A Randomized, Observer-blind, Phase 2 Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of Different Dose Levels of Ad26.COV2.S Administered as a One- or Two-dose Regimen in Healthy Adolescents From 12 to 17 Years Inclusive
Phase: PHASE2
Conditions: Coronavirus Disease-2019 (COVID-19) Prevention
Sponsor: Janssen Vaccines & Prevention B.V.

CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
1
Status: Approved, Date: 15 Aug 2022
Janssen Vaccines & Prevention B.V. *
Clinical Protocol
Protocol Title
A Randomized, Observer-blind, Phase 2 Study to Evaluate the Safety, Reactogenicity, and
Immunogenicity of Different Dose Levels of Ad26.COV2.S Administered as a One- or
Two-dose Regimen in Healthy Adolescents From 12 to 17 Years Inclusive
HORIZON 2
Protocol VAC31518COV3006; Phase 2
AMENDMENT 4
VAC31518  (JNJ-78436735)
*Janssen Vaccines & Prevention B.V. is a Janssen pharmaceutical company of Johnson & Johnson and is
hereafter referred to as the sponsor of the study. The sponsor is identified on the Contact Information page
that accompanies the protocol.
United States (US)sites of this study will be conducted under US Food & Drug Administration
Investigational New Drug (IND) regulations (21 CFR Part 312).
Regulatory Agency Identifier Number(s):
IND:  22657
EudraCT NUMBER:  
 2020-005720-11
Status: 
Approved
Date: 
15 Aug 2022
Prepared by: Janssen Vaccines & Prevention B.V.
EDMS number: 
EDMS-RIM-195615, 8.0
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.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
2
Status: Approved, Date: 15 Aug 2022
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE
DOCUMENT HISTORY
Document 
Date
Amendment 4 
This document
Amendment 3 
28 February 2022
Amendment 2 
26 October 2021
Amendment 1 
13 July 2021
Original Protocol 
22 January 2021
Amendment 4:
Overall Rationale for the Amendment:
Part 1 of Study VAC31518COV3006 has been ongoing since 29 September 2021. Since the start of
enrollment, there has been a slower than desired participant enrollment rate mainly due to the success of
the national vaccination programs in the countries where Part 1 is being conducted and a high number of
participants being seropositive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) at
screening/randomization. Thus, the current design of Part 2 in vaccine naïve participants is no longer
feasible nor relevant and will, therefore, be removed from this study. However, Part 1 will continue as
planned and the results may yield a preferred dose to be used in potential future studies.
A further change introduced in this amendment consists of removal of the booster vaccination (or third
active vaccination) for participants initially enrolled to receive 2 active vaccinations in the primary
vaccination regimen. This change is performed in order to align participants in all groups to receive 2 active
study vaccinations, ie, to have the same vaccination exposure. Also, the follow-up period post last active
vaccinationwas reduced from 12 months to 6 months on the basis of the well-defined vaccine safety profile.
Given that approved COVID-19 vaccines exist for the adolescent population in all countries in which
VAC31518COV3006 is being conducted, if participants need to receive further boosters, they may be
vaccinated outside of the study as a part of their national vaccination campaign after the participants have
completed their last study visit.
Section Number 
and Name
Description of Change 
Brief Rationale
1.1 Synopsis 
1.2 Schema 
1.3 Schedule of Activities (SoA) 
1.3.1 Part 1: Dose Selection Cohort (Groups 1, 
2 and 3) Booster 6 Months Post-dose 1
1.3.2 Part 1: Dose Selection Cohort (Groups 4, 
5, and 6) 
3 Objectives and Endpoints
4.1 Overall Design
4.4 End of Study Definition
6.1 Study Vaccine(s) Administered
6.3 Measures to Minimize Bias:
Randomization and Blinding
6.8 Study Vaccination Pausing Rules
8.1 Immunogenicity Assessments
9.1 Statistical Hypotheses
9.2 Sample Size Determination
9.5 Planned Analyses
Removal of Part 2 of the study 
throughout the protocol, which 
included deleting Section 1.3.3 and
Section 1.3.4.
Subsequent subsections were
renumbered accordingly.
See overall rationale for
amendment.
Cover page 
1.1 Synopsis 
Changed to a Phase 2 study 
Study is no longer a
Phase 2/3 adaptive study
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
3
Status: Approved, Date: 15 Aug 2022
Section Number 
and Name
Description of Change 
Brief Rationale
4.1 Overall Design  
as Part 2 has been
removed.
1.1 Synopsis 
1.2 Schema 
1.3 Schedule of Activities (SoA) 
1.3.1 Part 1: Dose Selection Cohort (Groups 1, 
2, and 3) Booster 6 Months Post-dose 1 
1.3.2 Part 1: Dose Selection Cohort (Groups 4, 
5, and 6)
4.1 Overall Design
Removal of the booster 
vaccination (or third active 
vaccination) for participants 
initially enrolled to receive 2 
active vaccinations in the primary
vaccination regimen.
To align participants in
all groups to receive 2
active study
vaccinations.
1.1 Synopsis 
1.2 Schema 
1.3 Schedule of Activities (SoA) 
1.3.1 Part 1: Dose Selection Cohort (Groups 1,
2 and 3) Booster 6 Months Post-dose 1
1.3.2Part 1: Dose Selection Cohort (Groups 4,
5 and 6)
4.1 Overall Design
4.4 End of Study Definition
10.2 Appendix 2: AESI Clinical Laboratory
Tests
The follow-up period post last 
active vaccination reduced from 
12 months to 6 months. 
The vaccine has a
well-defined safety
profile.
1.1 Synopsis 
1.3 Schedule of Activities (SoA) 
1.3.1 Part 1: Dose Selection Cohort (Groups 1, 
2, and 3) Booster 6 Months Post-dose 1
1.3.2 Part 1: Dose Selection Cohort (Groups 4,
5, and 6)
4.1 Overall Design
Finger-prick test specified to test 
for SARS-CoV-2 antibodies at
screening.
Clarification
1.1 Synopsis 
3 Objectives and Endpoints 
4.1 Overall Design  
9.1 Statistical Hypotheses
Vaccine immunogenicity will be 
compared between study groups in
VAC31518COV3006.
Clarification
1.1 Synopsis 
6.3 Measures to Minimize Bias: 
Randomization anexplorad Blinding 
9.5 Planned Analyses 
The primary analysis of safety, 
reactogenicity and immunogenicity
will include data up to 28 days
post-dose 2 from which the
selected dose level for any future
study in adolescents will be
determined.
Clarification
1.1 Synopsis 
4.1 Overall Design  
6.3 Measures to Minimize Bias: 
Randomization and Blinding
The randomization has been 
revised to having not more than 
70% males or females
To allow more flexibility
in recruitment.
1.3.3 Procedures for Participants With 
(Suspected) COVID-19 
Footnote f has been updated in the 
vaccination schedule table 
regarding combining visits. 
To clarify and limit
blood draw volumes if
multiple visits overlap in
the same windows.
1.3.1 Part 1: Dose Selection Cohort (Groups 1, 
2 and 3) Booster 6 Months Post-dose 1 
1.3.2 Part 1: Dose Selection Cohort (Groups 4, 
5 and 6) 
8.2.2 Vital Signs
9.4.2 Primary/Secondary Endpoints
Text has been updated to add 
preferably supine systolic and
diastolic blood pressure in the
body and footnote h in the SoA.
Clarification
2 Introduction  
2.3.1 Risks Related to Study Participation 
Updated reference to the 
Investigator’s Brochure to latest
Update
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
4
Status: Approved, Date: 15 Aug 2022
Section Number 
and Name
Description of Change 
Brief Rationale
5.2 Exclusion Criteria 
6.1 Study Vaccine(s) Administered
11 References
version (6.0).
10.2 Appendix 2: AESI Clinical Laboratory 
Tests 
Title changed from Hematology 
Clinical Laboratory Tests to AESI
Clinical Laboratory Tests.
Clarification made between local
and central laboratory hematology
tests. The table for suspected
MIS-C AESI assessments merged
with the table for suspected TTS
AESI assessments.
Clarification
6.3 Measures to Minimize Bias: 
Randomization and Blinding 
Addition of vaccine/dose volume 
as an example of data that may 
potentially unblind the vaccine
assignment.
Additional example for
clarification.
Throughout the protocol 
Minor grammatical, formatting, or 
spelling changes were made.
Minor clarifications were also
made throughout the protocol.
Minor errors were noted.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
5
Status: Approved, Date: 15 Aug 2022
TABLE OF CONTENTS
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ............................................................... 2
TABLE OF CONTENTS ............................................................................................................................... 5
LIST OF IN-TEXT TABLES AND FIGURES................................................................................................ 7
1. 
PROTOCOL SUMMARY..................................................................................................................... 8
1.1. 
Synopsis........................................................................................................................................... 8
1.2. 
Schema.......................................................................................................................................... 17
1.3. 
Schedule of Activities (SoA)........................................................................................................... 18
1.3.1. 
Part 1: Dose Selection Cohort (Groups 1, 2 and 3) Booster 6 Months Post-dose 1 (SoA
visits identical up to Visit 8 for all groups in Part 1).................................................................... 18
1.3.2. 
Part 1: Dose Selection Cohort (Groups 4, 5 and 6) (SoA visits identical up to Visit 8 for
all groups in Part 1)..................................................................................................................... 23
1.3.3. 
Procedures for Participants With (Suspected) COVID-19.......................................................... 27
1.3.4. 
Participants With an AESI........................................................................................................... 30
2. 
INTRODUCTION................................................................................................................................ 32
2.1. 
Study Rationale.............................................................................................................................. 35
2.2. 
Background.................................................................................................................................... 37
2.3. 
Benefit-Risk Assessment............................................................................................................... 42
2.3.1 
Risks Related to Study Participation .......................................................................................... 42
2.3.2 
Benefits of Study Participation.................................................................................................... 48
2.3.3 
Benefit-Risk Assessment of Study Participation ........................................................................ 48
3. 
OBJECTIVES AND ENDPOINTS ..................................................................................................... 50
4. 
STUDY DESIGN ................................................................................................................................ 53
4.1. 
Overall Design................................................................................................................................ 53
4.2. 
Scientific Rationale for Study Design............................................................................................. 57
4.2.1. 
Study-Specific Ethical Design Considerations ........................................................................... 58
4.3. 
Justification for Dose...................................................................................................................... 59
4.4. 
End of Study Definition................................................................................................................... 59
5. 
STUDY POPULATION ...................................................................................................................... 59
5.1. 
Inclusion Criteria............................................................................................................................ 60
5.2. 
Exclusion Criteria........................................................................................................................... 62
5.3. 
Lifestyle Considerations................................................................................................................. 65
5.4. 
Screen Failures.............................................................................................................................. 65
5.5. 
Criteria for Temporarily Delaying Administration of Study Vaccine ............................................... 66
6. 
STUDY VACCINE(S) AND CONCOMITANT THERAPY ................................................................. 66
6.1. 
Study Vaccine(s) Administered...................................................................................................... 66
6.2. 
Preparation/Handling/Storage/Accountability ................................................................................ 67
6.3. 
Measures to Minimize Bias: Randomization and Blinding............................................................. 68
6.4. 
Study Vaccination Compliance ...................................................................................................... 70
6.5. 
Dose Modification........................................................................................................................... 70
6.6. 
Treatment of Overdose .................................................................................................................. 70
6.7. 
Prestudy and Concomitant Therapy .............................................................................................. 71
6.8. 
Study Vaccination Pausing Rules.................................................................................................. 72
7. 
DISCONTINUATION OF STUDY VACCINATION AND PARTICIPANT
DISCONTINUATION/WITHDRAWAL............................................................................................... 74
7.1. 
Discontinuation of Study Vaccination............................................................................................. 74
7.2. 
Participant Discontinuation/Withdrawal From the Study................................................................ 75
7.2.1. 
Withdrawal From the Use of Research Samples ....................................................................... 75
7.3. 
Lost to Follow-up............................................................................................................................ 76
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
6
Status: Approved, Date: 15 Aug 2022
8. 
STUDY ASSESSMENTS AND PROCEDURES ............................................................................... 76
8.1. 
Immunogenicity Assessments ....................................................................................................... 79
8.1.1. 
Immunogenicity Assessments .................................................................................................... 79
8.1.2. 
Procedures in Case of (Suspected) COVID-19.......................................................................... 81
8.1.3. 
Procedures for Adolescents Whose Close Relative/Contact Has Suspected or
Confirmed COVID-19.................................................................................................................. 86
8.1.4. 
Symptomatic SARS-COV-2 Infection ......................................................................................... 87
8.1.5. 
Asymptomatic SARS-CoV-2 Infection ........................................................................................ 87
8.2. 
Safety Assessments....................................................................................................................... 87
8.2.1. 
Physical Examinations................................................................................................................ 87
8.2.2. 
Vital Signs................................................................................................................................... 88
8.2.3. 
Pregnancy Testing...................................................................................................................... 88
8.2.4. 
Hematology Clinical Laboratory Assessments ........................................................................... 88
8.3. 
Adverse Events, Serious Adverse Events, Medically-attended Adverse Events, Adverse
Events of Special Interest, and Other Safety Reporting ................................................................ 89
8.3.1. 
Time Period and Frequency for Collecting Adverse Event, Medically-attended Adverse
Event, Adverse Event of Special Interest, and Serious Adverse Event Information .................. 89
8.3.2. 
Method of Detecting Adverse Events, Medically-attended Adverse Events, Adverse
Events of Special Interest, and Serious Adverse Events ........................................................... 91
8.3.3. 
Follow-up of Adverse Events, Medically-attended Adverse Events, Adverse Events of
Special Interest, and Serious Adverse Events ........................................................................... 92
8.3.4. 
Regulatory Reporting Requirements for Serious Adverse Events ............................................. 93
8.3.5. 
Pregnancy................................................................................................................................... 93
8.3.6. 
Adverse Events of Special Interest............................................................................................. 93
8.4. 
Virology Assessments.................................................................................................................... 95
8.5. 
Biomarkers..................................................................................................................................... 96
8.6. 
Medical Resource Utilization and Health Economics .................................................................... 96
9. 
STATISTICAL CONSIDERATIONS.................................................................................................. 96
9.1. 
Statistical Hypotheses.................................................................................................................... 96
9.2. 
Sample Size Determination ........................................................................................................... 96
9.2.1. 
Immunogenicity........................................................................................................................... 96
9.2.2. 
Safety.......................................................................................................................................... 97
9.3. 
Populations for Analysis Sets ........................................................................................................ 97
9.4. 
Statistical Analyses ........................................................................................................................ 97
9.4.1. 
General Considerations.............................................................................................................. 97
9.4.2. 
Primary/Secondary Endpoints.................................................................................................... 98
9.4.3. 
Exploratory Endpoints................................................................................................................. 99
9.4.4. 
Other Analyses ........................................................................................................................... 99
9.5. 
Planned Analyses .......................................................................................................................... 99
10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS .......................... 101
10.1. 
Appendix 1: Abbreviations and Definitions .................................................................................. 101
10.2. 
Appendix 2: AESI Clinical Laboratory Tests ................................................................................ 103
10.3. 
Appendix 3: Regulatory, Ethical, and Study Oversight Considerations....................................... 105
10.3.1. 
Regulatory and Ethical Considerations .................................................................................... 105
10.3.2. 
Financial Disclosure.................................................................................................................. 108
10.3.3. 
Informed Consent Process and Assent Form .......................................................................... 108
10.3.4. 
Data Protection ......................................................................................................................... 109
10.3.5. 
Long-Term Retention of Samples for Additional Future Research .......................................... 110
10.3.6. 
Safety Monitoring Committees Structure.................................................................................. 110
10.3.7. 
Publication Policy/Dissemination of Clinical Study Data.......................................................... 111
10.3.8. 
Data Quality Assurance............................................................................................................ 113
10.3.9. 
Case Report Form Completion................................................................................................. 113
10.3.10. Source Documents ................................................................................................................... 114
10.3.11. Monitoring ................................................................................................................................. 114
10.3.12. On-Site Audits........................................................................................................................... 115
10.3.13. Record Retention...................................................................................................................... 115
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
7
Status: Approved, Date: 15 Aug 2022
10.3.14. Study and Site Start and Closure ............................................................................................. 116
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............................................... 117
10.4.1. 
Adverse Event Definitions and Classifications ......................................................................... 117
10.4.2. 
Attribution Definitions................................................................................................................ 118
10.4.3. 
Severity Criteria........................................................................................................................ 119
10.4.4. 
Special Reporting Situations .................................................................................................... 119
10.4.5. 
Procedures ............................................................................................................................... 120
10.4.6. 
Product Quality Complaint Handling......................................................................................... 121
10.4.7. 
Contacting Sponsor Regarding Safety, Including Product Quality........................................... 122
10.5. 
Appendix 5: Toxicity Grading Scales in Adolescents (12 to 17Years of Age)............................ 123
10.6. 
Appendix 6: Contraceptive Guidance .......................................................................................... 126
10.7. 
Appendix 7: Symptoms of Infection with Coronavirus-19............................................................ 127
10.8. 
Appendix 8: Multisystem Inflammatory Syndrome in Children .................................................... 128
10.9. 
Appendix 9: Case Definitions for COVID-19................................................................................ 130
10.9.1. 
Case Definitions for Adolescents 12 to 17Years of Age.......................................................... 130
10.9.2. 
US FDA Harmonized Case Definition for COVID-19................................................................ 132
10.9.3. 
Case Definition for Asymptomatic or Undetected COVID-19................................................... 132
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
Adolescents.................................................................................................................................. 133
10.11. Appendix 11: Symptoms of Coronavirus (US Centers for Disease Control and Prevention)
in Children .................................................................................................................................... 134
10.12. Appendix 12: TTS AESI Form...................................................................................................... 135
10.13. Appendix 13: MIS-C AESI Form .................................................................................................. 139
10.14. Appendix 14: Thrombotic Events to be Reported as AESIs ........................................................ 142
10.15. Appendix 15: Protocol Amendment History................................................................................. 143
11. REFERENCES................................................................................................................................. 155
INVESTIGATOR AGREEMENT............................................................................................................... 161
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 ......................................................................................................................... 42
Table 2: 
Part 1 Vaccination Schedules (Dose Selection Cohort) ........................................................... 55
Table 3: 
Summary of Immunogenicity Assays (Part 1)........................................................................... 80
Table 4 : 90% Two-sided CI for Possible Observed Rate of Adverse Events......................................... 96
Table 5 : Upper Limit of the 95% One-sided CI if no Cases are Observed for Different Sample
Sizes ......................................................................................................................................... 97
FIGURES
Figure 1: Schematic Overview of the Study*........................................................................................... 17
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
8
Status: Approved, Date: 15 Aug 2022
1. 
PROTOCOL SUMMARY
1.1. 
Synopsis
A Randomized, Observer-blind, Phase 2 Study to Evaluate the Safety, Reactogenicity, and Immunogenicity
of Different Dose Levels of Ad26.COV2.S Administered as a One- or Two-dose Regimen in Healthy
Adolescents From 12 to 17 Years Inclusive
Ad26.COV2.S (also known as Ad26COVS1, VAC31518, JNJ-78436735) is a monovalent vaccine
composed of a recombinant, replication-incompetent human Ad26 vector, constructed to encode the
SARS-CoV-2 spike (S) protein, stabilized in its prefusion conformation.
The term “adolescents” in this study refers to participants from 12 to 17years of age inclusive.
OBJECTIVES AND ENDPOINTS
Part 1 Primary Objectives and Endpoints
Objectives 
Endpoints
Primary
 
To assess the safety and reactogenicity of 
Ad26.COV2.S administered intramuscularly  
(IM) as a 1-dose regimen (at 2.5×1010 vp per
0.25 mL, 1.25×1010 vp, and 0.625×1010 vp
dose level) or as a 2-dose (56-day interval)
regimen 
(2.5×1010 
vp 
per 
0.5 mL, 
1.25×1010 vp, and 0.625×1010vp dose levels) 
in adolescents. 
 
Solicited local and systemic adverse events
(AEs)for 7 days post-dose 1 and 2.
 
Unsolicited AEs for 28 days post-dose 1 and
2.
 
Medically-attended adverse events (MAAEs)
from the first vaccination until 6 months post-
dose 1 or post-dose 2. MAAEs leading to
discontinuation will be collected during the
entire study.
 
Serious adverse events (SAEs) from the first
vaccination until the end of the study.
 
Adverse events of special interest (AESIs)
from first vaccination until end of the study
(incl multisystem inflammatory syndrome in
children [MIS-C]).
 
To assess the humoral immune response of 
Ad26.COV2.S administered IM as a 1-dose 
regimen (at 2.5×1010 vp per 0.25 mL, 
1.25×1010 vp, and 0.625×1010 vp dose level)or 
as a 2-dose (56-day interval) regimen 
(2.5×1010 vp per 0.5 mL, 1.25×1010 vp, and 
0.625×1010vp dose levels) in adolescents.
 Serological response to vaccination as
measured 
by 
spike-enzyme-linked
immunosorbent assay  (S-ELISA) (ELISA;
Units/mL [EU/mL]) or equivalent assay, or
virus neutralization assay (VNA) titers at
28 days post-dose 1 and 14 days post-dose 2.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
9
Status: Approved, Date: 15 Aug 2022
Part 1 Secondary and Exploratory Objectives and Endpoints
Secondary
 
To assess the humoral immune response to 
3 
dose 
levels 
of 
Ad26.COV2.S 
(2.5×1010 vp, 
1.25×1010 
vp, 
or 
0.625×1010vp) and regimens in all study 
groups at all blood collection timepoints.
 
Serological response to vaccination measured by
binding antibody titers to SARS-CoV-2 or
individual SARS-CoV-2 proteins (eg, S protein)
as measured by ELISA (or equivalent assay),
and/or
 
Serological response to vaccination measured by
neutralizing antibody titers to SARS-CoV-2
(VNA).
 
To assess the safety and reactogenicity of
Ad26.COV2.S administered IM as a
booster in adolescent participants (Groups
1-3).
 
Solicited local and systemic AEs for 7 days post-
booster.
 
Unsolicited AEs for 28 days post-booster.
 
MAAEs from the booster until 6 months
post-vaccination.
 
To evaluate the humoral immune response
in adolescent participants who receive a
booster dose during the study, pre-boost
and at selected time points post booster
vaccination (Groups 1-3).
 
Serological response to vaccination measured by
binding (S-ELISA and/or equivalent assay)
and/or neutralizing (VNA) antibody titers
Exploratory
 
To examine the immune response in
vaccinated adolescents after 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.
 
SARS-CoV-2-binding antibodies measured by
ELISA (or equivalent assay): Analysis of
antibodies binding to the SARS-CoV-2 S and/or
N protein.
 
Analysis of gene expression by ribonucleic acid
(RNA) transcript profiling in adolescents 12 to
17 years of age.
 
To assess the correlation between the
binding 
antibodies 
(S-ELISA) 
and
neutralizing antibody (VNA) titers to
SARS-CoV-2 at selected timepoints.
 
Correlation 
between 
binding 
antibodies
(S-ELISA; EU/mL, or equivalent assay) and
VNA (wtVNA and/or psVNA) titers at selected
timepoints.
 
To assess the occurrence of symptomatic
molecularly confirmed COVID-19 and
severity of COVID-19 signs and symptoms
in adolescents.
 
The number of adolescents with molecularly
confirmed COVID-19.
 
Presence and severity of COVID-19 signs and
symptoms as measured by the Symptoms of
Infection with Coronavirus-19 (SIC).
 
To 
assess 
for 
the 
occurrence 
of
asymptomatic SARS-CoV-2 infection.
 
Serologic conversion between baseline (Day 1;
pre-vaccination) and selected timepoints post-
vaccination 
using 
an 
ELISA 
and/or
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
10
Status: Approved, Date: 15 Aug 2022
SARS-CoV-2 immunoglobulin assay that is
dependent on the SARS-CoV-2 N protein.
 
The number of asymptomatic participants with a
SARS-CoV-2 positive molecular test.
 
For 
asymptomatic 
case 
definition, 
see
Section 10.9.3.
 
To assess the impact of pre-existing
humoral immunity against coronaviruses
other than SARS-CoV-2 at baseline on
Ad26.COV2.S vaccine immunogenicity.
 
Analysis of antibodies binding to coronaviruses
other than SARS-CoV-2 by ELISA or equivalent
assay.
 
To assess the impact of the Ad26.COV2.S
vaccine on the incidence of co-infections
with SARS-CoV-2 and other respiratory
pathogens in adolescents who have
received Ad26.COV2.S during the study.
 
Analysis of broad respiratory pathogens panel in
the nasal swabs collected during a confirmed
COVID-19 episode and in nasal swab samples
from adolescents with a symptomatic infection.
 
To assess the presence of SARS-CoV-2
variants during a confirmed COVID-19
episode in adolescents.
 
To assess SARS-CoV-2 viral load during a
confirmed 
COVID-19 
episode 
in
adolescents.
 
Identification of SARS-CoV-2 variants by
sequencing of nasal swabs and/or saliva samples
(as available) collected during a confirmed
COVID-19 episode.
 
Analysis of SARS-CoV-2 viral load (via
qRT-PCR) in nasal swabs and/or saliva samples
(as available) collected during a confirmed
COVID-19 episode.
 
To further explore the humoral immune
responses in participants who have
received Ad26.COV2.S.
Exploratory analyses may include the following
assays:
 
SARS-CoV-2 neutralization as assessed by
VNA.
 
Adenovirus neutralization as measured by VNA.
 
Analysis of neutralizing and binding antibodies
against emerging SARS-CoV-2 virus lineages.
 
Functional 
and 
molecular 
antibody
characterization including, but not limited to
avidity, Fc-mediated viral clearance, Fc
characteristics, Ig subclass and IgG isotype,
antibody glycosylation, and assessment of
antibody repertoire.
 
Analysis of antibodies to S, N, and the receptor
binding domain (RBD) of the SARS-CoV-2 S
protein, 
and 
surface proteins 
of other
coronaviruses.
 
Epitope-specificity 
characterization 
of
antibodies.
 
Cytokine profiling: Analysis of cytokines,
chemokines, and other proteins of the innate or
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
11
Status: Approved, Date: 15 Aug 2022
adaptive immune response in the serum or
plasma.
 
Passive transfer: Analysis of immune mediators
correlating with protection against experimental
SARS-CoV-2 challenge in a suitable animal
model.
 
Seroresponse rates according to different
responder definitions.
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 be performed in addition, as outlined in a
revised statistical analysis plan (SAP).
Hypotheses
No formal hypothesis testing is planned in Part 1. Descriptive statistics will be used to compare vaccine
immunogenicity in adolescents from study VAC31518COV3006 versus vaccine immunogenicity in young
adults (18 to 25 years of age) from study VAC31518COV3001 or VAC31518COV3009 and between study
groups in VAC31518COV3006.
OVERALL DESIGN
This is a randomized, observer-blind, pivotal Phase 2 study in healthy adolescents from 12 to 17 years of
age. The safety, reactogenicity, and immunogenicity of Ad26.COV2.S in a 1- and 2-dose (56-day interval)
vaccination regimen will be evaluated. The study will descriptively compare the immune responses
measured by S-ELISA (and potentially VNA) in adolescents versus the immune responses measured in
young adults from study VAC31518COV3001 (after administration of 1 dose of Ad26.COV2.S) or
VAC31518COV3009 (after administration of 2 doses of Ad26.COV2.S) and between study groups in
VAC31518COV3006. This study consists of the Dose Selection Cohort, and it is designed with dose and
regimen selection performed in 2 Independent Data Monitoring Committee (IDMC) analyses at established
timepoints (see Section 10.3.6).
Previously, this study was designed to comprise Part 1 and Part 2, wherein Part 2 included the Extension
Cohort of vaccine naïve participants for evaluation of the dose level and dose regimen selected after review
of the data in Part 1. Per protocol amendment 4, Part 2 will no longer be conducted.
Participants will receive Ad26.COV2.S  as a first dose and Ad26.COV2.S  or placebo as a second dose.
Ad26.COV2.S  will be administered IM at 1 of up to 3 dose levels: 2.5×1010 vp, 1.25×1010 vp, or
0.625×1010 vp. The 2.5×1010 vp has been tested before in adolescents, in study VAC31518COV2001. A
single dose of Ad26.COV2.S at 2.5×1010 vp was administered to a cohort of participants 16 to 17 years of
age (33 participants received active vaccine or placebo in a blinded manner, 10:1 ratio). Immunogenicity
and safety data in adolescents 16 to 17 years of age and adults from COV2001 were evaluated by an IDMC
and the Medicines and Healthcare products Regulatory Agency (MHRA) who allowed a continuation of
evaluation in participants of 12 to 15 years of age. This COV3006 study will be evaluating dose levels of
2.5×1010 vp and lower in participants from 12 to 17 years of age.
A target of approximately 300 adolescents seronegative for SARS-CoV-2 antibodies at baseline (as
assessed by local serology finger-prick testing) will be enrolled in a 2-dose vaccination regimen (56-day
interval) with 1 or 2 active vaccinations, with placebo administered as a second dose for those in the 1-dose
regimen.
Participants in a Dose Selection Cohort will be randomly assigned in a 1:1:1:1:1:1 ratio to 1 of 6 study
arms: (a) to receive one active vaccination of Ad26.COV.2 (either 2.5×1010 vp per 0.25 mL dose volume,
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
12
Status: Approved, Date: 15 Aug 2022
1.25×1010 vp, or 0.625×1010 vp) followed by placebo at Day 56 in a 1-dose regimen (Groups 1, 2, and 3,
respectively), or (b) to receive 2 active vaccinations of the same dose level (either 2.5×1010 vp per 0.5mL
dose volume, 1.25×1010 vp or 0.625×1010 vp) in a 2-dose (56-day interval) regimen (Groups 4, 5, and 6,
respectively). Each group will contain 50 participants, of which approximately 70% need to be 12 to
15 years of age and approximately 30% need to be 16 to 17years of age. Adolescents will be unblinded to
the primary vaccination regimen at 6 months after the first vaccination.
Participants in Groups 1-3 will be given a booster vaccination as of 6 months after the last vaccination with
active vaccine (Vaccination 1). The booster dose level for all participants in Groups 1-3 will be 2.5 ×1010 vp
per 0.5 mL.
Participants in Groups 4-6 will not be administered a booster vaccination, given they will receive 2 active
vaccinations in the primary vaccination regimen.
As a part of the COVID-19 program safety oversight, the IDMC will review the data on an ongoing basis,
in addition to two study-specific predefined IDMC analyses. A first IDMC analysis of Part 1 will be
performed on safety and reactogenicity data 28 days post-dose 1. A second IDMC
analysis ofPart 1 will be performed on safety and reactogenicity data 28 days post-dose 2. Selected
sponsor members will review group unblinded summaries of those data, as well as any available
immunogenicity data up to 28 days post-dose 1 and 14 days post-dose 2.. Based on the review, the sponsor
will select the dose level and the regimen for any future pediatric studies (either a 1-dose regimen, a 2-dose
regimen, or both regimens). The selection will be based on the safety and reactogenicity data (28 days after
each vaccination) and any available immunogenicity data (28 days post-dose 1 for the 1-dose regimen, and
14 days post-dose 2 for the 2-dose regimen). Non-binding guidelines on dose and regimen selection will be
described in the SAP. Decision making on the optimal dose and regimen may take into account safety,
reactogenicity and immunogenicity data from other Ad26.COV2.S clinical studies (such as that of young
adults in study VAC31518COV3001 and study VAC31518COV3009 and adolescents from study
VAC31518COV2001).
The randomization will take into account having not more than 70% males or females in each age group,
as evenly divided as possible over the different age groups. Stratificationis by sex and age group. Screening
will ensure participants are seronegative at baseline for SARS-CoV-2 antibodies by utilizing the
finger-prick test (by testing blood from a small puncture in the finger).
Table: 
Part 1 Vaccination Schedules (Dose Selection Cohort)
Vac 1 
Vac 2 
Vac 3d
Group  
Na,b,c 
Day 1 
Day 57 
Day 184
1 
50 
2.5×1010 vp (0.25 mL) 
Placebo 
2.5×1010 vp (0.5 mL)
2 
50 
1.25×1010 vp 
Placebo 
2.5×1010 vp (0.5 mL)
3 
50 
0.625×1010 vp 
Placebo 
2.5×1010 vp (0.5 mL)
4 
50 
2.5×1010 vp (0.5 mL) 
2.5×1010 vp (0.5 mL)
5 
50 
1.25×1010 vp 
1.25×1010 vp
6 
50 
0.625×1010 vp 
0.625×1010 vp
N  number of participants; Vac  vaccination; vp  virus particles.
a 
No more than 70% of males or females should be randomized in each age group.
b 
All participants must be seronegative for SARS CoV 2 antibodies at baseline.
c 
Approximately 30% of participants should be between 16 to 17 years age and approximately 70% should be between 12
to 15 years of age.
d 
Participants in Groups 1 3 will be given a booster vaccination as of 6 months after the last vaccination with the active
vaccine (Vaccination 1) and the booster dose level for these participants will be 2.5×1010 vp per 0.5 mL.
At the time of study entry, participants or parent(s)/caregiver(s) will need to indicate to the site staff, in case
they, or their child, respectively would get infected with SARS-CoV-2, the identity and location of their
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
13
Status: Approved, Date: 15 Aug 2022
routine medical care physician and/or facility where they would obtain emergency care and hospitalization
for the participant, if necessary. If this information is not available, a plan for where such care could be
obtained should be developed. If a participant should have COVID-19 and their symptoms deteriorate,
participants or parent(s)/caregiver(s) will be recommended to go to the health care professional or hospital
that has been identified in advance. For the duration of the study, the participant will be asked through the
eCOA, if they have experienced any new symptoms or health concerns that may require seeking emergency
care.
All adolescents with COVID-19-like signs or symptoms and adolescents with a positive RT-PCR test from
outside the study meeting the prespecified criteria for suspected COVID-19 should undertake the COVID-
19 procedures until 14 days after signs or symptom onset/positive RT-PCR test from outside the study
(COVID-19 Day 15) or until resolution of the COVID-19 episode, whichever comes last, unless it is
confirmed that the COVID-19 Day 1 to 3 nasal swab (for those that have it) is negative for SARS-CoV-2.
Resolution of the COVID-19 episode is defined as having 1 SARS-CoV-2 negative nasal swab and
2 consecutive days with no COVID-19-related signs or symptoms. The procedures in case of (suspected)
COVID-19 are described in the body of the document.
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 shown in the Schedule of Activities for the last participant
in the study.
NUMBER OF PARTICIPANTS
A target of approximately 300 adolescents seronegative for SARS-CoV-2 antibodies at baseline (as
assessed by local serology finger-prick testing) will be enrolled.
VACCINE GROUPS AND DURATION
Participants will be vaccinated at the study site according to the schedules detailed below:
 
Three dose levels of Ad26.COV2.S will be used, 2.5×1010 vp, 1.25×1010 vp, and 0.625×1010 vp.
Ad26.COV2.S will be supplied at a concentration of 1×1011 vp per mL as a suspension in single-use
vials, with an extractable volume of 0.5 mL. Formulation buffer will be supplied as diluent to prepare
the 2.5×1010 vp, 1.25×1010 vp, and 0.625×1010 vp dose level.
 
