenicity data for these 33 adolescent participants was evaluated (see current
version of Investigator’s Brochure0). While the IDMC endorsed further enrollment of adolescents

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that would receive Ad26.COV2.S at a 5x1010 vp dose level (see Section 4.1), the sponsor has
decided not to evaluate the 5x1010 vp dose level in pediatric participants based on the
immunogenicity data from the 2.5x1010 vp dose in Study VAC31518COV2001 and has decided
to redesign the pediatric studies. Study VAC31518COV3006 will focus on adolescent participants
12-17 years of age, and no further enrollment of this age group will take place in this study.
Therefore, per protocol Amendment 6, the 33 adolescents already enrolled at the time of
Amendment 6 will continue to be followed in this study in accordance with the planned Schedule
of Activities (Sections 1.3.5 and 1.3.6), but no further vaccination with Ad26.COV2.S will occur
in Groups A and B. Participants in Group C will receive a single dose of Ad26.COV2.S at
2.5x1010 vp.
6.7. 
Continued Access to Study Vaccine After the End of the Study
Adults in the placebo groups (Groups 6, 8 and 10) will receive a 2-dose active Ad26.COV2.S
vaccine regimen at a 28-day interval and at a dose level of 5x1010 vp, in an open-label manner All
adult participants will be followed up for safety until 6 months after the second dose of active
vaccine (see Schedule of Activities, Section 1.3.4). Adolescent participants who were initially
enrolled to receive placebo (Group C), will receive a single dose of Ad26.COV2.S vaccination
regimen at the 2.5 x1010 vp and 5x1010 vp dose level, respectively, at approximately 6 months of
study participation. All adolescent participants will be followed up for safety until approximately
12 months post vaccination 1 (see Schedule of Activities, Section 1.3.7).
As COVID-19 vaccines become authorized/licensed for use, some participants may become
eligible to receive such vaccines, 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 should request
individual unblinding to take up the offer of an authorized/licensed COVID-19 vaccine.
Participants who were already unblinded for any reason may receive Ad26.COV2.S vaccine upon
discussion with the investigator, provided that they did not receive another COVID-19 vaccine.
All data will be analyzed separately from the point of unblinding for safety, efficacy and
immunogenicity (under the conditions outlined in Section 6.3), as described in the SAP.
6.8. 
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 1 hour and will be closely monitored for allergic or other reaction by study staff.
Follow-up telephone calls 12 hours and 24 hours post vaccination will be made).
 
Document the quantity of the excess dose in the eCRF.
 
Report as a special reporting situation.

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6.9. 
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 the 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. All
other concomitant therapies should also be recorded if administered in conjunction with  a
confirmed COVID-19 case or with new or worsening AEs or suspected AESIs reported per
protocol requirements outlined in Section 8.3.1.
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 been given an anti-COVID-19 vaccine (other than study vaccine) or treatment
will not receive further study vaccination. Participants may not receive an investigational drug
(including investigational drugs for prophylaxis of COVID-19) or use an invasive investigational
medical device within 30 days or receive an investigational Ig or monoclonal antibodies within 3
months, or receive convalescent serum for COVID-19 treatment within 4 months or receive an
investigational vaccine (including investigational Adenoviral-vectored vaccines) within 6 months
before the planned administration of the first dose of study vaccine.
Licensed live attenuated vaccines should be given at least 28 days before or at least 28 days after
a study vaccination. Other licensed (not live) vaccines (eg, tetanus, hepatitis A, hepatitis B, rabies)
should be given at least 14 days before or at least 14 days after administration of study vaccine in
order to avoid potential confusion of adverse reactions and potential immune interference. The use
of any coronavirus vaccine (licensed or investigational) other than Ad26.COV2.S is disallowed at
any time prior to vaccination and during the study. If a vaccine is indicated in a post-exposure
setting (eg, rabies or tetanus), it must take priority over the study vaccine.
Antipyretics are recommended post vaccination for symptom relief as needed. Prophylactic
antipyretic use is not encouraged; however, in some instances, it could be considered for
participants with special circumstances and/or comorbidities.
Chronic or recurrent use of systemic corticosteroids18 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
18 Note: Ocular, topical or inhaled steroids are allowed.

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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.
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.
6.10. Study Vaccination Pausing Rules
The PI and the study responsible physician/scientist (SRP/S) 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 SMC, after which the SMC will recommend whether the pause can
be lifted or not, or whether other steps are needed.
The SMC will review blinded data first, but has the right to request the randomization codes and
review unblinded data if deemed necessary. The SMC 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 SMC meeting triggered by the occurrence of a given pausing rule, the SMC 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 of
adolescent participants only. Laboratory abnormalities noted below refer to cases where the study-
site personnel perform laboratory safety testing for investigation of an AE.
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 SMC information. Upon their review, the SMC 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 days (ie,
the day of occurrence of the AE is counted as Day 1) 19; OR
7. A study pause is triggered in the ongoing clinical studies.
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 SMC review of similar AE, 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 the 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 SMC members and coordination of a SMC 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 SMC 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 SMC, participant safety may be
threatened.
Resumption of vaccinations will start only upon receipt of written recommendations by the SMC.
If any pausing rule is met and, if following appropriate safety review it is deemed appropriate to
19 The day of occurrence of the AE is counted as Day 1.

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restart dosing, the sponsor must submit a request to restart dosing with pertinent data to competent
authority as a request for a substantial Amendment, as required by local regulations or authority
request (eg, the Medicines and Healthcare products Regulatory Agency [MHRA]). If needed, this
will be followed by a substantial amendment of the IB and/or protocol. The clinical site(s) will be
allowed to resume activities upon receipt of a written notification from the sponsor. These
communications from the SMC will be forwarded by the investigator to the IRB/IEC and by the
sponsor to the relevant health authorities, according to local standards and regulations. For further
details, refer to Section 10.3.6 in Appendix 3.
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
 
Unblinding on the participant level that, in the opinion of the sponsor, would compromise the
integrity of the data
 
Participant was unblinded and received an authorized/licensed COVID-19 vaccine
 
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 at immunosuppressive dose, and
administration of antineoplastic and immunomodulating agents or radiotherapy
 
Withdrawal from further study vaccination
 
During the double-blind period, participant has a positive test result for SARS-CoV-2
infection during the study (see Section 8.1.2, Procedures in Case of COVID-19-like Signs and
Symptoms)
 
Participant receives any experimental medication (including experimental vaccines other than
the study vaccine) or receives an anti-COVID-19 vaccine or treatment
 
Participant previously experienced TTS or heparin-induced thrombocytopenia (HIT)
 
Participant has a history ofcapillary leak syndrome (CLS), or experienced CLS after a study
vaccination.

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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/assent from the study
 
Death
 
Repeated failure to comply with protocol requirements
When a participant withdraws before study  completion, the reason for withdrawal is to be
documented in the eCRF and in the source document. If the reason for withdrawal from the study
is withdrawal ofconsent/assent, then no additional assessments are allowed, but an optional safety
visit will still be offered.
Withdrawal of Consent/assent
A participant declining to return for scheduled visits does not necessarily constitute withdrawal of
consent/assent. Alternate follow-up mechanisms that the participant agreed to when signing the
consent/assent 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/assent for use of samples for research (refer to Long-Term
Retention of Samples for Additional Future Research in Section 10.3). 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
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.

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 
Should the participant continue to be unreachable, they will be considered to have withdrawn
from the study.
Should a study site close, eg, for operational, financial, or other reasons, and the investigator cannot
reach the participant to inform them, their contact information will be transferred to another study
site.
8. 
STUDY ASSESSMENTS AND PROCEDURES
Overview
The Schedule of Activities (Section 1.3) summarizes the frequency and timing of safety,
reactogenicity, immunogenicity and other measurements applicable to this study. All participants
in the study will be counseled on COVID-19 prevention each time that they have a contact with
study site staff in line with local guidelines.
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/legal guardian(s) (where appropriate for adolescent participants) to avoid missing or
incorrect data. The diary will be reviewed by the study personnel at visits indicated in 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 for documentation of body temperature and pulse
oximetry results) and a kit to collect nasal swabs if they experience COVID-19-like symptoms
during the study (see Section 8.1.2and Section 8.1.2.1). Baseline pulse oximetry will be conducted
at Visit 1.
For adults, the total blood volume to be collected over the course of the study will be
approximately:
 
Groups 1-5
 
460.5 mL for the subset of participants for which both humoral and
cellular immunogenicity (PBMC) will be assessed,
 
155.5 mL for the subset of participants in which only humoral immunogenicity will be
assessed;

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 
Group 6
 
563 mL for the subset of participants for which both humoral and cellular
immunogenicity (PBMC) will be assessed,
 
258 mL for the subset of participants in which only humoral immunogenicity will be
assessed;
 
Groups 7 and 9:140.5 mL;
 
Groups 8 and 10: 243 mL.
For adolescents in Groups A and B, the total blood volume will be approximately 68 mL. The total
blood volume will be approximately 87mL for participants in Group C.
For adult participants in Groups 1-10 and adolescent participants in Groups A-C who need a repeat
serological test at Day 1, an additional 8 mL of blood will be drawn. For participants with
(suspected) COVID-19, additional blood samples of a total of 35 mL (adults) or 20 mL
(adolescents) might be collected. For participants who experience a suspected AESI, up to an
additional 30 mL of blood may be collected. Refer to Section 1.3, Schedule of Activities for the
total blood volume (serum and, as applicable, PBMC and whole blood samples) to be collected at
each visit and over the complete course of the study for each group and in case of COVID-19-like
symptoms. Repeat or unscheduled samples may be taken for safety reasons or for technical issues
with the samples.
Study visits, other than screening and visits at which study vaccination is scheduled, may take
place at the participant’s home if there are travel restrictions in case of an ongoing pandemic.
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 6.10), efforts will be made to
still vaccinate the participant as soon as possible, even if out of window. 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.
In October 2020, the current study was temporarily paused because one of the pausing rules was
met in study COV3001. When the pause was lifted, most of the participants in Groups 7-8 had
missed their visit window for Vaccination 2 (Visit 4), rendering the intent of the 28-day vaccination
interval in these groups futile. As their actual vaccination might coincide with the intervals from

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who test positive 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, the Schedule of Activities for the timing and frequency of
all sample collections.
Instructions for the collection, handling, storage, and shipment of samples are found in the
laboratory manual that will be provided. Collection, handling, storage, and shipment of samples
must be under the specified, and where applicable, controlled temperature conditions as indicated
in the laboratory manual.
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)
 
An approved pulse oximeter, if necessary
 
Pharmacy manual/SIPPM
 
Laboratory manual
 
IWRS Manual
 
eCRF completion guidelines
 
Sample ICF
 
Participant diaries
 
Nasal swab kit
 
Participant instructions and booklet: COVID-19-like signs and symptoms daily surveillance,
nasal swab instructions, SIC (for daily completion, if symptomatic), and for documentation of
temperature and pulse oximetry
 
Contact information pages
8.1. 
Immunogenicity Assessments
8.1.1. 
Immunogenicity Assessments
Venous blood samples will be collected for assessment of humoral immune responses and cellular
immunogenicity (RNA sequencing) in all participants. Blood for evaluation of humoral and
cellular (PBMC in subset only) immune responses will be drawn from participants at the time
points specified in the Schedule of Activities. Cellular immune responses (PBMC) will only be

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assessed in a subset of adult participants in Groups 1-6 (approximately 112; 21 participants per
group in Groups 1-5, 7 participants in Group 6; at selected sites) Immunogenicity assessments may
include, but are not limited to, the humoral and cellular immunogenicity assays (as available and
feasible) summarized in the below table. Sample volumes and time points are detailed in the
Schedules of Activities in Section 1.3.
If the participant is unable to complete the study without withdrawing consent/assent,
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 8.
Table 8: 
Summary of Humoral and Cellular Immunogenicity Assays
Assay 
Purpose
Humoral Immunogenicity
Primary/Secondary/Exploratory
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 SARS-CoV-2 or individual SARS-CoV-2
proteins (eg, S protein)
Exploratory endpoints
SARS-CoV-2 binding antibodies 
(ELISA) 
Analysis of antibodies binding to the SARS-CoV-2 N protein, if such an
assay is available
SARS-CoV-2 binding antibodies 
(MSD) 
Analysis of antibodies binding to the SARS-CoV-2 S protein (different than
the assays supportive of the secondary objectives) and the RBD of the
SARS-CoV-2 S protein
Functional and molecular antibody 
characterization  
Analysis of antibody characteristics including Fc-mediated viral clearance,
avidity, Fc characteristics, Ig subclass and IgG isotype
Passive transfer 
Analysis of immune mediators correlating with protection against
experimental SARS-CoV-2 challenge in a suitable animal model
SARS-CoV-2 neutralizing 
antibodies
Analysis of neutralizing antibodies against emerging SARS-CoV-2 variants
Adenovirus neutralization 
(neutralization assays)
Analysis of neutralizing antibodies to adenovirus
Cellular Immunogenicity
Exploratory endpoint
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
Gene expression analysis 
Analysis of gene expression by RNA transcript profiling
CD = cluster of differentiation; ELISA = enzyme-linked immunosorbent assay; IFNγ = interferon gamma;
IL = interleukin; MSD = meso scale discovery; PBMC = peripheral blood mononuclear cell; RBD = receptor-
binding domain; RNA = ribonucleic acid; S = Spike protein; SARS-CoV-2 = severe acute respiratory syndrome
coronavirus-2; Th = T helper; TNFα = tumor necrosis factor alpha; VNA = virus neutralization assay

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8.1.2. 
Procedures in Case of (Suspected) COVID-19
Participants will be provided with a booklet including a daily question on whether they are
experiencing COVID-19-like symptoms, and for documentation of body temperature and pulse
oximetry results. Baseline pulse oximetry will be conducted at Visit 1. During the study, study-
site personnel will remind participants to complete the SIC in the event of any signs and symptoms
and to contact the site at the time of symptom onset or in case of a positive RT-PCR test for SARS-
CoV-2 (regardless of where the testing was performed). This positive RT-PCR test will need to be
captured in the eCRF.
If a participant meets one of the prespecified criteria for (suspected) COVID-1922 (see
Section 8.1.2.1), the following should take place (for details, see the Schedule of Activities in
Section 1.3.7):
 
Participants should contact the study site at the time of symptom onset/at time of becoming
aware of the positive RT-PCR test.
 