Placebo will be supplied as a 0.9% NaCl solution.
Participants allocated to the 2.5×1010 vp dose level in Part 1 will receive 1 of 2 volumes: 0.5 or 0.25 mL. A
volume of 0.5 mL will be administered to participants in all other dose groups.
Study duration for participants in Part 1 is approximately 8 months (Groups 4-6) to12 months (Groups 1-
3), provided the intervals in the SoA are respected.
IMMUNOGENICITY EVALUATIONS
Blood for evaluation of humoral immune response will be drawn from participants at the timepoints
specified in the SoA.
Immunogenicity assessments may include, but are not limited to, the immunogenicity assays (as available
and feasible) summarized in the below table.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
14
Status: Approved, Date: 15 Aug 2022
Table: Summary of Immunogenicity Assays (Part 1)
Assay 
Purpose
Supportive of primary endpointsa
SARS-CoV-2 binding antibodies 
(ELISA)
Analysis of antibodies binding to the SARS-CoV-2 S protein
SARS-CoV-2 neutralization 
(VNA) 
Analysis of neutralizing antibodies to wild-type virus and/or
pseudovirion expressing S protein
Supportive of secondary/exploratory endpoints
SARS-CoV-2 binding antibodies 
(ELISA and/or equivalent assay) 
Analysis of antibodies binding to the SARS-CoV-2 S protein, or
SARS-CoV-2 variant proteins
SARS-CoV-2 neutralization 
(VNA) 
Analysis of neutralizing antibodies to wild-type virus and/or
pseudovirion expressing S protein, or SARS-CoV-2 variants
SARS-CoV-2 binding antibodies 
(ELISA and/or SARS-CoV-2
immunoglobulin assay)
Analysis of antibodies binding to the SARS-CoV-2 N protein
Adenovirus neutralization 
(neutralization assay)
Analysis of neutralizing antibodies to adenovirus
Binding antibodies to S protein, N 
protein, RBD of S protein of 
SARS-CoV-2 and other 
coronaviruses (MSD, ELISA or
equivalent assay)
Analysis of antibodies to S, N, and the RBD of the SARS-CoV-2
S protein or SARS-CoV-2 variants, and coronaviruses other than
SARS-CoV-2
Functional and molecular 
antibody characterization  
Analysis of antibody characteristics including, but not limited to
avidity, Fc-mediated viral clearance, Fc characteristics, Ig
subclass, IgG isotype, antibody glycosylation, and assessment of
antibody repertoire
Epitope-specificity 
characterization
Analysis of site-specificity, epitope mapping
Cytokine profiling 
Analysis of cytokines, chemokines, and other proteins of the
immune response in serum or plasma
Passive transfer 
Analysis of immune mediators correlating with protection against
experimental SARS-CoV-2 challenge in a suitable animal model
Gene expression analysis (RNA- 
seq)
Analysis of gene expression by RNA transcript profiling
ELISA = enzyme-linked immunosorbent assay; Fc = crystallizable fragment; Ig = immunoglobulin; SARS-CoV-2 =
severe acute respiratory syndrome coronavirus-2; MSD = Meso Scale Diagnostics, LLC; RBD = receptor
binding domain; RNA = ribonucleic acid; VNA = virus neutralization assay
a. Either Spike-ELISA or VNA will be used to support the primary endpoint in Part 1.
A rapid SARS-CoV-2 serologic finger-prick test for past infection with SARS-CoV-2 will be performed
for all participants at Day 1. Participants who test positive will be informed of the result by the study staff.a
Participants who test positive will not be included.
a Vaccination with Ad26.COV2.S may interfere with some serologic assays utilized at local community health
clinics/commercial laboratories, by seeking and identifying the spike protein in the vaccine and rendering a false
positive result. For this reason, participants will be encouraged to not seek testing outside the study. If a participant
requires testing outside of the protocol-mandated testing schedule, the site will guide them on the appropriate assay
that identifies the viral nucleocapsid protein (and not the spike protein).
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
15
Status: Approved, Date: 15 Aug 2022
BIOMARKER EVALUATIONS
For participants with a positive molecular test result for SARS-CoV-2 infection, biomarker analysis
(PAXgene, RNA-seq) may be performed for evaluation of COVID-19 cases and to explore potentially
informative biomarkers, eg, those associated with severe COVID-19.
SAFETY EVALUATIONS
After each vaccination, participants will remain under observation at the study site for at least 30 minutes
(or longer if required by institutional/local practice) for the presence of any acute reactions and solicited
events.
Participants will be asked to note in the reactogenicity diary local 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 reactogenicity 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 reactogenicity diary on a daily basis for 7 days
post-vaccination (day of vaccination and the subsequent 7 days), for the following systemic events: fatigue,
headache, nausea, and myalgia.
All 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 informed consent/assent form (ICF) is obtained until the end of the study/early
withdrawal. Solicited AEs, collected through a reactogenicity diary as part of the eCOA, will be recorded
for each vaccination from the time of vaccination until 7 days post-vaccination. Thrombosis with
thrombocytopenia syndrome is considered to be an AESI. Suspected AESIs (thrombosis with
thrombocytopenia syndrome [TTS] [defined as platelet count below 150,000/µL]) and MIS-C  will be
reported fromthe 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
cases of TTS. All other unsolicited AEs and special reporting situations, whether serious or nonserious, 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) 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. MAAEs are to be reported for all
participants from the first vaccination until 6 months after each vaccination, except for MAAEs leading to
study discontinuation which are to be reported during the entire study.
STATISTICAL METHODS
Sample Size Determination
The sample size for Part 1 shall enable the selection of the dose and dose schedule for any future pediatric
studies.
With a sample size of 50 participants per group, the width of the 90% confidence interval (CI) for the
observed proportion of adverse events will vary between 5.8% and 24.8% depending on the observed
proportion. Assuming pooling of adverse event data after the first dose of the 1- and 2-dose regimen, the
width of this confidence interval will vary between 3% and 17.3% depending on the observed proportion.
Non-binding guidelines on dose and regimen selection will be described in the SAP. Decision making on
the optimal regimen will take safety and reactogenicity data, as well as any available immunogenicity data,
and data from other Janssen clinical trials of Ad26.COV2.S into account.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
16
Status: Approved, Date: 15 Aug 2022
A target of approximately 300 adolescents seronegative for SARS-CoV2 antibodies at baseline (as assessed
by local serology finger-prick testing) will be enrolled.
Populations for Analysis Set
For purposes of analysis, the following populations are defined:
The Full Analysis Set (FAS) will include all participants with at least one vaccine administration
documented.
The Per Protocol Immunogenicity (PPI)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 samples obtained from participants after SARS-CoV-2 infection (if confirmed by molecular testing or
non-S-ELISA [or equivalent assay]) occurring during the study after randomization (if applicable), after
other SARS-CoV-2 vaccination outside the study, and samples obtained outside predefined windows will
be excluded from the analysis set. Participants who were seronegative by local serology finger-prick test
on Day 1 prior to study entrybut were determined to be seropositive at baseline by central N- orS- serology
testing will also be included in the PPI. More details will be provided in the SAP.
Primary/Secondary Endpoints
Safety
No formal statistical testing of safety data is planned. Safety data will be analyzed descriptively by vaccine
group and by age group (12 to 15 and 16 to 17 years of age). In addition, for selected tables, tabulations
pooled by vaccine dose will also be provided. All safety analyses will be done on the FAS.
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 GMC [ELISA] or GMT [VNA]). Graphical representations of
immunologic parameters will be made as applicable. Frequency tabulations will be calculated for discrete
(qualitative) immunologic parameters, as applicable.
In addition, the ratio between neutralizing and binding antibodies as determined by VNA and S protein
ELISA, respectively, will be calculated together with confidence intervals. More details will be provided
in the SAP.
S-ELISA or VNA may be used as endpoint for decision making on dose and regimen selection. Correlation
between S-ELISA and VNA and between other relevant humoral immunogenicity readouts will be
evaluated.
Planned Analyses
Part 1
A first IDMC analysis of Part 1 will be performed on safety and reactogenicity data 28 days post-dose 1.
A second IDMC analysis of Part 1 will be performed on safety and reactogenicity data 28 days post-dose
2.
Selected sponsor members will review group unblinded summaries of those data, as well as any available
immunogenicity data up to 28 days post-dose 1 and 14 days post-dose 2.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
17
Status: Approved, Date: 15 Aug 2022
A primary analysis of safety, reactogenicity and immunogenicity data up to 28 days post-dose 2 will be
performed and the selected dose level will be determined for any future pediatric studies. The sponsor will
be unblinded at the time of the primary analysis, but the blind will be maintained at a participant and study
site level up to the unblinding visit. Interim analyses may be performed for safety and/or immunogenicity,
to facilitate decision making with regards to planning of future studies or for regulatory submission
purposes.
The final analysis will be performed when all participants have completed the last visit or discontinued
earlier.
1.2. 
Schema
Figure 1: 
Schematic Overview of the Study*
G=group; IDMC=Independent Data Monitoring Committee; Rand=randomization; Vacc=vaccination; vp=virus
particle
*Note: Study duration for participants in Part 1 is approximately 8 months (Groups 4-6) to12 months (Groups 1-3)
provided the intervals in the SoA are respected.
a. Dose Selection Cohort: 50 participants per group will receive 1 or 2 doses of the active vaccine.
Participants in Groups 1-3 will be given a booster vaccination as of 6 months after the last vaccination with
active vaccine (Vaccination 1) and the booster dose level for these participants will be 2.5 ×1010 vp per 0.5 mL.
Unblinding to the primary vaccination regimen will take place approximately 6 months after the first vaccination
in Part 1.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
21
Status: Approved, Date: 15 Aug 2022
h. 
Pulse/heart rate, preferably supine systolic and diastolic blood pressure, respiratory rate, and body temperature. Pulse/heart rate measurements should be taken
preceded by at least 5 minutes of rest (if feasible) in a quiet setting without distractions (eg, television, cell phones). Vital signs measurements are recommended
before blood sampling. Body temperature will be measured preferably orally (routes to be recorded in the eCOA).
i. 
Rapid serological test for anti-SARS-CoV-2 antibody will collect blood from a small puncture in the finger (finger-prick test at screening).
j. 
If a rapid serologic test is completed ≤3 days before vaccination, a repeat test is not required on Day 1
k. 
Investigator must check for clinically significant 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 ifany other reasons, as listed in Section 7.1, have been met and would prevent further study vaccination.
l. 
For participant of childbearing potential only.
m. Whole blood samples will be used for complete blood cell count, including platelet count (hematology, see Section 10.2, Appendix 2), 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 centrally for future testing
to evaluate the impact of any potential thromboembolic events. Samples can also be tested (centrally) for anti-PF4 antibodies and platelet activation assay (if
HIT/PF4 is positive). Unused samples may be used for immunogenicity testing.
n. 
After each vaccination, participants will remain under observation at the study site for at least 30 minutes (or longer if required by institutional/local practice) for
the presence of any acute reactions and solicited events. 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 required minimum post-vaccination observation period is complete.
o. 
Adverse events 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.
p. 
MAAEs are to be reported for all participants from the moment of the first vaccination until 6 months after vaccination, except for MAAEs leading to study
discontinuation which are to be reported during the entire study. New onset of chronic diseases will be collected as part of the MAAEs.
q. 
All SAEs and AESIs 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 and AESIs are to be reported from the moment of vaccination until completion of the participant’s last
study-related procedure.
r. 
Concomitant therapies such as, but not limited to, analgesic/antipyretic medications and non-steroidal anti-inflammatory drugs, corticosteroids, antihistamines,
and vaccinations must be recorded from first dose to 28 days post-dose 2 and post-booster (vaccination 3). 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. Concomitant therapies associated with an SAE meeting the criteria outlined in Section 10.4.1 will be collected and recorded in the eCRF from the
moment of first vaccination through the end of the study. Concomitant therapies associated with MAAEs will be collected and recorded in the eCRF from the
moment of vaccination until 6 months after vaccination. Concomitant therapies associated with MAAEs leading to study discontinuation will be recorded in the
eCRF from first vaccination through the end of the study.
s. 
If an event is still ongoing on Day 8 the participant should continue to collect information in the reactogenicity diary until resolution. The reactogenicity diary
should be reviewed again at the next visit.
t. 
Participants will complete the reactogenicity diary using the eCOA on their own eDevice (smartphone or tablet) when feasible. Provisioned devices will be
available on a limited basis.
u. 
Nasal swabs, and saliva (if feasible) during the 7-day cycles may be collected at home by the participant (if sample pick up from the participant’s home is
feasible).
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
22
Status: Approved, Date: 15 Aug 2022
v. 
The SIC questionnaire asks the participant if they had any of the prespecified signs or symptoms (see Section 10.7) during the past 24 hours (including highest
temperature in the last 24 hours), and (when applicable) to rate the severity. The baseline SIC questionnaire (Visit 2) must be completed the same day as
vaccination (ie, to prevent influencing participant responses). If a participant is unable to complete the SIC in the eCOA, a study site staff member can collect
information on the participant’s behalf as detailed in Section 8.1.2.
w. Participants will be asked, through the eCOA, if they have experienced any new symptoms or health concerns that may require seeking emergency care. Sites
should reach out to participants or parent(s)/caregiver(s) if they fail to complete the surveillance question upon any of these reminders. The questionnaire will be
accessible on the eCOA platform in between scheduled reminders and participants will be encouraged to answer the surveillance question in the eCOA as soon
as possible after the onset of COVID-19-like signs or symptoms. Every effort will be made to document the status of all participants that are lost to follow-up
due to not completing the eCOA and for whom hospitalization has not been recorded. If a participant meets the prespecified criteria for (suspected) COVID-19
(see Section 8.1.2.1), refer to Section 1.3.3, Procedures for Participants With (Suspected) COVID-19.
Enrolled participants and their parent(s)/caregiver(s) will be counselled on SARS-CoV-2 infection prevention each time that they have a contact with site staff,
in line with local guidelines.
At the time of study entry, participants or parent(s)/caregiver(s) will need to indicate to the study site, in case they, or their child, respectively would get infected
with SARS-CoV-2, the identity and location of their routine medical care physician and/or facility where they would obtain emergency care and hospitalization
for the participant, if necessary. If this information is not available, a plan for where such care could be obtained should be developed. If a participant should
have COVID-19 and their symptoms deteriorate, participants or parent(s)/caregiver(s) will be recommended to go to the HCP or hospital that has been identified
in advance.
x. 
Participants will be asked daily up to Day 30, through the eCOA, if they experience any new symptoms or health concerns that could be related to TTS or MIS-C
(Section 8.3.6).
y. 
Approximately 6 months after the vaccination 1, participants will be unblinded to the primary vaccination regimen. The IWRS unblinding may occur up to 7
days before the scheduled visit date to allow for appropriate planning and preparations to take place. Participants who do not wish to receive the booster
vaccination (vaccination 3) can ask to be withdrawn from the study. An early exit visit will be conducted as soon as possible. Participants who wish to withdraw
consent or assent from participation in the study will be offered an optional visit for safety follow-up. This includes the safety assessments of the early exit visit
(no blood sampling for immunogenicity [see Section 7.2]). Note that assessments on Visit 9 are to be performed for all participants, irrespective of the outcome
of the unblinding.
AE = adverse event; AESI=adverse event of special interest, COVID-19 = coronavirus disease-2019; eCOA = electronic clinical outcome assessment; d = day(s);
HCP = health care practitioner; ICF = informed consent form; IWRS = interactive web response system; MAAE = medically-attended adverse event;
meds = medication; m = months; MIS-C = multisystem inflammatory syndrome in children; PROs = Patient-reported Outcomes; SAE = serious adverse event;
SARS-CoV-2 = severe acute respiratory syndrome coronavirus-2; SIC = Symptoms of Infection with Coronavirus-19; TTS = thrombosis with thrombocytopenia
syndrome; vac = vaccination.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
25
Status: Approved, Date: 15 Aug 2022
e. 
A full physical examination, including length/height, 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.
f. 
Pulse oximetry at Day 1 is mandatory, at all other visits only if applicable.
g. 
Adolescent (12 to 17 years of age) participants will be provided a pulse oximeter at baseline to measure blood oxygen saturation and pulse rate during a COVID-
19 episode (see Section 1.3.3)
h. 
Pulse/heart rate, preferably supine systolic and diastolic blood pressure, respiratory rate, and body temperature. Pulse/heart rate measurements should be taken
preceded by at least 5 minutes of rest (if feasible) in a quiet setting without distractions (eg, television, cell phones). Vital signs measurements are recommended
before blood sampling. Body temperature will be measured preferably orally (routes to be recorded in the eCOA).
i. 
Rapid serological test for anti-SARS-CoV-2 antibody will collect blood from a small puncture in the finger (finger-prick test at screening).
j. 
If a rapid serologic test is completed ≤3 days before vaccination, a repeat test is not required on Day 1
k. 
Investigator must check for clinically significant 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.
l. 
For participant of childbearing potential only.
m. Whole blood samples will be used for complete blood cell count, including platelet count (hematology, see Section 10.2, Appendix 2), 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 centrally for future testing
to evaluate the impact of any potential thromboembolic events. Samples can also be tested (centrally) for anti-PF4 antibodies and platelet activation assay (if
HIT/PF4 is positive). Unused samples may be used for immunogenicity testing.
n. 
After each vaccination, participants will remain under observation at the study site for at least 30 minutes (or longer if required by institutional/local practice) for
the presence ofany acute reactions and solicited events. 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 required minimum post-vaccination observation period is complete.
o. 
Adverse events 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.
p. 
MAAEs are to be reported for all participants from the moment of the first vaccination until 6 months after vaccination, except for MAAEs leading to study
discontinuation which are to be reported during the entire study. New onset of chronic diseases will be collected as part of the MAAEs.
q. 
All SAEs and AESIs 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 and AESIs are to be reported from the moment of vaccination until completion of the participant’s last
study-related procedure.
r. 
Concomitant therapies such as, but not limited to, analgesic/antipyretic medications and non-steroidal anti-inflammatory drugs, corticosteroids, antihistamines,
and vaccinations must be recorded from first dose to 28 days post-dose 2 and post-booster (vaccination 3). 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. Concomitant therapies associated with an SAE meeting the criteria outlined in Section 10.4.1 will be collected and recorded in the eCRF from the
moment of first vaccination through the end of the study. Concomitant therapies associated with MAAEs will be collected and recorded in the eCRF from the
moment of vaccination until 6 months after vaccination. Concomitant therapies associated with MAAEs leading to study discontinuation will be recorded in the
eCRF from first vaccination through the end of the study.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
26
Status: Approved, Date: 15 Aug 2022
s. 
If an event is still ongoing on Day 8 the participant should continue to collect information in the reactogenicity diary until resolution. The reactogenicity diary
should be reviewed again at the next visit.
t. 
Participants will complete the reactogenicity diary using the eCOA on their own eDevice (smartphone or tablet) when feasible. Provisioned devices will be
available on a limited basis.
u. 
Nasal swabs, and saliva (if feasible) during the 7-day cycles may be collected at home by the participant (if sample pick up from the participant’s home is
feasible).
v. 
The SIC questionnaire asks the participant if they had any of the prespecified signs or symptoms (see Section 10.7) during the past 24 hours (including highest
temperature in the last 24 hours), and (when applicable) to rate the severity. The baseline SIC questionnaire (Visit 2) must be completed the same day as
vaccination (ie, to prevent influencing participant responses). If a participant is unable to complete the SIC in the eCOA, a study site staff member can collect
information on the participant’s behalf as detailed in Section 8.1.2.
w. Participants will be asked, through the eCOA, if they have experienced any new symptoms or health concerns that may require seeking emergency care. Sites
should reach out to participants or parent(s)/caregiver(s) if they fail to complete the surveillance question upon any of these reminders. The questionnaire will be
accessible on the eCOA platform in between scheduled reminders and participants will be encouraged to answer the surveillance question in the eCOA as soon
as possible after the onset of COVID-19-like signs or symptoms. Every effort will be made to document the status of all participants that are lost to follow-up
due to not completing the eCOA and for whom hospitalization has not been recorded. If a participant meets the prespecified criteria for (suspected) COVID-19
(see Section 8.1.2.1), refer to Section 1.3.3, Procedures for Participants With (Suspected) COVID-19.
Enrolled participants and their parent(s)/caregiver(s) will be counselled on SARS-CoV-2 infection prevention each time that they have a contact with site staff,
in line with local guidelines.
At the time of study entry, participants or parent(s)/caregiver(s) will need to indicate to the study site, in case they, or their child, respectively would get infected
with SARS-CoV-2, the identity and location of their routine medical care physician and/or facility where they would obtain emergency care and hospitalization for
the participant, if necessary. If this information is not available, a plan for where such care could be obtained should be developed. If a participant should have
COVID-19 and their symptoms deteriorate, participants or parent(s)/caregiver(s) will be recommended to go to the HCP or hospital that has been identified in
advance.
x. 
Participants will be asked daily up to Day 30, through the eCOA, if they experience any new symptoms or health concerns that could be related to TTS or MIS-C
(Section 8.3.6).
y. 
Approximately 6 months after vaccination 1, participants will be unblinded to the primary vaccination regimen. The IWRS unblinding may occur up to 7 days
before the scheduled visit date to allow for appropriate planning and preparations to take place. Participants who do not wish to receive an additional
vaccination(s) (Vaccination 2) can ask to be withdrawn from the study. An early exit visit will be conducted as soon as possible. Participants who wish to
withdraw consent or assent from participation in the study will be offered an optional visit for safety follow-up. This includes the safety assessments of the early
exit visit (no blood sampling for immunogenicity [see Section 7.2]). Note that assessments on Visit 9 are to be performed for all participants, irrespective of the
outcome of the unblinding.
AE = adverse event; AESI = adverse event of special interest; COVID-19 = coronavirus disease-2019; eCOA = electronic clinical outcome assessment; d = day(s);
HCP = health care practitioner; ICF = informed consent form; IWRS = interactive web response system; MAAE = medically-attended adverse event;
meds = medication; m = months; MIS-C = multisystem inflammatory syndrome in children; PROs = Patient-reported Outcomes; SAE = serious adverse event;
SARS-CoV-2 = severe acute respiratory syndrome coronavirus-2; SIC = Symptoms of Infection with Coronavirus-19; TTS = thrombosis with thrombocytopenia
syndrome; vac = vaccination.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
28
Status: Approved, Date: 15 Aug 2022
e. Participants should undertake the COVID-19 procedures until 14 days after signs or symptom onset/positive molecular test from outside the study (COVID-19
Day 15) or until resolution of the COVID-19 episode, whichever comes last. Resolution of a COVID-19 episode is defined as having 1 SARS-CoV-2 negative nasal
swab and 2 consecutive days with no COVID-19-related signs or symptoms. Once past COVID-19 Day 15, collection of nasal swab and saliva samples (if feasible)
from participants should be stopped as soon as 1 nasal swab sample is SARS-CoV-2 negative, but (if still symptomatic at that time) the participant should continue
completing the PROs (including SIC, body temperature, and pulse oximetry) in the eCOA until 2 consecutive days with no COVID-19-related signs or symptoms.
f. 
If any of the COVID-19 visits coincide with a scheduled visit in the main SoA, combining the visits is preferred and any blood samples that are listed in both visits
should only be collected once. For example: if the COVID-19 visit Day 29 falls within the main SoA Day 29 visit window, visits can be combined and the
COVID-19 humoral immunity (serum) sample is not necessary, as a sample will be collected as part of the main SoA Day 29 visit.
g. If a participant has a positive test result for SARS-CoV-2 infection and/or depending on the medical status of the participant, the participant may be requested to not
visit the study site (per local or institutional regulations) but to keep the participant at home. If necessary, study-site personnel will visit the participant at home, if
allowed by local regulations. Under these circumstances, the participant will be contacted by the site at least once per week to follow-up on the participant’s
condition and the participant’s medical care provider will be notified.
The site staffor HCP visiting the participant at home will use personal protective equipment according to local regulations.
h. In case of COVID-19 like signs or symptoms, based on the information collected through the SIC, the site will reach out to the participant at the latest on COVID-
19 Day 2 (the day after the day of signs or symptom onset) to assess whether the reported signs and symptoms qualify as a suspected COVID-19 episode using
prespecified criteria (Section 8.1.2.1). As several of the prespecified criteria for suspected COVID-19 overlap with vaccine-related reactogenicity, investigators’
clinical judgement is required to exclude vaccine-related events when assessing suspected COVID-19. In case the parent(s)/caregiver(s) or participant would
actively reach out to the site already on COVID-19 Day 1, the site should already make a first assessment on COVID-19 Day 1 to check whether the reported signs
and symptoms qualify as a suspected COVID-19 episode using prespecified criteria (Section 8.1.2.1).
i. 
A nasal swab and saliva sample (if feasible) should be collected from the participant by qualified site staffas soon as the prespecified criteria for suspected
COVID-19 are met and, in case of COVID-19 like signs or symptoms, preferably on the day of sign/symptom onset or in the 2 days thereafter (COVID-19 Day 1
to 3). In case of a positive molecular test, a saliva sample (if feasible) should be collected on COVID-19 Day 4 to 7and nasal swabs and saliva samples (if feasible)
should also be collected once every 7 days thereafter until 14 days after signs or symptoms onset/positive RT-PCR test from outside the study (COVID-19 Day 15,
if applicable) or until resolution of the COVID-19 episode, whichever comes last. If the nasal swab and saliva sample (Day 1 to 3, 7-day cycle) is collected at the
participant’s home, site staff should arrange transfer of the sample(s) to the study site as soon as possible after collection. Details are provided in the laboratory
manual.
j. 
All nasal swabs will be tested by a local laboratory for case management. For participants with suspected COVID-19 after a positive local test, confirmation of
SARS-CoV-2 infection by a central laboratory will be used for the analysis of the case definition. Nasal swabs will also be used to determine SARS-CoV-2 variants
and the viral load. Nasal swabs may also be tested for the presence of other respiratory pathogens using a broad respiratory pathogens panel.
k. The nasal swab and saliva sample (if feasible) should be collected and pulse oximetry 3 times a day should be started (if not started already) as soon as possible
after it has been confirmed that the prespecified criteria for suspected COVID-19 (Section 8.1.2.1) are met.
l. 
Saliva sample for all participants (if feasible), nasal swab only for participants who had a positive RT-PCR test from outside the study.
m. Nasal swabs and saliva (if feasible) during the 7-day cycles may be collected at home by the participant (if sample pick up from the participant’s home is feasible).
It should be ensured that the participant has sufficient supplies.
n. Participants should complete the (suspected) COVID-19 surveillance (symptom check). In case of COVID-19 like signs and symptoms, participants should be
encouraged by the site to complete the SIC daily, preferably in the evening around the same time each day, starting on the first day the participant experiences signs
or symptoms. Sites should remind the participant to complete the SIC, unless special circumstances occur such as hospitalization or ventilation, in which case the
reason for not completing the SIC should be recorded by site staff in the clinical database.
If a participant is unable to complete the eCOA, a site staff member can collect information on the participant’s behalf as detailed in Section 8.1.2.
Participants should measure body temperature daily (in accordance with the local standard of care).
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
29
Status: Approved, Date: 15 Aug 2022
o. If the participant does not have signs or symptoms at that time, the participant will only need to complete the (suspected) COVID-19 surveillance (symptom check).
p. Includes measurement of heart rate, respiratory rate [after at least 5 minutes rest, if feasible], and body temperature. It is recommended that vital signs are measured
before collection of nasal swabs or saliva samples and blood draws.
q. In case of COVID-19 like signs or symptoms, the participant will be asked to measure blood oxygen saturation and pulse rate at home 3 times a day (preferably in
the morning, at lunch time, and in the evening). The results will be recorded by the participant in the eCOA. On the first day the participant experiences
signs/symptoms, the participant should record at least 1 of the 3 pulse oximetry readings in the last 24 hours in the eCOA.
Upon closure of the COVID-19 episode and procedures, all participants will fall back to the default Schedule of Activities (Section 1.3.1, 1.3.2). If the participant
experiences new signs or symptoms suggesting possible COVID-19 at a later point in time, the participant would restart the COVID-19 procedures from COVID-19
Day 1 onwards.
COVID-19 = coronavirus disease-2019; d = day(s); eCOA = electronic clinical outcome assessment; PROs = Patient-reported Outcomes; RNA = ribonucleic acid;
RT-PCR = real time reverse-transcriptase polymerase chain reaction; SARS-CoV-2 = severe acute respiratory syndrome coronavirus-2; SIC = Symptoms of Infection
with Coronavirus-19
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
30
Status: Approved, Date: 15 Aug 2022
1.3.4. 
Participants With an AESI
1.3.4.1. 
Thrombosis With Thrombocytopenia Syndrome
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, ASH 2021,
BSH 2021, CDC 2021a). 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, thrombocytopenia, or TTS, local laboratory
assessments might be needed 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). Refer to the laboratory manual for further details. For the follow-up visit,
the volume of blood to be collected may vary depending on the clinical evaluation of the case. If any of the AESI
visits coincide with a scheduled visit in the main SoA or COVID-19 SoA, combining the visits is preferred, when
feasible, and any blood samples that are listed in both visits should only be collected once. For example: if the
AESI visit Day 29 falls within the main SoA Day 29 visit window, visits can be combined and the Clinical
laboratory blood sample (15 mL, whole blood/serum/plasma) is not necessary, as a sample will be collected as
part of the main SoA Day 29 visit.
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 10.12 for
further details.
f. Refer to Section 6.7for 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 laboratory blood sample (whole blood/plasma/serum), 15 mLd 
 

TTS AESI forme 
Continuous
Concomitant therapiesf 
 

NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
31
Status: Approved, Date: 15 Aug 2022
1.3.4.2. 
Multisystem Inflammatory Syndrome in Children (MIS-C)
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). Refer to the laboratory manual for further details. For the follow-up visit,
the volume of blood to be collected may vary depending on the clinical evaluation of the case. If any of the AESI
visits coincide with a scheduled visit on the main SoA or COVID-19 SoA, combining the visits is preferred, when
feasible, and any blood samples that are listed in both visits should only be collected once. For example: if the
AESI visit Day 29 falls within the main SoA Day 29 visit window, visits can be combined and the Clinical
laboratory blood sample (15 mL, whole blood/serum/plasma) is not necessary, as a sample will be collected as
part of the main SoA Day 29 visit.
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 for
further details.
f. Refer to Section 6.7for collection and recording of concomitant therapies associated with a suspected AESI.
AE = adverse event; AESI = adverse event of special interest; MIS-C = multisystem inflammatory syndrome in
children.
Timing relative to onset of suspected AESI
AESI 
Day 1a 
AESI
Day 29b
Visit Window  
 
±7 d
Site to report suspected AESIc 

Clinical laboratory blood sample (whole blood/plasma/serum), 15 mLd 
 

MIS-C AESI forme 
Continuous
Concomitant therapiesf 
 

NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
32
Status: Approved, Date: 15 Aug 2022
2. 
INTRODUCTION
Ad26.COV2.S (also known as Ad26COVS1, VAC31518, JNJ-78436735) is a monovalent vaccine
composed of a recombinant, replication-incompetent human Ad26 vector, constructed to encode
the SARS-CoV-2 spike (S) protein, stabilized in its prefusion conformation.
Information about the disease, correlates of immunity, and safety issues concerning this new
pandemic-causing virus are rapidly evolving. Therefore, it is critical to recognize that the approach
outlined in this document might change as insights and discussions evolve.
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  (IB Ad26.COV2.S
2022). As the IB might be further updated after protocol finalization, refer to the latest version of
the IB (and addenda, if applicable) for the most recent information.
The term “study vaccine” throughout the protocol, refers to Ad26.COV2.S or placebo as defined
in Section 6.1. The term “sponsor” used throughout this document refers to the entities listed in
the Contact Information page(s), which will be provided as a separate document. 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 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. For the purposes of this study, all references to participants refer to the participants
(adolescents) 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.
The term “caregiver” refers to the delegated primary caregiver(s) who will be responsible for
ensuring the study activities are conducted per protocol, eg, accompany the participant to the study
site on each assessment day according to the Schedule of Activities (SoA); consistently and
consecutively be available to provide information on the participant using the rating scales during
the scheduled study visits; help the study-site personnel ensure follow-up. This person may be the
legal guardian, or another appropriate person delegated by the legal guardian.
The term “adolescents” when referring to the participants in this study are 12 to 17 years of age
inclusive.
COVID-19 Vaccine and Considerations
Currently, there is only limitedavailabilityof authorized vaccines for the prevention of COVID-19
in the pediatric population. The continued development of safe and effective COVID-19 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 SARS-CoV and MERS-CoV S protein have
been associated with protection against experimental SARS-CoV and MERS-CoV infection in
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
33
Status: Approved, Date: 15 Aug 2022
nonclinical models (Chen 2005;Zhao 2017). Recent studies suggest that SARS-CoV-2 has several
similarities to SARS-CoV based on the full-length genome phylogenetic analysis and the
putatively similar cell entry mechanism and human cell receptor usage (Letko 2020; Lu 2020;
Zhou 2020). 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 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).
The immunogenicity profile of other Ad26-based vectors is illustrated by data obtained following
the immunization of adults with HIV vaccines (Ad26.ENVA.01, Ad26.Mos.HIV and
Ad26.Mos4.HIV), an Ebola vaccine (Ad26.ZEBOV), respiratory syncytial virus (RSV) vaccines
(Ad26.RSV.FA2 and Ad26.RSV.preF), a Zika virus vaccine (Ad26.ZIKV.001), and a malaria
vaccine (Ad26.CS.01). Antigen-specific antibody responses are observed in almost all participants
after one dose, in both naïve and pre-immune individuals (RSV). These antibodies may persist for
a year or more (RSV) after a single dose in pre-immune participants. They have functional
properties of neutralization (RSV, Zika), Fc-mediated antibody-dependent cell-mediated
cytotoxicity and antibody-dependent cell-mediated phagocytosis (HIV, malaria). Furthermore,
these data support an immunogenicity profile with emphasis on T helper (Th)1 responses and
demonstrate predominantly interferon gamma (IFN-γ) and tumor necrosis factor alpha production
in CD4+ and CD8+ T cells (Barouch 2013; Milligan 2016; Mutua 2019; Janssen Vaccines &
Prevention B.V. Data on file).
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 (Chen 2005; Faber 2005; Modjarrad 2019). The S protein is the major surface protein on
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
34
Status: Approved, Date: 15 Aug 2022
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 (Zumla 2016).
In this study, a 1-dose vaccination regimen at the 2.5×1010 virus particles (vp), 1.25×1010 vp, and
0.625×1010 vp dose level and a 2-dose (56-day interval) vaccination regimen at the 2.5×1010 vp,
1.25×1010 vp, and 0.625×1010 vp dose level will be evaluated in adolescents 12 to 17years of age.
SARS-CoV-2 Virology and COVID-19 Disease Burden
SARS-CoV-2 is an enveloped, positive-sense, single-stranded RNA Betacoronavirus
(Coronaviridae Study Group of the International Committee on Taxonomy of Viruses 2020;
Wu 2020). It was first identified following reports of a cluster of acute respiratory illness cases in
Wuhan, Hubei Province, China in December 2019 (Chen 2020; Li 2020). 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 (Lu 2020; WHO 2020c). Phylogenetic analysis of the complete viral genome
revealed that the virus, SARS-CoV-2, is part of the subgenus Sarbecovirus of the genus
Betacoronavirus, and is most closely related (approximately 88% identity) to a group of
SARS-CoV-like coronaviruses previously sampled from bats in China (Lu 2020; Zhou 2020).
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 30 January 2020 and declared the outbreak to be a pandemic on 11 March 2020 (WHO 2020a;
WHO 2020c). As of 21 January 2021, approximately 96,984,258 cases and 2,077,803 deaths from
COVID-19 have been reported worldwide (Johns Hopkins CSSE 2021).
Respiratory symptoms of COVID-19 typically appear 5 to 6 days following exposure to the virus,
but may appear from 2 to 14 days following exposure, with the clinical manifestations ranging
from mild symptoms to severe illness or death (CDC 2020b; Guan 2020; Linton 2020; UC San
Diego Health 2020; WHO 2020b). Severe or critical illness has been reported in 4% of pediatric
cases based on  a systematic review  (Meena 2020) and meta-analysis (Mantovani 2020) of
4,857and 2,855 children, respectively (ECDC 2020b). Descriptions of COVID-19 clinical case
definitions compiled by the US Centers for Disease Control and Prevention (CDC) and
Janssen-sponsored interviews with COVID-19-experienced clinicians include the following: 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. Other less common gastrointestinal
symptoms have been reported by CDC (nausea, vomiting, diarrhea) (CDC 2020j).
At present, it appears that individuals aged 65 years or older, especially those with comorbidities,
such as cardiovascular disease, diabetes, hypertension and underlying pulmonary disease, are
subject to the highest incidence of morbidity and mortality (CDC 2020h;Garg 2020;Verity 2020).
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
35
Status: Approved, Date: 15 Aug 2022
Clinical manifestations of disease are less severe in children than adults, with the majority of cases
reported as being asymptomatic, mild or moderate (CDC 2020e, Deming 2006, Dong 2020). A
study of 149,082 COVID-19 cases reported in the US found that only 1.7% of these cases occurred
in persons aged <18 years, with relatively few pediatric COVID-19 cases hospitalized, indicating
that COVID-19 might have a mild course among younger patients. Analysis of the COVID-NET
found that, one third of children hospitalized with COVID-19 were admitted to the intensive care
unit (ICU), while estimates of ICU admission  of children hospitalized with seasonal influenza
virus infection ranged from 16% to 25%. The case-fatality rate remains low though, even among
children hospitalized with more severe COVID-19 associated complications (Kim 2020; Collins
2019). Recent reports have also described several cases of MIS in children with Kawasaki disease-
like features (ie, fever, laboratory markers of inflammation, severe illness requiring
hospitalization, multisystem organ involvement). As of May 2020, approximately 230 suspected
cases of MIS associated with SARS-CoV-2 infection have been reported in EU/EEA countries and
the UK, including 2 fatalities (1 in the UK and 1 in France) (ECDC 2020c). As of 08 January2021,
1,659 confirmed pediatric cases of MIS have been reported to the CDC in the US and 26 deaths,
with the majority (85%) of these cases occurred in children >1 year to 14 years, with an average
age of 8 years. Almost all (1,638/1,659 cases) children with MIS had tested positive for current or
recent SARS-CoV-2 infection, while the remaining 1% had been in contact with a COVID-19
case. Most children developed MIS 2 to 4 weeks after infection with SARS-CoV-2. It is currently
unknown if MIS is specific to children or if it may also occur in adults as it has been reported up
to an age of 20 years old(CDC 2020g; CDC 2020d; Verdoni, 2020).
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 (Anderson 2020). In addition, evidence points to
Hispanic and Black children likely being at increased risk for severity of COVID-19 infection
(Feldstein 2020; Goyal 2020; Kim 2020).
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 one of the most important tools to help control
this highly contagious respiratory virus.
2.1. 
Study Rationale
Detailed information about the rationale for the selected doses can be found in Section 4.2.
Although children appear to be at lower risk of developing severe COVID-19 and death is rare
(Dong 2020), children can develop serious complications such as MIS (CDC 2020g;ECDC 2020c;
Verdoni, 2020). Children with underlying conditions and those with immune deficiency or who
are immunocompromised are at higher risk for severe disease (CDC 2020c). Also, recent studies
suggest that children are likely to be important vectors of community spread, including
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
36
Status: Approved, Date: 15 Aug 2022
SARS-CoV-2 transmission from young children in childcare settings and have higher levels of
viral load than adults (Heald-Sargent 2020; Yonker 2020; Lopez 2020). The availability of a
COVID-19 vaccine for the pediatric population is therefore warranted.
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 (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 antibodies (Buchholz 2004; Sui 2005; Zhang 2004; Zhou 2004)and the only viral
protein that can elicit protective immunity in animal models (Berry 2004; Bisht 2004; Bukreyev
2004; Subbarao 2004; Yang 2004). Based on these findings, the S protein  was selected as the
sponsor’s candidate vaccine antigen.
Available platform data, as well as initial immunogenicity and safety data from the first-in-human
study VAC31518COV1001 (COV1001) and the Phase 2a study VAC31518COV2001 have
demonstrated Ad26.COV2.S at the 5×1010 vp and 1×1011 vp dose level induces an immune
response that meets prespecified minimum criteria and has an acceptable safety profile
(Sadoff2021a), support initiating evaluation of Ad26.COV2.S in the pediatric population, with
the dose level 2.5×1010 vp (see Section 2.2 and Section 2.3.1). The most extensive safety
information of the single-dose regimen of Ad26.COV2.S at 5×1010 vp is available from ≥43,000
participants, 18 years of age and above, including adults 60 years of age and above, enrolled in the
ongoing pivotal Phase 3 study COV3001. A 2-dose vaccine regimen of Ad26.COV2.S at
5×1010 vp is currently under evaluation in the ongoing Phase 3 study COV3009. Supportive safety
information (AEs, clinical laboratory abnormalities, vital signs and physical examination findings)
is available from the interim analysis of the Phase 1 and 2 studies COV1001, COV1002, and
COV2001. In COV2001, Ad26.COV2.S is being evaluated at a range of doses and intervals
(1.25×1010 vp, 2.5×1010 vp, 5×1010 vp, and 1×1011 vp) in adolescents 12 to 17 years of age, adults
18 to 55 years of age and 65 years of age and above. Ad26.COV2.S has an acceptable safety and
reactogenicity profile when administered as a single-dose or as a 2-dose regimen in adults 18 years
of age and above, including adults 60 years of age and above. Immunogenicity and safety data in
adolescents 16 to 17 years of age and adults from COV2001 were evaluated by an Independent
Data Monitoring Committee (IDMC) and the Medicines and Healthcare products Regulatory
Agency (MHRA) who allowed a continuation of evaluation in participants of 12 to 15 years of
age. While the IDMC endorsed further enrollment of adolescents that would receive
Ad26.COV2.S at a 5×1010 vp dose level, Janssen (the Sponsor) has decided not to evaluate the
5×1010 vp dose in the pediatric population based on the immunogenicity data from the 2.5×1010 vp
dose in Study VAC31518COV2001 and has decided to redesign the pediatric studies. Therefore,
this study protocol has been modified, also taking health authority feedback on the original
VAC31518COV3006 study protocol into account. This study will focus on adolescent participants
12 to 17 years of age, and no further enrollment of this age group will take place in
VAC31518COV2001. 
The 33 
adolescent participants 
already enrolled in 
Study
VAC31518COV2001 will continue to be followed for safety and immunogenicity.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
37
Status: Approved, Date: 15 Aug 2022
Ad26.COV2.S will be evaluated in the pediatric population through a dose-confirmation approach.
In the present study (COV3006), the safety and immunogenicity of Ad26.COV2.S will be assessed
at a 2.5×1010 vp, 1.25×1010 vp, and 0.625×1010 vp dose level in a 1- and 2-dose (56-day interval)
regimen in adolescents from 12 to 17 years of age. Furthermore, it will be determined if the
2.5×1010 vp per0.25 mL dose volume has an acceptable safety profile and similar immunogenicity
compared with  a 2.5×1010 vp per 0.5 mL dose volume. This comparison will generate safety,
reactogenicity, and immunogenicity data at a lower injection volume of the currently approved
and available Ad26.COV2.S vaccine.
Enrollment of the age groups will start simultaneously (16 to 17years of age and 12 to 15 years of
age). Within each age group, enrollment for all dose levels will start simultaneously for both the
1- and 2-dose regimens. Note that if it is deemed more appropriate to continue with a lower dose
level than either 2.5×1010 vp or a 1.25×1010 vp dose level, then the use of these doses may be
removed in a future protocol amendment.
2.2. 
Background
Nonclinical Pharmacology
Nonclinical pharmacology of Ad26.COV2.S was evaluated in murine, rabbit, Syrian hamster, and
nonhuman primate (NHP) animal models for immunogenicity, including assessment of
immunological parameters relevant to the theoretical risk of vaccine associated enhanced
respiratory disease (VAERD). In addition, vaccine efficacy of Ad26.COV2.S including lung
histopathology assessment was evaluated in Syrian hamsters and NHPs. Details are provided in
the IB (IB Ad26.COV2.S 2022).
Nonclinical Safety
Biodistribution
To assess distribution, persistence, and clearance of the Ad26 viral vector platform, 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 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.
A biodistribution study specifically with Ad26.COV2.S has not been performed.
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
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
38
Status: Approved, Date: 15 Aug 2022
(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 in
any of the available GLP toxicology studies with Ad26-based vaccines up to the highest dose level
tested (1.2×1011 vp). A combined GLP repeated dose toxicity and local tolerance study with
Ad26.COV2.S is currently ongoing in New Zealand White rabbits.
Reproductive and Developmental Toxicology
A GLP compliant combined embryo-fetal and pre- and postnatal development study is currently
ongoing with Ad26.COV2.S in female NZW rabbits. A draft report of this study is expected in
December 2020, while the final report is expected to be issued in January 2021. In this study,
female NZW rabbits are injected IM with a control solution (0.9% sodium chloride) or 1×1011 vp
(2 times the human dose) Ad26.COV2.S on Day 1 (ie, 7 days prior to mating), Gestation Day
(GD)6 and GD 20. The study includes 2 subgroups: 1 group consisting of animals that are
necropsied on GD 29 and have a uterine and fetal examination (external, visceral, and skeletal
exams), and 1 group consisting of animals that are allowed to give birth and in which the survival
and development of the kits is evaluated through Lactation Day 28. An immunogenicity
assessment of maternal and fetal/kit serum will be performed to confirm maternal transfer of
antibodies.
A further GLP compliant combined embryo-fetal and pre- and postnatal development study has
been conducted in female NZW rabbits using an Ad26-based Ebola vaccine, ie, Ad26.ZEBOV
(Ad26 vector encoding the glycoprotein of Zaïre ebolavirus Mayinga variant) in a 2-dose regimen
with MVA-BN-Filo (Study TOX11212). This study is considered to provide supportive
reproduction and development toxicity data for Ad26.COV2.S, as Ad26.ZEBOV is produced from
the same Ad26 vector backbone as Ad26.COV2.S.
In study TOX11212, the first vaccination with either Ad26.ZEBOV (1×1011 vp) or MVA-BN-Filo
(3.61×108 Inf U) was administered 8 days prior to mating female rabbits with untreated male
rabbits. This was followed by a second vaccination with either vaccine component 6 days after
mating (ie, on GD 6) to maximize exposure of the developing embryo or fetus to the
vaccine-induced (maternal) immune response. The study also included a study group that received
Ad26.ZEBOV in a homologous regimen, ie, these rabbits received 2 doses of Ad26.ZEBOV. Half
the females (Study Phase 1) were necropsied on GD 29 and a uterine and fetal (external, visceral,
and skeletal) examination was conducted. The remaining females (Study Phase 2) were allowed
to give birth and raise their offspring until weaning; the survival and development of the pups were
evaluated through Lactation Day 28.
No adverse effect of Ad26.ZEBOV or MVA-BN-Filo was seen on reproductive performance,
fertility, litter data (corpora lutea count, number of implantation sites, viable fetuses, litter size,
pre- and post-implantation loss, and number of resorptions), parturition, or macroscopic
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
39
Status: Approved, Date: 15 Aug 2022
evaluations in parental females. Similarly, no adverse effect of vaccination was seen on fetal body
weights, external, visceral, and skeletal evaluations or first filial generation pup evaluations from
Lactation Day 0 to 28 (sex ratios, survival, body weights, clinical findings, developmental
evaluations, and macroscopic evaluations). The vaccine regimens elicited detectable maternal
antibody titers that were transferred to the fetuses.
In conclusion, the Ad26.ZEBOV (tested alone or in a regimen with MVA-BN-Filo) did not induce
maternal or developmental toxicity in rabbits following maternal exposure during the premating
and gestation period.
Clinical Studies
At the time of protocol writing, Phase 1/2a (COV1001, COV1002) and Phase 2a (COV2001)
clinical studies to assess the safety, reactogenicity, and immunogenicity of Ad26.COV2.S, as well
as Phase 3 (COV3001, COV3009) clinical studies to assess the efficacy of Ad26.COV2.S in the
prevention of molecularly confirmed moderate to severe/critical COVID-19 in adults are ongoing
and data from interim analyses from these studies are available. These data demonstrate that a
single-dose of Ad26.COV2.S at 5×1010 vp and 1×1011 vp induces an immune response that meets
prespecified minimum criteria and has an acceptable safety profile (Sadoff2021a). Data from
study COV1001 supports the evaluation of Ad26.COV2.S vaccine in younger age groups. In
COV2001, single dose of Ad26.COV2.S at 2.5×1010 vp was administered to a limited number of
participants 12 to 17 years of age (33 participants received active vaccine or placebo in a blinded
manner, 10:1 ratio) (see Section 2.1).
Refer to the latest IB for a high-level description of all ongoing studies with Ad26.COV2.S.
Clinical Safety Experience With Ad26-based Vaccines
Safety of other Ad26-vectored vaccines has been evaluated in adults in other studies by the
sponsor. Replication-incompetent Ad26 is being used as a vector in the development of vaccines
against diseases such as malaria, RSV, HIV, Zika virus, and filovirus, and has been used in the
now licensed Ebola virus vaccine (Zabdeno/Ad26.ZEBOV).
As of 21 December 2020, Ad26-based vaccines developed by the sponsor have been administered
to approximately 193,000 participants. The majority of these participants (more than 153,000)are
enrolled in an ongoing Ebola vaccine study in the Democratic Republic of the Congo and an
ongoing immunization campaign in Rwanda (UMURINZI Ebola Vaccine Program campaign)and
approximately 35,000 participants are enrolled in other ongoing studies.
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. The studies used the
following Ad26-based vaccines: Ad26.ZEBOV (Ebola program; 10 studies), Ad26.ENVA.01,
Ad26.Mos.HIV, and Ad26.Mos4.HIV (HIV program; 8 studies), Ad26.CS.01 (malaria program;
1 study), Ad26.RSV.FA2 and Ad26.RSV.preF (RSV program; 6 studies), and Ad26.Filo (filovirus
program; 1 study) (AdVac Safety Database V5.0 2020). In these 26 studies, 4,224 adult
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
40
Status: Approved, Date: 15 Aug 2022
participants were vaccinated with an Ad26-based vaccine and 938 adult participants received
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
(ie, the highest dose level tested).
As of 21 December 2020, more than 188,000 participants were enrolled in ongoing studies and 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 either
because the studies were still blinded, the studies were unblinded but their analysis took place after
the AdVac® safety database report cut-offdate, 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 for a summary of data from the
AdVac® safety database report.
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
(Chin 1969; Fulginiti 1969; Kapikian 1969; Kim 1969). 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 Th2-skewed type T-cell
response (Moghaddam 2006).
VAERD has also been described for SARS-CoV and MERS-CoV in some animal models, in which
candidate vaccines induced a Th2-biased immune response (Agrawal 2016; Bolles 2011;
Deming 2006; Honda-okubo 2015; Houser 2017, Smatti 2018), but proof of human SARS-CoV
or MERS-CoV VAERD does not exist as these candidate vaccines were never tested for efficacy
nor used in outbreak situations. For SARS and MERS, the mechanism of ERD 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, ERD 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-skewed immune response, also induction of a high
proportion of neutralizing antibodies compared with virus binding antibodies is desirable to
prevent predisposition to ERD as observed for RSV vaccines.
While VAERD 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
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
41
Status: Approved, Date: 15 Aug 2022
yet. Antibodies against the receptor binding domain 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-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
(IB Ad26.COV2.S 2022). The Ad26 vector was chosen due to its ability to induce humoral and
strong cellular responses with a Th1 immune phenotype (Anywaine 2019; Barouch 2018;
Colby 2020; 
Milligan 2016; 
Salisch 2019; 
Stephenson 2020; 
van der Fits 2020;
Widjojoatmodjo 2015; Zahn 2012). 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 IFN-γ and TNF-α production in CD4+ and CD8+ T cells
(Anywaine 2019; Barouch 2013; Barouch 2018). In Study COV1001, initial data showed that
Ad26.COV2.S induced cellular immune responses as assessed by intracellular cytokine staining
and ELISpot. Robust CD4+ T and CD8+ T-cell responses were seen following a single vaccination
with Ad26.COV2.S at the 5×1010 vp and 1×1011 vp dose levels. Following vaccination, CD4+ T
cells had a Th1-skewed phenotype and no, or very limited, Th2 responses were observed. The
Th1/Th2 ratio was above 1 (median of 7.60 for 5×1010 vp and 10.24 for 1×1011 vp Ad26.COV2.S)
in all participants with a positive CD4+ T-cell response (Sadoff 2021a).
Ad26-based Vaccines in the Pediatric Population
Ad26.RSV.preF in Toddlers:
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 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 dosing.
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.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
42
Status: Approved, Date: 15 Aug 2022
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
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 (5×1010 vp)
vaccine as Dose 1 of the heterologous Ebola vaccine regimen, which also includes MVA-BN-Filo
(1×108 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, SAEs considered related to study vaccine, or AEs leading to discontinuation were
reported in children or adolescents.
In the mass vaccination campaign in Rwanda (UMURINZI), 9 SUSARs of febrile seizures have
been reported in toddlers within 5.5 to 8.5 hours after vaccination with Ad26.ZEBOV (reporting
rate of 3.98 per 10,000 persons).
2.3. 
Benefit-Risk Assessment
More detailed information about the known and expected benefits and risks ofAd26.COV2.S may
be found in the IB (IB Ad26.COV.2.S 2022).
2.3.1 Risks Related to Study Participation
The following potential risks for Ad26.COV2.S  will be monitored during the study and are
specified in the protocol:
Risks Related to Ad26.COV2.S
At the time of initial protocol writing, the post-Dose 1 safety and reactogenicity profiles of
Ad26.COV2.S (5×1010 and 1×1011 vp)were considered acceptable, as demonstrated in the interim
analyses of blinded safety data from approximately 800 participants (18 to 55 years of age
[Cohort 1a (377 participants)] and Cohort 1b (25 participants)] and ≥65 years of age [Cohort 3
(403 participants)]) in the first-in-human study VAC31518COV1001 (Sadoff 2021a). Local
solicited adverse events (injection site) were observed in 58.9%, 52.0% and 36.0% of participants
in Cohort 1a, 1b and Cohort 3, respectively. Solicited systemic adverse events were reported in
63.7%, 72.0% and 44.9% of participants in Cohorts 1a, 1b, and Cohort 3, respectively. Fevers
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
43
Status: Approved, Date: 15 Aug 2022
(pyrexia, defined as oral body temperature ≥38.0oC/100.4oF) occurred in 19.1% (5.6% Grade 3)
and 16.0% (4.0% Grade 3) of participants in Cohorts 1a and 1b, and 5.2% (0.5% Grade 3) of
participants in Cohort 3, and were mostly mild or moderate, and resolved within 1 to 2 days after
vaccination. The most frequent solicited local adverse event was injection site pain and the most
frequent solicited systemic adverse events were fatigue, headache and myalgia. The safety and
reactogenicity profiles of 2 dose levels, 5×1010 and 1×1011 vp were considered acceptable. No data
are available in children.
For the most comprehensive nonclinical and clinical information regarding Ad26.COV2.S, refer
to the latest version of the IB (IB Ad26.COV2.S 2022).
Thrombosis in combination with thrombocytopenia (thrombosis with thrombocytopenia syndrome
[TTS]), has been observed very rarely following vaccination with Ad26.COV2.S. These cases
occurred approximately 1-2 weeks following vaccination, mostly in adult women (CDC 2021b).
Even though thrombosis in combination with thrombocytopenia can be fatal, the exact physiology
of TTS is unclear. TTS is considered a post-vaccination risk for Ad26.COV2.S  vaccine.
Participants will be asked daily if they have experienced any health concerns (including new onset
of symptoms such as shortness of breath, chest pain, leg swelling, persistent abdominal pain,
severe or persistent headaches or blurred vision, easy bruising, or tiny blood spots under the skin
beyond the site of the injection) within the 30-day time period post‑vaccination, and if so,
participants will be advised to contact the study center. 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, ASH 2021; BSH 2021; CDC 2021a). 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.
The sponsor's own independent benefit-risk assessment in children younger than 18 years of age,
demonstrated that the key benefits of vaccinating with the Ad26.COV2.S vaccine (ie, protection
against the risk of COVID-19 related deaths, COVID-19 related hospitalizations, Multisystemic
Inflammatory syndrome in Children [MIS-C], and deaths due to MIS-C  [CDC 2020k]) greatly
outweighed the potential key risk of thrombosis with thrombocytopenia.
Reports of adverse events following use of the Ad26.COV2.S vaccine under emergency use
authorization (EUA) suggested an increased risk of Guillain-Barré syndrome (GBS) during the 42
days following vaccination. Investigators should be alert to GBS signs and symptoms to facilitate
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
44
Status: Approved, Date: 15 Aug 2022
diagnosis, to initiate adequate supportive care and treatment, and to rule out other causes. Refer to
the latest version of the IB and its addenda (if applicable) for further details.
Risks Related to a 3rd  vaccination with Ad26.COV2.S
In an interim analysis of study COV1001 (cut-off 21 Jul 2021) in which 15 participants (>18 years
of age) received 3 doses of Ad26.COV2.S at the 5×1010 vp dose level (Month 0, 2, and 8) and 46
participants received 2 doses of Ad26.COV2.S at the 5×1010 vp dose level at Month 0 and 2,
followed by placebo at Month 8, no safety concerns were identified. Lower frequencies of solicited
systemic AEs and unsolicited AEs were observed post-dose 3 compared to post-dose 1.
In an interim analysis of study COV2001 (cut-off 11 May 2021) in which 264 participants (which
included 33 adolescents) received 3 doses of Ad26.COV2.S (first 2 doses at 1.25×1010, 2.5×1010,
or 5×1010 vp dose level, 3rd dose [antigen presentation] at 1.25×1010 vp dose level) and 44
participants received placebo, reactogenicity post-antigen presentation (3rd dose) was generally
similar with no sign of increase compared to post-dose 1.
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, 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 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.
The most frequently experienced solicited local AE in children was injection site pain, reported in
13.9% of children aged 1 to 3 years, 29.8% of children aged 4 to 11 years, and 24.8% of children
aged 12 to 17 years after vaccination with an Ad26-based vaccine. For placebo, these percentages
were 29.2% in children aged 4 to 11 years and 14.3% in adolescents aged 12 to 17 years. No
children aged 1 to 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 to 11 years. No children in the other 2 age groups and no placebo participants experienced
severe injection site pain.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
45
Status: Approved, Date: 15 Aug 2022
There was a trend toward an increase in the frequency of some local AEs in adults 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 to 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 to 11 years (reported in ≥15% of
Ad26 participants) were headache (23.6%; no data are available for the placebo group 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
adolescents aged 12 to 17 years (reported in ≥15% of Ad26 participants) were headache (34.6%)
and fatigue (24.0%), compared with 33.3% and 19.0% of placebo participants, respectively. Most
of the frequently experienced solicited systemic AEs in children and adolescents 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
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).
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
46
Status: Approved, Date: 15 Aug 2022
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 to 3 years, in 19.0% ofchildren aged 4 to 11 years, and in 10.6% of adolescents
aged 12 to 17 years. One adolescent (4.8%) in the 12 to 17 years group 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
to 11 years [vs 4.2% with placebo] and 2.4% of adolescents aged 12 to 17 years [vs 4.8% with
placebo]). No AEs in children aged 1 to 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 in
adults and children ≥6 to <12 years of age and fever, loss of appetite, diarrhea, vomiting, decreased
activity, lethargy, irritability, and crying in children <6 years of age. These side effects will be
monitored but are generally short-term. Instructions regarding use of antipyretic medication can
be found in Section 6.7.
Syncope can occur in association with administration of injectable vaccines. Syncope can be
accompanied by falls. Procedures should be in place to avoid falling injury. If syncope develops,
participants should be observed until the symptoms resolve. Fear of injection might lead to fainting
and fast breathing, vomiting, breath-holding, and rarely to seizures.
Participants may have an allergic reaction to the vaccination. An allergic reaction may cause a
rash, urticaria, or even anaphylaxis, severe reactions are rare (IB Ad26.COV2.S 2022). Participants
with a known or suspected allergy or history of anaphylaxis, or other serious adverse reactions,
related to vaccines or their excipients (including specifically the excipients of the study vaccine)
will be excluded from the study.
After each vaccination, participants will remain under observation at the study site for at least
30 minutes for the Dose Selection Cohort (or longer if required by institutional/local practice)and
will be closely observed by study site staff. Necessary emergency equipment and medications must
be available in the clinic to treat severe allergic reactions.
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 (MenACWY) of study VAC52150EBL3001 was not included in the pooling.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
47
Status: Approved, Date: 15 Aug 2022
Capillary Leak Syndrome
Capillary leak syndrome (CLS) is a rare disease that causes edema, hypoproteinemia, episodic
hypotension, dyspnea, hyponatremia, and weight gain that can be life-threatening. Although the
underlying pathology is currently unknown, CLS is thought to be secondary to disruption of the
endothelium and generalized edema. No cases of CLS have been reported in Ad26.COV2.S
vaccine studies. Individuals with a history of CLS will be excluded from participating in this study
(Section 5.2; Exclusion Criterion 24) and CLS is a contraindication for administering a second
dose of the study vaccine (Section 7.1).
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.
Participants of childbearing potential will be required to agree to practicing an acceptable effective
method of contraception and agree to remain on such a method of contraception from providing
consent or assent until 3 months after receiving study vaccine (see Section 5.1). Participants who
are pregnant or breastfeeding will be excluded from the study. Participants who become pregnant
during the study will not receive further study vaccine but should continue to undergo all
procedures for surveillance and follow-up of COVID-19 and all safety follow-up as outlined in the
protocol for all participants.
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 Swab Samples
Collection of a nasal swab sample may cause a nosebleed.
Theoretical Risk of Enhanced Disease
VAERD  has been described for SARS-CoV and MERS-CoV in some animal models
(Agrawal 2016; Bolles 2011; Deming 2006; Honda-okubo 2015; Houser 2017), and is associated
with non-neutralizing antibodies and a Th2-skewed immune response, but proof of human
SARS-CoV or MERS-CoV VAERD does not exist as these candidate vaccines were never tested
for efficacy nor used in outbreak situations. In contrast, the Ad26-based vaccines have been shown
to induce a clear Th1-skewed immune response and generate potent neutralizing antibody
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
48
Status: Approved, Date: 15 Aug 2022
responses in both humans and animal models (see Section 2.2). The initial clinical immunogenicity
data from Study COV1001 have also demonstrated the induction of a Th1-skewed response in all
participants in both Ad26.COV2.S vaccine dose groups, indicating that the theoretical risk for
predisposition of VAERD is minimal, also in case antibodies are transferred to the infant via the
placenta (IB Ad26.COV2.S  2022). Participants in the present study will be informed of the
theoretical risk of disease enhancement in the ICF/assent form. Furthermore, as a risk mitigation
strategy, adolescents in the study will be monitored for acquisition of molecularly confirmed
COVID-19 (see Section 4.1, Section 8.1.2, and Section 10.9). This 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. In addition, selected members of the Statistical Support Group (SSG), not otherwise
involved in the study, will receive individual level unblinded data pertaining to Study COV3006
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. The SSG will immediately inform the IDMC 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 IDMC 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 in pediatric population have yet to be established. Currently,
there is only limited availability of authorized vaccines for the prevention of COVID-19 in the
pediatric population. No efficacy can be concluded yet from current data on Ad26.COV2.S. 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) 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 (Section 1.3).
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
49
Status: Approved, Date: 15 Aug 2022
 
After each vaccination, participants will remain under observation at the study site for at
least 30 minutes (or longer if required by institutional/local practice) and will be closely
observed by study site staff. Necessary emergency equipment and medications must be
available in the clinic to treat severe allergic reactions. Participants will use a
reactogenicity diary in the eCOA to document solicited signs and symptoms. Details are
provided in Section 8.3.
 