If the trigger was a sign or symptom: a nasal swab should be collected by 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. It
is preferred that the swab is taken by a caregiver (spouse, partner, relative, friend, or health
care professional). If that is not possible, the participant can collect the swab himself or
herself. The nasal swab sample collection and storage instructions will be described
separately. The site should arrange transfer of the sample to the study site as soon as possible
after sample collection. If the trigger was a positive RT-PCR test, then this first nasal swab is
not needed.
 
A second nasal swab will be obtained on COVID-19 Day 3-8 following the same procedures
as the first nasal swab. The second nasal swab may also be collected at home, at the hospital,
or at another location, if needed, by a study site staff, if appropriate procedures are in place.
The presence of SARS-CoV-2 infection will be assessed at the study site by molecular testing
using the nasal swab samples. The nasal swabs may be tested at the central laboratory for the
presence of SARS-CoV-2 and other respiratory pathogens using a broad respiratory pathogens
panel. 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. A physical examination, vital signs measurements and pulse oximetry will be
performed and a blood sample for assessment of the humoral immune response and other
biomarkers will be taken.
 
From COVID-19 Day 3-8 onwards: Additional swabs should be taken by a healthcare
professional from the participant as soon as possible, but with a minimum of 1 day between
the swabs, until 2 consecutive negative swabs are obtained, ie, twice weekly or more
frequently until resolution. These precautionary measures are to ensure that site staff who
22 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.

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come into physical contact with a participant deemed to be a COVID-19 case undertake the
proper safety procedures such as wearing of personal protective equipment.
 
Participants should complete the SIC  (see Section  10.7) and record their highest body
temperature daily starting on the first day of trigger onset. Blood oxygen saturation and pulse
rate should be measured using a pulse oximeter 3 times a day, preferably in the morning, at
lunch time, and in the evening.
 
Collection of data will continue until resolution of the COVID-19 episode, defined as having
2 consecutive days with no COVID-19-related signs or symptoms and 2 consecutive
SARS-CoV-2 negative nasal swabs.
 
For participants with a positive test result for SARS-CoV-2 infection, a study visit will be
conducted 28 days after trigger onset to assess the clinical course of the infection, record
concomitant medications since trigger onset, and obtain a blood sample for assessment of the
humoral immune response (VNA, ELISA, and Fc functionality) and other biomarkers (RNA-
seq). 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 will be notified
and may be requested to remain at home and not visit the study site. If necessary, study-site
personnel will visit the participant at home23. 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. The participant will be followed until
resolution of clinical symptoms. The sponsor recommends to follow these participants until 2
consecutive SARS-CoV-2 negative nasal swabs could be obtained.
If a participant has a positive test result for a respiratory infection other than COVID-19, study
visits will continue per the Schedule of Activities (Section 1.3).
8.1.2.1. 
Prespecified Criteria for (Suspected) COVID-19
The criteria for (suspected) COVID-19 (ie, the triggers to start procedures explained in
Section 8.1.2) are prespecified as follows:
23 The study staff visiting participants at home will use personal protective equipment according to local regulations.

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Positive RT-PCR result for SARS-CoV-2, regardless where the testing was performed
(under the auspices of the study or through a private or public laboratory independent of
the study), whether symptomatic or asymptomatic
OR
New onset or worsening of any 1 of these symptoms, which lasts for at least 24 hours, not
otherwise explained:
 
Headache
 
Malaise (appetite loss, generally unwell, fatigue, physical weakness)
 
Myalgia (muscle pain)
 
Chest congestion
 
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)
 
Pulse oximetry value ≤95%, which is a decrease from baseline
 
Heart rate ≥90 beats/minute at rest, which is an increase from baseline
 
Gastrointestinal symptoms (diarrhea, vomiting, nausea, abdominal pain)
 
Neurologic symptoms (numbness, difficulty forming or understanding speech)
 
Red or bruised looking toes
 
Skin rash
 
New or changing olfactory or taste disorders
 
Symptoms of blood clots: pain/cramping, swelling or redness in your legs/calves
 
Confusion
 
Bluish lips or face
 
Clinical suspicion/judgment by investigator of symptoms suggestive of COVID-19, including
MIS-C (multisystem inflammatory syndrome in children [adolescent participants only])

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As several of the prespecified criteria for suspected COVID-19 overlap with vaccine-related
reactogenicity, investigators’ clinical judgment is required to exclude vaccine-related events.
8.1.3. 
Asymptomatic SARS-CoV-2 Infection
A non-S protein ELISA (eg, SARS-CoV-2 N-ELISA), will be performed to identify cases of
asymptomatic SARS-CoV-2 infection (see also Table 8). For adults, this assay will be performed
on samples obtained on Day 1, 28 days after antigen presentation, and 6 months after
Vaccination 2. For adolescents, this assay will be performed on samples obtained on Day 1,
28 days after Vaccination 2, at Vaccination 3, and 6 months after Vaccination 3.
Any asymptomatic participant with a positive RT-PCR result for SARS-CoV-2, regardless of
where the testing was performed (under the auspices of the study or through a private or public
laboratory independent of the study) will be considered. The positive RT-PCR result will need to
be captured in the eCRF.
8.2. 
Safety Assessments
Details regarding the SMC are provided in Section 10.3.6.
AEs will be reported and followed by the investigator as specified in Section 8.3and Section 10.4.
Any clinically relevant changes occurring during the study must be recorded on the AE 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 (Section 1.3).
8.2.1. 
Physical Examinations
A history-directed physical examination, including height and body weight, will be carried out at
screening. To obtain the actual body weight, participants must be weighed lightly clothed. The
height should be measured without footwear.
At all other visits, an abbreviated, symptom-directed examination might be performed by the
investigator based on any clinically relevant issues or symptoms, and medical history. Symptom-
directed physical examination may be repeated if deemed necessary by the investigator.
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.

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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.
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
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.
For an adolescent participant who becomes pregnant, this information will be shared with the study
participant’s legal guardian as required or permitted by local regulations.
8.2.4. 
Hematology Clinical Laboratory Assessments
Blood samples for hematology (as detailed in Section 10.2) to evaluate D-dimers and Lupus
anticoagulant, anti-β2 glycoprotein, anti-cardiolipin (adults) and anti-PF4 (adults and adolescents)
will be collected at the timepoints indicated in the Schedules of Activities (see Section 1.3). For
timepoints that have already passed before protocol Amendment 2 was approved and implemented,
the D-dimers, Lupus anticoagulant, and anti-PF4 tests will not be performed retrospectively, as
these tests are to be performed in plasma samples. Serum samples originally drawn or yet to be
drawn for the humoral immunogenicity assessments will be used for the testing of Anti-β2
glycoprotein, anti-PF4 and anti-cardiolipin. Collection of plasma and serum samples for testing of
D-dimers, Lupus anticoagulant, Anti-β2 glycoprotein, anti-PF4, and Anti-cardiolipin will be
performed for all groups from the time of approval of Amendment 3.
The investigator must review the laboratory results, document this review, and record any
clinically relevant changes occurring during the study in the AE or medical history section of the
case report form (CRF), as applicable.
In case of a thrombotic event or TTS, every effort should be made to collect local
hospital/laboratory test results obtained by the treating physician to allow rapid diagnosis and
treatment. This information should be reported through the TTS AESI form (see Section 10.13,
Appendix 13) electronically per instructions in the eCRF completion guidelines. In addition, every

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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 1.3.8 and Section 10.2, Appendix 2). The Investigator will
review the laboratory test results to assist the investigation of the AESI.
See Section 8.3.6.1 for details on laboratory test details to be reported for an AE of
thrombocytopenia.
8.3. 
Adverse Events, Serious Adverse Events, Adverse Events of Special
Interest, and Other Safety Reporting
Timely, accurate, and complete reporting and analysis of safety information, including AEs,
suspected AESIs, SAEs, and product quality complaint (PQC), 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.
8.3.1. 
Time Period and Frequency for Collecting Adverse Event, Adverse
Event of Special Interest, and Serious Adverse Event Information
All Adverse Events
AEs and special reporting situations, whether serious or non-serious, that are related to study
procedures or that are related to non-investigational sponsor products will be reported 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 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.
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.

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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.
All AEs will be followed until resolution or until clinically stable.
Adverse Events of Special Interest
From the time of local approval of protocol Amendment 5 onwards, TTS is considered to be an
AESI. Suspected AESIs (thrombotic events and thrombocytopenia [defined as platelet count below
150,000/µL0]) will be recorded from the moment of vaccination until the end of the study/early
withdrawal. An AESI Adjudication Committee with appropriate expertise will be established to
evaluate each suspected AESI and determine whether it is a case of TTS. (see Section 8.3.6).
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 CRF, which must be completed and reviewed by a physician
from the study site and transmitted to the sponsor within 24 hours. The initial and follow-up reports
of an SAE should be transmitted electronically or by facsimile (fax). Telephone reporting should
be the exception and the reporter should be asked to complete the appropriate form(s) first.
Adolescents
Signs and symptoms of Multisystem Inflammatory Syndrome in Children (MIS-C) will be
monitored and reported as SAE in children with (suspected) COVID-19 as confirmed by a positive
RT-PCR result for SARS-CoV-2, and in children of mothers or close relatives with prior (within
4-weeks) or current suspected or confirmed COVID-19. Further details on case definition and
reporting of MIS-C in children can be found in section 10.12.
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.

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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 1
hour for the presence of any acute reactions and solicited events.
In addition, participants (or parents/legal guardians of the minor 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 days post-vaccination (day of
vaccination and the subsequent 7days). 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.0,0
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 7 days 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.0
After each vaccination, participants will remain under observation at the study site for at least
1 hour to monitor for the presence of any acute reactions and solicited events.
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 in the
participant diary.

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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, suspected
AESI, SAE, or PQC as fully as possible. This may include additional laboratory tests or
investigations, histopathological examinations, or consultation with other health care
professionals.
AEs, including pregnancy, will be followed by the investigator as specified in Section 10.4.
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 participants or partners of male participants must be reported to
the sponsor by the study-site personnel within 24 hours of their knowledge of the event using the
appropriate pregnancy notification form. Abnormal pregnancy outcomes (eg, spontaneous
abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy) are considered SAEs and
must be reported using an SAE reporting form. Any participant who becomes pregnant during the
study must discontinue further study vaccination.
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 class effects, or based on nonclinical signals. AESIs
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.

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8.3.6.1. 
Thrombosis with Thrombocytopenia Syndrome (TTS)
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.
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 10.13, Appendix 13. A suspected TTS case is defined as:
 
Thrombotic events: suspected deep vessel venous or arterial thrombotic events as detailed in
Section 10.14, Appendix 14 OR,
 
Thrombocytopenia, defined as platelet count below 150,000/μL0
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.
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 10.13, Appendix 13 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, or TTS  reported prior to
protocol Amendment 5.

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8.4. 
Virology Assessments
Nasal swabs collected by or from participants with COVID-19-like symptoms may be tested at the
central laboratory for the presence of SARS-CoV-2 and other respiratory pathogens using a broad
respiratory pathogens panel.
8.5. 
Biomarkers
For participants with a positive test result for SARS-CoV-2 infection, blood will be drawn for
evaluation of biomarkers (eg, those associated with severe COVID-19), as indicated in
Section 1.3.7).
8.6. 
Medical Resource Utilization and Health Economics
Health Economics/Medical Resource Utilization and Health Economics parameters are not
evaluated in this study.
9. 
STATISTICAL CONSIDERATIONS
Statistical analysis will be done by the sponsor or under the authority of the sponsor. A general
description of the statistical methods to be used to analyze the efficacy and safety data is outlined
below. Specific details will be provided in the SAP.
9.1. 
Statistical Hypotheses
No formal hypothesis testing will be performed in this study.
9.2. 
Sample Size Determination
The number of adult participants chosen for this study will provide a preliminary safety and
immunogenicity assessment.
Sample size for the adolescent participants was originally calculated based on assessment of non-
inferiority of immune responses with adults; however, following the initial vaccination of the first
33 adolescent participants (sentinels + safety cohort) in the 16-17 year old age group at a dose of
2.5x1010 vp, the entire COVID-10 vaccine program, was paused to evaluate the safety concern of
TTS in adults. During the pause, the safety and immunogenicity data for these 33 adolescent
participants was evaluated (see current version of Investigator’s Brochure0). Based on these
results, the sponsor decided to cease enrollment of additional adolescents in this study.  Instead,
further evaluation of safety, reactogenicity and immunogenicity in pediatric populations, including
dose selection of Ad26.COV2.S, will proceed under separate study protocols.
9.2.1. 
Immunogenicity
The primary objective in the adult population of the study is to explore the dose-response and
interval-response relationship of humoral immune responses induced by different dose levels and
different vaccine administration timings of Ad26.COV2.S using VNA titers and ELISA U/mL.