The investigator or the designee will document unsolicited AEs, SAEs and MAAEs as
indicated in Section 8.3 and Section 10.4.
 
From the time of local approval of protocol Amendment 1 onwards, TTS is considered to
be an AESI (Section 8.3.6.1). Suspected AESIs (thrombotic events and thrombocytopenia
[defined as platelet count below 150,000/µL] [BC 2021]) 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 1.3.4.1.
 
From the time of local approval of protocol Amendment 1 onwards, MIS-C is considered
to be an AESI (Section 8.3.6.2). Suspected AESIs 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 1.3.4.2.
 
Any clinically significant abnormalities (including those persisting at the end of the
study/early withdrawal) will be followed by the investigator until resolution or until
clinically stable.
 
An IDMC will be established to monitor safety data on an ongoing basis to ensure the
continuing safety of the participants enrolled in this study. This committee will review
unblinded data. The IDMC will also review Day 29 and Day 85 safety data at specific
occasions during the sequential enrollment of adolescents, as described in Section 4.1.
Additional ad hoc reviews may be performed further to the occurrence of any SAE
leading to a study pausing situation as outlined in Section 6.8, or at request of the
sponsor’s medical monitor or designee. The IDMC responsibilities, authorities, and
procedures will be documented in the IDMC Charter.
 
Several safety measures are included in this protocol to minimize the potential risk to
participants, including the following:
 
Eligibility will be reassessed pre-vaccination at the day of the first vaccination.
 
The study will start enrollment of the different age groups (16 to 17years of age and 12 to
15 years of age) simultaneously. Enrollment will begin with the recruitment of
participants to a Dose Selection Cohort in both the 1- and 2-dose regimen. Both the 1-
and 2-dose regimen will start simultaneously. If it is deemedmore appropriate to continue
with a lower dose level than either 2.5×1010 vp or a 1.25×1010 vp dose level, then the use
of these doses may be considered and removed in a future protocol amendment.
 
Adolescents will be monitored in this study to rapidly diagnose COVID-19 and refer for
treatment, if applicable. This will mitigate the theoretical potential risk for VAERD when
immunized individuals are infected with the virus. The observed inductionof neutralizing
antibodies and Th1-skewed response by this vaccine in Study COV1001 indicate that the
theoretical risk for predisposition of VAERD is minimal.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
50
Status: Approved, Date: 15 Aug 2022
 
There are prespecified rules for all participants, that if met would result in pausing of
further vaccinations (see Section 6.8), preventing exposure of new participants to study
vaccine until the IDMC reviews all safety data (see Section 10.3.6).
 
Study vaccinations will be discontinued in participants for the reasons included in
Section 7.
 
Contraindications to vaccination are included in Section 5.5.
3. 
OBJECTIVES AND ENDPOINTS
Part 1 Primary Objectives and Endpoints
Objectives 
Endpoints
Primary
 
To assess the safety and reactogenicity of
Ad26.COV2.S administered intramuscularly
(IM) as a 1-dose regimen (at 2.5×1010 vp per
0.25 mL, 1.25×1010 vp, and 0.625×1010 vp
dose level) or as a 2-dose (56-day interval)
regimen 
(2.5×1010 
vp 
per 
0.5 mL,
1.25×1010 vp, and 0.625×1010vp dose levels)
in adolescents.
 
Solicited local and systemic adverse events
(AEs)for 7 days post-dose 1 and 2.
 
Unsolicited AEs for 28 days post-dose 1 and
2.
 
Medically-attended adverse events (MAAEs)
from the first vaccination until 6 months post-
dose 1 or post-dose 2. MAAEs leading to
discontinuation will be collected during the
entire study.
 
Serious adverse events (SAEs) from the first
vaccination until the end of the study.
 
Adverse events of special interest (AESI)
from first vaccination until end of the study
(incl. MIS-C).
 To assess the humoral immune response of
Ad26.COV2.S administered IM as a 1-dose
regimen (at 2.5×1010 vp per 0.25 mL,
1.25×1010 vp, and 0.625×1010 vp dose level) or
as a 2-dose (56-day interval) regimen
(2.5×1010 vp per 0.5 mL, 1.25×1010 vp, and
0.625×1010 vp dose levels) in adolescents.
 Serological response to vaccination as
measured 
by 
spike-enzyme-linked
immunosorbent assay (S-ELISA) (ELISA;
Units/mL [EU/mL]) or equivalent assay, or
virus neutralization assay (VNA) titers at
28 days post-dose 1 and 14 days post-dose 2.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
51
Status: Approved, Date: 15 Aug 2022
Part 1 Secondary and Exploratory Objectives and Endpoints
Secondary
 
To assess the humoral immune response to 
3 
dose 
levels 
of 
Ad26.COV2.S 
(2.5×1010 vp, 
1.25×1010 
vp, 
or 
0.625×1010vp) and regimens in all study 
groups, at all blood collection timepoints.
 
Serological response to vaccination measured by
binding antibody titers to SARS-CoV-2 or
individual SARS-CoV-2 proteins (eg, S protein)
as measured by ELISA (or equivalent assay),
and/or
 
Serological response to vaccination measured by
neutralizing antibody  titers to SARS-CoV-2
(VNA).
 
To assess the safety and reactogenicity of
Ad26.COV2.S administered IM as a
booster in adolescent participants (Groups
1-3).
 
Solicited local and systemic AEs for 7 days post-
booster.
 
Unsolicited AEs for 28 days post-booster.
 
MAAEs from the booster until 6 months
post-vaccination.
 
To evaluate the humoral immune response
in adolescent participants who receive a
booster dose during the study, pre-boost
and at selected time points post booster
vaccination (Groups 1-3).
 
Serological response to vaccination measured by
binding (S-ELISA and/or equivalent assay)
and/or neutralizing (VNA) antibody titers
Exploratory
 
To examine the immune response in
vaccinated adolescents after 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.
 
SARS-CoV-2-binding antibodies measured by
ELISA (or equivalent assay): Analysis of
antibodies binding to the SARS-CoV-2 S and/or
N protein.
 
Analysis of gene expression by RNA transcript
profiling in adolescents 12 to 17 years of age.
 
To assess the correlation between the
binding 
antibodies 
(S-ELISA) 
and
neutralizing antibody (VNA) titers to
SARS-CoV-2 at selected timepoints.
 
Correlation 
between 
binding 
antibodies
(S-ELISA; EU/mL, or equivalent assay) and
VNA (wtVNA and/or psVNA) titers at selected
timepoints.
 
To assess the occurrence of symptomatic
molecularly confirmed COVID-19 and
severity of COVID-19 signs and symptoms
in adolescents.
 
The number of adolescents with molecularly
confirmed COVID-19.
 
Presence and severity of COVID-19 signs and
symptoms as measured by the Symptoms of
Infection with Coronavirus-19 (SIC).
 
To 
assess 
for 
the 
occurrence 
of
asymptomatic SARS-CoV-2 infection.
 
Serologic conversion between baseline (Day 1;
pre-vaccination) and selected timepoints post-
vaccination using an ELISA and/or SARS-CoV-
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
52
Status: Approved, Date: 15 Aug 2022
2 immunoglobulin assay that is dependent on the
SARS-CoV-2 N protein
 
The number of asymptomatic participants with a
SARS-CoV-2 positive molecular test.
 
For 
asymptomatic 
case 
definition, 
see
Section 10.9.3.
 
To assess the impact of pre-existing
humoral immunity against coronaviruses
other than SARS-CoV-2 at baseline on
Ad26.COV2.S vaccine immunogenicity.
 
Analysis of antibodies binding to coronaviruses
other than SARS-CoV-2 by ELISA or equivalent
assay.
 
To assess the impact of the Ad26.COV2.S
vaccine on the incidence of co-infections
with SARS-CoV-2 and other respiratory
pathogens in adolescents who have
received Ad26.COV2.S during the study.
 
Analysis of broad respiratory pathogens panel in
the nasal swabs collected during a confirmed
COVID-19 episode and in nasal swab samples
from adolescents with a symptomatic infection.
 
To assess the presence of SARS-CoV-2
variants during a confirmed COVID-19
episode in adolescents.
 
To assess SARS-CoV-2 viral load during a
confirmed 
COVID-19 
episode 
in
adolescents.
 
Identification of SARS-CoV-2 variants by
sequencing of nasal swabs and/or saliva samples
(as available) collected during a confirmed
COVID-19 episode.
 
Analysis of SARS-CoV-2 viral load (via
qRT-PCR) in nasal swabs and/or saliva samples
(as available) collected during a confirmed
COVID-19 episode.
 
To further explore the humoral immune
responses in participants who have
received Ad26.COV2.S.
Exploratory analyses may include the following
assays:
 
SARS-CoV-2 neutralization as assessed by
VNA.
 
Adenovirus neutralization as measured by VNA.
 
Analysis of neutralizing and binding antibodies
against emerging SARS-CoV-2 virus lineages.
 
Functional 
and 
molecular 
antibody
characterization including, but not limited to
avidity, Fc-mediated viral clearance, Fc
characteristics, Ig subclass and IgG isotype,
antibody glycosylation, and assessment of
antibody repertoire.
 
Analysis of antibodies to S, N, and the receptor
binding domain  (RBD) of the SARS-CoV-2 S
protein, 
and 
surface 
proteins 
of other
coronaviruses.
 
Epitope-specificity 
characterization 
of
antibodies.
 
Cytokine profiling: Analysis of cytokines,
chemokines, and other proteins of the innate or
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
53
Status: Approved, Date: 15 Aug 2022
adaptive immune response in the serum or
plasma.
 
Passive transfer: Analysis of immune mediators
correlating with protection against experimental
SARS-CoV-2 challenge in a suitable animal
model.
 
Seroresponse rates according to different
responder definitions.
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 be performed in addition,
as outlined in a revised SAP.
Refer to Section 8 for evaluations related to endpoints.
HYPOTHESIS
No formal hypothesis testing is planned in Part 1. Descriptive statistics will be used to compare
vaccine immunogenicity in adolescents from study VAC31518COV3006 versus vaccine
immunogenicity in young adults (18 to 25 years of age) from study VAC31518COV3001 or
VAC31518COV3009 and between study groups in VAC31518COV3006. Descriptive statistics
will be used to summarize the safety and reactogenicity endpoints.
4. 
STUDY DESIGN
4.1. 
Overall Design
This is a randomized, observer-blind, pivotal Phase 2 study in healthy adolescents from 12 to 17
years of age. The safety, reactogenicity, and immunogenicity of Ad26.COV2.S in a 1- and 2-dose
(56-day interval) vaccination regimen will be evaluated. The study will descriptively compare the
immune responses measured by S-ELISA (andpotentiallyVNA)in adolescents versus the immune
responses measured in young adults (18 to 25 years of age)from study VAC31518COV3001 (after
administration of 1 dose of Ad26.COV2.S) or VAC31518COV3009 (after administration of 2
doses of Ad26.COV2.S) and between study groups in VAC31518COV3006. This study consists
of a Dose Selection Cohort (Table 2).
Previously, this study was designed to comprise Part 1 and Part 2, wherein Part 2 included the
Extension Cohort of vaccine naïve participants for evaluation of the dose level and dose regimen
selected after review of the data in Part 1. Per protocol amendment 4, Part 2 will no longer be
conducted
Participants will receive Ad26.COV2.S as a first dose and Ad26.COV2.S or placebo as a second
dose. Ad26.COV2.S will be administered IM at 1 of up to 3 dose levels: 2.5×1010 vp, 1.25×1010 vp,
or 0.625×1010 vp.
A target of approximately 300 adolescents seronegative for SARS-CoV-2 antibodies at baseline
(as assessed by local serology finger-prick testing) will be enrolled in a 2-dose vaccination regimen
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
54
Status: Approved, Date: 15 Aug 2022
with 1 or 2 active vaccinations, with placebo administered as a second dose for those in the 1-dose
regimen.
Participants in a Dose Selection Cohort will be randomly assigned in a 1:1:1:1:1:1 ratio to 1 of 6
study arms: a) to receive one active vaccination of Ad26.COV.2 (either 2.5×1010 vp per 0.25 mL
dose volume, 1.25×1010 vp, or 0.625×1010 vp) followed by placebo at Day 57in a 1-dose regimen
(Groups 1, 2, and 3, respectively), or b) to receive 2 active vaccinations of the same dose level
(either 2.5×1010 vp per 0.5 mL dose volume, 1.25×1010 vp, or 0.625×1010 vp) in a 2-dose (56-day
interval) regimen (Groups 4, 5, and 6, respectively). Each group will contain 50 participants, of
which approximately 70% need to be 12 to 15 years of age and approximately 30% need to be 16
to 17 years of age to limit unnecessary exposure in case of safety concerns (including specific
pausing rules, see Section 6.8). Adolescents will be unblinded to the primary vaccination regimen
at 6 months after the first vaccination.
Participants in Groups 1-3 will be given a booster vaccination as of 6 months after the last
vaccination with active vaccine (Vaccination 1). The booster dose level for all participants in
Groups 1-3 will be 2.5 ×1010 vp per 0.5 mL.
Participants in Groups 4-6 will not be administered a booster vaccination, given they will receive
2 active vaccinations in the primary vaccination regimen.
As a part of the COVID-19 program safety oversight, the IDMC will review the data on an ongoing
basis, in addition to two study-specific predefined IDMC analyses. A first IDMC analysis of Part
1 will be performed on safety and reactogenicity data 28 days post-dose 1. A second IDMC
analysis ofPart 1 will be performed on safety and reactogenicity data 28 days post-dose 2.
Selected sponsor members will review group unblinded summaries of those data, as well as any
available immunogenicity data up to 28 days post-dose 1 and 14 days post-dose 2. Based on the
review, the sponsor will select the dose level for any future pediatric studies based on the safety
and reactogenicity data (28 days after each vaccination) and any available immunogenicity data
(28 days post-dose 1 for the 1-dose regimen, and 14 days post-dose 2 for the 2-dose regimen).
Non-binding guidelines on dose and regimen selection will be described in the SAP. Decision
making on the optimal dose and regimen may take into account safety, reactogenicity and
immunogenicity data from other Ad26.COV2.S clinical studies (such as that of young adults in
study VAC31518COV3001 and study VAC31518COV3009 and adolescents from study
VAC31518COV2001).
The randomization will take into account having not more than 70% males or females in each age
group, as evenly divided as possible over the different age groups. Stratification is by sex and age
group. Screening will aim to ensure participants are seronegative for SARS-CoV-2 antibodies at
baseline by utilizing the finger-prick test (by testing blood from a small puncture in the finger).
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
55
Status: Approved, Date: 15 Aug 2022
Table 2: 
Part 1 Vaccination Schedules (Dose Selection Cohort)
Vac 1 
Vac 2 
Vac 3d
Group  
Na,b,c 
Day 1 
Day 57 
Day 184
1 
50 
2.5×1010 vp (0.25 mL) 
Placebo 
2.5×1010 vp (0.5 mL)
2 
50 
1.25×1010 vp 
Placebo 
2.5×1010 vp (0.5 mL)
3 
50 
0.625×1010 vp 
Placebo 
2.5×1010 vp (0.5 mL)
4 
50 
2.5×1010 vp (0.5 mL) 
2.5×1010 vp (0.5 mL)
5 
50 
1.25×1010 vp 
1.25×1010 vp
6 
50 
0.625×1010 vp 
0.625×1010 vp
N  number of participants; Vac  vaccination; vp  virus particles.
a 
Not more than 70% of males or females should be randomized in each age group.
b 
All participants must be seronegative for SARS CoV 2 antibodies at baseline (by finger prick test).
c 
Approximately 30% of participants should be between 16 to 17 years age and approximately 70% should be between 12
to 15 years of age.
d 
Participants in Groups 1 3 will be given a booster vaccination as of 6 months after the last vaccination with active
vaccine (Vaccination 1) and the booster dose level for these participants will be 2.5 ×1010 vp per 0.5 mL.
Study Duration
The study duration from screening until the last follow-up visit will be, excluding the 28-day
screening phase, approximately 8 months (Groups 4-6) to12 months (Groups 1-3) provided the
intervals in the SoA are respected, consisting of:
 Groups 1-3: ~12-month study duration comprising a 6-month study period including
vaccination with 1 active dose and a placebo vaccination (56-day interval), followed by a
booster vaccination at 6 months and follow-up (safety and immunogenicity) until at least
6 months after booster vaccination.
 Groups 4-6: ~8-month study duration comprising 2 active doses (56-day interval) and
follow-up (safety and immunogenicity) until at least 6 months after second vaccination.
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, MAAEs, SAEs, and AESIs. Other safety assessments include vital
signs measurements (heart rate, preferably supine systolic and diastolic blood pressure, respiratory
rate, and body temperature) and physical examinations at the time points indicated in Section 1.3,
Schedule of Activities.
After each vaccination, participants will remain under observation at the study site for at least
30 minutes (or longer if required by institutional/local practice) for presence of any acute reactions
and solicited events. Any solicited local or systemic AEs, unsolicited AEs, SAEs, AESIs,
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
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
56
Status: Approved, Date: 15 Aug 2022
documented that the post-vaccination observation period is complete. In addition, participants will
record solicited signs and symptoms in a reactogenicity diary for 7 days post-vaccination.
The reporting periods of AEs, MAAEs, SAEs, AESIs, and special reporting situations are detailed
in Section 8.3. Reporting periods for concomitant therapy are outlined in Section 6.7.
A final safety follow-up visit is foreseen 6 months after the last active vaccination.
Enrolled participants and parents/caregivers will be counselled on SARS-CoV-2 infection
prevention each time that they have a contact with site staff, in line with local guidelines.
At the time of study entry, participants or parent(s)/caregiver(s) will need to indicate to the site
staff, in case they, or their child, respectively would get infected with SARS-CoV-2, and contact
details of a local physician and/or facility where they would obtain emergency care and
hospitalization for the participant, if necessary. If a participant should have COVID-19 and their
symptoms deteriorate, participants or parent(s)/caregiver(s)will be recommended to go to the HCP
or hospital that has been identified in advance. For the duration of the study, the participant will
be asked, through the eCOA, if they have experienced any new symptoms or health concerns that
may require seeking emergency care.
All adolescents with COVID-19-like signs or symptoms and adolescents with a positive RT-PCR
test from outside the study meeting the prespecified criteria for suspected COVID-19a should
undertake the COVID-19 procedures until 14 days after signs or symptom onset/positive RT-PCR
test from outside the study (COVID-19 Day 15) or until resolution of the COVID-19 episode,
whichever comes last, unless it is confirmed that the COVID-19 Day 1 to 3 nasal swab (for those
that have it) is negative for SARS-CoV-2. Resolution of the COVID-19 episode is defined as
having 1 SARS-CoV-2 negative nasal swab and 2 consecutive days with no COVID-19-related
signs or symptoms. The procedures in case of (suspected) COVID-19 are detailed in
Section 8.1.2.1. At the time of resolution of the COVID-19 episode, the collected information will
be applied against the clinical case definition (see Section 10.9).
All necessary precautions (per local regulation) should be taken to protect medical staff and other
contacts of adolescents who are suspected to have COVID-19 or have a positive molecular test
from inside the study or RT-PCR test from outside the study for SARS-CoV-2. In the event of a
confirmed SARS-CoV-2 infection, participant’s medical care provider will be notified, and the
participant will be asked to adhere to the appropriate measures and restrictions as defined by local
regulations. Site staff and participants will not be blinded as to the outcome of the molecular test
results from the local (hospital) laboratory. Their routine HCP can obtain external diagnostics,
a As several of the prespecified criteria for suspected COVID-19 overlap with vaccine-related reactogenicity,
investigator’s clinical judgement is required to exclude vaccine-related events when assessing suspected COVID-
19.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
57
Status: Approved, Date: 15 Aug 2022
including molecular diagnostic RT-PCR or other molecularly confirmed viral tests, as medically
needed.
The occurrence of asymptomatic SARS-CoV-2 infection will be assessed in adolescents by a
non-S protein ELISA and/or SARS-CoV-2 immunoglobulin assay (eg, SARS-CoV-2 N-ELISA)
(see Section 8.1.5)and by collection of any positive molecularresults 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).
From all participants, blood samples will be collected at selected timepoints for humoral
immunogenicity assessments, with an emphasis on binding and neutralizing antibody responses.
Additional blood samples for humoral immunogenicity assessments will be taken in case of a
COVID-19 episode. Blood sampling timepoints are indicated in the SoAin Section 1.3, and further
details about the immunogenicity assessments are provided in Section 8.1.1.
An IDMC will be commissioned for this study, committee membership responsibilities,
authorities, and procedures will be documented in its charter. Refer to Committees Structure in
Section 10.3.6.
The planned IDMC, interim, primary, and final analyses are detailed in Section 9.5.
A diagram of the study design is provided in Section 1.2.
4.2. 
Scientific Rationale for Study Design
Dose Selection
The rationale behind the selection ofthe 3 dose levels is described in Section 4.3.
Blinding, Control, Study Phase/Periods, Intervention Groups
Randomization will be used to minimize bias in the assignment of participants to vaccine groups,
to increase the likelihood that known and unknown participant attributes (eg, demographic and
baseline characteristics) are evenly balanced across vaccine groups, and to enhance the validity of
statistical comparisons across vaccine groups. Blinded study vaccine will be used to reduce
potential bias during data collection and evaluation of study endpoints.
Blinding will be guaranteed by the preparation of the study vaccine by an unblinded pharmacist or
other qualified study-site personnel with primary responsibility for study vaccine preparation and
dispensing, and by the administration of vaccine in a masked syringe by a unblinded study vaccine
administrator. Adolescents 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 and using the IWRS (see also Section 6.3).
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
58
Status: Approved, Date: 15 Aug 2022
Biomarker Collection
For adolescents with a positive molecular test result for SARS-CoV-2 infection, biomarker
analysis (PAXgene®, RNA-seq) may 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 guardian 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 if
participants, and their legal guardian 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 adolescents whose benefit from
participation in the study is unknown.
The potential risks to 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. See Section 2.3 for details
on potential and known benefits and risks, and for the safety measures taken to minimize risk to
participants.
Participants will be monitored for AEs throughout the study, and an IDMC will be established as
described in Section 10.3, Regulatory, Ethical, and Study Oversight Considerations.
Before the performance of any study-related assessments, written informed consent and assent (if
applicable) must be obtained following the process described under Informed Consent Process and
Assent Form in Section 10.3.3.
When referring to the signing of the informed consent/assent form (ICF), the terms legal guardian
and legally acceptable representative refer to the legally appointed guardian(s)of the adolescent with
authority to authorize participation in research. For each adolescent 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 must be obtained from adolescents (minors) capable of understanding the nature of the study
depending on the institutional policies and local regulations. 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 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
parent(s)or legal guardian still want them to participate.
The total blood volume to be collected in adolescents is considered to be an acceptable amount of
blood to be collected over this time period from the population in this study  (US FDA 1998;
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
59
Status: Approved, Date: 15 Aug 2022
US DHHS 1998; EU 2008; EMA 2017; Howie 2011; Peplow 2019; Veal 2014). The total blood
volume to be collected at a single time will not exceed approximately 28.5 mL per blood draw for
adolescents 12 to 17years of age.
4.3. 
Justification for Dose
The regimen and dose selection in this study are aimed at providing information on safety,
reactogenicity, and immunogenicity of 1- and 2-dose schedules of Ad26.COV2.S at 3 dose levels
(2.5×1010 vp, 1.25×1010 vp, and 0.625×1010 vp) in adolescents. Available platform data, as well as
safety data from the VAC31518COV1001 and VAC31518COV2001 studies, (see Section 2.2 and
Section 2.3.1) support initiating evaluation of Ad26.COV2.S in the pediatric population, at the
dose levels 2.5×1010 vp, 1.25×1010 vp, and 0.625×1010 vp.
In this study, 3 dose levels of Ad26.COV2.S will be evaluated: 2.5×1010 vp, 1.25×1010 vp, and
0.625×1010 vp.
 
The 2.5×1010 vp dose level is currently being evaluated in the VAC31518COV2001 study. In
COV2001, Ad26.COV2.S is being evaluated at a range of doses and intervals (1.25×1010 vp,
2.5×1010 vp, 5×1010 vp, and 1×1011 vp) in adolescents 12 to 17 years of age, adults 18 to 55
years of age and 65 years of age and above. This lower 2.5×1010 vp dose is being evaluated
since the Ad26-based Ebola vaccine demonstrated higher immune response in younger age
groups. Therefore, a2.5×1010 vp dose level in adolescents might elicit a similar response when
compared with a 5×1010 vp dose level in adults.
Details about dose modification during the study are described in Section 6.5.
4.4. 
End of Study Definition
End of Study Definition
The end of study is considered as the last visit shown in the Schedule of Activities 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
A participant will be considered to have completed the study if he or she has completed
assessments at the 6-month post last active vaccination visit. Note that, in case participants do not
receive a booster vaccination in Groups 1-3, they will nevertheless be considered to have
completed the study provided they have completed a 6-month follow-up post active vaccination.
Participants who prematurely discontinue study vaccination for any reason before that time will
not be considered to have completed the study.
5. 
STUDY POPULATION
Screening for eligible participants will be performed within 28 days before the first study
vaccination. Eligibility will be reassessed pre-vaccination on Day 1.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
60
Status: Approved, Date: 15 Aug 2022
The inclusion and exclusion criteria for enrolling participants in this study are described below. If
there is a question about these criteria, the investigator must consult with the appropriate sponsor
representative and resolve any issues before enrolling a participant in the study. Waivers are not
allowed.
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
vaccine 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 is described in Section 10.3.10.
5.1. 
Inclusion Criteria
Each potential participant must satisfy all of the following criteria to be enrolled in the study:
1 
Criterion modified per Amendment 1:
1.1 Criterion modified per Amendment 3
1.2 Each participant and/or participant’s parent(s)/legal guardian(s) must sign an ICF
according to local regulations, indicating that they understand the purpose of, and
procedures required for the study, are willing to participate or for their child to participate
in the study and attend all scheduled visits, and are willing and able to adhere to the
prohibitions and restrictions specified in the protocol and study procedures, including
maintaining contact with the site until 6 months after the last vaccination. Participants
will be asked to give positive assent per local practices and regulations.
Note: For each participant, at least one parent or legal guardian, if applicable according
to local regulations, must give written consent. In countries where regulation requires
that both parents/legal guardians give consent, this will be applicable.
2 
Participant has given written assent as required by local regulations after the nature of
the study has been explained to them according to local regulatory requirements.
3 
Criterion modified per Amendment 1:
3.1 
Participant’s age is 12 to 17years of age at the time offirst vaccination.
4 
Criterion removed by Amendment 1
5 
Participant must be healthy, in the investigator’s clinical judgement, 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.
6 
Contraceptive (birth control) use by a participant of childbearing potential 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 10.6, Contraceptive Guidance):
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
61
Status: Approved, Date: 15 Aug 2022
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/ligation procedure
5. vasectomized partner (the vasectomized partner should be the sole
partner for that participant)
6. sexual abstinence*
*Sexual abstinence is considered an effective method only if defined as refraining from
heterosexual intercourse from signing the informed consent until 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 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 on the day of and prior to
each study vaccine administration.
Note: If the pregnancy test result is positive, in order to maintain participant
confidentiality, the investigator will ensure adequate counselling and follow-up will be
made available.
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 and/or parent(s)/legal guardian(s) are available and willing to participate for
the duration of the study visits and follow-up.
10 
Participant and/or 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.
11 
Each participant or participant’s parent(s)/legal guardian(s) must have access to a
consistent means of contact either by telephone contact or email/computer.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
62
Status: Approved, Date: 15 Aug 2022
12 
Criterion modified per Amendment 1:
12.1 
Participant must be able to read, understand, and complete questionnaires in the
eCOA (ie, the COVID-19 signs and symptoms surveillance question, the SIC as a PRO,
and the reactogenicity diary).
Note: Participants with visual impairment are eligible for study participation and may
have caregiver assistance in completing the questionnaires in the eCOA.
5.2. 
Exclusion Criteria
Any potential participant who meets any of the following criteria will be excluded from
participating in the study:
1 
Participant has a clinically significant acute illness (this does not include minor
illnesses such as diarrhea or mild upper respiratory tract infection) or temperature
≥38.0ºC (100.4°F) within 24 hours prior to the planned first dose of study vaccine;
randomization at a later date is permitted at the discretion of the investigator and
after consultation with the sponsor.
2 
Participant has a history of malignancy, bone marrow transplant, or solid organ
transplant within 5 years before screening.
3 
Participant has a known or suspected allergy, history of anaphylaxis, or other serious
adverse reactions, related to vaccines or their excipients (including specifically the
excipients of the study vaccine) (refer to the IB Ad26.COV2.S 2022).
4 
Use of systemic corticosteroids at an immunosuppressive dose (treatment duration
more than 14 days for one course or recurrent use) within 6 months before
administration of study vaccine and during the study
Note: For corticosteroids, this means prednisone, or equivalent, ≥20 mg/day. For
participants below 45 kg, the dose is above 1 mg/kg/day.
Ocular, topical, or inhaled steroids are allowed.
Non-immunomodulator treatment is allowed as well as steroids at a physiologic
dose.
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 
Criterion modified per Amendment 1:
6.1 
Any serious, chronic, or progressive disease (eg, diabetes, cardiac disease,
hepatic disease, progressive neurological disease or seizure disorder; autoimmune
disease, AIDS  infection, blood dyscrasias, bleeding diathesis, signs of cardiac or
renal failure, or severe malnutrition).
Note: Stable and medically well controlled chronic conditions (defined as no change
in medication over the past 6 months, other than weight-based adjustments for
normal growth) are allowed per investigator discretion such as:
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
63
Status: Approved, Date: 15 Aug 2022
 Diabetes: HgbA1c <7% and/or no episodes of diabetic ketoacidosis in the
past 6 months.
 Cardiac disease (eg, arrhythmias, heart murmurs): Repaired cardiac defects
without residual lesions. No surgery or intervention (eg, trans catheter
procedures) in the past 6 months and no anticipated procedures for 6 months
post first vaccination.
 Blood dyscrasias: (eg, thalassemia) with no blood transfusions in the
4 months before the planned administration of the first dose of study vaccine.
 Autoimmune disease not requiring immune-modifying or steroid treatment.
 HIV.
a. CD4 cell count ≥500 cells/mm3
b. HIV viral load <50 copies/mL
c. Participant must be on a stable anti-retroviral treatment (ART) for
6 months (unless the change is due to tolerability, in which case the
regimen can be for only the previous 3 months; changes in
formulation are allowed) and the participant must be willing to
continue his/her ART throughout the study as directed by his/her
local physician.
Note: Participants with ongoing and progressive comorbidities associated with
HIV infection will be excluded but comorbidities associated with HIV infection
that have been clinically stable for the past 6 months are not an exclusion
criterion.
Laboratory methods for confirming a diagnosis of HIV infection are: Any
evidence (historic or current) from medical records, such as ELISA with
confirmation by Western Blot or PCR, or of a detectable viral load (country-
specific regulatory approved tests). A laboratory result within 6 months of
screening does not need to be repeated.
If a potential participant does not have HIV viral load and CD4 cell count data
in their medical records from the last 6 months, they will be instructed to go to
their local health care provider and obtain the necessary data for potential entry
into the study.
7 
Participant has extreme obesity (body mass index [BMI] ≥35 or as defined by the
Growth Chart being used as appropriate in the participant’s country, eg, the CDC
Growth Chart [CDC 2020i]).
8 
Criterion modified per Amendment 1:
8.1 
Participant has a history of chronic dermatologic conditions such as urticaria
(recurrent hives), eczema or atopic dermatitis.
9 
Participant has a known history of Kawasaki disease.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
64
Status: Approved, Date: 15 Aug 2022
10 
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.
11 
Criterion modified per Amendment 1:
11.1 Participant received or plans to receive:
a. Licensed live attenuated vaccines within 28 days before or after planned
administration of a study vaccination (14 days before and after for
rotavirus vaccine in adolescents).
b. Other licensed (not live) vaccines within 14 days before or after planned
administration of a study vaccination.
12 
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 immunoglobulin 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 18) and during the study.
13 
Participant is pregnant.
14 
Participant has a contraindication to IM injections and blood draws eg, bleeding
disorders.
15 
Participant is a family member 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, or a known family member of the sponsor.
16 
Participant has chronic active hepatitis B or hepatitis C infection per medical history.
17 
Participant or participant’s parent(s)/legal guardian  who, in the opinion of the
investigator, is unlikely to adhere to the requirements of the study or participant who
is unlikely to complete the full course of vaccination and observation.
18 
Participant previously received a coronavirus vaccine.
19 
History of confirmed SARS or MERS.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
65
Status: Approved, Date: 15 Aug 2022
20 
Criterion removed per Amendment 1
21 
An  adolescent of a parent/legal guardian  not capable of understanding the key
aspects of the study and their requirements for participation  (only applicable if
parent[s]/legal guardian must sign the ICF according to local regulations).
22 
Participant’s parent(s)/legal guardian is <18 years of age and not of legal age
according to local regulations.
23 
Criterion added per Amendment 1
23.1 
For Part 1 only: Participant has a positive diagnostic test result for past
(serological testing) SARS-CoV-2 infection at screening.
24  
Criterion added per Amendment 1
24.1 
History of CLS.
25 
Criterion added per Amendment 1
25.1 A participant that is on medication that may lead to risk of blood dyscrasias
or thrombotic events.
26 
Criterion added per Amendment 1
26.1 A participant has a history of any serious, chronic, or progressive
neurological disorders or seizures including Guillain-Barré syndrome, with the
exception of febrile seizures during childhood.
27 
Criterion added per Amendment 2
27.1    History of Heparin-induced thrombocytopenia
5.3. 
Lifestyle Considerations
Potential participants must be willing and able to adhere to the following prohibitions and
restrictions during the study to be eligible for participation:
1 
Refer to Section 6.7 for details regarding prohibited and restricted therapy during the
study.
2 
Agree to follow all requirements that must be met during the study as noted in the
Inclusion and Exclusion Criteria (Section 5.1 and 5.2).
3 
Agree to follow requirements for the electronic completion of the COVID-19 signs and
symptoms surveillance question in the eCOA.
5.4. 
Screen Failures
Participant Identification, Enrollment, and Screening Logs
The investigator agrees to complete a participant identification and enrollment log to permit easy
identification of each participant during and after the study. This document will be reviewed by
the sponsor study site contact for completeness.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
66
Status: Approved, Date: 15 Aug 2022
The participant identification and enrollment log will be treated as confidential and will be filed
by the investigator in the study file. To ensure participant confidentiality, no copy will be made.
All reports and communications relating to the study will identify participants by participant
identification and age at initial informed consent/assent. In cases where the participant is not
randomized into the study, the date seen and age at initial informed consent/assent will be used.
An individual who does not meet the criteria for participation in this study (screen failure) may be
rescreened on one occasion only. Participants who are rescreened will be assigned a new
participant number, undergo the informed consent/assent process, and then restart a new screening
phase.
Participants who were screened and randomized to the Placebo arm for Part 1 under Protocol
Amendment 1, will be given the option to rescreen and enroll in one of the active arms under
Protocol Amendment 2.
5.5. 
Criteria for Temporarily Delaying Administration of Study Vaccine
The following events assessed by the investigator 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. All participants may be rescreened once (see Section 5.4). If any of these
events occur at the scheduled time for one of the subsequent vaccinations, the vaccination can be
rescheduled, as long as this is in agreement with the allowed windows (see Visit Windows in
Section 8).
If the vaccination visit cannot be rescheduled within the allowed window or the contraindications
to vaccination persist, the sponsor should be contacted for further guidance.
6. 
STUDY VACCINE(S) AND CONCOMITANT THERAPY
6.1. 
Study Vaccine(s) Administered
Ad26.COV2.S will be supplied at a concentration of 1×1011 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. Placebo will be supplied as a 0.9% NaCl solution.
Participants allocated to the 2.5×1010 vp dose level will receive 1 of2 volumes: 0.5 or 0.25 mL. A
volume of 0.5 mL will be administered to participants in all other dose groups.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
67
Status: Approved, Date: 15 Aug 2022
Participants will be vaccinated at the study site according to the schedules detailed in Section 4.1.
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
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. Alternating
injection sites will be used for all study vaccinations unless there is a medically justifiable reason
in the judgement of the investigator.
For information on vaccination windows, see Section 8. If a participant cannot be vaccinated
within the allowed window (eg, if the window is missed due to a study pause [see Section 6.8]),
the decision regarding vaccination will be assessed on a case-by-case basis, upon discussion
between sponsor and investigator.
Study vaccine administration must be captured in the source documents and the electronic case
report form (eCRF).
Ad26.COV2.S will be manufactured and provided under the responsibility of the sponsor. Refer
to the IB (IB Ad26.COV2.S 2022)for a list of excipients.
Refer to the site investigational product and procedures manual (SIPPM) and the Investigational
Product Preparation Instructions (IPPI)for additional guidance on study vaccine administration.
6.2. 
Preparation/Handling/Storage/Accountability
Preparation/Handling/Storage
All study vaccine must be stored in a secured location with no access for unauthorized personnel
and at controlled temperatures as indicated on the clinical labels. If study vaccine is exposed to
temperatures outside the specified temperature range, all relevant data will be sent to the sponsor
to determine if the affected supplies can be used or will be replaced. The affected study vaccine
must be quarantined and not used until further instruction from the sponsor is received.
Refer to the study SIPPM and the IPPI for additional guidance on study vaccine preparation,
handling, and storage.
An unblinded study-site pharmacist, or other qualified individual, who will have no blinded study
function will prepare the appropriate vials and syringes, labeled with the participant’s
identification number, and provide the syringes for the study vaccine to the unblinded vaccine
administrator (a trained and qualified study nurse, medical doctor, otherwise qualified HCP) 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
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
68
Status: Approved, Date: 15 Aug 2022
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 unblinded 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 has an authorized destruction unit and study vaccine supplies are destroyed on-site, this must
also be documented on the vaccine accountability form.
Potentially hazardous materials containing hazardous liquids, should be disposed of immediately
in a safe manner and therefore will not be retained for vaccine accountability purposes.
Study vaccine should be dispensed under the supervision of the investigator or a qualified member
of the study site personnel, or by a hospital/clinic pharmacist. Study vaccine will be administered
only to participants participating in the study. Returned study vaccine must not be dispensed again,
even to the same participant. Study vaccine may not be relabeled or reassigned for use by other
participants. The investigator agrees neither to dispense the study vaccine from, nor store it at, any
site other than the study sites agreed upon with the sponsor. Further guidance and information for
the final disposition of unused study 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 for adolescents 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. The randomization
will be balanced by using randomly permuted blocks and will be stratified by age group
(adolescents 16 to 17 years and 12 to 15 years), and sex (boys and girls). The participants in the
Dose Selection Cohort (Table 2)will be randomly assigned in a 1:1:1:1:1:1 ratio to 1 of3 cohorts
to receive Ad26.COV.2 (either 2.5×1010 vp per 0.25 mL dose volume, 1.25×1010 vp, or
0.625×1010 vp) followed by placebo in a 1-dose regimen, or 1 of 3 cohorts to receive the same
dose level of 2.5×1010 vp per 0.5 mL dose volume, 1.25×1010 vp or 0.625×1010 vp, in a 2-dose
(56-day interval) regimen. The randomization will take into account having not more than 70% of
males or females in each age group, as evenly divided as possible over the different groups.
The 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.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
69
Status: Approved, Date: 15 Aug 2022
Blinding
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 unblinded study vaccine
administrator. Adolescents 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 and using the IWRS.
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 vaccine assignment (ie, immunogenicity data, study vaccine
accountability data, study vaccine allocation, biomarker, vaccine/dose volume) will be handled
with special care to ensure that the integrity of the blind is maintained and the potential for bias is
minimized. This can include making special provisions, such as segregating the data in question
from view by the investigators, clinical team, or others as appropriate until the time of database
lock and unblinding.
The sponsor will be unblinded at the time of primary  analysis. Note that for potential interim
analyses before the primary analysis, unblinded data at the vaccination group level may  be
available for sponsor personnel involved and an independent SSG will receive individual level
unblinded data, when unblinding at the participant level is required. Table 3 Details will be
provided in the IDMC Charter. The investigator may in an emergency determine the identity of
the intervention by contacting the IWRS. While the responsibility to break the intervention code
in emergency situations resides solely with the investigator, the investigator should attempt to
discuss with the sponsor or representative prior to breaking the blind. Telephone contact of the
sponsor will be made available. 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 eCRF. The documentation received from the IWRS indicating the code break must be
retained with the participant’s source documents in a secure manner.
Participants who have had their intervention assignment unblinded prior to the scheduled
unblinding timepoint, 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 locked. 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.
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
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
70
Status: Approved, Date: 15 Aug 2022
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 upon written
communication form the sponsor. 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 be documented in the eCRF. The name and
date(s) of administration of the other COVID-19 vaccine should be recorded (see Section 6.7).
If it is determined that the participant received the SARS-CoV-2 vaccine upon  unblinding, the
participant will be informed that there are no data on the safety of receiving one of 3 different
doses of COVID-19 vaccines. Unblinded participants, whether in the vaccine or control group,
will be asked to continue to be followed in this study in line with the SoA to the extent that they
permit. Safety, efficacy, and immunogenicity evaluations will be identical for all participants,
including participants that are unblinded to obtain an authorized/licensed COVID-19 vaccine and
who remain in the study, if applicable and feasible. All data will be analyzed separately from the
point of unblinding for safety, efficacy, and immunogenicity, as described in the SAP.
6.4. 
Study Vaccination Compliance
Study vaccines will be administered IM by a unblinded qualified study vaccine administrator a
trained and qualified study nurse, medical doctor, or otherwise qualified HCP at the study site.
For blinding procedures, see Section 6.3. The date and time of study vaccine administration and
the location of injection will be recorded in the eCRF.
6.5. 
Dose Modification
The safety, reactogenicity and available immunogenicity data of participants in the Dose Selection
Cohort (2.5×1010 vp, 1.25×1010 vp, and 0.625×1010 vp dose levels) will be reviewed by the IDMC
(see Section 4.1). The lowest dose level (and any/all lower dose levels) that is deemed to produce
acceptable reactogenicity, provided it induces adequate immunogenicity, as identified during this
review, will be considered for future development.
6.6. 
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/MAAEs: the participant will remain at the
study site for at least 1 hour and will be closely monitored for allergic or other reactions by
site staff. Follow-up telephone calls 12 hours and 24 hours post-vaccination will be made.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
71
Status: Approved, Date: 15 Aug 2022
 
Document the quantity of the excess dose in the eCRF.
 
Report as a special reporting situation.
6.7. 
Prestudy and Concomitant Therapy
Prestudy 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, but not limited to, analgesic/antipyretic medications and non-
steroidal anti-inflammatory drugs, corticosteroids, antihistamines, and vaccinations must be
recorded from the moment of first vaccination until 28 days after administration of study vaccine,
and thereafter, pre-dose on the day of any subsequent vaccination and for 28 days after that
vaccination. 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. Concomitant therapies associated with an SAE
meeting the criteria outlined in Section 10.4.1 will be collected and recorded in the eCRF from the
moment of first vaccination through the end of the study. Concomitant therapies associated with
MAAEs will be collected and recorded in the eCRF from the moment of vaccination until 6 months
after vaccination. Concomitant therapies associated with MAAEs leading to study discontinuation
will be recorded in the eCRF from the moment of first vaccination through the end of the study.
Use of any experimental medication (including experimental vaccines other than the study
vaccine) will lead to discontinuation of administration of any subsequent 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 investigational or other immunoglobulin or monoclonal antibodies within 3 months, or
receive convalescent serum for COVID-19 treatment within4 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. During the study, the use of
investigational vaccines other than the study vaccine is not allowed, and the use of investigational
drugs is only allowed if medically indicated. Treatment with investigational COVID-19 drugs after
diagnosis of a COVID-19 case is allowed during the follow-up period and needs to be recorded in
the COVID-19 episode description.
Licensed live attenuated vaccines should be given at least 28 days before or at least 28 days after
a study vaccination (14 days before and after for rotavirus vaccine in adolescents) and must be
recorded. Other licensed (not live) vaccines (eg, the DTaP [reduced Diphtheria toxoid, Tetanus
toxoid, and acellular Pertussis], influenza, tetanus, hepatitis A, hepatitis B, rabies) should be given
at least 14 days before or at least 14 days after a study vaccination in order to avoid potential
confusion of adverse reactions and potential immune interference and must be recorded.
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 and should
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
72
Status: Approved, Date: 15 Aug 2022
be discussed with the sponsor to determine if continued study vaccination is feasible, and any
vaccinations must be recorded. Adolescents receiving routine immunizations according to their
local vaccination schedules (eg, in Europe, the applicable national immunization schedules, and
the equivalent in other countries) should not be postponed due to study participation  and all
vaccinations must be recorded.
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 only in special circumstances.
Chronic (>14 days) or recurrent use of systemic corticosteroidsa, at immunosuppressive doses and
administration of antineoplastic and immunomodulating agents or radiotherapy are prohibited
during the study and within 6 months before the planned administration of the first dose of study
vaccine. If any of these agents are indicated in a disease setting, these must take priority over the
study vaccine.
Refer to Section 5.2, Exclusion Criteria for further details of prohibited therapy.
The sponsor must be promptly  notified 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, a participant who receives a prohibited concomitant
medication will not be included in the immunogenicity analyses.
6.8. 
Study Vaccination Pausing Rules
The principal investigator (PI) and the study responsible physician/scientist (SRP/SRS) 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 IDMC, after which the IDMC will recommend whether the pause can be lifted or
not, or whether other steps are needed.
The IDMC will review blinded data first but has the right to request the randomization codes and
review unblinded data if deemed necessary. The IDMC 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 IEC / IRB, and applicable health
authorities as appropriate.
After the first IDMC meeting triggered by the occurrence of a given pausing rule, the IDMC 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
(once the pause is lifted, the decision regarding subsequent vaccination [if applicable] will be
a Note: Ocular, topical, or inhaled steroids are allowed. Non-immunomodulator treatment is allowed as well as steroids
at a physiologic dose.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
73
Status: Approved, Date: 15 Aug 2022
assessed on a case by-case basis, upon discussion between sponsor and investigator). 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 to IDMCfor information. Upon their review, IDMC 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 laboratoryabnormality 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. One or more participants experience MIS-C which is assessed as at least possibly related to
study vaccine; OR
5. Three participants from the Dose Selection Cohort (of the same dose level group, within the
same age group, and from the same 2 dose vaccination regimen with 1 or 2 active vaccinations,
with placebo administered as a second dose for those in the 1-dose regimen) experience a
Grade 3 unsolicited AE of the same type (per medical judgement of the sponsor), that is
determined to be related to study vaccine; OR
6. Three participants from the Dose Selection Cohort (of the same dose level group, within the
same age group, and from the same 2 dose vaccination regimen (56-day interval) with 1 or 2
active vaccinations, with placebo administered as a second dose for those in the 1-dose
regimen) experience a persistent (upon repeat testing) Grade 3 laboratory abnormality related
to the same laboratory parameter and considered related to study vaccine; OR
7. Three participants from the Dose Selection Cohort (of the same dose level group, within the
same age group, and from the same 2 dose vaccination regimen (56-day interval) with 1 or 2
active vaccinations, with placebo administered as a second dose for those in the 1-dose
regimen)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).
8. One or more cases of suspected TTS, possibly related to the vaccine.
For number 2 and number 6: 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 5, number 6, and number 7: after each IDMC review of similar AE, the committee
will indicate the conditions under which it requires further notification and review of the
subsequent similar AEs.
Note: the occurrence of a study pause in any other ongoing study with Ad26.COV2.S may trigger
a study pause in further vaccination in the current study, if considered to be medically relevant.
Any subsequent delayed study visits as a result of a delayed vaccination following a study pause
are not considered to be protocol violations.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
74
Status: Approved, Date: 15 Aug 2022
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 confirmed study pause. The sponsor’s medical monitor or designee is responsible for
the immediate notification of IDMC members and coordination of an IDMC meeting in case of a
study pause no later than 24 hours after becoming aware.
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 may initiate IDMC review
for any single event or combination of multiple events which, in their professional opinion, could
jeopardize the safety of the participants or the reliability of the data.
Vaccinations for the study may be suspended for safety concerns other than those described above,
or before pausing rules are met, if, in the judgement of the IDMC, participant safety may be
threatened.
Resumption of vaccinations will start only upon receipt of written recommendations by the IDMC.
The clinical site(s) will be allowed to resume activities upon receipt of a written notification from
the sponsor. These recommendations from the IDMC  will be communicated to investigators,
IRB/IEC and relevant health authorities, according to local standards and regulations.
7. 
DISCONTINUATION OF STUDY VACCINATION AND PARTICIPANT
DISCONTINUATION/WITHDRAWAL
7.1. 
Discontinuation of Study Vaccination
Study vaccinations will be withheld for the reasons listed below. These participants must not
receive any further doses of study vaccine but should remain on study for follow-up of safety and
immunogenicity as indicated in the Schedule of Activities (Section 1.3). 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 (other than scheduled unblinding) on the participant level that, in the opinion of
the sponsor, would compromise the integrity of the data
 
Anaphylactic reaction following vaccination, not attributable to causes other than vaccination
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
75
Status: Approved, Date: 15 Aug 2022
 
SAE or other potentially life-threatening (Grade 4) event that is determined to be related to
study vaccine
 
Chronic (>14 days) or recurrent use of systemic corticosteroids and administration of
antineoplastic and immunomodulating agents or radiotherapy
 
Withdrawal of consent/assent to receive further study vaccination (second vaccination of the
2-dose regimen)
 
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), GBS or
MIS-C.
 
Per the implementation of Amendment 1, the participant has a history of CLS.
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 or 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.
For those participants who are unable to continue participation in the study up to the last planned
study visit, but for whom consent or assent is not withdrawn, an early exit visit will be conducted
as soon as possible. Participants who wish to withdraw consent or assent from participation in the
study will be offered an optional visit for safety follow-up. This includes the safety assessments
of the early exit visit (no blood sampling for immunogenicity).
Withdrawal of Consent or Assent
A participant declining to return for scheduled visits does not necessarily constitute withdrawal of
consent or assent. Alternate follow-up mechanisms that the participant agreed to when signing the
consent or 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 or refuse the use of samples for future research (refer
to Long-Term Retention of Samples for Additional Future Research in Section 10.3, Regulatory,
Ethical, and Study Oversight Considerations). In such a case, samples will be destroyed after they
are no longer needed for the clinical study. Details of the sample retention for research are
presented in the main ICF.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
76
Status: Approved, Date: 15 Aug 2022
7.3. 
Lost to Follow-up
To reduce the chances of a participant being deemed lost to follow-up, prior to randomization
attempts should be made to obtain contact information for each participant, eg, home, work, and
mobile telephone numbers and email addresses for both the participant as well as appropriate
family members. A participant will be considered lost to follow-up if he or she repeatedly fail 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 or parent/caregiver to
reschedule the missed visit as soon as possible, to counsel the participant or parent/caregiver
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 or parent/caregiver (where possible,
3 telephone calls), e-mails, fax, and, if necessary, a certified letter to the participant’s last
known mailing address, or local equivalent methods. Locator agencies may also be used as
local regulations permit. These contact attempts should be documented in the participant’s
medical records.
 
Should the participant (or their parent/caregiver) 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 or parent/caregiver to inform them, their contact information will be
transferred to another study site.
8. 
STUDY ASSESSMENTS AND PROCEDURES
Overview
The SoA  (Section 1.3) summarizes the frequency and timing of safety, reactogenicity,
immunogenicity and other measurements applicable to this study. All participants or
parent(s)/caregiver(s)in the study will be counselled on COVID-19 prevention each time that they
have contact with study site staff in line with local guidelines.
Adolescent participants will be provided access to an eCOA and given a SIC reference card to
assist the participant. This eCOA  will be used to collect COVID-19 signs and symptoms
surveillance info, for PRO (SIC, including the highest body temperature recorded within 24 hours,
blood oxygen saturation levels, and pulse rate) in case of COVID-19-like signs and symptoms, to
collect data on 7-day reactogenicity (solicited signs and symptoms, including body temperature),
and to collect suspected symptoms of TTS.
All PRO assessments (SIC, including body temperature and pulse oximetry results) should be
conducted/completed before any tests, procedures, or other consultations to prevent influencing
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
77
Status: Approved, Date: 15 Aug 2022
participant responses. Refer to the Participant Instructions for instructions on the administration of
PROs.
If multiple assessments are scheduled for the same timepoint, it is recommended that procedures
be performed in the following sequence: first the SIC, then vital signs, then blood draws. Actual
dates and times of assessments will be recorded in the source document and in the eCRF.
All participants will be provided with a thermometer (to measure body temperature) and 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. Adolescent participants will
also be provided with a pulse oximeter to measure blood oxygen saturation and pulse rate during
a COVID-19 episode. The reactogenicity 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 site staff is responsible for providing appropriate training to the participant on how to
capture the data in the eCOA to avoid missing or incorrect data. The reactogenicity diary will be
reviewed by the study personnel at visits indicated in Section 1.3. If the reactogenicity diary review
is unavailable, the reactogenicity diary will be reviewed during the following visit. If a participant
misses a vaccination, the reactogenicity diary covering the period after the missed vaccination does
not have to be completed.
Blood draw volumes allow for an acceptable amount of blood to be collected in each participant
throughout the study (EU 2008; EMA 2017; Howie 2011; Veal 2014; Peplow 2019;
US FDA 2019). For adolescents with a positive molecular test result for SARS-CoV-2 infection
(regardless ofwhere the testing was performed), 2 additional serum samples for the assessment of
humoral immunogenicity will be collected: 1 to 6 days after signs or symptom onset (COVID-19
Day 4 to 7) and on COVID-19 Day 29 (±7 days). Repeat or unscheduled samples may be taken
for safety reasons or for technical issues with the samples. In case there are difficulties collecting
sufficient blood from adolescents, the following sequence should be followed: first serum, then
PAXgene® tubes. For participants who experience a suspected AESI, up to an additional 30 mL of
blood may be collected. Refer to the laboratory manual and Schedule of Activities (Section 1.3)
for further details.
Study visits, other than screening and visits at which study vaccination is scheduled, may take
place at the participant’s home by site staff or a trained and delegated HCP if there are travel
restrictions in case of an ongoing pandemic and if allowed by local regulations. The PI continues
to be responsible for reviewing all protocol-related assessments. If home visits are not allowed by
local regulations, procedures and activities may be done by other methods where possible (such as
telephone or video conferencing).
Visit Windows
Visit windows are provided in Section 1.3. The participant should be encouraged to come on the
exact day planned and use the visit window only if absolutely necessary.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
78
Status: Approved, Date: 15 Aug 2022
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 6.8), efforts will be made to
still vaccinate the participant, 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 would overlap with
other scheduled visits, in which case the sponsor should be contacted and a case-by-case
assessment is to be agreed upon.
Screening
Screening will be performed within 28 days prior to the first study vaccination or on the day of
vaccination. If screening is performed on the day of vaccination, Visit 1 and Visit 2 will both occur
on Day 1. Screening must be completed, and all eligibility criteria must be fulfilled prior to
randomization and vaccination.
Screening may be conducted in part via a sponsor- and IRB/IEC-pre-approved non-study-specific
screening consent process, but only if the relevant pre-screening tests are identical to the per
protocol screening tests and are within 28 days prior to first vaccination. However, no
study-specific procedures, other than these pre-approved pre-screening assessments, will be
performed until the participant has signed the study-specific ICF. Participants who test positive on
the molecular test or the serological test (antibodies) will be informed of the result by the study
site 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 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/IPPI
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
79
Status: Approved, Date: 15 Aug 2022
 
Laboratory manual
 
IWRS Manual
 
eCRF completion guidelines
 
Sample ICF
 
eCOA platform access and user instructions (participants may use their own eDevice using an
application if their device [smartphone or tablet] is compatible). Provisioned devices will be
available on a limited basis
 
Contact information pages
8.1. 
Immunogenicity Assessments
8.1.1. 
Immunogenicity Assessments
No generally accepted immunological correlate of protection has been demonstrated for
SARS-CoV-2 to date. 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 be
performed in addition, as outlined in a revised analytical plan. If the correlate or threshold of
protection will be used as an endpoint the definition of seroconversion and seroconversion rate
will be described in the SAP for the study.
Blood samples will be collected for assessment of humoral immune responses in all participants
at the timepoints specified in the SoA. Blood sample timepoints and blood sample volumes are
detailed in Section 8 and Section 1.3.
In case there are difficulties collecting sufficient blood, the following sequence should be
followed: first serum, then PAXgene® tubes in case of a COVID-19 event.
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 for further details.
Immunogenicity assays may include, but are not limited to, the assays summarized in Table 3.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
80
Status: Approved, Date: 15 Aug 2022
Table 3: 
Summary of Immunogenicity Assays (Part 1)
Assay 
Purpose
Supportive of primary endpointsa
SARS-CoV-2 binding antibodies 
(ELISA)
Analysis of antibodies binding to the SARS-CoV-2 S protein
SARS-CoV-2 neutralization 
(VNA) 
Analysis of neutralizing antibodies to wild-type virus and/or
pseudovirion expressing S protein
Supportive of secondary/exploratory endpoints
SARS-CoV-2 binding antibodies 
(ELISA) and/or equivalent assay  
Analysis of antibodies binding to the SARS-CoV-2 S protein, or
SARS-CoV-2 variant proteins
SARS-CoV-2 neutralization 
(VNA) 
Analysis of neutralizing antibodies to wild-type virus and/or
pseudovirion expressing S protein, or SARS-CoV-2 variants
SARS-CoV-2 binding antibodies 
(ELISA and/or SARS-CoV-2
immunoglobulin assay)
Analysis of antibodies binding to the SARS-CoV-2 N protein
Adenovirus neutralization 
(neutralization assay)
Analysis of neutralizing antibodies to adenovirus
Binding antibodies to S protein, N 
protein, RBD of S protein, of 
SARS-CoV-2 and other 
coronaviruses (MSD, ELISA or
equivalent assay)
Analysis of antibodies to S, N, and the RBD of the SARS-CoV-2
S protein or SARS-CoV-2 variants, and coronaviruses other than
SARS-CoV-2
Functional and molecular 
antibody characterization  
Analysis of antibody characteristics including, but not limited to
avidity, Fc-mediated viral clearance, Fc characteristics, Ig
subclass, IgG isotype, antibody glycosylation, and assessment of
antibody repertoire
Epitope-specificity 
characterization
Analysis of site-specificity, epitope mapping
Cytokine profiling 
Analysis of cytokines, chemokines, and other proteins of the
immune response in serum or plasma
Passive transfer 
Analysis of immune mediators correlating with protection against
experimental SARS-CoV-2 challenge in a suitable animal model
Gene expression analysis 
(RNA-seq)
Analysis of gene expression by RNA transcript profiling
ELISA = enzyme-linked immunosorbent assay; Fc = crystallizable fragment; Ig = immunoglobulin;
SARS-CoV-2 = severe acute respiratory syndrome coronavirus-2; MSD = Meso Scale Diagnostics, LLC;
RBD = receptor binding domain; VNA = virus neutralization assay
a. Either S-ELISA or VNA will be used to support the primary endpoint in Part 1.
A rapid SARS-CoV-2 serologic finger-prick test for past infection with SARS-CoV-2 will be
performed for all participants at Day 1. Participants who test positive may be informed of the result
by the study staff.a Participants who test positive will not be included.
a Vaccination with Ad26.COV2.S may interfere with some serologic assays utilized at local community health
clinics/commercial laboratories, by seeking and identifying the spike protein in the vaccine and rendering a false
positive result. For this reason, participants will be encouraged to not seek testing outside the study. If a participant
requires testing outside of the protocol-mandated testing schedule, the site will guide them on the appropriate assay
that identifies the viral nucleocapsid protein (and not the spike protein).
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
81
Status: Approved, Date: 15 Aug 2022
8.1.2. 
Procedures in Case of (Suspected) COVID-19
Procedures to be performed in the event a participant experiences signs or symptoms suggesting
possible COVID-19 (see Section 8.1.2.1), or a participant became aware of a positive RT-PCR test
result for SARS-CoV-2 outside the study context, whether symptomatic or asymptomatic, are
detailed in the Schedule of Activities in Section 1.3.3.
Note: if for any reason a site visit per the procedures described below is not feasible, a member of
the study site staff can visit the participant at home (or at the hospital or other location, if needed),
if allowed by local regulations. If site staff are unable to perform home visits, a trained and
delegated HCP may perform the visits and assessments described below if allowed by local
regulations. The PI continues to be responsible for reviewing all protocol-related assessments. Site
staff/HCPs visiting participants at home will use personal protective equipment according to local
regulations. If a home visit is not feasible, procedures and activities may be done by other methods
where possible (such as telephone or video conferencing).
In case the participant experienced any signs or symptoms suggesting possible COVID-19,
medical management of the case should follow local recommendations/guidelines.
The following procedures are specific for the study:
Day 1to 3 Procedures in Case of Signs and Symptoms
If a participant records in the eCOA or informs the site that they experienced any signs or
symptoms suggesting possible COVID-19, this will be considered COVID-19 Day 1 (day of onset
of signs and symptoms). The participant will be asked to complete the PRO (ie, the SIC, including
body temperature and pulse oximetry) in the eCOA.
Notes:
 
For ease of completion, reference cards have been developed to describe some of the
terms included in the SIC. (Refer to Section 10.7for details)
 
The SIC questionnaire asks the participant if they had any of the prespecified signs or
symptoms during the past 24 hours, and (when applicable) to rate the severity.
 
The participant should take the temperature of the participant in the evening at the same
time each day and record their highest temperature in the last 24 hours in the SIC.
 
The participant should record at least 1 of the 3 pulse oximetry readings in the last
24 hours in the eCOA.
 