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To explore the dose-response relationship between VNA/ELISA and different dose levels of the
Ad26.COV2.S vaccine, a separate linear regression model will be fitted for:
 
all active groups 14 days post vaccination 1
 
all active groups 28 days post vaccination 1
 
the 2-dose active groups using data of Groups 1-3, 28 days post vaccination 2
 
the single-dose active groups using data of Groups 4-5, 28 days post vaccination 2
 
the 2-dose active groups, using data of groups 1-3, 14 days post vaccination 2
In the linear regression model the log transformed VNA/ELISA titers at each timepoint will be
used as dependent variable and the dose levels as independent variable.
Depending on the model fit, other models (eg, log-linear models or EMAX models) may be
explored as well for the 56-day interval regimen.
Details on the comparison between the different dose levels and vaccination interval groups will
be outlined in the SAP.
9.2.2. 
Safety
Placebo recipients are included for blinding and safety purposes and will provide additional control
specimens for the 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. The observation of 0 events (eg, SAEs) is associated with 95%
confidence that the true event rate is below the rates specified in Table 9 for the considered number
of participants.
Table 9 : 
Upper Limit of the 95% One-sided Confidence Interval if no Cases are Observed for Different
Sample Sizes
Sample Size 
N=25 
N=50 
N=75 
N=150
Upper Limit 95% one-
sided CI
11.3%  
5.8%  
3.9%  
2.0%
CI = confidence interval, N = number of participants
Table 10 provides the probability of observing at least one AE in a group of the considered sample
size given several true AE rates.

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Table 10: 
Probability of Observing at Least One AE in a Group of the Considered Sample Size Given
Several True AE Rates
True AE Rate 
(%) 
Probability of Observing at Least One AE in N Participants (%)
N=25 
N=50 
N=75 
N=150
0.5 
12 
22 
31 
53
1 
22 
39 
53 
78
2.5 
47 
72 
85 
98
10 
93 
99 
>99.9 
>99.9
25 
>99.9 
>99.9 
>99.9 
>99.9
50 
>99.9 
>99.9 
>99.9 
>99.9
AE = adverse event, N = number of participants
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.
PPI24: The per protocol immunogenicity population will include all randomized and vaccinated
participants for whom immunogenicity data are available excluding participants with major
protocol deviations expected to impact the immunogenicity outcomes. In addition, samples
obtained after missed vaccinations or participants with natural SARS-CoV-2 infection occurring
after screening (if applicable) will be excluded from the analysis.
9.4. 
Statistical Analyses
The SAP will be finalized prior to the first data base lock (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. Safety and
immunogenicity sub-analyses will also be performed by age category. Immunogenicity
sub-analyses will also be performed by BMI, ethnicity, and other factors as will be described in
the SAP.
24 If a participant would be vaccinated out of window due to a study pause, 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 SAP.

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With the implementation of Amendment 5, all adult participants will be unblinded to the primary
vaccination regimen, and adults who received placebo in the primary vaccine regimen will receive
a 2-dose active Ad26.COV2.S vaccine regimen at a 28-day interval and at a dose level of
5x1010 vp, in an open-label manner, at which point the sponsor will also be unblinded.
With the implementation of Amendment 6, the 33 adolescent participants will be unblinded to the
primary vaccination regimen, and those who received placebo (Group C) will receive a single dose
of active Ad26.COV2.S at a dose level of 2.5x1010 vp, in an open-label manner. Limited pooled
safety and reactogenicity data (planned for IDMC review) and group unblinded immunogenicity
data (summary of S-ELISA, including GMC, and seroresponse rates for all participants and
seronegative at baseline participants, in Ad26.COV2.S 2.5x1010 vp only) were reviewed by the
sponsor prior to Amendment 6 (see Section 4.1 Overall Design).
9.4.2. 
Primary/Secondary Endpoints
Immunogenicity Endpoints
Descriptive statistics (geometric mean and confidence intervals, or median and interquartile range
Q1-Q3, as appropriate) will be calculated for continuous immunologic parameters. Several
definitions of serological response will be applied (fold increases in GMT [VNA] or GMC
[ELISA]). 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 together with confidence intervals.
For adults, all data will be analyzed separately from the point of unblinding for safety and
immunogenicity. Details will be described in the SAP.
For adolescents, limited pooled safety and reactogenicity data (planned for IDMC review) and
group unblinded immunogenicity data (summary of S-ELISA, including GMC, and seroresponse
rates for all participants and seronegative at baseline participants, in Ad26.COV2.S 2.5x1010 vp
only) were reviewed by the sponsor prior to Amendment 6 (see Section 4.1 Overall Design).
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).
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 done on the FAS.

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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 one 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, and
AESI or an SAE (including Multisystem Inflammatory Syndrome in Children [MIS-C];
adolescents only).
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 of the abnormalities will
be made.
9.4.3. 
Tertiary/Exploratory Endpoints
Detailed statistical methodology for analysis of exploratory endpoints will be described in the
SAP.
9.4.4. 
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 SAP.

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Statistical analysis of biomarker responses (eg, RNA-seq responses) will be detailed in a separate
SAP.
9.5. 
Planned Analysis
Interim and Primary Analyses for Adult Participants
An interim analysis of safety and immunogenicity will be performed, including all available
immunogenicity data up to Day 29 (if applicable) and all available safety data post vaccination 1
of all groups in the adult cohort. Unblinded data at the vaccination group level will be available to
the sponsor and might be used for regulatory submissions.
The primary analysis of safety and immunogenicity post-vaccination 2 will be performed when all
adult participants have completed the visit that takes place 28 days after the second study
vaccination in all groups or discontinued earlier. The analysis will include safety and
immunogenicity data (VNA and ELISA) for all participants through Day 85 (Groups 1-6), Day 57
(Groups 7-8) or Day 113 (Groups 9-10). It will also include Th1-Th2 responses assessed only in
Groups 1-6 (as available and feasible) through Day 85 (ie, 28 days after the second study
vaccination). Unblinded data at the vaccination group level will be available to the sponsor and
might be used for regulatory submissions.
A second interim analysis of safety and immunogenicity will be performed, including 28-day
immunogenicity and 28-day safety data post antigen presentation of all groups.
The final analysis of the adult cohort will be performed when all included adult participants have
completed the last visit or discontinued earlier.
Additional interim analyses may be performed for safety and/or immunogenicity to facilitate
decision making with regards to the planning of future studies.
Analysis of the adolescent cohort will be performed when all included adolescent participants have
completed the last visit or discontinued earlier.
Additional interim analyses may be performed for safety and/or immunogenicity to facilitate
decision making with regards to the planning of future studies.
General
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 Support Group (SSG) will provide individual level unblinded data pertaining to
study VAC31518COV2001 when unblinding at the participant level is required (see
Section 10.3.6). In addition, they will monitor the number and severity of molecularly confirmed

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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 SMC as soon as an
imbalance between groups is detected. Participants, clinical staff, and study-site personnel will
remain blinded to the study vaccine allocation until implementation of protocol Amendment 5
(adults) or Amendment 6 (adolescents). A prespecified threshold (imbalance above a certain
percentage and/or number of cases) that will trigger notification of the SMC will be described in
the SAP.
The SAP will describe the planned analyses in greater detail.
Participants unblinded due to administration of 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
recommendation 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 data on the safety of receiving 2
different COVID-19 vaccines. Participants who were already unblinded for any reason may
receive Ad26.COV2.S vaccine upon discussion with the investigator, provided that they did not
receive a COVID-19 vaccine. Unblinded participants, whether in the vaccine or control group, will
be asked to continue to be followed in this study in line with the Schedule of Activities to the
extent that the participant is amenable. All data will be analyzed separately from the point of
unblinding for safety and immunogenicity, as described in the SAP.

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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Abbreviations
Ad26 
adenovirus type 26
ADCC  
antibody-dependent cell-mediated cytotoxicity
AdVAC® 
adenoviral vaccine (vector platform)
AE 
adverse event
AESI 
adverse event of special interest
ALT  
alanine aminotransferase
AP  
antigen presentation
AST  
aspartate aminotransferase
BMI 
body mass index
BUN  
Blood Urea Nitrogen
CD  
cluster of differentiation
CDC  
Centers for Disease Control and Prevention
CLS  
Capillary leak syndrome
COPD  
chronic obstructive pulmonary disease
COVID-19 
coronavirus disease-2019
CPK  
creatine phosphokinase
eCRF  
Electronic case report form(s)
CT  
computed tomographic
DBL 
data base lock
DIC  
disseminated intravascular coagulation
DNA  
deoxyribonucleic acid
DRC  
data review committee
DVT  
deep vein thrombosis
eDC  
electronic data capture
ELISA  
enzyme-linked immunosorbent assay
ELISpot 
enzyme-linked immunospot
ERD  
enhanced respiratory disease
EUA  
Emergency Use Authorization
FAS  
full analysis set
Fc 
crystallizable fragment
FDA  
Food and Drug Administration
FI 
formalin-inactivated
FIH  
first-in-human
FOIA  
Freedom of Information Act
GCP  
Good Clinical Practice
GLP  
good laboratory practice
GMC  
Geometric mean concentration
GMT  
Geometric mean titer
HIT  
heparin-induced thrombocytopenia
HIV  
human immunodeficiency virus
IB  
investigator’s brochure
ICF  
informed consent form
ICS  
intracellular cytokine staining
ICH  
International Conference on Harmonisation
ICMJE 
International Committee of Medical Journal Editors
ICU  
intensive care unit
IDMC  
Independent Data Monitoring Committee
IEC  
Independent Ethics Committee
IFN-γ 
interferon gamma
IL 
interleukin
IM  
intramuscular
IND  
Investigational New Drug

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IPPI 
Investigational Product Preparation Instructions
IRB  
Institutional Review Board
IUD  
intrauterine device
IUS  
intrauterine hormone-releasing system
IWRS  
interactive web response system
MedDRA  
Medical Dictionary for Regulatory Activities
MERS (-CoV) 
Middle East respiratory syndrome (coronavirus)
MIS-C 
multisystem inflammatory syndrome in children
MSD  
meso scale discovery
N 
nucleocapsid
NI 
non-inferiority
NIAID  
National Institute of Allergy and Infectious Diseases
PBMC  
peripheral blood mononuclear cells
PI 
principal investigator
PPI 
per protocol immunogenicity
PQC  
product quality complaint
PRBC  
packed red blood cells
PSRC  
Prevention Science Review Committee
PT  
prothrombin time
PTT  
partial thromboplastin time
RBD  
receptor-binding domain
RNA  
ribonucleic acid
RSV  
respiratory syncytial virus
RT-PCR  
real-time reverse-transcriptase polymerase chain reaction
S 
spike
SAE 
serious adverse event
SAP  
statistical analysis plan
SARS  
severe acute respiratory syndrome
SARS-CoV(-2) 
severe acute respiratory syndrome coronavirus(-2)
SIC  
Symptoms of Infection with Coronavirus-19
SIPPM  
site investigational product and procedures manual
SMC  
Safety Monitoring Committee
SoA  
Schedule of Activities
SRP/S  
study responsible physician/scientist
SUSAR  
suspected unexpected serious adverse reaction
Th 
T helper
TNF-α 
tumor necrosis factor alpha
TTS  
thrombosis with thrombocytopenia syndrome
ULN  
upper limit ofthe normal range
US  
United States
VNA  
virus neutralization assay
vp 
virus particle
WBC  
white blood cell
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.
Good Clinical Practice is an international ethical and scientific quality standard for designing,
conducting, recording, and reporting studies that involve the participation of human participants.
Compliance with this standard provides public assurance that the rights, safety, and well-being of
study participants are protected, consistent with the principles that originated in the Declaration of
Helsinki, and that the study data are credible.
The investigator will be responsible for reporting cases of suspected child abuse or neglect
according to local regulations.
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
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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)

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 
IB (or equivalent information) and amendments/addenda
 
Sponsor-approved participant recruiting materials
 
Information on compensation for study-related injuries or payment to participants for
participation in the study, if applicable
 
Investigator's curriculum vitae or equivalent information (unless not required, as documented
by the 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

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For all protocol amendments (excluding the ones that are purely administrative, with no
consequences for participants, data or study conduct), the amendment and applicable ICF revisions
must be submitted promptly to the IEC/IRB for review and approval before implementation of the
change(s).
At least once a year, the IEC/IRB will be asked to review and reapprove this study, where required.
At the end of the study, the investigator (or sponsor where required) will notify the IEC/IRB about
the study completion.
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 and Assent Form
For adults:
Each participant must give written consent according to local requirements after the nature of the
study has been fully explained. 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.
For adolescents:
Legal guardian(s) (as defined in Section 2), as per local requirements must give written consent
and the child (minor) must give assent according to local requirements after the nature of the study
has been fully explained and before the child can be enrolled in the study. Assent must be obtained
from children (minors) capable of understanding the nature of the study, typically participants

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7years of age and older, depending on the institutional policies; it should be written in language
appropriate to the child’s developmental and functional status. Written assent should be obtained
from participants who are able to write. A separate assent form written in language the participant
can understand should be developed for adolescents. The participant (as appropriate) and legal
guardian(s)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/assent should be appropriately recorded
by means of the participant's, if appropriate, and legal guardian’s personally dated signature. After
having obtained the ICF and assent form, a copy of each form must be given to the participant and
to the participant's legal guardian(s). For the purposes of this study, all references to participants
who have provided consent (and assent as applicable) refer to the participants and his or her legal
guardian(s) who have provided consent according to this process. Minor participants who assent to
a study and later withdraw that assent should not be maintained in the study against their will, even
if their legal guardian still wants them to participate. Minor participants must be reconsented if they
reach the age of majority during the course of the study, in order to continue participation.
Emancipated minors may be permitted to enroll as allowed by local regulations.
The source document must include a statement that the consent signed by the legal guardian(s)and
the assent signed by the participant (if appropriate) were obtained before the participant was
enrolled in the study as well as the date the written consent was obtained. The authorized person
obtaining the informed consent and assent must also sign the ICF and assent forms.
For adults and adolescents:
The ICF(s) and assent form must be signed before performance of any study-related activity. The
ICF(s) and assent form 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
and assent form 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 or their legally acceptable representatives (in case
of an adolescent participant, as appropriate) the aims, methods, reasonably anticipated benefits,
and potential hazards of the study, and any discomfort participation in the study may entail. They
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 and legal guardian(s) (in case of an adolescent participant, as
appropriate) are authorizing such access. It also denotes that the participant and legal guardian(s)
agree to allow his or her study physician to recontact them for the purpose of obtaining consent
for additional safety evaluations, if needed.

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Participants who are rescreened are required to sign a new ICF.
If the participant, if appropriate, or legal guardian(s) are unable to read or write, an impartial
witness should be present for the entire informed consent and assent process (which includes
reading and explaining all written information) and should personally date and sign the ICF after
the oral consent of the participant andlegal guardian(s)(as appropriate for adolescents)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/assent obtained from the participant includes explicit consent for the
processing of personal data and for the investigator/institution to allow direct access to his or her
original medical records (source data/documents) for study-related monitoring, audit, IEC/IRB
review, and regulatory inspection. This consent also addresses the transfer of the data to other
entities and to other countries.
The participant has the right to request through the investigator access to his or her personal data
and the right to request rectification of any data that are not correct or complete. Reasonable steps
will be taken to respond to such a request, taking into consideration the nature of the request, the
conditions of the study, and the applicable laws and regulations.
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 intervention  responders, and to develop

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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/assent for their samples
to be stored for research (refer to Section 7.2.1, Withdrawal From the Use of Research Samples).
10.3.6. 
Safety Monitoring Committees Structure
Safety Monitoring Committee
Initially, an internal DRC was commissioned for this study. Since then, an Independent Data
Monitoring Committee (IDMC) was installed for the different studies throughout the COVID-19
vaccine program. In light of the transition of DRC to IDMC, when the term Safety Monitoring
Committee (SMC) is mentioned, it can refer to either.
The SMC  consists 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 SMC reviews data as indicated in
Section 4.1, Overall Design. When appropriate, the conclusions of the SMC 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 6.10, Study Vaccination Pausing Rules, or at
request of the sponsor’s medical monitor or designee. The PI(s) and SRP will inform the SMC of
any AE of concern.
The SMC reviews 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 SMC 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
the case, a biomarker representative (not involved in the conduct of the study) will be part of the
SMC.
This committee consists of at least one medical expert in the relevant therapeutic area and at least
one statistician. The SMC responsibilities, authorities, and procedures will be documented in its
charter.
If any pausing rule is met (refer to Section 6.10) and, if following appropriate safety review it is
deemed appropriate to restart dosing, the sponsor must submit a request to restart dosing with
pertinent data to competent authority as a request for a substantial amendment, as required by local
regulations or authority request (eg, the Medicines and Healthcare products Regulatory Agency
[MHRA]). If needed, this will be followed by a substantial amendment of the IB and/or protocol.

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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.
Statistical Support Group
The SSG is the statistical support group to the IDMC; they are provided with the statistical analysis
data. As the IDMC, they are independent to the company.
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
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

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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 eCRF for accuracy and completeness during on-site monitoring visits and
after transmission to the sponsor; any discrepancies will be resolved with the investigator or
designee, as appropriate. After upload of the data into the study database they will be verified for
accuracy and consistency with the data sources.

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10.3.9. 
Case Report Form Completion
Case report forms are prepared and provided by the sponsor for each participant in electronic
format. All data relating to the study must be recorded in eCRF. All eCRF entries, corrections, and
alterations must be made by the investigator or authorized study-site personnel. The investigator
must verify that all data entries in the eCRF are accurate and correct.
The study data will be transcribed by study-site personnel from the source documents onto an
eCRF, if applicable. Study-specific data will be transmitted in a secure manner to the sponsor.
Worksheets may be used for the capture of some data to facilitate completion of the eCRF. Any
such worksheets will become part of the participant's source documents. Data must be entered into
the eCRF in English. The eCRF must be completed as soon as possible after a participant visit and
the forms should be available for review at the next scheduled monitoring visit.
All participative measurements (eg, questionnaires) will be completed by the same individual who
made the initial baseline determinations whenever possible.
If necessary, queries will be generated in the electronic data capture (eDC) tool. If corrections to
a CRF 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  (including medical history  and prestudy medication), and
study identification; study discussion and date of signed informed consent/assent; 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. The

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documentation of the positive RT-PCR result that serves as a trigger to start procedures for
COVID-19 follow-up, will be considered source data.
Specific details required as source data for the study and source data collection methods will be
reviewed with the investigator before the study and will be described in the monitoring guidelines
(or other equivalent document).
An eSource system may be utilized, which contains data traditionally maintained in a hospital or
clinic record to document medical care (eg, electronic source documents) as well as the clinical
study-specific data fields as determined by the protocol. This data is electronically extracted for
use by the sponsor. If eSource is utilized, references made to the eCRF in the protocol include the
eSource system but information collected through eSource may not be limited to that found in the
eCRF.
10.3.11. 
Monitoring
The sponsor will use a combination of monitoring techniques central, remote, 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.

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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
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.

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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.
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, Serious Adverse Events, Adverse Events of
Special Interest, Product Quality Complaints, and Other Safety Reporting:
Definitions and Procedures for Recording, Evaluating, Follow-up, and
Reporting
10.4.1. 
Adverse Event Definitions and Classifications
Adverse Event
An AE is any untoward medical occurrence in a clinical study participant administered a
pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have
a causal relationship with the 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

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 
Is Medically Important*
*Medical and scientific judgment should be exercised in deciding whether expedited reporting is
also appropriate in other situations, such as important medical events that may not be immediately
life-threatening or result in death or hospitalization but may jeopardize the participant or may
require intervention to prevent one of the other outcomes listed in the definition above. These
should usually be considered serious.
If a serious and unexpected AE occurs for which there is evidence suggesting a causal relationship
between the study vaccine and the event (eg, death from anaphylaxis), the event must be reported
as a serious and unexpected suspected adverse reaction even if it is a component of the study
endpoint (eg, all-cause mortality).
Any respiratory tract infection fulfilling the criteria of an SAE will be reported as such during the
entire study period if molecular testing indicates it is not a SARS-CoV-2 infection. If the molecular
test is positive for SARS-CoV-2, the event should not be reported as an SAE. If molecular test
results are not available within 24 hours of knowledge of the event, the event will be reported as
an SAE, but will be subsequently downgraded from SAE status if it later turns out to be positive
for SARS-CoV-2 by molecular testing.
Unlisted (Unexpected) Adverse Event/Reference Safety Information
An AE is considered unlisted if the nature or severity is not consistent with the applicable product
reference safety information. For Ad26.COV2.S, the expectedness of an AE will be determined
by whether or not it is listed in the IB.
10.4.2. 
Attribution Definitions
Assessment of Causality
The causal relationship to the study vaccine is determined by the Investigator. The following
selection should be used to assess all AEs.
Related
There is a reasonable causal relationship between study vaccine administration and the AE.
Not Related
There is not a reasonable causal relationship between study vaccine administration and the AE.
The term "reasonable causal relationship" means there is evidence to support a causal relationship.
By definition, all solicited AEs at the injection site (local) will be considered related to the study
vaccine administration.

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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 the version of September 20070, included in Section 10.6.
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. (Note: severity of the measured events will be derived from
the diameter [for erythema and swelling] and the temperature measurements [for fever])
10.4.4. 
Special Reporting Situations
Safety events of interest on a sponsor study vaccine in an interventional study that may require
expedited reporting or safety evaluation include, but are not limited to:
 
Overdose of a sponsor study vaccine
 
Suspected abuse/misuse of a sponsor study vaccine
 
Accidental or occupational exposure to a sponsor study vaccine
 
Medication error, intercepted medication error, or potential medication error involving a
Johnson & Johnson medicinal product (with or without patient exposure to the Johnson &
Johnson medicinal product, eg, product name confusion, product label confusion, intercepted
prescribing or dispensing errors)
 
Exposure to a sponsor study vaccine from breastfeeding
Special reporting situations should be recorded in the eCRF. Any special reporting situation that
meets the criteria of an SAE should be recorded on the SAE page of the eCRF.

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10.4.5. 
Procedures
All Adverse Events
All AEs, regardless of seriousness, severity, or presumed relationship to study vaccination, 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 (and semi-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
Serious Adverse Events
All SAEs that have not resolved by the end of the study, or that have not resolved upon  the
participant's discontinuation from the study, must be followed until any of the following occurs:
 
The event resolves
 
The event stabilizes
 
The event returns to baseline, if a baseline value/status is available
 
The event can be attributed to agents other than the study vaccine or to factors unrelated to
study conduct
 
It becomes unlikely that any additional information can be obtained (participant or health care
practitioner refusal to provide additional information, lost to follow-up after demonstration of
due diligence with follow-up efforts)
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:

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 
Hospitalizations not intended to treat an acute illness or AE (eg, social reasons such as pending
placement in long-term care facility)
 
Surgery or procedure planned before entry into the study (must be documented in the eCRF).
Note: Hospitalizations that were planned before the signing of the ICF, and where the
underlying condition for which the hospitalization was planned has not worsened, will not be
considered SAEs. Any AE that results in a prolongation of the originally planned
hospitalization is to be reported as a new SAE.
The cause of death of a participant in a study, whether or not the event is expected or associated
with the study vaccine, is considered an SAE.
Information regarding SAEs will be transmitted to the sponsor using an SAE reporting form and
safety report form of the eCRF, which must be completed and reviewed by a physician from the
study site, and transmitted in a secure manner to the sponsor within 24 hours. The initial and
follow-up reports of an  SAE should be transmitted in a secure manner electronically or by
facsimile (fax). Telephone reporting should be the exception and the reporter should be asked to
complete the appropriate form(s) first.
Adverse Events of Special Interest
AESIs will be carefully monitored during the study by the sponsor. Suspected AESIs must be
reported to the sponsor within 24 hours of awareness irrespective of seriousness (ie, serious and
non-serious AEs) or causality assessment, following the procedure described above for SAEs and
will require enhanced data collection.
10.4.6. 
Product Quality Complaint Handling
Definition
A 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.
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 an acceptable 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).0
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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Clinical Protocol VAC31518COV2001 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved,  Date: 21 July 2021
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
Creatine phosphokinase 
(CPK) –mg/dL 
1.25 –1.5 x  
ULN***
1.6 –3.0 x ULN  3.1 –10 x ULN  
> 10 x ULN
Albumin –Hypoalbuminemia g/dL 
2.8 –3.1 
2.5 –2.7 
< 2.5 
--
Total Protein –Hypoproteinemia g/dL 
5.5 –6.0 
5.0 –5.4 
< 5.0 
--
Alkaline phosphate – 
increase by factor
1.1 –2.0 x ULN  2.1 –3.0 x ULN  3.1 –10 x ULN  > 10 x ULN
Liver Function Tests –ALT, AST  
increase by factor
1.1 –2.5 x ULN  2.6 –5.0 x ULN  5.1 –10 x ULN  > 10 x ULN
Bilirubin –when accompanied 
by any increase in Liver Function Test 
increase by factor
1.1 –1.25 x 
ULN  
1.26 –1.5 x 
ULN  
1.51 –1.75 x 
ULN
> 1.75 x ULN

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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 
1 - 10 
11 –50 
> 50 and/or 
gross
Hospitalization or

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high power field (rbc/hpf) 
blood 
packed red blood cells (PRBC)
transfusion
* The laboratory values provided in the tables serve as guidelines and are dependent upon institutional normal
parameters. Institutional normal reference ranges should be provided to demonstrate that they are appropriate.
10.7. Appendix 7: Symptoms of Infection with Coronavirus-19 (SIC)
The following questions ask about symptoms people with coronavirus-19 infection may
experience. Answer each question carefully by choosing ‘yes’ if you have experienced the
symptom or ‘no’ if you have not experienced the symptom in the last 24 hours. If you choose
‘yes’, select the rating that best matches your experience.
In the last 24 hours, 
have you
experienced…
Please rate the severity of each symptom you experienced.
Feeling generally 
unwell (run down)
Yes No
  If yes, 
How severe was your feeling (generally unwell or run down) in the last 24 hours?
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10
None 
Worst
possible
Fatigue (tiredness)
Yes No
  If yes, 
How severe was your fatigue (tiredness) in the last 24 hours?
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10
None 
Worst
possible
Physical weakness
Yes No
  If yes, 
How severe was your feeling of physical weakness in the last 24 hours?
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10
None 
Worst
possible
Cough
Yes No
  If yes, 
How severe was your cough in the last 24 hours?
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10
None 
Worst
possible
Shortness of breath
(difficulty
breathing)
Yes No
  If yes, 
How severe was your shortness of breath (difficulty breathing) in the last 24 hours?
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10
None 
Worst
possible
Sore throat
Yes No
  If yes, 
How severe was your sore throat in the last 24 hours?
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10
None 
Worst
possible
Nasal congestion
(stuffy nose)
Yes No
  If yes, 
How severe was your nasal congestion (stuffy nose) in the last 24 hours?
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10
None 
Worst
possible

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Clinical Protocol VAC31518COV2001 Amendment 6
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Status: Approved,  Date: 21 July 2021
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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Status: Approved,  Date: 21 July 2021
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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Status: Approved,  Date: 21 July 2021
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 forehead 
rectal
In the last 24 hours, have you experienced…
Uncontrollable body shaking/shivering
Yes 
No
Decreased sense of smell
Yes 
No
Decreased sense of taste
Yes 
No
Red or bruised looking feet or toes
Yes 
No

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Please rate the severity of your symptoms in the last 24 hours?
  No Symptoms
  Mild
  Moderate
  Severe

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Status: Approved,  Date: 21 July 2021
10.8. Appendix 8: Case Definitions for COVID-19
10.8.1. 
Case Definition for Moderate to Severe/Critical 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 observation until signs and symptoms disappear:
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 investigator judgment.
** Having 2 or more elements of a symptom (eg, vomiting and diarrhea or fatigue and loss of appetite) is counted only as 1
symptom for the case definition. To meet the case definition, a participant would need to have at least 2 different symptoms.