If a participant is unable to complete the SIC in the eCOA, a site staff member can collect
information on the participant’s signs or symptoms, body temperature, and pulse
oximetry, over the telephone or visit of the participant at home (if allowed by local
regulations), reading the questions aloud to the participant and entering the responses on
the participant’s behalf. More details are provided in the PRO completion guidelines.
Based on the information collected through the SIC, the site will reach out to the participant at the
latest on COVID-19 Day 2 (the day after the day of signs/symptom onset) to assess whether the
reported signs and symptoms qualify as a suspected COVID-19 episode using prespecified criteria
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
82
Status: Approved, Date: 15 Aug 2022
(Section 8.1.2.1). As several of the prespecified criteria for suspected COVID-19 overlap with
vaccine-related reactogenicity, investigators’ clinical judgement is required to exclude vaccine-
related events when assessing suspected COVID-19. If the participant or parent(s)/caregiver(s)
would actively reach out to the site already on COVID-19 Day 1, the site should already make a
first assessment on COVID-19 Day 1 to check whether the reported signs and symptoms qualify
as a suspected COVID-19 episode using prespecified criteria (Sections 8.1.2.1). As soon as the
prespecified criteria for suspected COVID-19 are met (COVID-19 Day 1 to 3), the participant
will be asked to undertake the COVID-19 procedures. In particular:
 
The participant will be asked to continue to complete the PROs in the eCOA, as specified
above for COVID-19 Day 1:
o 
SIC (including body temperature): every day, preferably in the evening around the
same time each day.
o 
Blood oxygen saturation and pulse rate using a pulse oximeter 3 times a day,
preferably in the morning, at lunch time, and in the evening.
Note: if the PROs are not able to be completed due to special circumstances, such as
the adolescent being too ill, hospitalization or ventilation, the reason for not
completing the PROs should be recorded by site staff in the eCRF.
 
A nasal swab  and saliva sample (if feasible) will be collected from the participant by
study site staffon COVID-19 Day 1 to 3, as soon as possible after it has been confirmed
that the prespecified criteria for suspected COVID-19 are met. In case the nasal swab and
saliva sample (if applicable)is taken at home, the study site should arrange transfer of the
nasal swab and saliva sample (if applicable) to the study site as soon as possible after
collection (within at most 24 hours).
Day 1to 3 Procedures in Case of a Positive RT-PCR Test Outside the Study Site Context
(Including a Positive RT-PCR Test of a Close Relative/Contact)
If a participant or a close relative/contact from the participant has a positive RT-PCR test for
SARS-CoV-2 outside the study context, the participant or parent/caregiver should contact the site
as soon as possible after becoming aware of the positive test. The day the participant or
parent/caregiver became aware of the positive RT-PCR test will be considered COVID-19 Day 1.
Regardless of whether the participant is symptomatic or asymptomatic, the participant will be
asked to:
 
Complete the (suspected) COVID-19 surveillance (symptom check) in the eCOA. In case
of COVID-19-like signs and symptoms they will need to complete the SIC including
recoding body temperature and pulse oximetry in the eCOA.
 
In case of a positive RT-PCR test from a close relative/contact from outside the study:
site staff will collect a nasal swab and saliva sample (if feasible) from the participant on
COVID-19 Day 1 to 3, as described for participants with signs and symptoms (see
above).
 
In case of a positive RT-PCR  test for the participant from outside the study: the
COVID-19 Day 4to 7 procedures will be initiated, as described below.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
83
Status: Approved, Date: 15 Aug 2022
If a participant has a positive test result for SARS-CoV-2 infection, the participant will be notified.
The participant may be requested to stay at home and not visit the study site. If necessary,
study-site personnel will visit the participant at homea (if allowed by local regulations). The
participant will be contacted by the site at least once per week to follow-up on the participant’s
condition and the participant’s medical care provider will be notified. The SIC will be reviewed
by site staff during these contacts (phone call or visit).
If a participant has a negative test result for SARS-CoV-2 infection, the participant will not
undertake any further COVID-19 procedures and will fall back to the default Schedule of
Activities (Section 1.3).
Day 4to 7 Procedures for all Participants Who Have met the Prespecified Criteria for
COVID-19(see Section 8.1.2.1)
The participant will be asked to come to the site on COVID-19 Day 4to 7 (between 1 and 6 days
after signs/symptom onset and becoming aware of a positive molecular test on COVID-19 Day
1 to 3)or a positive RT-PCR test from outside the study.
 
For all participants with confirmed COVID-19 (by molecular test), study staff will
measure vital signs (body temperature, heart rate, and respiratory rate) and oxygen
saturation (via pulse oximetry). A targeted physical examination will be performed based
on the judgement of the investigator.
 
A nasal swab (only for participants who had a positive RT-PCR test from outside the
study) and saliva sample (if feasible) will be collected from the participant by a trained
member of the study site staff. In case the nasal swab and saliva sample (if applicable) is
taken at home, the study site should arrange transfer of the nasal swab and saliva sample
(if applicable) to the study site as soon as possible after collection (within at most
24 hours).
 
A blood sample for exploration of biomarkers that correlate with SARS-CoV-2 infection
and COVID-19 severity and for exploration of antibody responses to infection with
SARS-CoV-2 will be collected by study staff and the procedures for the 7-day cycles
should be started (see below). The medical history and description of COVID-19 episode
will be collected by interview with the participant.
Procedures During the 7-Day Cycles
If a participant has a positive nasal swab sample for SARS-CoV-2 at COVID-19 Day 1 to 3 or a
positive RT-PCR test from outside the study, the participant will be asked to undertake the
COVID-19 procedures, in particular:
 
In case of signs and symptoms: The participant will be reminded to further complete the
PROs daily in the eCOA as described for COVID-19 Day 1 to 3.
a The study site staff visiting participants at home will use personal protective equipment according to local
regulations.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
84
Status: Approved, Date: 15 Aug 2022
In case of positive molecular test and asymptomatic: The participant will be reminded to
further complete (suspected) COVID-19 surveillance (symptom check) at least twice a
week.
 
A member of the study staffwill collect a nasal swab and saliva sample (if feasible)from
the participantonce every 7 days*. If the sample is collected at home, the study site should
arrange transfer of the nasal swabs and saliva sample (if applicable) to the study site as
soon as possible after collections (within 3 days after collection)
Note: The participant should be encouraged by the site to allow the collection of nasal
swabs and saliva sample (if feasible)from the participant as indicated in Section 1.3.3. If
the participant is unable or unwilling to have all samples collected as requested, the
participant should still complete the other COVID-19 assessments, including the visit at
COVID-19 Day 29.
*Note: Nasal swabs and saliva (if feasible) during the 7-day cycles may be collected at
home by the participant (if sample pick up from the participant’s home is feasible).
Day 29 Procedures
If a participant has a SARS-CoV-2 positive nasal swab collected on COVID-19 Day 1 to 3 or from
outside the study, then the participant will be asked to return to the site on COVID-19 Day 29
(±7days) where a blood sample will be drawn from the participant for sero-confirmation, for
exploration of antibody responses to infection with SARS-CoV-2, and exploration of biomarkers
that correlate with SARS-CoV-2 infection and COVID-19 severity. Study staffwill measure vital
signs (body temperature, heart rate, and respiratory rate) and oxygen saturation (via pulse
oximetry). A targeted physical examination will be performed based on the judgement of the
investigator. The medical history and description of COVID-19 episode will be collected by
interview with the participant. If the participant is still symptomatic, the participant will complete
the SIC in the eCOA. For asymptomatic participants, the (suspected) COVID-19 surveillance
(symptom check) will be completed by the participant.
Notes: This visit can be combined with a regular study visit if within the applicable visit windows.
Closure of the COVID-19 Episode
The participant should continue the COVID-19 procedures until any of the following occurs, based
on molecular test results:
 
If the nasal swab collected from the participant on COVID-19 Day 1 to 3 is negative for
SARS-CoV-2, the participant will not undertake any further COVID-19 procedures and
will fall back to the default Schedule of Activities (Section 1.3).
 
If the participant has a SARS-CoV-2 positive nasal swab collected on COVID-19
Day 1 to 3 or from outside the study, then the participant will be asked to undertake the
COVID-19 procedures until 14 days after signs or symptom onset/positive RT-PCT test
from outside the study  (COVID-19 Day 15, if applicable) or until resolution of the
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
85
Status: Approved, Date: 15 Aug 2022
COVID-19 episode, whichever comes lasta. Resolution of the COVID-19 episode is
defined as having 1 SARS-CoV-2 negative nasal swab and 2 consecutive days with no
COVID-19-related signs or symptoms. Once past COVID-19 Day 15, nasal swabs and
saliva sample will no longer be collected from the participant as soon as 1 nasal swab is
SARS-CoV-2 negative, but (if the participant is still symptomatic at that time) the
participant should continue completing the PROs (including SIC, body temperature, and
pulse oximetry) in the eCOA until 2 consecutive days with no COVID-19-related signs
or symptoms.
Note: for participants who have signs and symptoms present at baseline (assessed
pre-vaccination), only signs and symptoms that are associated with COVID-19 and that
developed during the COVID-19 episode are to be taken into account.
Upon closure of the COVID-19 episode and procedures, all participants will fall back to the default
Schedule of Activities (Section 1.3). If the participant experiences new signs or symptoms
suggesting possible COVID-19 at a later point in time, the participant would restart the COVID-19
procedures from COVID-19 Day 1 onwards (Section 1.3.3).
All confirmed COVID-19 episodes will be communicated to the participant and to other authorities
according to local regulations.
8.1.2.1. 
Prespecified Criteria for (Suspected) COVID-19(Adolescents)
The criteria for (suspected) COVID-19 (ie, the triggers to start procedures explained in
Section 8.1.2) are prespecified as follows:
Positive RT-PCR result for SARS-CoV-2 for the participant, through a private or public
laboratory independent of the study, whether symptomatic or asymptomatic
OR
A positive RT-PCR result for SARS-CoV-2 for a parent/caregiver, or any other close
relative/contact of the participant, 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 by an alternative diagnosis and in the presence of a suspected exposure:
a long-term sequelae of COVID-19 will not be followed until their resolution
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
86
Status: Approved, Date: 15 Aug 2022
 
Fever (≥38.0°C or ≥100.4°F) or chills
 
Pulse oximetry value ≤95%, which is a decrease from baseline
 
Tachycardia (according to age)
 
Cough
 
Nasal congestion or runny nose (rhinorrhea)
 
Shortness of breath, difficulty breathing, or wheezing
 
Diarrhea
 
Vomiting
 
Lethargy/tiredness/decreased activity
 
Poor appetite or poor feeding
 
Mood behaviors (frequently crying, irritability)
 
Tachypnea (according to age)
 
Bluish lips or face
 
Red or bruised looking feet or toes
 
New loss of taste or smell
 
Muscle or body aches
 
Neurologic symptoms (numbness, difficulty forming or understanding speech)
 
Symptoms of blood clots: pain/cramping, swelling or redness in the legs/calves
 
Other nonspecific symptoms such as: rash, bloodshot eyes or eye irritation/drainage, sore
throat, stomachache, headache
 
Clinical suspicion/judgement by investigator of symptoms suggestive of COVID-19,
including MIS-C
As several of the prespecified criteria for suspected COVID-19 overlap with vaccine-related
reactogenicity, investigators’ clinical judgement is required to exclude vaccine-related events.
8.1.3. 
Procedures for Adolescents Whose Close Relative/Contact Has
Suspected or Confirmed COVID-19
Testing for SARS-CoV-2 should be performed for all adolescents, regardless of whether there are
signs of infection in the adolescent if their parent/caregiver or close relative/contact from the same
household has suspected or confirmed COVID-19, refer to the procedures in Section 8.1.2.
Testing of asymptomatic and symptomatic adolescents should be performed according to the
procedures in Section 8.1.2, within 48 hours after becoming aware of a positive test from the
parent/caregiver or the close relative/contact.
For adolescents presenting with signs of infection suggestive of COVID-19 (see Section 8.1.2.1),
or with a positive SARS-CoV-2 test, refer to the procedures in Section 8.1.2.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
87
Status: Approved, Date: 15 Aug 2022
8.1.4. 
Symptomatic SARS-COV-2 Infection
Identification and local molecular confirmation of SARS-CoV-2 infection and symptomatic
COVID-19 will be performed throughout the study as described in Section 8.1.2 and 8.1.3. The
PRO to evaluate exploratory vaccine efficacy parameters will be the SIC.
Molecular confirmation of SARS-CoV-2 infection will be performed for the exploratory analysis
of the case definition. The severity of all COVID-19 cases will be assessed using the case
definitions in Section 10.9.
8.1.5. 
Asymptomatic SARS-CoV-2 Infection
A non-S protein ELISA (eg, SARS-CoV-2 N-ELISA) or SARS-CoV-2 immunoglobulin assaywill
be performed to identify cases of asymptomatic SARS-CoV-2 infection (see also Table 3). This
assay will be performed at the timepoints specified in the SoA (Section 1.3).
Any asymptomatic participant with a positive molecular test result for SARS-CoV-2, regardless
ofwhere 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 molecular test result will
need to be captured in the eCRF.
8.2. 
Safety Assessments
Details regarding the IDMC are provided in Section 10.3.6. The IDMC responsibilities, authorities,
and procedures will be documented in the IDMC Charter.
Adverse events will be reported and followed by the investigator as specified in Section 8.3 and
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 length/height, body weight, will be assessed 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.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
88
Status: Approved, Date: 15 Aug 2022
Physical examinations will be performed by the investigator or designated qualified person. Any
clinically relevant abnormalities or changes in severity observed during the review of body systems
should be documented in the eCRF.
8.2.2. 
Vital Signs
Body temperature (in accordance with the local standard of care for adolescents), pulse/heart rate,
preferably supine systolic and diastolic blood pressure, respiratory rate, and blood oxygen
saturation will be assessed.
Pulse/heart rate measurements will be assessed with a completely automated device. Manual
techniques will be used only if an automated device is not available. Pulse/heart rate measurements
should be preceded by at least 5 minutes of rest (if feasible) in a quiet setting without distractions
(eg, television, cell phones). Assessment of vital signs is recommended prior to blood sampling.
Participants will utilize a reactogenicity diary in the eCOA to record body temperature, preferably
orally, measurements post-vaccination from the time of vaccination until 7days after each
vaccination.
Participants with (suspected) COVID-19 should measure blood oxygen saturation 3 times a day
and body temperature daily (the highest temperature in the last 24 hours each day) and record it in
the eCOA for the duration of follow-up of COVID-19 episodes (as defined in Section 8.1.2).
8.2.3. 
Pregnancy Testing
A urine pregnancy test for participants 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 a 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
8.2.4.1. 
Thrombosis With Thrombocytopenia Syndrome
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 10.12)
electronically per instructions in the eCRF completion guidelines. In addition, every effort should
be made to collect blood samples from the participant for a platelet count (local laboratory or
substitute for local laboratory) and other applicable testing (central laboratory) (see the Schedule
of Activities in Section 1.3.4.1 and Section 10.2). The investigator will review the laboratory test
results to assist the investigation of the AESI.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
89
Status: Approved, Date: 15 Aug 2022
See Section 8.3.6.1 for details on laboratory test details to be reported for an AE of
thrombocytopenia.
8.2.4.2. 
Multisystem Inflammatory Syndrome in Children
In case of MIS-C, 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 MIS-C AESI form (see Section 10.13) electronically per instructions in
the eCRF completion guidelines. In addition, every effort should be made to collect and other
applicable testing (central laboratory) (see the Schedule of Activities in Section 1.3.4.2 and
Section 10.2). The investigator will review the laboratory test results to assist the investigation of
the AESI.
See Section 8.3.6.2 for details on laboratory test details to be reported for an AE of MIS-C.
8.3. 
Adverse Events, Serious Adverse Events, Medically-attended Adverse
Events, Adverse Events of Special Interest, and Other Safety Reporting
Timely, accurate, and complete reporting and analysis of safety information, including AEs, SAEs,
MAAEs, AESIs, 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.
Adverse events will be reported by the participant (or, when appropriate, by a caregiver, surrogate,
or the participant’s legally acceptable representative) for the duration of the study.
Further details on AEs, SAEs, MAAEs, AESIs, and PQC can be found in Section 10.4.
8.3.1. 
Time Period and Frequency for Collecting Adverse Event, Medically-
attended Adverse Event, Adverse Event of Special Interest, and
Serious Adverse Event Information
All Adverse Events
All 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 reactogenicity diary as part of the eCOA, will be recorded for
each vaccination from the time of vaccination until 7 days post-vaccination.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
90
Status: Approved, Date: 15 Aug 2022
All other unsolicited AEs and special reporting situations, whether serious or non-serious, will be
reported for each vaccination from the time of vaccination until 28 days post-vaccination.
Unsolicited AEs with the onset date outside the timeframe defined above (>28 days after previous
study vaccination), which are ongoing on the day of the subsequent vaccination, should be
recorded as such.
All SAEs and AEs leading to discontinuation from the study/vaccination (regardless of the causal
relationship) are to be reported for all participants from the moment of first vaccination  until
completion of the participant’s last study-related procedure, which may include contact for safety
follow-up. The sponsor will evaluate any safety information that is spontaneously reported by an
investigator beyond the time frame specified in the protocol.
MAAEs are defined as AEs with medically-attended visits including hospital, emergency
department, urgent care clinic, or other visits to or from medical personnel for any reason. Routine
study visits will not be considered medically-attended visits. New onset of chronic diseases will
be collected as part of the MAAEs. MAAEs are to be reported for all participants from the first
vaccination until 6 months after each  vaccination, except for MAAEs leading to study
discontinuation which are to be reported during the entire study.
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 as described in Section 6.8.
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 1 onwards, TTS (Section 8.3.6.1) and
MIS-C (Section 8.3.6.2) are considered to be AESIs. Suspected AESIs (thrombotic events and
thrombocytopenia [defined as platelet count below 150,000/µL] [BC 2021], and MIS-C) 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 cases of TTS (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.
Serious adverse events, including those spontaneously reported to the investigator, must be
reported using an SAE form. The sponsor will evaluate any safety information that is
spontaneously reported by an investigator beyond the time frame specified in the protocol.
Information regarding SAEs will be transmitted to the sponsor using the Serious Adverse Event
Form and Safety Report Form of the eCRF, which must be completed and reviewed by a physician
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
91
Status: Approved, Date: 15 Aug 2022
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.
Signs and symptoms of MIS-C will be monitored and reported as SAE in adolescents with
(suspected) COVID-19 as confirmed by a positive molecular test result for SARS-CoV-2, and in
adolescents whose parents/caregivers or close relatives/contacts have a prior (within 4-weeks) or
current suspected or confirmed COVID-19. Further details on case definition and reporting of
MIS-C in adolescents can be found in Section 10.8.
8.3.2. 
Method of Detecting Adverse Events, Medically-attended Adverse
Events, Adverse Events of Special Interest, and Serious Adverse
Events
Care will be taken not to introduce bias when detecting AEs, MAAEs, suspected AESIs, or SAEs.
Open-ended and nonleading verbal questioning of the participant is the preferred method to inquire
about AE occurrence.
Study-site personnel, as well as parents and caregivers, should be instructed how to interpret signs
and symptoms (eg, crying and pain) in their individual child. They will be instructed to report both
specific and nonspecific symptoms (including vomiting, diarrhea, sleepiness, variation in the
intensity and pattern of crying, etc). These nonspecific symptoms may be the only manifestations
of some adverse reaction observed in adolescents. Care should be taken that the clinical
presentation of adverse reactions is not misinterpreted as the manifestation of a pre-existing or
unrelated condition.
Moreover, symptoms that are dependent on participant communication ability (eg, nausea, pain,
mood alterations) in younger or mentally-disabled adolescents could potentially be at risk for
under- or mis-reporting.]
These events may or may not have been noted in the participant’s reactogenicity diary.
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 reactogenicity diary.
After each vaccination, adolescents will remain under observation at the study site for at least
30 minutes (or longer if required by institutional/local practice) for the presence of any acute
reactions and solicited events.
In addition, participants will record solicited signs and symptoms in a reactogenicity diary for
7days post-vaccination. All participants will be provided with a reactogenicity diary and
instructions on how to complete the reactogenicity diary (see Overview in Section 8).
Reactogenicity diary information will be transferred to the sponsor. After review and verbal
discussion of the initial reactogenicity diary entries with the participant, the investigator will
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
92
Status: Approved, Date: 15 Aug 2022
complete his/her own assessment in the relevant sections of the eCRF. Once a solicited sign or
symptom from a reactogenicity 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 reactogenicity diary occurrences of injection site
pain/tenderness, erythema and swelling at the study vaccine injection site daily for 7 days
post-vaccination (day of vaccination and the subsequent 7 days). The extent (largest diameter) of
any erythema and swelling should be measured (using the ruler supplied) and recorded daily. The
case definitions for solicited injection site events can be found in the references (ECDC 2020;
Ad26.COV2.S IB).
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 reactogenicity 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 or ≥100.4° F, as recorded
in at least 1 measurement (Marcy 2004).
Participants will also be instructed on how to note signs and symptoms in the reactogenicity diary
on a daily basis for 7 days post-vaccination (day of vaccination and the subsequent 7 days), for the
following systemic 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 reactogenicity diary.
Medically-attended Adverse Events
MAAEs are AEs with medically-attended visits including hospital, emergency department, urgent
care clinic, or other visits to or from medical personnel for any reason. New onset of chronic
diseases will be collected as part of the MAAEs. Routine study visits will not be considered
medically-attended visits.
For details about AESIs, refer to Section 8.3.6.
8.3.3. 
Follow-up of Adverse Events, Medically-attended Adverse Events,
Adverse Events of Special Interest, and Serious Adverse Events
The investigator is obligated to perform or arrange for the conduct of supplemental measurements
and evaluations as medically indicated to elucidate the nature and causality of the AE, AESI, SAE,
MAAE, or PQC as fully as possible. This may include additional laboratory tests or investigations,
histopathological examinations, or consultation with other health care professionals.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
93
Status: Approved, Date: 15 Aug 2022
Adverse events, 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 AESIs are described below.
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
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
94
Status: Approved, Date: 15 Aug 2022
responsible for reporting any suspected AESI of TTS using the SAE form and the form detailed in
Section 10.12. A suspected TTS case is defined as:
 
Thrombotic events: suspected deep vessel venous or arterial thrombotic events as detailed in
Section 10.14 OR,
 
Thrombocytopenia, defined as platelet count below 150,000/μL (BC 2021)
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 1.3.4.1). 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 10.12 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 1.
8.3.6.2. 
Multisystem Inflammatory Syndrome in Children
The Multisystem Inflammatory Syndrome in Children (MIS-C) is considered to be an AESI.
Unlike adults, the vast majority of children with COVID-19 have mild symptoms. However, some
children have a significant respiratory disease, and some children  may develop a
hyperinflammatory response similar to what has been observed in adults with COVID-19.
The CDC issued a Health Advisory on May 2020, that outlines the following case definition for
MIS-C (CDC, 2020):
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
95
Status: Approved, Date: 15 Aug 2022
 
An individual aged <21 years presenting with fevera, laboratory evidence of inflammationb,
and evidence of clinically severe illness requiring hospitalization, with multisystem (≥2) organ
involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic, or
neurological); AND
 
No alternative plausible diagnoses; AND
 
Positive for current or recent SARS-CoV-2 (COVID-19) infection by RT-PCR, serology, or
antigen test; or COVID-19 exposure within the 4 weeks prior to the onset of symptoms.
In the event of a suspected (MIS-C) event, laboratory assessments (AAP 2020; CDC 2020l;
Henderson 2020) are required to facilitate diagnosis and determine treatment options, including
but not limited to:
 
Levels of inflammatory markers in the blood, including elevated erythrocyte sedimentation
rate (ESR)/C-reactive protein (CRP)and ferritin, lactate dehydrogenase (LDH), and absolute
lymphocyte count.
 
Complete blood count and platelet count.
 
B-type natriuretic peptide (BNP) or NT-proBNP (pro-BNP) and sodium,
 
D-dimer
SARS-CoV-2 related syndromes in the pediatric population continues to evolve and
recommendations provided in this document do not replace the importance of clinical judgment
tailored to the unique circumstances of an individual patient.
8.4. 
Virology Assessments
The presence of SARS-CoV-2 infection in nasal swabs will be assessed by the local laboratory for
case management. Molecular confirmation of SARS-CoV-2 infection (via molecular diagnostic
RT-PCR or equivalent, referred to as ‘molecular test’ throughout the document) by a central
laboratory will be used for the exploratory analysis of the case definition. Nasal swabs will also be
used to determine the presence of SARS-CoV-2 viral variants using whole genome sequencing. In
addition, saliva samples collected from participants during a confirmed COVID-19 episode may
be tested for the presence of and quantification of SARS-CoV-2 by a central laboratory.
Nasal swabs collected from participants with COVID-19-like signs or symptoms will also be tested
at the central laboratory to determine the presence of other respiratory pathogens using a broad
respiratory pathogens panel. The results from this test may be shared with the study site.
a Fever >38.0°C for ≥24 hours, or report of subjective fever lasting ≥24 hours.
b 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.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
96
Status: Approved, Date: 15 Aug 2022
8.5. 
Biomarkers
Blood will be drawn at selected timepoints during the study for evaluation of biomarkers
(eg, related to vaccine immunogenicity and SARS-CoV-2 infection including relations with
COVID-19 disease severity, PAXgene®), as indicated in Section 1.3.
8.6. 
Medical Resource Utilization and Health Economics
Health Economics/Medical Resource Utilization and Health Economics parameters are not
evaluated in this study.
9. 
STATISTICAL CONSIDERATIONS
Statistical analysis will be done by the sponsor or under the authority of the sponsor. A general
description of the statistical methods to be used to analyze the immunogenicity and safety data is
outlined below. Specific details will be provided in the SAP.
9.1. 
Statistical Hypotheses
No formal hypothesis testing is planned in Part 1. Descriptive statistics will be used to compare
vaccine immunogenicity in adolescents from study VAC31518COV3006 versus vaccine
immunogenicity in young adults (18 to 25 years of age) from study VAC31518COV3001 or
VAC31518COV3009 and between study groups in VAC31518COV3006. Descriptive statistics
will be used to summarize the safety and reactogenicity endpoints.
9.2. 
Sample Size Determination
With a sample size of 50 participants per group, the width of the 90% CI for the observed
proportion of adverse events will vary between 5.8% and 24.8% depending on the observed
proportion. Assuming pooling of adverse event data after the first dose of the 1- and 2-dose
regimen, the width of this confidence interval will vary between 3% and 17.3% depending on the
observed proportion (Table 4).
Non-binding guidelines on dose and regimen selection will be described in the SAP. Decision
making on the optimal regimen will take safety and reactogenicity data, as well as any available
immunogenicity data, and data from other Janssen clinical trials of Ad26.COV2.S into account.
9.2.1. 
Immunogenicity
The VNA and S-ELISA have been selected as primary endpoints and samples from participants
(young adults and adolescents) will be analyzed using these assays. Correlation between S-ELISA
and VNA and between other relevant humoral immunogenicity readouts will be evaluated. See
Section 9.4.2 for immunogenicity endpoints.
Table 4: 
90% Two-sided CI for Possible Observed Rate of Adverse Events
Observed Rate 
0% 
5% 
10% 
25% 
50%
50 Participants 
(0, 5.8%) 
(1.2%, 13.4%) 
(4%, 19.9%) 
(15.3%, 37%) (37.6%, 62.4%)
100 Participants 
(0, 3%) 
(2%, 10.2%) 
(5.5%, 16.4%) (18%, 33.1%) (41.4%, 58.6%)
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
97
Status: Approved, Date: 15 Aug 2022
9.2.2. 
Safety
While mild to moderate vaccine reactions (local site and systemic responses) are expected, AEs
that preclude further vaccine 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 5 for the considered number
of participants.
9.3. 
Populations for Analysis Sets
For purposes of analysis, the following populations are defined:
The Full Analysis Set (FAS) will include all participants with at least one vaccine administration
documented.
The Per Protocol Immunogenicity (PPIa) 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 samples obtained from participants after SARS-CoV-2
infection (if confirmed by molecular testing or non-S-ELISA [or equivalent assay]) occurring
during the study after randomization (if applicable), after other SARS-CoV-2 vaccination outside
the study, and samples obtained outside predefined windows will be excluded from the analysis
set. Participants who were seronegative by local serology finger-prick test on Day 1 prior to study
entry but were determined to be seropositive at baseline by central N- or S- serology testing will
also be included in the PPI. More details will be provided in the SAP.
9.4. 
Statistical Analyses
The SAP will be finalized prior to the first database lock 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. Planned analyses are defined in Section 9.5.
a 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.
Table 5 : 
Upper Limit of the 95% One-sided CI if no Cases are Observed for Different Sample Sizes
Sample Size 
N=25 
N=50 
N=100 
N=250 
N=1,000
Upper Limit 95% one-sided CI 
11.3%  
5.8%  
3.0% 
1.2% 
0.3%
CI = confidence interval, N = number of participants
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
98
Status: Approved, Date: 15 Aug 2022
For safety and immunogenicity analyses, results will be analyzed by vaccine group and will be
performed by age group in adolescents. Immunogenicity subgroup analyses will also be performed
by BMI, ethnicity, and other factors as will be described in the SAP.
9.4.2. 
Primary/Secondary Endpoints
Safety Endpoints
No formal statistical testing of safety data is planned. Safety data will be analyzed descriptively
by vaccine group  and by age group (12 to 15, and 16 to 17). In addition, for selected tables,
tabulations pooled by vaccine dose will also be provided. All safety analyses will be done on the
FAS.
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 study vaccine due to an AE, or who experience a severe AE,
AESI, or an SAE (including MIS-C).
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.
Vital Signs
Vital signs including temperature, pulse/heart rate, preferably supine systolic and diastolic blood
pressure, and respiratory rate 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.
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
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
99
Status: Approved, Date: 15 Aug 2022
definitions of serological response will be applied (fold increases in GMC [ELISA] or GMT
[VNA]). Graphical representations of immunologic parameters will be made as applicable.
Frequency tabulations will be calculated for discrete (qualitative) immunologic parameters, as
applicable.
In addition, the ratio between neutralizing and binding antibodies as determined by VNA and
S protein ELISA, respectively, will be calculated together with confidence intervals. More details
will be provided in the SAP.
S-ELISA or VNA may be used as endpoint for decision making on dose and regimen selection.
Correlation between S-ELISA and VNA and between other relevant humoral immunogenicity
readouts will be evaluated.
The immunogenicity analyses will be performed on the PPI population.
COVID-19 Infections and Severity
Symptomatic and asymptomatic infections will be descriptively presented.
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.
9.4.3. 
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.
Statistical analysis of biomarker responses (eg, RNA-seq responses) will be detailed in a separate
SAP.
9.5. 
Planned Analyses
Part 1:
A first IDMC analysis of Part 1 will be performed on safety  and reactogenicity data 28 days
post-dose 1. A second IDMC analysis of Part 1 will be performed on safety and reactogenicity
data 28 days post-dose 2.
Selected sponsor members will review group unblinded summaries of those data, as well as any
available immunogenicity data up to 28 days post-dose 1 and 14 days post-dose 2.
A primary analysis of safety, reactogenicity and immunogenicity data up to 28 days post-dose 2
will be performed and the selected dose level will be determined for any future pediatric studies.
The sponsor will be unblinded at the time of the primary analysis, but the blind will be maintained
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
100
Status: Approved, Date: 15 Aug 2022
at a participant and study site level up to the unblinding visit. Interim analyses may be performed
for safety and/or immunogenicity, to facilitate decision making with regards to planning of future
studies or for regulatory submission purposes.
The final analysis will be performed when all participants have completed the last visit or
discontinued earlier.
The SAP will describe the planned analyses in greater detail.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
101
Status: Approved, Date: 15 Aug 2022
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Abbreviations and Definitions
Ad26 
adenovirus type 26
AdVAC® 
adenoviral vaccine (vector platform)
AE 
adverse event
AESI 
adverse event of special interest
BMI 
body mass index
CD  
cluster of differentiation
CDC  
Centers for Disease Control and Prevention
ChIP  
Chromatin immunoprecipitation
COPD  
chronic obstructive pulmonary disease
COVID-19 
coronavirus disease-2019
eCRF  
electronic case report form(s)
DNA  
deoxyribonucleic acid
DVT  
deep vein thrombosis
eDC  
electronic data capture
ELISA  
enzyme-linked immunosorbent assay
ELISpot 
enzyme-linked immunospot
ERD  
enhanced respiratory disease
FAS  
full analysis set
Fc 
crystallizable fragment
FDA  
Food and Drug Administration
FI 
formalin-inactivated
FOIA  
Freedom of Information Act
FWER 
family-wise error rate
GBS  
Guillain-Barré Syndrome
GCP  
Good Clinical Practice
GLP  
Good Laboratory Practice
GMC  
geometric mean concentration
GMR  
geometric mean ratio
GMT  
geometric mean titer
HCP  
health care practitioner
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
IPPI 
Investigational Product Preparation Instructions
IRB  
Institutional Review Board
IUD  
intrauterine device
IUS  
intrauterine hormone-releasing system
IWRS  
interactive web response system
MAAE 
medically-attended adverse event
MedDRA  
Medical Dictionary for Regulatory Activities
MERS (-CoV) 
Middle East respiratory syndrome (coronavirus)
MHRA  
Medicines and Healthcare products Regulatory Agency
MIS-C 
multisystem inflammatory syndrome in children
MSD  
Meso Scale Diagnostics, LLC
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
102
Status: Approved, Date: 15 Aug 2022
N 
nucleocapsid
NHP  
nonhuman primate
PI 
principal investigator
PPI 
per protocol immunogenicity
PQC  
product quality complaint
RBD  
receptor binding domain
RNA  
ribonucleic acid
RSV  
respiratory syncytial virus
(q)RT-PCR  
(quantitative) 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)
SDL 
selected dose level
SIC  
Symptoms of Infection with Coronavirus-19
SIPPM  
site investigational product and procedures manual
SoA  
Schedule of Activities
SRP/SRS 
study responsible physician/scientist
SSG  
Statistical Support Group
SUSAR  
suspected unexpected serious adverse reaction
Th 
T helper
TNF-α 
tumor necrosis factor alpha
TTS  
thrombosis with thrombocytopenia syndrome
US  
United States
VAERD  
vaccine associated enhanced respiratory disease
VNA  
virus neutralization assay
vp 
virus particle
WHO  
World Health Organization
Definitions of Terms
COVID-19 
COVID-19 is the disease caused by the virus SARS-CoV-2. COVID-19 refers to SARS-
CoV-2 infection with symptoms, and can range from mild to severe disease, the latter
including pneumonia, severe acute respiratory syndrome, multiorgan failure, and death. (US
FDA 2020a,b).
eCOA  
Electronic clinical outcome assessment. An umbrella term encompassing different types of
outcomes assessments which may include the COVID-19 signs and symptoms surveillance
question and Symptoms of Infection with COVID-19 Questionnaire (SIC) (as a PRO) in
participants 12 to 17 years of age, and the reactogenicity diary  (to record vaccine
reactogenicity) in adolescents.
The term eCOA is also used throughout the document to refer to the digital tool in which the
clinical outcome assessments are collected (eg, via an app).
Observer-blind 
The vaccine recipient and those responsible for analyzing the data are blinded.
PRO  
Patient-reported Outcomes. Used to collect the patient-reported outcome data. This includes
the SIC questionnaire (Symptoms of Infection with Coronavirus-19) and the recording of
pulse oximetry results.
reactogenicity diary  
Used to record solicited signs and symptoms by the participants.
Electronic source 
system  
Contains data traditionally maintained in a hospital or clinic record to document medical
care or data recorded in a case report form (CRF)as determined by the protocol. Data in this
system may be considered source documentation.
Study Name 
Convention 
In this document, studies are mostly referred to using the short study name (preceding letters
and final digits of the study identifier) only (eg, COV2001).
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
103
Status: Approved, Date: 15 Aug 2022
10.2. Appendix 2: AESI Clinical Laboratory Tests
Samples will be taken according to the SoA in Section 1.3. The following tests may be performed:
Protocol-Required AESI Laboratory Assessments
Laboratory 
Assessments 
Parameters for Participants Evaluated at Prespecified Study Timepoints and, in
Addition, upon Experiencing a Suspected AESI
Performed locally (or centrally if local laboratory is not available)
Blood sample obtained and tested at study Day 1, Day 29, Day 57, Day 71 (for all participants), for visits
Day 184 and Day 198 (for Groups 1-3),
AND
Day 1/29 for each occurrence of any suspected AESI (TTS and/or MIS-C)
Hematology  
Whole blood sample for platelet count which at some sites may be part of a complete blood
count with differential.
Suspected TTS AESI
Stored and performed centrally
Only analyzed if participant experienced suspected TTS, upon request from central study team:
Blood sample obtained at Day 1/29 for each occurrence of suspected TTS AESI and for visits Day 1, Day 29,
Day 57, Day 71 (for all participants), for visits Day 184 and Day 198 (for Groups 1-3)*.
Clinical Laboratory 
Assessments
(Section 8.2.4.1)
Serum/plasma samples for coagulation-related assays such as but not limited to:
 