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Case Definition for Severe/Critical COVID-19
 
A SARS-CoV-2 positive RT-PCR or molecular test result from any available respiratory tract
sample (eg, nasal swab sample, sputum sample, throat swab sample, saliva sample) or other
sample
AND any 1 of the following at any time during the course of observation:
 
Clinical signs at rest indicative of severe systemic illness (respiratory rate ≥30 breaths/minute,
heart rate ≥125 beats/minute, oxygen saturation (SpO2) ≤93% on room air at sea level*, or
partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) <300 mmHg)
* SpO2 criteria will be adjusted according to altitude.
 
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 observation:
 
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.

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10.8.3. 
US FDA Harmonized Case Definition for COVID-19
If a participant presents with symptoms as those listed by the US FDA harmonized case definition0
(see Section 10.11), 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
 
COVID-19 symptoms consistent with those defined by the US FDA harmonized case
definition0 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 fulfill the criteria for suspected COVID-19 based on signs and symptoms
(see Section 8.1.2.1),
AND
 
has a SARS-CoV-2 positive RT-PCR
OR
 
develops a positive serology (non-S protein) test
Then, the participant will be considered to have experienced asymptomatic or undetected
COVID-19.
A positive RT-PCR for SARS-CoV-2 regardless of where the testing was performed (under the
auspices of the study or through a private or public laboratory independent of the study) will need
to be captured in the eCRF.
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: Summary of Guidance from CDC Website25 on Underlying
Medical Conditions That Lead or Might Lead to Increased Risk for Severe
Illness From COVID-19 –Used for Adult Cohort
People of any age with certain underlying medical conditions are at increased risk for severe
illness from the virus that causes COVID-19. Severe illness from COVID-19 is defined as
hospitalization, admission to the ICU, intubation or mechanical ventilation, or death.
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 but < 40 kg/m²)
 
Severe Obesity (BMI ≥ 40 kg/m²)
 
Heart conditions, such as heart failure, coronary artery disease, or cardiomyopathies
 
Pregnancy
 
Sickle cell disease
 
Smoking
 
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
25 
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 03 December 2020.

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 
Neurologic conditions, such as dementia
 
Liver disease
 
Pulmonary fibrosis (having damaged or scarred lung tissues)
 
Thalassemia (a type of blood disorder)
 
Type 1 diabetes mellitus

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10.10. Appendix 10: Summary of Guidance from CDC Website26 on Underlying
Medical Conditions That Lead or Might Lead to Increased Risk for Severe
Illness From COVID-19 –Used for Adolescent Cohort
CDC and partners are investigating a rare but serious medical condition associated with COVID-19
in children called Multisystem Inflammatory Syndrome in Children (MIS-C). We do not yet know
what causes MIS-C and who is at increased risk for developing it.
Babies under 1 year old might be more likely to have severe illness from COVID-19. Other
children, regardless of age, with the following underlying medical conditions might also be at
increased risk of severe illness compared to other children:
 
Asthma or chronic lung disease
 
Diabetes
 
Genetic, neurologic, or metabolic conditions
 
Heart disease since birth
 
Immunosuppression (weakened immune system due to certain medical conditions or being on
medications that weaken the immune system)
 
Medical complexity (children with multiple chronic conditions that affect many parts of the
body who are often dependent on technology and other significant supports for daily life)
 
Obesity
This list does not include every underlying condition that might increase the risk for severe illness
in children. As more information becomes available, CDC will continue to update and share
information about risk for severe illness among children.
26 Source: https://www.cdc.gov/coronavirus/2019-ncov/daily-life-
coping/children/symptoms.html#:~:text=Babies%20under%201%20year%20old%20might%20be%20more%20l
ikely%20to,Asthma%20or%20chronic%20lung%20disease. Accessed: 03 December 2020.

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10.11. Appendix 11: 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 and were still accurate at the time of finalization of this protocol Amendment 2:

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10.12. Appendix 12: Multisystem Inflammatory Syndrome in Children
Multisystem Inflammatory Syndrome in Children (MIS-C)
MIS-C is a serious and potentially fatal condition that can arise in infants and children infected
with SARS-CoV-2, and which can result in inflammation of a range of organs. Patients with
MIS-C usually present with persistent fever, fatigue and a variety of signs and symptoms including
multiorgan (eg, cardiac, gastrointestinal, renal, hematologic, dermatologic, neurologic)
involvement, elevated inflammatory markers and, in severe cases, hypotension and shock.
MIS-C may present weeks after a child is infected with SARS-CoV-2. The child may have been
infected from an asymptomatic contact and, in some cases, the infant and their
parent(s)/caregiver(s) may not even know that they have been infected.
Although different presentations have been described, common symptoms include:
 
Kawasaki disease-like features: conjunctivitis, red eyes; red or swollen hands and feet; rash;
red cracked lips, swollen glands. Coronary artery enlargement and/or aneurysms have been
described. Other symptoms include gastrointestinal (abdominal pain or diarrhea) and
neurologic (headaches/meningitis) manifestations.
 
Toxic shock syndrome-like features with hemodynamic instability.
 
Cytokine storm/macrophage activation or hyperinflammatory features.
 
Thrombosis, poor heart function, diarrhea and gastrointestinal symptoms, acute kidney injury.
 
Shortness of breath suggestive of congestive heart failure.
The Center for Disease Control and Prevention issued a Health Advisory on 14 May 2020 that
outlines the following case definition for MIS-C (https://www.cdc.gov/mis-c/hcp/index.html):
Case definition for MIS-C
 
An individual aged <21 years presenting with fever27, laboratory evidence of inflammation28,
and evidence of clinicallysevere illness requiring hospitalization, with multisystem (>2) organ
involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic or
neurological); AND
 
No alternative plausible diagnoses; AND
27 *Fever >38.0°C for ≥24 hours, or report of subjective fever lasting ≥24 hours
28 Including, but not limited to, one or more of the following: an elevated C-reactive protein (CRP), erythrocyte
sedimentation rate (ESR), fibrinogen, procalcitonin, d-dimer, ferritin, lactic acid dehydrogenase (LDH), or
interleukin 6 (IL-6), elevated neutrophils, reduced lymphocytes and low albumin

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 
Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test; or
exposure to a suspected or confirmed COVID-19 case within the 4 weeks prior to the onset of
symptoms.
Common Signs and Symptoms associated with MIS-C include the following:
 
Fever (fever ≥38.0oC for ≥24 hours, or report of subjective fever lasting ≥24 hours)
 
Abdominal pain
 
Vomiting
 
Diarrhea
 
Neck pain
 
Rash
 
Bloodshot eyes
 
Feeling extra tired
Note: not all children will have the same signs and symptoms, and some children may have
symptoms that are not listed here.
Immediate emergency care is required in the event of the child showing any of the following
signs of MIS-C:
 
Trouble breathing
 
Pain or pressure in the chest that does not go away
 
New confusion
 
Inability to wake or stay awake
 
Bluish lips or face
 
Severe abdominal pain
Common laboratory findings include:
 
An abnormal level of inflammatory markers in the blood, including elevated erythrocyte
sediment rate (ESR)/C-reactive protein (CRP) and ferritin, lactate dehydrogenase (LDH).
 
Lymphopenia <1000, thrombocytopenia <150,000, neutrophilia.
 
Elevated B-type natriuretic peptide (BNP) or NT-proBNP (pro-BNP), hyponatremia, elevated
D-dimers.

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10.13. Appendix 13: TTS AESI Form
The form below represents the type of information that may be collected in case of a suspected
AESI in order to help adjudicate whether the event is a case of TTS. Additional data may be
requested by the sponsor for investigation of the event.
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:

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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:
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)
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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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
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
Anti-cardiolipin antibodies (IgG
and IgM) or beta-2
glycoproteins antibodies

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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)
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
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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10.14. Appendix 14: Thrombotic Events to be Reported as Suspected AESIs
At the time of protocol Amendment 5 writing, the list of thrombotic events to be reported to the
sponsor as suspected 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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10.15. Appendix 15: Protocol Amendment History
The Protocol Amendment Summary of Changes Table for the current amendment is located
directly before the Table of Contents.
Amendment 5 (18 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.
The purpose of this amendment is to update safety procedures for all enrolled participants (adults
and adolescents). At the time of protocol Amendment 5, enrollment and vaccination of adolescents is
paused pending further evaluation of benefit-risk in adolescents. Enrollment and vaccination of
adolescents will resume with protocol Amendment 6.
Section Number
and Name
Description of Change 
Brief Rationale
1.1 Synopsis
1.3.1 Groups 1 to 6 (56-day interval
schedule [2-dose and single dose
regimens]) –Adults
1.3.2 Groups 7 and 8 (28-day
interval schedule)- Adults$
1.3.3 Groups 9 and 10 (84-day
interval schedule) –Adults
1.3.4 Active Vaccine Regimen:
Placebo Groups 6, 8 and 10 (28-day
interval schedule [2-dose and single
dose regimens]) –Adults
1.3.5 Groups A to F (56-day
interval [2-dose and 1- dose
regimens, with booster]) –
Adolescents
1.3.8 Participants with a Suspected
AESI –Adults & Adolescents
2.3.1 Risks Related to Study
Participation
2.3.3 Benefit-Risk Assessment of
Study Participation
3 OBJECTIVES AND
ENDPOINTS
6.9 Prestudy and Concomitant
Therapy
7.1 Discontinuation of Study
Vaccination
8 STUDY ASSESSMENTS AND
PROCEDURES
8.2.4 Hematology Clinical
Laboratory Assessments
8.3 Adverse Events, Serious
Adverse Events, Adverse Events of
Special Interest, and Other Safety
Reporting
8.3.1 Time Period and Frequency
for Collecting Adverse Event,
Adverse Event of Special Interest,
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
TTS, with onset of symptoms
approximately 1-2 weeks after
vaccination. Therefore, additional
reporting and data collection
procedures are implemented to
follow-up thrombotic events and
thrombocytopenia and identify
cases of TTS.

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Section Number 
and Name
Description of Change 
Brief Rationale
and Serious Adverse Event
Information
8.3.2 Method of Detecting Adverse
Events, Adverse Events of Special
Interest, and Serious Adverse
Events
8.3.3 Follow-up of Adverse Events,
Adverse Events of Special Interest,
and Serious Adverse Events
8.3.6 Adverse Events of Special
Interest
8.3.6.1 Thrombosis with
Thrombocytopenia Syndrome
9.4.2 Primary/Secondary Endpoints
10.2 Appendix 2: Hematology
Clinical Laboratory Tests
10.3.6 Safety Monitoring
Committees Structure
10.4 Appendix 4: Adverse Events,
Serious Adverse Events, Adverse
Events of Special Interest, Product
Quality Complaints, and Other
Safety Reporting: Definitions and
Procedures for Recording,
Evaluating, Follow-up, and
Reporting
10.4.5 Procedures
10.13 Appendix 13: TTS AESI
Form (added)
10.14 Thrombotic Events to be
Reported as Suspected AESIs
(added)
1.1 Synopsis 
1.2 Schema 
1.3.1 Groups 1 to 6 (56-day interval 
schedule [2-dose and single dose 
regimens]) –Adults 
1.3.2 Groups 7 and 8 (28-day 
interval schedule)- Adults 
1.3.3 Groups 9 and 10 (84-day 
interval schedule) –Adults 
4.1 Overall Design  
6.4 Unblinding and Open-label 
Phase (added) 
8 STUDY ASSESSMENTS AND 
PROCEDURES 
9.4.1 General Considerations
Text/tables were updated to 
indicate that all adult groups 
received injection 3, either antigen
presentation (Group 1-5, 7, 9) or
placebo (Groups 6, 8, 10), followed
by an on-site unblinding visit
between Injection 3 and 6 months
post Injection 3. Due to a second
study pause in April 2021, no
groups will have been unblinded on
a group level prior to
implementation of protocol
Amendment 5. Unblinding visit
was added to Figures 1, 2 and 3.
To reflect what actually occurred
during the study.
1.1 Synopsis 
4.1 Overall Design  
4.3 Justification for Dose 
Justification for the 2-dose regimen 
in adult participants who originally 
received placebo was added. 
the total number of placebo
recipients from Groups 6, 8 and 10
(target n=75) is intended to fulfill
the original target enrollment for
Group 7, which was meant to
receive 2 doses at a 28-day interval.

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Section Number 
and Name
Description of Change 
Brief Rationale
1.3.1 Groups 1 to 6 (56-day interval 
schedule [2-dose and single dose 
regimens]) –Adults 
1.3.2 Groups 7 and 8 (28-day 
interval schedule)- Adults
1.3.3 Groups 9 and 10 (84-day
interval schedule) –Adults
8 STUDY ASSESSMENTS AND
PROCEDURES
Additional 5 mL blood draw for 
plasma at Visit 10 is deleted. 
All participants received Injection 3
prior to implementation of protocol
Amendment 4, so this draw was not
collected from any participants.
1.1 Synopsis 
1.3.1 Groups 1 to 6 (56-day interval 
schedule [2-dose and single dose 
regimens]) –Adults
1.3.2 Groups 7 and 8 (28-day
interval schedule)- Adults
1.3.3 Groups 9 and 10 (84-day
interval schedule) –Adults
1.3.4 Active Vaccine Regimen:
Placebo Groups 6, 8 and 10 (28-day
interval schedule [2-dose and single
dose regimens]) –Adults
3 OBJECTIVES AND
ENDPOINTS
8.2.4 Hematology Clinical
Laboratory Assessments
10.2 Appendix 2: Hematology
Clinical Laboratory Tests
Anti-PF4 was added as a 
hematology endpoint. 
This was added to fully evaluate
coagulation parameters per current
medical practice
1.1 Synopsis 
1.3.1 Groups 1 to 6 (56-day interval 
schedule [2-dose and single dose 
regimens]) –Adults 
1.3.2 Groups 7 and 8 (28-day 
interval schedule)- Adults 
1.3.3 Groups 9 and 10 (84-day 
interval schedule) –Adults
4.1 Overall Design
6.3 Measures to Minimize Bias:
Randomization and Blinding
6.4 Unblinding and Open-label
Phase
9.4.1 General Considerations
Reference to EUA or other 
approval and reference to “at 
approximately 6 months of study
participation” were deleted in the
adult sections, and unblinding
procedures were instead linked to
implementation of Amendment 5.
Clarification of timing around
unblinding
1.2 Schema 
1.3.4 Active Vaccine Regimen: 
Placebo Groups 6, 8 and 10 (28-day 
interval schedule [2-dose and single 
dose regimens]) –Adults 
8 STUDY ASSESSMENTS AND 
PROCEDURES  
The Visits were renumbered in 
Figure 4 and SoA for Placebo 
Groups to clarify that the start of
the open-label portion of the study
from the time of unblinding and
subsequent visits are not linked to
prior vaccinations.
Clarification of changes made in
protocol Amendment 4.

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Section Number 
and Name
Description of Change 
Brief Rationale
1.1 Synopsis 
6.3 Measures to Minimize Bias: 
Randomization and Blinding 
6.4 Unblinding and Open-label 
phase 
6.7 Continued Access to Study 
Vaccine After the End of the Study  
7.1 Discontinuation of Study 
Vaccination
9.5 Planned Analysis
Text was modified to indicate that 
participants who were already 
unblinded for any reason may 
receive Ad26.COV2.S vaccine 
upon discussion with the 
investigator, provided that they did 
not receive another COVID-19 
vaccine.
Since all participants will now be
unblinded, it is permissible for
those who were previously
unblinded but who have not been
vaccinated with another COVID-19
vaccine to be offered
Ad26.COV2.S.
1.1 Synopsis 
4.1 Overall Design  
10.3.6 Safety Monitoring 
Committees Structure 
The text regarding the Safety 
Monitoring Committees (SMC) was
streamlined and updated to reflect
the installation of the IDMC for
VAC31518COV2001.
Update
4.1 Overall Design  
4.4 End of Study Definition  
Study duration/end of study 
definition was corrected based on
the Schedule of Activities.
Correction
2.3.1 Risks Related to Study 
Participation  
It has been clarified that 
anaphylaxis is considered an 
important identified risk.
To align with the vaccine’s
identified risks.
5.2.1 Exclusion Criteria for Adults 
Exclusion criterion is reinstated to 
exclude participation by employees 
of the sponsor or the study sites and
their family members.
Reinstatement per health authority
request.
6.4 Unblinding and Open-label 
Phase 
Section was added to indicate what 
procedures should be followed
around unblinding.
Clarification
7.1 Discontinuation of Study 
Vaccination  
Text was modified to indicate that 
discontinuation of study 
vaccination for a positive test result 
for SARS-CoV-2 infection is only 
applicable for the double-blind 
phase. 
At the time of protocol Amendment
5, all adult participants had
received Injection 3.  Following
unblinding, all placebo participants
will be offered a 2-dose (28-day
interval) Ad26.COV2.S
vaccination regimen at the 5x1010
vp dose level.
1.3.1 Groups 1 to 6 (56-day interval 
schedule [2-dose and single dose 
regimens]) –Adults 
1.3.2 Groups 7 and 8 (28-day
interval schedule)- Adults
1.3.3 Groups 9 and 10 (84-day
interval schedule) –Adults
1.3.4 Active Vaccine Regimen:
Placebo Groups 6, 8 and 10 (28-day
interval schedule [2-dose and single
dose regimens]) –Adults
4.1 Overall Design
8 STUDY ASSESSMENTS AND
PROCEDURES
Total blood volumes to be drawn 
were updated to align with changes
in Section 1.3.
Update/alignment
1.3.7 Procedures for Participants 
With (Suspected) COVID-19 – 
Adults and Adolescents 
8.1.2 Procedures in Case of 
(Suspected) COVID-19 
Schedule/text was clarified to 
indicate that nasal swabs should be
performed twice weekly or more
often from Day 3 of COVID-19
episode until resolution.
Clarification

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Section Number 
and Name
Description of Change 
Brief Rationale
Throughout the protocol 
Minor grammatical, formatting, or 
spelling changes were made.
A statement was added to the 
adolescent portions to indicate that 
enrollment and vaccination of 
adolescents is paused pending 
further evaluation of the risk- 
benefit in adolescents. 
Minor errors were noted
Emphasis that the adolescent
portions of the protocol should not
be followed; they will be updated
with Amendment 6, at which time
adolescent vaccinations may
resume.
Amendment 4 (04 March 2021)
Overall Rationale for the Amendment: In this amendment, the adolescent participants will be
stratified by age into 2 groups (16 to 17 years of age, inclusive and 12 to 15 years of age, inclusive). A
staggered approach will be implemented, with the initial safety assessments conducted in the older
adolescents (16 to 17 years of age) and limited to 11 sentinels. Tolerability to the Ad26.COV2.S vaccine at
the 2.5x1010 virus particle (vp) dose level will initially be evaluated at Day 4 (3 days post-vaccination) by
the Safety Monitoring Committee (SMC), with further safety assessments conducted in a safety cohort of
22 participants at Day 8 (7 days post-vaccination). If the safety and reactogenicity profile is acceptable
within the 16-17 years age group, then the 2.5x1010 vp dose level will be assessed as described above in
adolescents at 12 to 15 years of age, inclusive. Similarly, the safety and reactogenicity profile of the
Ad26.COV2.S (5x1010 vp) dose level, that has been shown to be safe and efficacious in adults (≥18 years
of age) will be assessed within adolescents at 16-17 years of age, before proceeding to the younger age
group and full enrollment of adolescent participants.
Adolescents who were initially assigned to receive a single dose of Ad26.COV2.S at 2.5 1010 vp, will now
receive 2 doses of Ad26.COV2.S at 2.5x1010 (56-day interval), as a single dose at 2.5x1010 may provide
suboptimal protection. Adolescents in Groups A and B will now receive the same dose of active vaccine.
Group naming has been retained to facilitate the transition of participants enrolled under the previous
protocol amendment.
In addition, this amendment outlines procedures to be followed after Emergency Use Authorization (EUA),
or similar program/authorization or approval, or approval in any country for both the Ad26.COV2.S vaccine
and the current protocol Amendment 4 by both health authority and Independent Ethics Committee
(IEC)/Institutional Review Board (IRB) have been obtained, where a single dose of Ad26.COV2.S will be
offered to enrolled participants who initially received placebo, resulting in de facto unblinding of
participants and investigators.
Section number 
and Name
Description of Change 
Brief Rationale
Section 1.1. Synopsis;
Section 4.1. Overall Design;
Section 6.3. Measures to
Minimize Bias:
Randomization and Blinding;
Section 8.1.1. Immunogenicity
Assessments;
Section 9.1. Statistical
Hypotheses;
Section 9.2.1.
Immunogenicity;
Randomization of adolescent participants
will be stratified by study site and age
group (half of the participants 12 to 15
years of age, inclusive, and half of the
participants 16 to 17 years of age,
inclusive). Enrollment will progress in
parallel, with the safety profile of the
Ad26.COV.2 vaccine doses (2.5x1010 vp
and 5x1010 vp dose levels) in adolescents
assessed separately by age group.
The Adolescent group will be split
into 2 groups based on age (12 to
15 years, inclusive and 16 to
17years of age, inclusive) for the
purpose of randomization  and
stratification.
The purpose of this staggered and
age-stratified approach is to collect
safety 
data 
on 
adolescent
participants 16 to 17 years of age at
the 2.5x1010 vp dose level, prior to

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Section number 
and Name
Description of Change 
Brief Rationale
Section 9.3 Populations for 
Analysis Sets; 
Section 9.5 Planned Analysis 
This is reflected in the revised sections on 
Statistical Analysis, including Table 10. 
proceeding 
to 
the 
younger
adolescent cohort and/or to the
higher dose level of 5x1010 vp.
Section 1.1. Synopsis; 
Section 1.2. Schema; 
Section 1.3.1. Schedule of 
Activities (SoA): Adult 
Groups 1 to 6; 
Section 1.3.2. SoA Adult 
Groups 7 and 8; 
Section 1.3.3. SoA Adult 
Groups 9 and 10; 
Section 1.3.4. SoA Active 
Vaccination Regimen: Adult 
Placebo Groups 6, 8 and 10; 
Section 1.3.5. SoA Adolescent 
Groups A to F; 
Section 1.3.4. SoA Active 
Vaccination Regimen: 
Placebo Group 10; 
4.1. Overall Design; 
Section 6.3. Measures to 
Minimize Bias: 
Randomization and Blinding; 
Section 6.7Continued Access 
to Study vaccine After the End 
of the Study  
Section 8 Study Assessments 
and Procedures. 
Once Emergency Use Authorization 
(EUA), or similar program/authorization 
or approval, or approval in any country 
for both the Ad26.COV2.S vaccine and 
the current protocol Amendment 4 by 
both Health Authority and Independent 
Ethics Committee (IEC)/Institutional 
Review Board (IRB) have been obtained, 
all study participants and investigators 
will be partially unblinded (informed 
whether they received placebo or 
Ad26.COV2.S) and the study will 
continue as a (semi) open-label study. 
- At approximately 6 months of study 
participation, adult participants who were 
initially enrolled to receive placebo 
(Groups 6, 8 and 10), will be offered a 
2-dose (28-day interval) Ad26.COV2.S 
vaccination regimen at the 5x1010 vp dose 
level. The time point at which adult 
participants 
reach 
approximately 
6 months of study participation is 
independent of the 3rd vaccination, 
therefore participants may or may not
have already received the 3rd vaccination
by the time of unblinding.
At approximately 6 months of study
participation or on receipt of EUA, or
similar 
program/authorization 
or
approval, or approval in any country for
both the Ad26.COV2.S vaccine and the
current protocol Amendment 4 by both
Health Authority and IEC/IRB have been
obtained, all adolescent participants will
be unblinded to the primary vaccination
regimen. Participants who were initially
enrolled to receive placebo (Groups C and
F), will be offered a 2-dose (56-day
interval) 
Ad26.COV2.S 
vaccination
regimen at the 2.5 x1010 vp and 5x1010 vp
dose level, respectively.
- As the vaccine is highly efficacious
against 
severe 
disease,
hospitalization, and death, it is
considered ethical to offer the active
vaccine to the adult and adolescent
placebo controls in this study. An
unblinding visit will be scheduled to
inform all participants about their
study vaccine allocation, as well as
to offer all placebo recipients
Ad26.COV2.S after EUA, or similar
program/authorization or approval,
or approval in any country for both
the Ad26.COV2.S vaccine and the
current protocol Amendment 4 by
both Health Authority and IEC/ IRB.
- The 6 Month visit with a broadened
visit window will be used as an
unblinding visit to allow for rapid
crossover in the context of logistic
issues. 
Investigators 
will 
be
encouraged 
to 
follow 
health
authority guidelines on prioritization
of immunization when feasible.
Section 1.1. Synopsis;
Section 4.1. Overall Design
The following statement has been added:
Countries may participate in the adult and
adolescent portions of the study or they
may participate in either the adult or
adolescent portion.
Clarification

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Section number 
and Name
Description of Change 
Brief Rationale
Section 1.1. Synopsis; 
Section 9.5. Planned Analysis 
Adult Participants: The primary analysis 
will include safety and immunogenicity 
data (VNA and ELISA) for all 
participants through Day 85 (Groups 1-6), 
Day 57 (Groups 7-8) or Day 113
(Groups 9-10).
Adolescent Participants: Interim analysis
will be performed once 250 participants
in the 16-17 years of age group (including
all adolescents in Group A-C receiving
the 2.5x1010 dose [n=75] plus placebo
controls, and a substantial proportion of
participants [n ≥125] in Groups D-F
receiving the 5x1010 dose) have reached
the Day 28 post-dose 1 time point.
Unblinded data at the vaccination group
level will be available to the sponsor and
might be used for regulatory submissions.
A separate interim analysis of safety and
immunogenicity will be performed for all
groups in the adolescent cohort (Groups
A-C and D-F) to include both the 12-15
years and 16-17 years age groups, and
will include 28-day immunogenicity (ie,
the 1-dose non-inferiority comparisons)
and 28-day safety data post-dose 1 of all
groups in the adolescent cohort. The
sponsor will be unblinded, 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 until the end of study.
Updates to the interim and primary
analysis 
for 
both 
adult 
and
adolescent participants to reflect the
changes in study design.
Section 1.1. Synopsis;
Section 4.1. Overall Design;
Section 8.3.2. Method of
Detecting Adverse Events,
Medically-attended Adverse
Events, and Serious Adverse
Events Information
Addition of the following statement:
After each vaccination, all participants
will remain under observation at the study
site for at least 1 hour (including
participants in the Sentinel and Safety
Cohort) to monitor for the presence of any
acute reactions and solicited events.
Clarification and alignment.
Section1.1. Synopsis,
Section 3. Objectives and
Endpoints;
Section 4.1. Overall Design;
Section 8.1.1 Immunogenic
Assessments;
Section 8.1.2. Procedures in
case of (Suspected)
COVID-19
Endpoint Analysis:
- Serological response to vaccination as
measured by virus neutralization assay
(VNA) 
titers 
and 
enzyme-linked
immunosorbent assay (S-ELISA, ELISA
Units/mL 
[EU/mL]), 
28 days 
after
Vaccination 2.
Updated to reflect the inclusion of
the virus neutralization assay in
analysis of serological responses to
vaccination (in addition to the use of
the enzyme-linked immunosorbent
assay).