Activated partial thromboplastin time
 
Prothrombin time
 
International normalized ratio
 
Fibrinogen
 
Lupus anticoagulant
 
Beta-2 glycoprotein
 
Anti-cardiolipin
 
D-dimers
 
Anti-PF4
 
Heparin Induced Thrombocytopenia (HIT)/PF4 Ab, IgG·(HIT assay)
 
Platelet activation assay (if HIT/PF4 is positive)
 
Homocysteine
 
ADAMTS13 Activity and Inhibitor Profile
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
104
Status: Approved, Date: 15 Aug 2022
Laboratory 
Assessments 
Parameters for Participants Evaluated at Prespecified Study Timepoints and, in
Addition, upon Experiencing a Suspected AESI
Suspected MIC-S AESI
Stored and performed centrally:
Only analyzed if participant experienced suspected MIS-C, upon request from central study team:
Blood sample obtained at Day 1/29 for each occurrence of suspected MIS-C AESI and for visits Day 1, Day 29,
Day 57, Day 71 (for all participants), for visits Day 184 and Day 198 (for Groups 1-3)*.
Clinical Laboratory 
Assessments 
(Section 8.2.4.2)
 
Serum/plasma samples for coagulation-related assays such as, but not limited to,
D-dimers
 
Levels of inflammatory markers in the blood, including elevated ESR/CRP and
ferritin, LDH, and ALC
 
B-type natriuretic peptide (BNP) or NT-proBNP (pro-BNP)
 
Sodium
* Based on the clinical evaluation of the suspected AESI (eg, whether thrombocytopenia is observed with athrombotic
event), all or some of these tests may be conducted on the stored pre‑vaccination sample (retrospective test) and on
the samples obtained as part of the AESI investigation.
AESI = adverse event of special interest; MIS-C = Multisystem Inflammatory Syndrome in Children;
TTS = thrombosis with thrombocytopenia syndrome
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
105
Status: Approved, Date: 15 Aug 2022
10.3. Appendix 3: Regulatory, Ethical, and Study Oversight Considerations
10.3.1. 
Regulatory and Ethical Considerations
Investigator Responsibilities
The investigator is responsible for ensuring that the study is performed in accordance with the
protocol, current 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
requirements are met.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
106
Status: Approved, Date: 15 Aug 2022
Required Prestudy Documentation
The following documents must be provided to the sponsor before shipment of study vaccine to the
study site:
 
Protocol and amendment(s), if any, signed and dated by the PI.
 
A copy of the dated and signed (or sealed, where appropriate per local regulations), written
IEC/IRB approval of the protocol, amendments, ICF, any recruiting materials, and if
applicable, participant compensation programs. This approval must clearly identify the
specific protocol by title and number and must be signed (or sealed, where appropriate per
local regulations) by the chairman or authorized designee.
 
Name and address of the IEC/IRB, including a current list of the IEC/IRB members and their
function, with a statement that it is organized and operates according to GCP and the
applicable laws and regulations. If accompanied by a letter of explanation, or equivalent, from
the IEC/IRB, a general statement may be substituted for this list. If an investigator or a
member of the study site personnel is a member of the IEC/IRB, documentation must be
obtained to state that this person did not participate in the deliberations or in the vote/opinion
of the study.
 
Regulatory authority approval or notification, if applicable.
 
Signed and dated statement of investigator (eg, Form FDA 1572), if applicable.
 
Documentation of investigator qualifications (eg, curriculum vitae).
 
Completed investigator financial disclosure form from the PI, where required.
 
Signed and dated Clinical Trial Agreement, which includes the financial agreement.
 
Any other documentation required by local regulations.
The following documents must be provided to the sponsor before enrollment of the first
participant:
 
Completed investigator financial disclosure forms from all subinvestigators
 
Documentation of subinvestigator qualifications (eg, curriculum vitae)
 
Name and address of any local laboratory conducting tests for the study, and a dated copy of
current laboratory normal ranges for these tests, if applicable
 
Local laboratory documentation demonstrating competence and test reliability
(eg, accreditation/license), if applicable
Independent Ethics Committee or Institutional Review Board
Before the start of the study, the investigator (or sponsor where required) will provide the IEC/IRB
with current and complete copies of the following documents (as required by local regulations):
 
Final protocol and, if applicable, amendments
 
Sponsor-approved ICF (and any other written materials to be provided to the participants)
 
IB (or equivalent information) and amendments/addenda
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
107
Status: Approved, Date: 15 Aug 2022
 
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
vaccination
 
New information that may adversely affect the safety of the participants or the conduct of the
study
 
Deviations from or changes to the protocol to eliminate immediate hazards to the participants
 
Report of deaths of participants under the investigator’s care
 
Notification if a new investigator is responsible for the study at the site
 
Development Safety Update Report and Line Listings, where applicable
 
Any other requirements of the IEC/IRB
For all protocol amendments (excluding the ones that are purely administrative, with no
consequences for participants, data or study conduct), the amendment and applicable ICF revisions
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
108
Status: Approved, Date: 15 Aug 2022
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.
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
Legal guardian(s) (as defined in Section 2), per local requirements must give written consent and
the adolescent (minor) must give assent according to local requirements after the nature of the
study has been fully explained and before the adolescent can be enrolled in the study. Assent must
be obtained from adolescents (minors) capable of understanding the nature of the studydepending
on the institutional policies; it should be written in language appropriate to the adolescent’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
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
109
Status: Approved, Date: 15 Aug 2022
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.
The ICF(s) and assent form must be signed before performance of any study-related activity. The
ICF(s) and assent form that 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 ICF 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 (as appropriate for age and per local regulations)
as well as the legally acceptable representatives of potential participants (if applicable), 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 or assent 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 (if applicable) are authorizing such access.
It also denotes that the participant and legal guardian (if applicable)agree to allow the participant’s
study physician to recontact them for the purpose of obtaining consent for additional safety
evaluations, if needed.
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, and legal 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.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
110
Status: Approved, Date: 15 Aug 2022
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 vaccination with Ad26-based
vaccines including Ad26.COV2.S, to understand SARS-CoV-2 infection, to understand
differential vaccine responders, to develop tests/assays related to Ad26.COV2.S and SARS-CoV-2
infection, and to perform other tests/assays related to other Ad26-based vaccines and infection
with other viruses. The research may begin at any time during the study or the post-study storage
period.
Stored samples and other health recordings 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).
10.3.6. 
Safety Monitoring Committees Structure
Independent Data Monitoring Committee
An IDMC will be established to monitor safety data on an ongoing basis to ensure the continuing
safety of the participants enrolled in this study. The IDMC 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 IDMC
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
111
Status: Approved, Date: 15 Aug 2022
will consist of at least 1 medical expert in the relevant therapeutic area of pediatrics and at least 1
external statistician independent of the sponsor and not involved in the final analysis of the study
who will prepare the data and perform all IDMC safety analyses for review by the IDMC.
Committee membership responsibilities, authorities, and procedures will be documented in its
charter.
The IDMC will review data as indicated in Section 4.1. IDMC safety reviews will be based on
descriptive safety tables and listings from all accumulated safety data at that point in time. After
each review, the IDMC will make recommendations regarding the continuation of the study. When
appropriate, the conclusions of the IDMC will be communicated to the investigators, the IRB/IEC,
and the national regulatory authorities.
Molecularly confirmed COVID-19 cases will be reported to the IDMC on a regular basis.
The IDMC responsibilities, authorities, and procedures will be provided in its charter.
Ad hoc review may be performed further to the occurrence of any AE/SAE leading to a study
pausing situation as outlined in Section 6.8, or at request of the sponsor’s medical monitor or
designee. The PI and sponsor’s study responsible physician will inform the IDMC of any AE of
concern.
If any pausing rule is met (refer to Section 6.8) 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, MHRA). If needed, this will be followed by a substantial
amendment of the IB and/or protocol.
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 unblinded and provided with the
statistical analysis based on unblinded data. As the IDMC, they are independent to the company.
The SSG may include a clinician, a statistician, a statistical programmer, and a regulatory person.
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
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
112
Status: Approved, Date: 15 Aug 2022
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 per protocol. Recruitment
performance or specific expertise related to the nature and the key assessment parameters of the
study will be used to determine a coordinating investigator for the study. Results of analyses
performed after the Clinical Study Report has been issued will be reported in a separate report and
will not require a revision of the Clinical Study Report.
Study participant identifiers will not be used in publication of results. Any work created in
connection with performance of the study and contained in the data that can benefit from copyright
protection (except any publication by the investigator as provided for below) shall be the property
of the sponsor as author and owner of copyright in such work.
Consistent with Good Publication Practices and International Committee of Medical Journal
Editors (ICMJE) guidelines, the sponsor shall have the right to publish such primary (multicenter)
data and information without approval from the investigator. The investigator has the right to
publish study site-specific data after the primary data are published. If an investigator wishes to
publish information from the study, a copy of the manuscript must be provided to the sponsor for
review at least 60 days before submission for publication or presentation. Expedited reviews will
be arranged for abstracts, poster presentations, or other materials. If requested by the sponsor in
writing, the investigator will withhold such publication for up to an additional 60 days to allow for
filing of a patent application. In the event that issues arise regarding scientific integrity or
regulatory compliance, the sponsor will review these issues with the investigator. The sponsor will
not mandate modifications to scientific content and does not have the right to suppress information.
For multicenter study designs and sub-study approaches, secondary results generally should not
be published before the primary endpoints of a study have been published. Similarly, investigators
will recognize the integrity of a multicenter study by not submitting for publication data derived
from the individual study site until the combined results from the completed study have been
submitted for publication, within 18 months after the study end date, or the sponsor confirms there
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
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
113
Status: Approved, Date: 15 Aug 2022
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.
10.3.9. 
Case Report Form Completion
Case report forms are prepared and provided by the sponsor for each participant in electronic
format. All data relating to the study must be recorded in the eCRF. All eCRF entries, corrections,
and alterations must be made by the investigator or authorized study-site personnel. The
investigator must verify that all data entries in the eCRF are accurate and correct.
The study data will be transcribed by study-site personnel from the source documents onto an
eCRF, if applicable. Study-specific data will be transmitted in a secure manner to the sponsor.
Worksheets may be used for the capture of some data to facilitate completion of the eCRF. Any
such worksheets will become part of the participant’s source documents. Data must be entered into
the eCRF in English. The eCRF must be completed as soon as possible after a participant visit and
the forms should be available for review at the next scheduled monitoring visit.
All participative measurements (eg, questionnaires) will be completed by the same individual who
made the initial baseline determinations whenever possible.
If necessary, queries will be generated in the electronic data capture (eDC) tool. If corrections to
an eCRF are needed after the initial entry into the eCRF, this can be done in either of the following
ways:
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
114
Status: Approved, Date: 15 Aug 2022
 Investigator and study-site personnel can make corrections in the eDC tool at their own
initiative or as a response to an auto query (generated by the eDC tool).
 Sponsor or sponsor delegate can generate a query for resolution by the investigator and study-
site personnel.
10.3.10. 
Source Documents
At a minimum, source documents consistent in the type and level of detail with that commonly
recorded at the study site as a basis for standard medical care must be available for the following:
participant identification, eligibility, and study identification; study discussion and date of signed
informed consent and 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; study vaccine
receipt/dispensing/return records; study vaccine administration information; and date of study
completion and reason for early discontinuationof study vaccination 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,
reactogenicity diary to record solicited AEs, daily signs and symptoms surveillance question, SIC)
will be recorded and will be considered source data. The participant’s reactogenicity diary used to
collect information regarding solicited signs and symptoms after vaccination 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
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
115
Status: Approved, Date: 15 Aug 2022
sponsor study-site contact. If electronic records are maintained at the study site, the method of
verification must be discussed with the study-site personnel.
Direct access to source documents (medical records) must be allowed for the purpose of verifying
that the recorded data are consistent with the original source data. Findings from this review will
be discussed with the study-site personnel. The sponsor expects that, during monitoring visits, the
relevant study-site personnel will be available, the source documents will be accessible, and a
suitable environment will be provided for review of study-related documents. The monitor will
meet with the investigator on a regular basis during the study to provide feedback on the study
conduct.
In addition to on-site monitoring visits, remote contacts can occur. It is expected that during these
remote contacts, study-site personnel will be available to provide an update on the progress of the
study at the site.
Central monitoring will take place for data identified by the sponsor as requiring central review.
10.3.12. 
On-Site Audits
Representatives of the sponsor’s clinical quality assurance department may visit the study site at
any time during or after completion of the study to conduct an audit of the study in compliance
with regulatory guidelines and company policy. Remote auditing techniques may also be utilized,
if necessary. These audits will require access to all study records, including source documents, for
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
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
116
Status: Approved, Date: 15 Aug 2022
responsibility of the sponsor to inform the investigator/institution as to when these documents no
longer need to be retained.
If the responsible investigator retires, relocates, or for other reasons withdraws from the
responsibility of keeping the study records, custody must be transferred to a person who will accept
the responsibility. The sponsor must be notified in writing of the name and address of the new
custodian. Under no circumstance shall the investigator relocate or dispose of any study documents
before having obtained written approval from the sponsor.
If it becomes necessary for the sponsor or the appropriate regulatory authority to review any
documentation relating to this study, the investigator/institution must permit access to such reports.
10.3.14. 
Study and Site Start and Closure
First Act of Recruitment
The first site open is considered the first act of recruitment and it becomes the study start date.
Study/Site Termination
The sponsor reserves the right to close the study site or terminate the study at any time for any
reason at the sole discretion of the sponsor. Study sites will be closed upon study completion. A
study site is considered closed when all required documents and study supplies have been collected
and a study site closure visit has been performed.
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
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
117
Status: Approved, Date: 15 Aug 2022
10.4. Appendix 4: Adverse Events, Serious Adverse Events, Adverse Events of
Special Interest, Product Quality Complaints, and Other Safety Reporting:
Definitions and Procedures for Recording, Evaluating, Follow-up, and
Reporting
10.4.1. 
Adverse Event Definitions and Classifications
Adverse Event
An AE is any untoward medical occurrence in a clinical study participant administered a
pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have
a causal relationship with the study vaccine. An AE can therefore be any unfavorable and
unintended sign (including an abnormal finding), symptom, or disease temporally associated with
the use of a medicinal (investigational or non-investigational) product, whether or not related to
that medicinal (investigational or non-investigational) product. (Definition per International
Conference on Harmonisation [ICH])
This includes any occurrence that is new in onset or aggravated in severity or frequency from the
baseline condition, or abnormal results of diagnostic procedures, including laboratory test
abnormalities.
Any respiratory tract infection that is not due to SARS-CoV-2 will be reported as an AE if it occurs
between the time of any vaccination through the following 28 days. Any respiratory tract infection
recorded as an AE in the eCRF will be excluded from any AE analysis if the molecular test is
subsequently found to be positive for SARS-CoV-2. Respiratory tract infections arising from
SARS-CoV-2 infection will not be reported as (S)AEs in the Clinical Study Report but will be
tabulated separately. In general, any (S)AEs caused by molecularly confirmed SAR-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.
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
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
118
Status: Approved, Date: 15 Aug 2022
 
Is Medically Important*
*Medical and scientific judgement 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 vaccination 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).
If a participant receives a positive SARS-CoV-2 result from a private/off-study test during the
study, and the positive result occurs within 28 days after vaccination, the event will be reported as
an AE. If it occurs after 28 days, the event will be recorded as an SAE only if the event qualifies
as serious. The participant can continue in the study if they choose to; however, this must be in
accordance with local country and site level recommendations for COVID-19.
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.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
119
Status: Approved, Date: 15 Aug 2022
10.4.3. 
Severity Criteria
Adolescents (12 to 17 Years of Age)
All AEs and laboratory data will be coded for severity using a modified version of the Food and
Drug Administration (FDA) grading table, based on the version of September 2007 (US DHHS
FDA CBER 2007), included in Section 10.5, Toxicity Grading Scale.
For AEs not identified in the grading table, the following guidelines will be applied:
Grade 1 
Mild 
Symptoms causing no or minimal interference with usual social
and functional activities
Grade 2 
Moderate 
Symptoms causing greater than minimal interference with usual
social and functional activities
Grade 3 
Severe 
Symptoms causing inability to perform usual social and
functional activities and requires medical intervention
Grade 4 
Potentially 
life- 
threatening 
Symptoms causing inability to perform basic self-care functions
OR medical or operative intervention indicated to prevent
permanent impairment, persistent disability OR ER visit or
hospitalization
The severity of solicited signs and symptoms will be graded in the reactogenicity diary by the
participant based on the severity assessment provided in the reactogenicity diary and then verified
by the investigator using the toxicity grading scale in Section 10.5. (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.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
120
Status: Approved, Date: 15 Aug 2022
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 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.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
121
Status: Approved, Date: 15 Aug 2022
Any event requiring hospitalization (or prolongation of hospitalization) that occurs during
participation in the study must be reported as an SAE, except hospitalizations for the following:
 
Hospitalizations not intended to treat an acute illness or AE (eg, social reasons such as pending
placement in long-term care facility).
 
Surgery or procedure planned before entry into the study (must be documented in the eCRF).
Note: Hospitalizations that were planned before the signing of the ICF, and where the
underlying condition for which the hospitalization was planned has not worsened, will not be
considered SAEs. Any AE that results in a prolongation of the originally planned
hospitalization is to be reported as a new SAE.
The cause of death of a participant in a study, whether or not the event is expected or associated
with the study vaccine, is considered an SAE.
Information regarding SAEs will be transmitted to the sponsor using an SAE reporting form and
safety report form of the eCRF, which must be completed and reviewed by a physician from the
study site, and transmitted in a secure manner to the sponsor within 24 hours. The initial and
follow-up reports of an SAE should be transmitted in a secure manner electronically or by
facsimile (fax). Telephone reporting should be the exception and the reporter should be asked to
complete the appropriate form(s) first.
Adverse Events of Special Interest
AESIs 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.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
122
Status: Approved, Date: 15 Aug 2022
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.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
123
Status: Approved, Date: 15 Aug 2022
10.5. Appendix 5: Toxicity Grading Scales in Adolescents (12 to 17 Years of
Age)
Adapted from the FDA Guidance document “Toxicity Grading Scale for Healthy Adult and
Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials” (September 2007) (US
DHHS FDA CBER 2007).
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 judgement when characterizing
bradycardia among some healthy participant populations, for example, conditioned athletes.
# Revised by the sponsor.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
124
Status: Approved, Date: 15 Aug 2022
Systemic (General) Mild (Grade 1) 
Moderate (Grade 2) Severe (Grade 3) 
Potentially Life
Threatening
(Grade 4)
Vomiting# 
No interference 
with activity or 1 –2 
episodes/24 hours 
Some interference 
with activity or > 2 
episodes/24 hours 
Prevents daily  
activity, requires 
outpatient IV
hydration
Hospitalization;
Hypotensive shock
Nausea# 
Minimal symptoms; 
causes minimal or no 
interference with 
work, school, or self- 
care activities 
Notable symptoms; 
Requires modification 
in activity or use of 
medications; 
Does NOT result in 
loss of work, school, 
or cancellation of 
social activities
Incapacitating 
symptoms; 
Requires bed rest 
and/or results in loss 
of work, school, or
cancellation of social
activities
Hospitalization;
Inability to perform
basic self-care
functions
Diarrhea# 
2 –3 loose stools or 
< 400 gms/24 hours 
38–5 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.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
125
Status: Approved, Date: 15 Aug 2022
Systemic Illness 
Mild (Grade 1) 
Moderate (Grade 2) Severe (Grade 3) 
Potentially Life
Threatening
(Grade 4)
Illness or clinical 
adverse 
event (as defined 
according to 
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.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
126
Status: Approved, Date: 15 Aug 2022
10.6. Appendix 6: Contraceptive Guidance
Participants must follow contraceptive measures as outlined in Section 5.1. Pregnancy information
will be collected and reported as noted in Section 8.3.5 and Section 10.4.
Definition of Person of Childbearing Potential
A Person of Childbearing Potential
A person is considered fertile following menarche and until becoming postmenopausal unless
permanently sterile (see below).
A Person 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 person
experiences menarche) or the risk of pregnancy changes (eg, a person of childbearing potential
who is not heterosexually active becomes active), the participant should have a negative pregnancy
test immediately prior to each study vaccine administration. Participants of childbearing potential
must be practicing a highly effective method of contraception, as described throughout the
inclusion criteria (Section 5.1).
For a participant who becomes pregnant, this information will be shared with the study
participant’s legal guardian if the participant’s age is <18 years of age, as required by local
regulations.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
127
Status: Approved, Date: 15 Aug 2022
10.7. Appendix 7: Symptoms of Infection with Coronavirus-19
Symptoms of Infection with Coronavirus-19 (SIC) (adolescents 12 to 17 years of age)
To assist adolescents (12 to 17 years of age) with some of the symptom descriptions, a reference
card is provided (COVID Survey Reference Card). A readability assessment determined the SIC
is at a 6th grade reading level based on the Lexile Framework for Reading.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
128
Status: Approved, Date: 15 Aug 2022
10.8. Appendix 8: 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 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 adolescent 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 fevera, laboratory evidence of inflammationb,
and evidence of clinically severe illness requiring hospitalization, with multisystem (>2) organ
involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic or
neurological); AND
 
No alternative plausible diagnoses; AND
 
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.
a *Fever >38.0°C for ≥24 hours, or report of subjective fever lasting ≥24 hours
b 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
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
129
Status: Approved, Date: 15 Aug 2022
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 adolescents will have the same signs and symptoms, and some adolescents may have
symptoms that are not listed here.
Immediate emergency care is required in the event of the adolescent 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)/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.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
130
Status: Approved, Date: 15 Aug 2022
10.9. Appendix 9: Case Definitions for COVID-19
10.9.1. 
Case Definitions for Adolescents 12 to 17 Years of Age
10.9.1.1. 
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 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
 
Other nonspecific symptoms such as: rash,
bloodshot eyes or eye irritation/drainage
* SpO2 criteria will be adjusted according to altitude per investigator judgement.
** Having 2 or more elements of a symptom (eg, vomiting and diarrhea or fatigue and loss of appetite) is counted only as 1
symptom for the case definition. To meet the case definition, a participant would need to have at least 2 different symptoms.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
131
Status: Approved, Date: 15 Aug 2022
Case Definition for Severe/Critical COVID-19
 
A SARS-CoV-2 positive RT-PCR or molecular test result from any available respiratory tract
sample (eg, nasal swab sample, sputum sample, throat swab sample, saliva sample) or other
sample
AND any 1 of the following at any time during the course of 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 mm Hg)
* 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 mm Hg, diastolic blood pressure
<60 mm Hg, or requiring vasopressors)
 
Significant acute renal, hepatic, or neurologic dysfunction
 
Neurologic dysfunction includes: Gross impairment in motor, cognitive, or speech and
language functions (LaRovere 2021). Other symptoms such as dizziness, somnolence, altered
mental, status, lethargy.
 