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Section number 
and Name
Description of Change 
Brief Rationale
- Antibody geometric mean titers (GMTs)
(VNA) 
and 
geometric 
mean
concentrations 
(GMCs) 
(S-ELISA),
28 days after Vaccination 2.
Section 5.2.1. Exclusion 
Criteria for Adults; 
Section 5.2.2. Exclusion 
Criteria for Adolescents 
Adolescents: 
- Exclusion criterion 15 modified to 
specify drug abuse. 
- Exclusion criterion 21 added to clarify 
that participants with a history of 
Kawasaki disease will be excluded. 
- Exclusion criterion 22 added to clarify
that participants with a history of an
underlying clinically significant acute or
chronic medical condition or physical
examination findings may be excluded as
per Investigator's judgment.
Adults and Adolescents:
Exclusion criteria 13 and 14, respectively,
deleted: There is no restriction on
enrollment of participants that are
employees of the investigator or study
site, as well as family members of the
employees or the investigator, or an
employee of the sponsor.
- Alignment of exclusion criteria in
adult and adolescent participants.
- Notably, exclusion of participants
with a history of Kawasaki disease,
is 
applicable 
to 
adolescent
participants, only.
Section 1.1. Synopsis; 
Section 1.3.7Schedule of 
Activities: Procedures for 
Participants With (Suspected) 
COVID-19; 
Section 8.1.2. Procedures in 
case of (suspected) COVID-19
The following text has been revised to 
clarify that the sponsor recommends to 
follow-up on participants with suspected
COVID-19 until 2 consecutive
SARS-CoV-2 negative nasal swabs
could be obtained.
Clarification of procedures in case
of suspected COVID-19 infection.
Throughout the protocol 
(naming of adolescent study 
groups) 
Groups A and B will be receiving the 
same vaccination regimen consisting of 
2 doses of Ad26.COV2.S at 2.5x1010 vp. 
Group naming has been retained in
protocol Amendment 4 to align
with protocol Amendment 2 and to
allow for transition from one
amendment to the next with the
same flow of participants in the
sentinel and safety cohorts.
Section 1.1. Synopsis; 
Section 1.3. Schedule of 
Activities; 
Section 4.1. Overall Design; 
Section 9.5. Planned Analysis 
Throughout the protocol 
(numbering of adult study 
groups) 
The 2 additional adult Groups 11 and 12 
that were added in the previous protocol 
Amendment 3 have been removed. The 
overall total number of adult participants 
to be enrolled will revert to the original 
planned enrollment of 550 participants. 
The original intention in adding
Groups 11 and 12 was to ensure
that the vaccination regimen
(28-day interval) originally
intended for Groups 7 and 8 prior to
the study pause in October 2020
were covered.
The vaccination regimen (2 doses
of Ad26.CoV2.S at 5x1010
administered at a 28-day interval) is
now covered by cross-vaccination
of the participants that originally
received placebo in the primary
vaccine regimen in Groups 6, 8
and 10.

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Section number 
and Name
Description of Change 
Brief Rationale
Section 1.1. Synopsis; 
Section 3. Objectives and 
Endpoints; 
Section 8.1.1. Immunogenicity 
Assessments 
Use of the Enzyme-linked Immunospot 
(ELISpot) assay to measure cellular
immunogenicity elicited by vaccination
has been removed as an endpoint from
the exploratory objectives.
Table 8: Summary of Humoral and
cellular Immunogenicity Assays has
been updated to reflect this.
Use of ELISpot assay removed.
Section 1.1. Synopsis; 
Section 3. Objectives and 
Endpoints; 
8.1.1. Immunogenicity 
Assessments 
The following Exploratory Endpoints 
have been added to the exploratory 
objectives: 
- To further assess the humoral immune 
response to Ad26.COV2.S: Analysis of 
neutralizing antibodies against emerging 
SARS-CoV-2 variants. 
- To further assess humoral immune 
responses 
generated 
by 
the 
Ad26.COV2.S 
vaccine 
using 
data 
obtained 
from 
cohorts 
of 
young 
participants (≥18 to ≤25 years of age, 
inclusive) in the sponsor's clinical 
program. 
- To increase understanding of the
protective immunity conferred by
the 
Ad26.COV2.S 
vaccine 
to
emerging SARS-CoV-2 variants in
young adults and adolescents.
- To increase the power of the
statistical analysis performed by
comparing the humoral immune
responses 
generated 
by 
the
Ad26.COV2.S vaccine in young
participants (≥18 to ≤25 years of
age, inclusive) across the various
clinical studies conducted by the
sponsor.
Section 6.10. Study 
Vaccination Pausing Rules 
Section 10.3.6. Safety 
Monitoring Committee 
Structure 
Text added, stating that the study 
vaccination pausing rules apply to 
"adolescent participants only". 
Text added stating that: "If any pausing 
rule is met and, if following appropriate 
safety review it is deemed appropriate to 
restart dosing, the sponsor must submit a 
request to restart dosing with pertinent 
data to competent authority as a request
for a substantial amendment, as required
by local regulations or authority request.".
Clarification that the study
vaccination pausing rules applies to
adolescent participants only.
Clarification of the procedures to be
followed in the event a pausing rule
is met; notably that the sponsor
must submit a request to restart
dosing to the appropriate
authorities.
Throughout the protocol 
Minor grammatical, formatting, or
spelling changes were made.
Minor errors were noted
Amendment 3 (22 December 2020)
Overall Rationale for the Amendment: In October 2020, the current study was temporarily paused
because one of the pausing rules was met in study COV3001. When the pause was lifted, most of the
participants in Groups 7-8 had missed their visit window for Vaccination 2, rendering the intent of the
28-day vaccination interval in these groups futile (see Table 2). Efforts will be made to vaccinate these
participants, preferably in a 56-day vaccination interval. In this amendment, 2 additional groups (Groups
11 and 12) have been added to determine to evaluate whether a 28-day interval between Vaccination 1 and
Vaccination 2 is acceptable. Groups 11 and 12 will have the same vaccination regimen as originally
intended for Groups 7 and 8 prior to the pause. Given the lack of sensitivity of the psVNA, and the high
correlation between the wtVNA and ELISA assays and high throughput of the ELISA assay, the ELISA
has been selected for the non-inferiority (NI) primary endpoint for the comparison of the humoral responses
between adults and adolescents. Procedures to be followed in the event that an investigator receives a
request to unblind study participants who may become eligible to receive an authorized/licensed COVID-19

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vaccine when these become available have been added. This amendment also describes that if a correlate
or threshold for protection against COVID-19 is established in terms of humoral immunity, then a statistical
comparison to that correlate or threshold will substitute non-inferiority testing to immune responses to
vaccine at release.
Section number
and Name
Description of Change 
Brief Rationale
1.1 Synopsis
1.2 Schema
1.3 Schedule of Activities
(SoA)
1.3.2 Groups 7, 8, 11 and 12
(28-day interval schedule)-
Adults
4.1 Overall Design
4.4 End of Study Definition
6.1 Study Vaccinations
Administered
8 STUDY ASSESSMENTS
AND PROCEDURES
9.5 Planned Analysis
Two additional groups (Groups 11 and
12) have been added that will have the
same vaccination regimen as originally
intended for Groups 7 and 8 prior to the
study pause in October 2020.
To evaluate a 28-day interval
between Vaccination 1 and
Vaccination 2.
1.1 Synopsis
3 Objectives and Endpoints
9.4.2 Primary/Secondary
Endpoints
psVNA has been replaced by ELISA
from the NI endpoints between adults
and adolescents.
Several psVNAs have been
evaluated by the sponsor, and this
evaluation showed that these assays
have a lack of sensitivity in
comparison to the wtVNA. The
ELISA and wtVNA show a high
correlation across different age
groups and timepoints. The use of
the ELISA has therefore been
selected for the non-inferiority
primary endpoints comparing the
humoral responses of adults and
adolescents.
1.1 Synopsis
3 Objectives and Endpoints
The option of the VNA assay has been
removed in the primary endpoints for the
adults.
The ELISA will be the assay used
for the primary endpoints.
1.1 Synopsis
3 Objectives and Endpoints
Description of the correlate or threshold
of protection against COVID-19 if
established in terms of humoral
immunity has been added.
A correlate or threshold of
protection will be a better
indication of efficacy.
1.1 Synopsis
3 Objectives and Endpoints
Addition of an exploratory 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)
Addition of one exploratory
objective/endpoint:
To assess the correlation between the
binding antibody (ELISA) titers and
neutralizing antibody (VNA) titers to
SARS-CoV-2, in a subset of participants
at selected timepoints.
For in-depth analysis of the binding
antibody generated by
Ad26.COV2.S
To further confirm the correlation
between ELISA and wtVNA in
different age groups and timepoints
and confirm the choice of the
ELISA as primary endpoint in the

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Section number 
and Name
Description of Change 
Brief Rationale
NI objectives comparing
immunogenicity of adults and
adolescents.
1.1 Synopsis 
8.1.1 Immunogenicity 
Assessments 
Addition of the MSD assay. 
For in-depth analysis of the binding
antibody generated by
Ad26.COV2.S
1.1 Synopsis 
6.3 Measures to Minimize 
Bias: Randomization and 
Blinding 
7.1 Discontinuation of Study 
Vaccination  
6.7Continued Access to Study 
Vaccine After the End of the 
Study
9.5 Planned Analysis
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 2 different COVID-19
vaccines.
1.3 Schedule of Activities 
8.2.4 Hematology Clinical 
Laboratory Assessments 
Clarification that upon implementation of 
this amendment blood draws for 
hematology assays will be plasma. 
It was confirmed that D-dimers and
Lupus anticoagulant tests cannot be
performed in serum. Therefore,
previously collected serum samples
will not be adequate for these tests.
Plasma samples will be collected
for the purpose of these testing in
all groups once protocol
Amendment 3 is approved and
implemented.
5.1.2 Inclusion Criteria for 
Adolescents (12-17 years 
inclusive) 
Modified inclusion criteria so that a 
participant or parent/legal guardian could 
sign the ICF, participate in all 
procedures/visits and provide verifiable 
identification.
In certain countries adolescent
participants who are 16 and 17
years of age are treated as adults in
clinical trials.
5.2.1 Exclusion Criteria for 
Adults (18-55, Inclusive and 
65 Years and Older) 
6.9 Prestudy and Concomitant 
Therapy  
7.1 Discontinuation of Study 
Vaccination  
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
5.2.1 Exclusion Criteria for 
Adults (18-55, Inclusive and 
65 Years and Older) 
6.9 Prestudy and Concomitant 
Therapy  
Clarified that investigational drug 
includes drugs for prophylaxis of
COVID-19.
Also 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.
5.2.2 Exclusion Criteria for 
Adolescents (12-17 Years, 
Inclusive) 
Clarified that investigational drug 
includes drugs for prophylaxis of
COVID-19.
Alignment with Phase 3 protocols.
5.2.1 Exclusion Criteria for 
Adults (18-55, Inclusive and 
65 Years and Older) 
Updated the list of conditions that 
increase the risk of progression to severe
COVID-19.
Alignment with Phase 3 protocols.

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Section number 
and Name
Description of Change 
Brief Rationale
5.2.1 Exclusion Criteria for 
Adults (18-55, Inclusive and 
65 Years and Older) 
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.
1.1 Synopsis 
3 Objectives and Endpoints 
8.1.2.1 Prespecified Criteria 
for (Suspected) COVID-19 
8.3.1 Time Period and 
Frequency for Collecting
Adverse Event and Serious
Adverse Event Information
9.4.2 Primary/Secondary
Endpoints
10.12 Appendix 12:
Multisystem Inflammatory
Syndrome in Children
Addition of multisystem inflammatory 
syndrome in children as an SAE. 
Description of the syndrome and
common signs has been added as an
appendix.
Alignment with Phase 3 pediatric
study protocols
1.3 Schedule of Activities 
7.1 Discontinuation of Study 
Vaccination  
7.2 Participant 
Discontinuation/Withdrawal 
from the Study 
Clarified that participants who 
discontinue 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.
6.3 Measure 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
9.5 Planned Analysis 
Additional wording added to explain the 
investigator or sponsor may have to be
unblinded due to unexpected events.
Clarification
6.8 Treatment of Overdose 
Definition of what can be regarded as an 
overdose was corrected.
Correction of inconsistency.
8.1.2 Procedures in Case of 
(Suspected) COVID-19 
Clarification that additional swabs should 
be taken by a healthcare professional
from the participant as soon as possible,
but with a minimum of 1 day between
the swabs.
Clarification
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 judgment.
Clarification
1.1 Synopsis 
9.2.1 Immunogenicity  
Standard deviations have been updated 
for NI in the statistical sections.
Per endpoint update
6.10 Study Vaccination 
Pausing Rules 
10.3.6 Safety Monitoring 
Committees Structure 
Text was added to clarify that if there 
will be any study pause, the sponsor will
submit a request to restart the study with
pertinent data to the Health Authorities
as a request for a substantial amendment,
as required by the local regulations.
Upon Health Authority feedback
Throughout the protocol 
Minor grammatical, formatting, or 
spelling changes were made.
Minor errors were noted

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Amendment 2 (29 October 2020)
Overall Rationale for the Amendment: In this amendment, adolescents (aged 12 to 17 years,
inclusive) are included in the study to demonstrate non-inferiority of the immune responses in
adolescents (5x1010 and 2.5x1010 vp dose levels, 1- and 2-dose regimens) to the immune
responses of adults in this COV2001 study (5x1010 vp dose levels, 1- and 2-dose regimens). The
5x1010 vp dose level is the one being used in the Phase 3 efficacy studies COV3001 (1-dose
regimen) and COV3009 (2-dose regimen).
The mitigation strategy after a study pause is clarified.
In October 2020, the current study was temporarily paused because one of the pausing rules was
met in study COV3001. When the pause was lifted, most of the participants in Groups 7-8 had
missed their visit window for Vaccination 2 (Visit 4), rendering the intent of the 28-day vaccination
interval in these groups futile. It is explained that efforts will be made to vaccinate these
participants, preferably in a 56-day vaccination interval.
Upon request of the CCMO (Centrale Commissie Mensgebonden Onderzoek) in The Netherlands,
hematology laboratory tests have been added to assess potential vaccine-induced anti-phospholipid
syndrome and potential vaccine-induced activation of coagulation.
Additional changes are listed below.
The changes made are listed below, including the rationale of each change and a list of all applicable
sections.
Section Number 
and Name
Description of Change 
Brief Rationale
1 PROTOCOL SUMMARY (and subsections) 
2 INTRODUCTION  
2.1 Study Rationale 
2.2 Background 
2.3.3 Benefit-Risk Assessment of Study 
Participation 
3 OBJECTIVES AND ENDPOINTS  
4 STUDY DESIGN (and subsections) 
5 STUDY POPULATION
5.1 Inclusion Criteria (and subsections)
5.2 Exclusion Criteria (and subsections)
5.4 Screen Failures
6.1 Study Vaccinations Administered
6.3 Measures to Minimize Bias: Randomization
and Blinding
6.6 Dose Modification
7.1 Discontinuation of Study Vaccination
7.2 Participant Discontinuation/Withdrawal
From the Study (and subsection)
8 STUDY ASSESSMENTS AND
PROCEDURES
8.1.1 Immunogenicity Assessments
8.1.3 Asymptomatic SARS-CoV-2 Infection
8.2.3 Pregnancy Testing
Inclusion of adolescents (aged 
12 to 17 years, inclusive) in the 
study. 
Blood volumes to be collected
have been adapted according to
the population and are reduced
versus the adult cohorts.
To demonstrate non-
inferiority to adult results
(in Phase 3) by
immunobridging

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Section Number 
and Name
Description of Change 
Brief Rationale
8.3.2 Method of Detecting Adverse Events, and
Serious Adverse Events
9.1 Statistical Hypotheses
9.2 Sample Size Determination (and
subsections)
9.4.2 Primary/Secondary Endpoints
9.5 Planned Analysis
10.1 Appendix 1: Abbreviations
10.3.1 Regulatory and Ethical Considerations
10.3.3 Informed Consent Process and Assent
Form
10.3.4 Data Protection
10.3.5 Long-Term Retention of Samples for
Additional Future Research
10.3.10 Source Documents
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 –Used for Adolescent Cohort
11 REFERENCES
1.1 Synopsis 
6.1 Study Vaccinations Administered 
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
In October 2020, the current
study was temporarily
paused because one of the
pausing rules was met in
study COV3001. When the
pause was lifted, most of the
participants in Groups 7-8
had missed their visit
window for Vaccination 2
(Visit 4), rendering the
intent of the 28-day
vaccination interval in these
groups futile. As the actual
vaccination might coincide
with the intervals from other
groups, it might be possible
to use the data according to
that interval.
1.1 Synopsis 
9.5 Planned Analysis 
Clarified that all available data 
will be included in the interim 
analysis of the adult cohort. 
Mitigation in case of study
pause: Clarification which
data will be included.
6.10 Study Vaccination Pausing Rules 
Text adapted to state that this 
study will also be paused if a 
pausing rule is met in study 
COV1002 or COV3001.
Mitigation in case of study
pause: Additional safety
measure
1.1 Synopsis 
1.3.1 Groups 1 to 6 (56-day interval schedule 
[2-dose and single dose regimens]) –Adults 
1.3.2 Groups 7 and 8 (28-day interval 
schedule)- Adults 
Addition of hematology 
clinical laboratory assessments 
for adults. 
Upon request of CCMO in
The Netherlands, to assess
potential vaccine-induced
antiphospholipid syndrome
and potential

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Section Number 
and Name
Description of Change 
Brief Rationale
1.3.3 Groups 9 and 10 (84-day interval 
schedule) –Adults 
2.3.3 Benefit-Risk Assessment of Study
Participation
3 OBJECTIVES AND ENDPOINTS
4.1 Overall Design
8 STUDY ASSESSMENTS AND
PROCEDURES
8.2.4 Hematology Clinical Laboratory
Assessments
10.2 Appendix 2: Hematology Clinical
Laboratory Tests
vaccine-induced activation
of coagulation
1.1 Synopsis 
2.3.1 Risks Related to Study Participation 
2.3.3 Benefit-Risk Assessment of Study 
Participation  
4.1 Overall Design  
6.10 Study Vaccination Pausing Rules 
8.2 Safety Assessments 
9.5 Planned Analysis 
10.1 Appendix 1: Abbreviations 
10.3.6 Safety Monitoring Committees Structure 
Explanation added that IDMC 
will take over responsibilities 
of DRC. 
Initially, an internal DRC
was commissioned for this
study. However, an
Independent Data
Monitoring Committee
(IDMC) will be installed for
the different studies
throughout the COVID-19
vaccine program. Once this
is in place, this IDMC will,
after a transition period,
take over the responsibilities
of the DRC in this study.
1.1 Synopsis 
1.3 Schedule of Activities (SoA) (and 
subsections) 
3 OBJECTIVES AND ENDPOINTS  
4.1 Overall Design  
8.1.2 Procedures in Case of (Suspected) 
COVID-19 (and subsection) 
8.1.3 Asymptomatic SARS-CoV-2 Infection 
10.3.10 Source Documents 
10.8.4 Case Definition for Asymptomatic or 
Undetected COVID-19 
An RT-PCR positive finding 
for SARS-CoV-2 from any 
source (within or outside the 
study), even if asymptomatic, 
will be considered as a
prespecified criterion for
(suspected) COVID-19 and
will therefore trigger follow-up
as described in Section 1.3.7.
In addition, any (suspected)
COVID-19 case (Section 1.3.7)
will be followed until
resolution of symptoms AND
until 2 consecutive SARS-
CoV-2 negative swabs are
available.
To ensure safety of staff and
other persons coming in
contact with the infected
participant.
1.1 Synopsis 
1.3.8 Procedures for Participants With 
(Suspected) COVID-19 –Adults and 
Adolescents 
4.1 Overall Design  
8.1.2 Procedures in Case of (Suspected) 
COVID-19 
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 judgment 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 
Vaccination with
Ad26.COV2.S may

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Section Number 
and Name
Description of Change 
Brief Rationale
discouraged and if testing 
would be needed, the site will 
guide the participant to an 
appropriate assay. 
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.
2.3.1 Risks Related to Study Participation 
9.5 Planned Analysis 
Clarified that selected members 
of the statistical programming 
and statistics group will receive
individual level unblinded data,
when unblinding at the
participant level is required.
Alignment with other
studies of the program
2.3.1 Risks Related to Study Participation 
6.9 Prestudy and Concomitant Therapy  
Guidance on the use of 
antipyretics during the study 
has been clarified. 
To clarify that antipyretics
are recommended post-
vaccination for symptom
relief, as needed.
Prophylactic antipyretic use
is not encouraged.
2 INTRODUCTION  
2.2 Background 
2.3.1 Risks Related to Study Participation  
Recent data from the first-in- 
human study COV1001 have
been added and background
information on COVID-19 and
information on non-COVID-19
Ad26-based vaccines has been
updated where relevant.
Alignment and transparency
5.2.1 Exclusion Criteria for Adults (18-55 
years, Inclusive and 65 Years or Older) 
6.7 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
program.
1.1 Synopsis 
3 OBJECTIVES AND ENDPOINTS  
8.1.1 Immunogenicity Assessments 
Addition of 2 exploratory 
humoral immunogenicity 
endpoints: Functional and 
molecular antibody 
characterization and passive 
transfer. 
For analysis of antibody
characteristics and analysis
of immune mediators
correlating with protection
against experimental SARS-
CoV-2 challenge in a
suitable animal model
1.3.1 Groups 1 to 6 (56-day interval schedule 
[2-dose and single dose regimens]) –Adults 
1.3.2 Groups 7 and 8 (28-day interval
schedule)- Adults
1.3.3 Groups 9 and 10 (84-day interval
schedule) –Adults
8 STUDY ASSESSMENTS AND
PROCEDURES
Blood volume of SARS-CoV-2 
serological test added.
correction

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Section Number 
and Name
Description of Change 
Brief Rationale
1.3.8 Procedures for Participants With 
(Suspected) COVID-19 –Adults and 
Adolescents 
8 STUDY ASSESSMENTS AND 
PROCEDURES  
8.5 Biomarkers
Clarified that humoral 
immunity and PAXgene
sample is also to be taken at
COVID-19 Day 3-8. Blood
volume added.
correction
1.1 Synopsis 
1.3.8 Procedures for Participants With 
(Suspected) COVID-19 –Adults and 
Adolescents
8.1.2 Procedures in Case of (Suspected)
COVID-19
Physical examination and vital 
signs assessment added to 
COVID-19 Days 3-8.
Alignment with Phase 3
program.
1.3.1 Groups 1 to 6 (56-day interval schedule 
[2-dose and single dose regimens]) –Adults 
1.3.2 Groups 7 and 8 (28-day interval 
schedule)- Adults 
1.3.3 Groups 9 and 10 (84-day interval 
schedule) –Adults
8.2.2 Vital Signs
Vital signs assessment are 
recommended before blood 
sampling. This instruction has
been made consistent
throughout the document.
Consistency throughout
document
9.4.2 Primary/Secondary 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 and
that in general, (S)AEs caused
by SARS-CoV-2 will also be
removed and presented
separately.
Clarification on criteria and
analysis of (S)AEs have
been made.
10.3.10 Source Documents 
It has been clarified that source 
documents for medical history 
and prestudy therapies 
determining eligibility of the 
participants needs to be
collected.
To ensure that all necessary
information to properly
assess SAEs (relatedness) is
collected.
Title page 
Prepared by line removed. 
To align with internal
guidelines on legal entity to
be mentioned on title page
Throughout the protocol 
Minor errors and 
inconsistencies were corrected 
throughout the protocol.
Correction of minor errors
and inconsistencies

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Amendment 1 (21 August 2020)
Overall Rationale for the Amendment: In this amendment, a more flexible window is allowed between
molecular test for SARS-CoV-2 infection and vaccination and a clarification is added to the eligibility
criteria on blood pressure for participants ≥65 years of age. In addition, other changes have been made for
alignment with other study protocols within the program.
Section Number 
and Name
Description of Change 
Brief Rationale
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.
Operational request
1.1 Synopsis
1.3 Schedule of Activities,
4.1 Overall Design
8.1.2 Procedures in Case of
COVID-19-like Signs and
Symptoms
Clarified that the nasal swab is preferably to be
taken by the caregiver (spouse, partner, relative,
friend, or health care professional).
Operational request
5.1 Inclusion Criteria,
5.2 Exclusion Criteria
Clarification added to the eligibility criteria on
blood pressure for participants aged 65 years
and older.
Alignment within the
program
5.2 Exclusion Criteria
6.8 Prestudy and Concomitant
Therapy
Clarified that the use of any coronavirus
vaccine (licensed or investigational) other than
Ad26.COV2.S is disallowed at any time prior to
vaccination and during the study.
Alignment within the
program, based on National
Institute of Allergy and
Infectious Diseases
(NIAID) Prevention Science
Review Committee (PSRC)
feedback
5.2 Exclusion Criteria 
It has been clarified that every effort will be
made to avoid inclusion of participants who
have been previously enrolled in coronavirus
studies and to prevent subsequent enrollment of
a participant in other coronavirus studies during
their participation in this study.
Based on NIAID PSRC
feedback
5.2 Exclusion Criteria 
It has been clarified that planning to become
pregnant within 3 months after study vaccine is
an exclusion criterion.
Alignment within the
program, based on NIAID
PSRC feedback
6.8 Prestudy and Concomitant 
Therapy  
A clarification has been made regarding the use
of analgesic/antipyretic medications and non-
steroidal anti-inflammatory drugs.
Alignment within the
program
8 Study Assessments and 
Procedures 
Added that all participants will be counseled on
COVID-19 prevention each time that they have
a contact with study site staff in line with local
guidelines.
Clarification and alignment
within the program
8.1.2.1 Prespecified Criteria 
for Suspected COVID-19 
Changed “new loss of taste or smell” to “new or
changing olfactory or taste disorders”.
To align wording across all
case definitions
10.7.1 Case Definition for 
Moderate to Severe COVID-19 
10.7.2 Case Definition for
Mild COVID-19
The case definitions of both mild and moderate
COVID-19 have been modified.
Based on FDA and NIAID
PSRC feedback to simplify
the case definitions
1.3.5 Procedures for 
Participants With COVID-19- 
like Signs and Symptoms
Clarified that a participant will be notified of a
confirmed positive SARS-CoV-2 infection.
Alignment within the
program, based on NIAID
PSRC feedback

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Section Number 
and Name
Description of Change 
Brief Rationale
8.1.2 Procedures in Case of
COVID-19-like Signs and
Symptoms
8.1.2 Procedures in Case of 
COVID-19-like Signs and 
Symptoms 
Clarified that study staff visiting participants at 
home will use personal protective equipment 
according to local regulations. 
Alignment within the
program, based on NIAID
PSRC feedback
Throughout the protocol 
Minor errors and inconsistencies were corrected 
throughout the protocol. 
Correction of minor errors
and inconsistencies

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11. 
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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): 
Javier Ruiz Guiñazú, MD
Institution: 
Janssen Vaccines & Prevention B.V.
Signature: 
Electronic signature appended to the end of this document 
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.

Signature
User 
Date 
Reason
Ruiz Guiñazú Javier 
 
21-Jul-2021 
16:49:22
(GMT)
Document Approval
PPD