Hepatic and renal impairment includes: Lower levels of albumin and elevated levels of
creatinine, alanine transaminase, and aspartate aminotransferase (Ahmed 2020)
 
Admission to the ICU
 
Death
10.9.1.2. 
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 10.9.1.1.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
132
Status: Approved, Date: 15 Aug 2022
10.9.2. 
US FDA Harmonized Case Definition for COVID-19
If a participant presents with symptoms as those listed by the US FDA harmonized case definition
(see Section 10.11, CDC 2020b), 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
definition (CDC 2020b) 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.
10.9.3. 
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.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
133
Status: Approved, Date: 15 Aug 2022
10.10. Appendix 10: Summary of Guidance from CDC Websitea on Underlying
Medical Conditions That Lead or Might Lead to Increased Risk for Severe
Illness From COVID-19 Adolescents
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.
Adolescents, regardless of age, with the following underlying medical conditions might also be at
increased risk of severe illness compared with other children:
 
Asthma or chronic lung disease
 
Diabetes
 
Genetic, neurologic, or metabolic conditions
 
Sickle cell disease
 
Congenital heart disease
 
Immunosuppression (eg, primary immunodeficiency)
 
Medical complexity (children with multiple chronic conditions that affect many organs of the
body, or are dependent on technology and other significant supports for daily life)
 
Obesity
This list is not exhaustive but intends to provide an overview of underlying medical conditions
that might increase the risk for severe illness in adolescents.
a 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 28 February 2022.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
134
Status: Approved, Date: 15 Aug 2022
10.11. Appendix 11: Symptoms of Coronavirus (US Centers for Disease Control
and Prevention) in Children
The following extract shows symptoms of coronavirus infection in children as listed on the US
CDC website dated 21 January 2021 and were still accurate at the time of finalization of this
protocol:
(https://www.cdc.gov/coronavirus/2019-ncov/daily-life-coping/children/symptoms.html)
The most common symptoms of COVID-19 in children are fever and cough.
The symptoms of COVID-19 are similar in adults and children and can look like symptoms of
other common illnesses, like colds, strep throat, or allergies. The most common symptoms of
COVID-19 in children are fever and cough, but children may have any of these signs or symptoms
of COVID-19:
 
Fever or chills
 
Cough
 
Nasal congestion or runny nose
 
New loss of taste or smell
 
Sore throat
 
Shortness of breath or difficulty breathing
 
Diarrhea
 
Nausea or vomiting
 
Stomachache
 
Tiredness
 
Headache
 
Muscle or body aches
 
Poor appetite or poor feeding, especially in babies under 1 year old
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
135
Status: Approved, Date: 15 Aug 2022
10.12. Appendix 12: 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:
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
136
Status: Approved, Date: 15 Aug 2022
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)
Hormone replacement therapy (including contraceptives)
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
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
137
Status: Approved, Date: 15 Aug 2022
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)
Complete blood count 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
Anticardiolipin antibodies (IgG
and IgM) or beta-2
glycoproteins antibodies
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
138
Status: Approved, Date: 15 Aug 2022
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:
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
139
Status: Approved, Date: 15 Aug 2022
10.13. Appendix 13: MIS-C 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 MIS-C. Additional data may be
requested by the sponsor for investigation of the event.
Adverse Event of Special Interest Questionnaire (AESIQ) for Multisystem Inflammatory
Syndrome in Children
Date of Report: 
[dd-MMM-yyyy]
1. Adverse Event Description
Participant’s clinical signs and symptoms
Tachycardia 
Cardiac conduction  
Gastrointestinal symptoms
Dyspnoea 
abnormalities 
Lymphadenopathy
Tachypnoea 
Severe headache 
Conjunctivitis
Fever ≥ 38 C  
Altered mental status 
Cranial nerve palsies
mucocutaneous 
Edema of hands/feet 
Paresthesias
findings (rash,
red/cracked lips, and
strawberry tongue)
Other symptoms found during the physical examination:
Does the patient have an epidemiologic link to SARS-CoV-2 infection? 
No 
Yes, details:
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
140
Status: Approved, Date: 15 Aug 2022
2. Medical History and Concurrent Conditions
Provide details:
Does the participant have a diagnosis of rheumatic disease? 
No 
Yes, details:
Does the participant have a diagnosis of cancer? 
No 
Yes, details:
Has the participant been treated with immunomodulating therapy? 
No 
Yes, details:
Has the participant ever been admitted to an ICU? 
No 
Yes, details:
Does the participant have arrhythmia recorded in their medical 
No 
Yes, details:
record?
Does the participant have a history of systemic juvenile idiopathic 
No 
Yes, details:
arthritis?
Does the participant have a history of a previous clotting 
No 
Yes, details:
disorder or a diagnosis of a hypercoagulable state?
Does the participant have a history of remote or recent thrombotic 
No 
Yes, details:
events?
Does the participant have family or personal history of 
No 
Yes, details:
thrombophilia?
Does the participant have any of the following genetic risk factors:
Blood-clotting disorder 
Thrombophilia
Dysfibrinogenemia 
Protein C or S deficiency
ABO blood types: A and B or Rh+ 
Antiphospholipid syndrome
Prothrombin gene mutation  
Factor V Leiden mutation
Anti-thrombin deficiency
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
141
Status: Approved, Date: 15 Aug 2022
Does the participant have any acquired risk factors:
Altered mobility  
Morbid Obesity
Recent trauma 
Recent surgery
If yes to any of the above, provide details:
3. Relevant results of diagnostic tests including laboratory tests, imaging, biopsies, etc. Provide
details of the levels/conclusion, date performed, normal ranges, etc. 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)
C-reactive protein
PT/INR/PTT
Erythrocyte sedimentation rate
Absolute lymphocyte count
B-type natriuretic peptide
Lactate dehydrogenase
Complete blood count
Platelet count
Ferritin
D-dimer
Albumin level
Troponin
Procalcitonin
Fibrinogen
Von Willibrand factor antigen
Electrocardiograma
a. For electrocardiogram, results at baseline should be provided if available.
Provide details of any additional diagnostic results:
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
142
Status: Approved, Date: 15 Aug 2022
10.14. Appendix 14: Thrombotic Events to be Reported as AESIs
At the time of protocol Amendment 1 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
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
143
Status: Approved, Date: 15 Aug 2022
10.15. Appendix 15: Protocol Amendment History
The Protocol Amendment Summary of Changes Table for the current amendment is located
directly before the Table of Contents (TOC).
Amendment 3 (28 February 2022):
Overall Rationale for the Amendment:
At the present time, the recommended schedule for individuals aged 18 years and above in the US
for the EUA approved Ad26.COV2.S consists of a single dose primary vaccination, followed by a
single booster dose as of two months or later. EMA also recently approved the administration of
an Ad26.COV2.S booster dose, at least two months after the initial dose in people aged 18 years
and above. The pandemic has shown that appearance of divergent variants may necessitate further
boosting in addition to the current recommended primary schedules. Hence, the main purpose for
this Protocol Amendment 3 is to investigate the safety and immunogenicity of a booster
vaccination with Ad26.COV2.S, following a primary vaccination regimen in adolescents. Note
that this amendment only pertains to changes to Part 1. Part 1 is ongoing and there is uncertainty
on the immune responses elicited in adolescent participants who are given lower doses of
Ad26.COV2.S; therefore, the sponsor wants to ensure participants in Part 1 receive a booster dose
of Ad26.COV2.S at the predefined time. Part 2 of the protocol will be amended at a later date and
will not commence until the amended version is approved by the respective Health Authorities.
Participants that received 1 active vaccination in the primary regimen will be given a booster
vaccination as of 6 months after the last vaccination (vaccination 1) with active vaccine. The
booster dose level for these participants will be 2.5 ×1010 vp per 0.5 mL.
Participants that received 2 active vaccinations in the primary regimen will be given a booster
vaccination as of 12 months after the last vaccination (vaccination 2) with active vaccine. The
booster dose level for these participants and the dose level and regimen for Part 2 will be based on
the IDMC and sponsor review of safety and immunogenicity data generated post-dose 1 and post-
dose 2. Booster vaccination may be performed earlier if some dose levels do not result in
acceptable immunogenicity outcomes after second vaccination in which case the booster dose level
will be 2.5 ×1010 vp per 0.5 mL. This is to ensure that the participants will receive their booster
under prespecified protocol timelines irrespective of when the selection of the final dose level (for
the booster at 12 months for participants that received 2 active vaccinations in the primary regimen
and for Part 2) will occur. A dose level of 2.5 ×1010 vp per 0.5 mL is already being administered
as a 2-dose regimen (56-day interval) as part of the primary vaccination regimen in this study. The
evaluation of the primary vaccination regimen data by the IDMC and sponsor will further support
the use of a single booster vaccination with the same dose.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
144
Status: Approved, Date: 15 Aug 2022
Section Number 
and Name
Description of Change 
Brief Rationale
1.1 Synopsis 
1.2 Schema1.3.1 Part 1: Dose Selection 
Cohort (Groups 1, 2 and 3) Booster 6 
Months Post-dose 1 
1.3.2 Part 1: Dose Selection Cohort (Groups 
4, 5 and 6) Booster 12 Month Post-dose 2 
4.1 Overall Design  
4.2.1 Study-Specific Ethical Design 
Considerations 
4.4 End ofStudy Definition  
5.1 Inclusion Criteria 
6.8 Study Vaccination Pausing Rules 
9.2 Sample Size Determination 
9.5 Planned Analyses
The option of receiving an additional 
vaccination after the primary regimen 
has been removed from Part 1. All
participants in Part 1 will now be
given a booster vaccination with
Ad26.COV2.S as of 6 months (for
participants who receive an active
vaccination followed by placebo) or
as of 12 months (for participants who
receive 2 doses of active vaccination)
after their last active vaccination
depending on which group the
participant was assigned.
See overall rationale for
amendment.
1.3.1 Part 1: Dose Selection Cohort (Groups 
1, 2 and 3) Booster 6 Months Post-dose 1 
1.3.2 Part 1: Dose Selection Cohort (Groups 
4, 5 and 6) Booster 12 Month Post-dose 2 
Text has been added clarifying that if 
a participant becomes infected with 
SAR-CoV-2 during the study they
can still receive a booster vaccination
of Ad26.COV2.S according to local
recommendations or 3 months after
the participant has recovered.
Consistency across the
COVID program.
2.3.1 Risks Related to Study Participation  
Risk related to a 3rd Ad26.COV2.S 
vaccination has been added. 
Alignment across
studies.
1.1 Synopsis 
3 OBJECTIVES AND ENDPOINTS  
Removed the seroresponse rate 
endpoint. 
Additional objectives have been 
added to Part 1/ 2 
 Assessment of safety and
reactogenicity post-booster
 Humoral immune response (pre-
and post-booster)
Serological response to
vaccination includes the
calculation of a
seroresponse rate.
As a result of
introducing a booster
vaccination to the study.
1.1 Synopsis 
4.1 Overall Design  
Footnote a has been updated in the 
vaccination schedule tables. 
To align with the text in
the synopsis and main
body of the protocol.
1.1 Synopsis 
8.1.1 Immunogenicity Assessments 
The summary of Humoral 
Immunogenicity Assays has been 
updated (ie, moved binding Abs for 
other coronaviruses to binding Abs 
row and addition of ELISA or
equivalent assay).
Clarifications were made
to better reflect the
assays that could be
used.
1.1 Synopsis 
9.5 Planned Analyses 
Updated text around the planned 
analysis for Part 1.
Text has been added to the definition
of PPI that other SARS-CoV-2
vaccination outside the study and
samples outside pre-defined windows
are excluded from the analysis set.
Clarification
8.1.1 Immunogenicity Assessments 
Text updated to reflect that PBMCs 
Clarification
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
145
Status: Approved, Date: 15 Aug 2022
Section Number 
and Name
Description of Change 
Brief Rationale
will be collected in a subset of
seronegative participants in Part 2.
10.1 Appendix 1: Abbreviations and 
Definitions 
Added the definition of observer- 
blind.
Clarification
10.3.6 Safety Monitoring Committees 
Structure 
Removal of the last part of the 
paragraph on reporting of 
molecularly confirmed COVID-19 
cases.
There is no arm
monitoring possible
without a placebo arm.
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 Adolescents
Minor corrections of the criteria have 
been made. 
To align with the
updated CDC
recommendations.
Throughout the protocol 
Minor grammatical, formatting, or 
spelling changes were made. Minor
clarifications were also made
throughout the protocol.
Minor errors were noted.
Amendment 2 (26 October 2021)
Overall Rationale for the Amendment: The main purpose of this amendment is to remove the
full placebo arms of the study due to the increasing availability of COVID-19 vaccines in
adolescents globally. The Argentinian Health Authority (ANMAT) was the first Authority to
provide feedback about the availability of the vaccines for adolescents in their Country;
therefore, they have requested to put a hold on ongoing vaccinations at sites in Argentina and
suggested to remove placebo arm of the study in that Country. As a result, participants who were
enrolled in Argentina under Protocol Amendment 1 will be unblinded to whether they received
active vaccine or placebo and given the option to stay in study or receive the COVID-19 vaccine
via their national vaccination program. Since it is foreseeable that the same situation will occur
in other Countries, the sponsor proactively decided to remove the placebo arm entirely from the
study protocol. Under the new design, all participants will receive active treatments regardless of
the allocation group. The changes implemented in this amendment may result in modifications of
Part 2 in a future amendment. Additionally, changes have been made throughout the protocol per
FDA feedback provided to the sponsor 17 September 2021.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
146
Status: Approved, Date: 15 Aug 2022
Section Number 
and Name
Description of Change 
Brief Rationale
1.1 Synopsis 
1.2 Schema 
1.3.4 Part 2: 2-dose Regimen 
3 OBJECTIVES AND ENDPOINTS  
4.1 Overall Design
4.2 Scientific Rationale for Study Design
6.3 Measures to Minimize Bias:
Randomization and Blinding
6.6 Continued Access to Study Vaccine for
Participants in Placebo Group: Removed
7.2 Participant Discontinuation/Withdrawal
From the Study
9.2 Sample Size Determination
9.2.1 Immunogenicity
10.3.6 Safety Monitoring Committees
Structure
Removal of placebo group 
throughout the protocol. 
Per Health Authority
request and availability
of vaccines for
adolescents globally.
1.1 Synopsis 
1.2 Schema 
3 OBJECTIVES AND ENDPOINTS  
4.1 Overall Design  
6.3 Measures to Minimize Bias: 
Randomization and Blinding
9.2 Sample Size Determination
Replaced placebo with a 2nd dose of 
2.5x1010 to the group that was 
planned to receive 2.5x1010 (0.5mL) 
as a first vaccination and then 
placebo as a second vaccination.
To explore a 2 dose
regimen to compare to
the 2 dose regimen in
study COV3009.
1.3.7.1 Participants With an AESI 
Included thrombocytopenia as a 
suspected AESI. 
Consistency across
COVID-19 studies.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
147
Status: Approved, Date: 15 Aug 2022
Section Number 
and Name
Description of Change 
Brief Rationale
1.1 Synopsis 
1.2 Schema 
1.3.1 Part 1: Dose Selection Cohort 
1.3.3 Part 2: 1-dose Regimen 
1.3.4 Part 2: 2-dose Regimen 
1.3.5 After the Primary Vaccination 
Regimen  
4.1 Overall Design
4.2 Scientific Rationale for Study Design
4.4 End of Study Definition
5.1 Inclusion Criteria
6.1 Study Vaccine(s) Administered
Changed cross-over vaccination to 
additional vaccination(s). 
Cross-over vaccination
was intended for the
placebo groups which no
longer applies with the
removal of the placebo
groups in Protocol
Amendment 2.
1.1 Synopsis 
1.2 Schema 
1.3.1 Part 1: Dose Selection Cohort 
1.3.4 Part 2: 2-dose Regimen 
1.3.5 After the Primary Vaccination
Regimen
4.1 Overall Design
Updated the 6 month and 12 month 
visits for the 2-dose regimens to 
occur 6 and 12 months after the
second dose.
To align with other
Phase 3 studies.
1.1 Synopsis 
3 OBJECTIVES AND ENDPOINTS  
8.1 Immunogenicity Assessments 
An exploratory endpoint to evaluate 
the immunogenicity against emerging 
variants has been added. 
To assess the humoral
immune response against
emerging variants in
adolescents.
1.1 Synopsis 
3 OBJECTIVES AND ENDPOINTS  
An exploratory endpoint to evaluate 
different definitions of seroresponse
has been added.
Per FDA request.
2.3.1 Risks Related to Study Participation  
7.1 Discontinuation of Study Vaccination 
10.1 Appendix 1: Abbreviations and 
Definitions 
Text has been added regarding the 
increased risk of Guillain-Barré 
Syndrome (GBS) following use of 
the Ad26.COV2.S vaccine. 
Based on the emerging
data following use of the
Ad26.COV2.S vaccine,
GBS has been identified
as an adverse drug
reaction for the use of
Ad26.COV2.S vaccine.
4.2 Scientific Rationale for Study Design  
6.2 
Preparation/Handling/Storage/Accountability  
6.3 Measures to Minimize Bias:
Randomization and Blinding
6.4 Study Vaccination Compliance
Text was updated to show that the 
vaccine administrator is also
unblinded.
Clarification
4.1 Overall Design  
4.4 End of Study Definition 
Study duration and completion 
definitions have been updated to
reflect changes in the timings of
visits.
Clarification
5.2 Exclusion Criteria 
A history of Heparin-induced 
thrombocytopenia has been added as
an exclusion criterion.
Per FDA request.
5.4 Screen Failures 
Text has been added stating that 
participants who were enrolled into 
the placebo arm under Protocol 
Amendment 1 are given the option to
rescreen into one of the active arms
under Amendment 2.
Removal of the Placebo
arm in the study under
Protocol Amendment 2.
1.1 Synopsis 
6.3 Measures to Minimize Bias: 
Randomization and Blinding 
Text added to note that the sponsor 
will be unblinded during the interim
analysis.
Clarification
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
148
Status: Approved, Date: 15 Aug 2022
Section Number 
and Name
Description of Change 
Brief Rationale
9.5 Planned Analyses
6.8 Study Vaccination Pausing Rules 
An additional pausing rule for 
suspected TTS, possibly related to
the vaccine, has been added.
Per FDA request.
1.1 Synopsis 
9.5 Planned Analyses 
Planned analyses in Part 1 have been 
updated. 
To accurately reflect the
data to be reviewed by
the IDMC and selected
sponsor members in the
first and second
analyses, and to add a
separate interim analysis.
Throughout the protocol 
Minor grammatical, formatting, or 
spelling changes were made. Minor
clarifications were also made
throughout the protocol.
Minor errors were noted.
Amendment 1 (13 July 2021)
Overall Rationale for the Amendment: The main purpose of this amendment is to focus on the
adolescent cohort due to the availability of new information from VAC31518COV2001. In
addition, and in alignment with feedback from the FDA guidance, this study amendment will allow
non-inferiority comparison of adolescents from this study versus young adults (18 to 25 years of
age) from efficacy trials. Therefore, adult participants and all participants <12 years of age have
been removed. The dose schedule and dose levels have also been modified and all boosters
removed. This study will now have 2 parts consisting of a Dose Selection Cohort and an Expansion
Cohort in selected dose levels and dosing regimens.
This amendment also includes 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.
Section Number 
and Name
Description of Change 
Brief Rationale
1.1 Synopsis
1.3.1 Part 1: Dose Selection
Cohort
1.3.2 Part 2: 1-dose Regimen
(Active and Placebo Groups)
1.3.3 Part 2: 2-dose Regimen
(Active and Placebo Groups)
2 INTRODUCTION
2.1 Study Rationale
2.3.3 Benefit-Risk
Assessment of Study
Participation
3 OBJECTIVES AND
Removal of participants who are either adults
or <12 years of age. Participants who are 12 to
17 years of age are identified as adolescents.
This study will use young
adults from
VAC31518COV3001 and
VAC31518COV3009 as
external controls and therefore
will only enroll participants
who are 12 to 17 years of age.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
149
Status: Approved, Date: 15 Aug 2022
Section Number 
and Name
Description of Change 
Brief Rationale
ENDPOINTS
4.1 Overall Design
4.2 Scientific Rationale for
Study Design
4.2.1 Study-Specific Ethical
Design Considerations
4.4 End of Study Definition
5 STUDY POPULATION
5.1 Inclusion Criteria
5.2 Exclusion Criteria
6.3 Measures to Minimize
Bias: Randomization and
Blinding
6.5 Dose Modification
6.8 Prestudy and
Concomitant Therapy
8 STUDY ASSESSMENTS
AND PROCEDURES
8.1.1 Immunogenicity
Assessments
8.2.1 Physical Examinations
8.2.2 Vital Signs
8.3.2 Method of Detecting
Adverse Events, Medically-
attended Adverse Events,
Adverse Events of Special
Interest, and Serious Adverse
Events
8.5 Biomarkers
9.1 Statistical Hypotheses
9.2 Sample Size
Determination
9.4.1 General Considerations
9.4.2 Primary/Secondary
Endpoints
9.4.4 Other Analyses
9.5 Planned Analyses
10.3.3 Informed Consent
Process and Assent Form
10.3.10 Source Documents
10.4.3 Severity Criteria
10.5 Appendix 5: Toxicity
Grading Scales
10.6 6: Contraceptive
Guidance
10.7Appendix 7: Symptoms
of Infection with
Coronavirus-19
10.9 Appendix 9: Case
Definitions for COVID-19
10.10 Appendix 10:
Summary of Guidance from
CDC Website on Underlying
Medical Conditions That
Lead or Might Lead to
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
150
Status: Approved, Date: 15 Aug 2022
Section Number 
and Name
Description of Change 
Brief Rationale
Increased Risk for Severe
Illness From COVID-19
1.1 Synopsis 
1.3.1 Part 1: Dose Selection 
Cohort 
1.3.2 Part 2: 1-dose Regimen 
(Active and Placebo Groups) 
1.3.3 Part 2: 2-dose Regimen 
(Active and Placebo Groups) 
2 INTRODUCTION  
2.3.3 Benefit-Risk 
Assessment of Study 
Participation  
3 OBJECTIVES AND 
ENDPOINTS  
4.1 Overall Design
4.3 Justification for Dose
6.1 Study Vaccine(s)
Administered
6.3 Measures to Minimize
Bias: Randomization and
Blinding
6.5 Dose Modification
6.9 Study Vaccination
Pausing Rules
9.1 Statistical Hypotheses
9.2 Sample Size
Determination
9.2.1 Immunogenicity
9.2.2 Safety
9.4.2 Primary/Secondary
Endpoints
9.5 Planned Analyses
Change of the overall study design to 
introduce: 
 
2 parts (Dose Selection Cohort and an 
Expansion Cohort) with co-primary 
endpoints 
 
Inclusion of a 1-dose regimen with 3 dose 
levels
 
Inclusion of 2 injection volumes for the
2.5×1010 vp dose level
 
Modification of the 2-dose regimen by
introducing 3 dose-levels; removing
sentinels; and removing booster
vaccinations
The change in study design
provides flexibility to the
dosing regimens as well as
allowing comparison with data
from VAC31518COV3001
and VAC31518COV3009.
1.1 Synopsis 
1.3.6.1 Participants With an 
AESI 
2.3.1 Risks Related to Study 
Participation  
2.3.3 Benefit-Risk 
Assessment of Study 
Participation  
3 OBJECTIVES AND 
ENDPOINTS  
6.8 Prestudy and 
Concomitant Therapy  
7.1 Discontinuation of Study 
Vaccination  
8 STUDY ASSESSMENTS
AND PROCEDURES
8.2.4.1 Thrombosis With
Thrombocytopenia
Syndrome
8.3 Adverse Events, Serious
Adverse Events, Medically-
attended Adverse Events,
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
up to 3 weeks after
vaccination. Therefore,
additional reporting and data
collection procedures are
implemented to follow-up
thrombotic events and
thrombocytopenia and identify
cases of TTS.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
151
Status: Approved, Date: 15 Aug 2022
Section Number 
and Name
Description of Change 
Brief Rationale
Adverse Events of Special
Interest, and Other Safety
Reporting
8.3.1 Time Period and
Frequency for Collecting
Adverse Event, Medically-
attended Adverse Event,
Adverse Event of Special
Interest, and Serious Adverse
Event Information
8.3.2 Method of Detecting
Adverse Events, Medically-
attended Adverse Events,
Adverse Events of Special
Interest, and Serious Adverse
Events
8.3.3 Follow-up of Adverse
Events, Medically-attended
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 (TTS)
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
10.12 Appendix 12: TTS
AESI Form
10.14 Appendix 14:
Thrombotic Events to be
Reported as AESIs
1.1 Synopsis 
1.3.6.2 Multisystem 
Inflammatory Syndrome in 
Children (MIS-C) 
2.3.1 Risks Related to Study 
Participation  
2.3.3 Benefit-Risk 
Multisystem Inflammatory Syndrome in 
Children (MIS-C) has been included as an 
AESI and a reason for pausing. Follow-up 
assessments will be performed in the event of a 
suspected AESI. 
Some children with
COVID-19 may develop a
hyperinflammatory response
leading to MIS-C. Therefore,
additional reporting and data
collection procedures are
implemented to follow-up
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
152
Status: Approved, Date: 15 Aug 2022
Section Number 
and Name
Description of Change 
Brief Rationale
Assessment of Study 
Participation  
3 OBJECTIVES AND
ENDPOINTS
6.9 Study Vaccination
Pausing Rules
7.1 Discontinuation of Study
Vaccination
8.2.4.2 Multisystem
Inflammatory Syndrome in
Children
8.3.1 Time Period and
Frequency for Collecting
Adverse Event, Medically-
attended Adverse Event,
Adverse Event of Special
Interest, and Serious Adverse
Event Information
8.3.6.2 Multisystem
Inflammatory Syndrome in
Children
9.4.2 Primary/Secondary
Endpoints
10.2 Appendix 2:
Hematology Clinical
Laboratory Tests
10.13 Appendix 13: MIS-C
AESI Form
symptoms of MIS-C and
identify cases of MIS-C.
1.1 Synopsis 
3 OBJECTIVES AND 
ENDPOINTS  
8.1.1 Immunogenicity 
Assessments 
Primary objectives and endpoints have been 
split for Part 1 and Part 2. Use of virus 
neutralization assay (VNA) titers has been 
added as an alternative to S-ELISA in the 
Part 1 and to replace S-ELISA in the Part 2 
primary endpoints. 
To improve clarity of
endpoints. For Part 1, VNA is
added to allow flexibility in
the type of assay used for dose
selection. For Part 2, VNA
replaces S-ELISA to
implement the use of a
functional assay for NI
assessment.
1.1 Synopsis 
3 OBJECTIVES AND 
ENDPOINTS
9 STATISTICAL
CONSIDERATIONS
Addition of seroresponse rate as a second 
immunogenicity co-primary endpoint. 
This addition has been made
in response to FDA feedback.
1.1 Synopsis 
1.3.5 Procedures for 
Participants With (Suspected) 
COVID-19 
3 OBJECTIVES AND
ENDPOINTS
8.4 Virology Assessments
Addition of sequencing of nasal swabs as an 
endpoint. 
To assess SARS-CoV-2
sequence during a confirmed
COVID-19 episode in
adolescents.
1.1 Synopsis 
3 OBJECTIVES AND 
ENDPOINTS  
Assessment of cellular and humoral immune 
response, and correlation between binding 
antibodies to SARS-CoV-2 have been moved 
from a secondary objective to an exploratory 
objective. Assessment of humoral immune 
response at all blood collection timepoints will 
Assessment of cellular
immune responses have been
moved to exploratory
endpoints as this assessment is
no longer conditional for dose
selection and recruitment of
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
153
Status: Approved, Date: 15 Aug 2022
Section Number 
and Name
Description of Change 
Brief Rationale
be performed in a subset of participants 
the Expansion Cohort.
Assessment of humoral
immune responses at all time
points in a subset of
participants was added in
response to FDA feedback to
assess kinetics and persistence
of humoral immune responses
post vaccination.
1.1 Synopsis 
8.1.1 Immunogenicity 
Assessments
Addition of “epigenetic sequencing” as a form 
of sequencing analysis. 
To allow greater flexibility in
the analysis methods.
1.1 Synopsis 
9 STATISTICAL 
CONSIDERATIONS
9.1 Statistical Hypotheses
Updated the Decision Tree-based Hypothesis 
Testing figure. 
Update due to the change in
study design.
1.1 Synopsis 
9 STATISTICAL 
CONSIDERATIONS
Sample size justification for Part 1 and Part 2 
Update due to the change in
study design.
1.1 Synopsis 
8.1.1 Immunogenicity 
Assessments
Update to the Summary of Humoral 
Immunogenicity Assays 
Clarification due to the change
in study design.
1.3.5 Procedures for 
Participants With (Suspected) 
COVID-19 
Clarification in the footnotes that central 
laboratory testing of nasal swabs for
SARS-CoV-2 infection will be done only after
a local positive test.
Clarification.
1.3.5 Procedures for 
Participants With (Suspected) 
COVID-19 
8 STUDY ASSESSMENTS 
AND PROCEDURES
Additional information added to support 
procedures in case a participant cannot attend 
the study site due to COVID-19. 
Clarification of procedures in
case of travel restrictions due
to the ongoing COVID-19
pandemic.
1.3.5 Procedures for 
Participants With (Suspected) 
COVID-19 
8 STUDY ASSESSMENTS 
AND PROCEDURES  
Clarification that adolescent self-sample 
collection is only ‘if feasible’ to indicate that if 
sites cannot support collection of the samples
from the participants home, health care
professional visits will be needed.
Alignment with other Phase 3
protocols.
2 INTRODUCTION  
11 REFERENCES  
Correction of reference citation and inclusion 
of 14 references in the list of references.
Correction.
1.3.1 Part 1: Dose Selection 
Cohort 
1.3.2 Part 2: 1-dose Regimen 
(Active and Placebo Groups) 
1.3.3 Part 2: 2-dose Regimen 
(Active and Placebo Groups)
4.2.1 Study-Specific Ethical
Design Considerations
8 STUDY ASSESSMENTS
AND PROCEDURES
The blood draw volumes have been updated for 
adolescents 12 to 17 years of age. 
Update to the blood draw
volumes based on regulatory
guidelines applicable for
pediatric participants 12 to
17years of age.
5.2 Exclusion Criteria 
7.1 Discontinuation of Study 
Vaccination  
Addition of an exclusion criterion and reason 
for discontinuation for capillary leak syndrome 
(CLS).
Based on emerging
postmarketing safety data.
5.2 Exclusion Criteria 
Addition of an exclusion criterion specific for 
Part 1 that excludes participants who are 
seropositive for SARS-CoV-2 antibodies 
In Part 1 (Dose Selection
Cohort), all participants must
be seronegative at baseline for
SARS-CoV-2 antibodies.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
154
Status: Approved, Date: 15 Aug 2022
Section Number 
and Name
Description of Change 
Brief Rationale
5.2 Exclusion Criteria 
Addition of an exclusion criterion for 
participants with a history of blood dyscrasias, 
autoimmune disease, or on medication that can
lead to dyscrasias or thrombotic events.
This addition has been made
in response to FDA feedback.
5.2 Exclusion Criteria 
Addition of an exclusion criterion for 
participants with a history of any serious, 
chronic, or progressive neurological disorders
or seizures including Guillain-Barré syndrome.
This addition has been made
in response to FDA feedback.
6.3 Measures to Minimize 
Bias: Randomization and
Blinding
Removal of “site” as a stratification item. 
Correction.
6.8 Prestudy and 
Concomitant Therapy  
Wording is added to stipulate that the 
administration of any vaccines other than the
study vaccine must be recorded.
Clarification.
10.1 Appendix 1: 
Abbreviations and 
Definitions
Reference to a paper format as an alternative of 
the eCOA has been removed. 
A paper format of the eCOA is
not available.
10.9.1.1 Case Definition for 
Moderate to Severe/Critical 
COVID-19
Update to case definitions for moderate and 
severe COVID-19. 
Update based on emerging
data.
Throughout the protocol 
Minor grammatical, formatting, or spelling 
changes were made.
Minor errors were noted.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
155
Status: Approved, Date: 15 Aug 2022
11. 
REFERENCES
Agrawal AS (2016), Tao X, Algaissi A, et al. Immunization with inactivated Middle East Respiratory Syndrome
coronavirus vaccine leads to lung immunopathology on challenge with live virus. Hum Vaccin Immunother.
2016;12(9):2351-2356.
Ahmed M (2020), Advani S, Moreira A, et al. Multisystem inflammatory syndrome in children: A systematic
review. EClinicalMedicine. 2020 Sep;26:100527.
American Academy of Pediatrics (AAP 2020). Multisystem Inflammatory Syndrome in Children (MIS-C) Interim
Guidance. https://services.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/clinical-
guidance/multisystem-inflammatory-syndrome-in-children-mis-c-interim-guidance/. Accessed 18 June 2021.
American Society of Hematology (ASH 2021). COVID-19 resources. Thrombosis with Thrombocytopenia
Syndrome (also termed Vaccine-induced Thrombotic Thrombocytopenia). https://www.hematology.org/covid-
19/vaccine-induced-immune-thrombotic-thrombocytopenia. Accessed: 27 April 2021.
Anderson EJ (2020), Campbell JD, Creech CB, et al. Warp Speed for COVID-19 Vaccines: Why are Children Stuck
in Neutral? Clin Infect Dis. 2020:ciaa1425. Epub ahead of print. PMID: 32945335.
Anywaine Z (2019), Whitworth H, Kaleebu P, et al. Safety and Immunogenicity of a 2-Dose Heterologous
Vaccination Regimen With Ad26.ZEBOV and MVA-BN-Filo Ebola Vaccines: 12-Month Data From a Phase 1
Randomized Clinical Trial in Uganda and Tanzania. J Infect Dis. 2019;220(1):46-56.
Barouch DH (2013), Liu J, Peter L, et al. Characterization of humoral and cellular immune responses elicited by a
recombinant adenovirus serotype 26 HIV-1 Env vaccine in healthy adults (IPCAVD 001). J Infect Dis.
2013:207(2);248-256.
Barouch DH (2018), Tomaka FL, Wegmann F, et al. Evaluation of a mosaic HIV-1 vaccine in a multicentre,
randomised, double-blind, placebo-controlled, phase 1/2a clinical trial (APPROACH) and in rhesus monkeys (NHP
13-19). Lancet. 2018;392(10143):232-243.
Berry JD (2004), Jones S, Drebot MA, et al. Development and characterization of neutralising monoclonal antibody
to the SARS-coronavirus. J Virol Methods. 2004;120(1):87-96.
Bisht H (2004), Roberts A, Vogel L, et al. Severe acute respiratory syndrome coronavirus spike protein expressed by
attenuated vaccinia virus protectively immunizes mice. Proc Natl Acad Sci USA. 2004;101(17):6641-6646.
Bolles M (2011), Deming D, Long K, et al. A double-inactivated severe acute respiratory syndrome coronavirus
vaccine provides incomplete protection in mice and induces increased eosinophilic proinflammatory pulmonary
response upon challenge. J Virol. 2011;85(23):12201-12215.
Brighton Collaboration (BC 2021). 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.
British Society for Haematology. (BSH 2021) Guidance produced from the Expert Haematology Panel (EHP)
focussed on Covid-19 Vaccine induced Thrombosis and Thrombocytopenia (VITT). https://b-s-
h.org.uk/media/19530/guidance-version-13-on-mngmt-of-thrombosis-with-thrombocytopenia-occurring-after-c-19-
vaccine 20210407.pdf. Version 1.3; 7 April 2021. Accessed: 27 April 2021.
Buchholz UJ (2004), Bukreyev A, Yang L, et al. Contributions of the structural proteins of severe acute respiratory
syndrome coronavirus to protective immunity. Proc Natl Acad Sci USA. 2004;101(26):9804-9809.
Bukreyev A (2004), Lamirande EW, Buchholz UJ, et al. Mucosal immunisation of African green monkeys
(Cercopithecus aethiops) with an attenuated parainfluenza virus expressing the SARS coronavirus spike protein for
the prevention of SARS. Lancet. 2004;363(9427):2122-2127.
Center 
for 
Disease 
Control 
and 
Prevention 
(CDC 
2020b). 
Symptoms 
of 
Coronavirus.
https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html. Accessed 21 January 2021.
Center for Disease Control and Prevention (CDC 2020c). Coronavirus Disease 2019 (COVID-19) Groups at Increased
Risk for Severe Illness. https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/groups-at-higher-
risk.html. Accessed 21 January 2021.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
156
Status: Approved, Date: 15 Aug 2022
Centers for Disease Control and Prevention (CDC 2020d) guidelines on Evaluation and Management Considerations
for Neonates at risk for COVID-19. https://www.cdc.gov/coronavirus/2019-ncov/hcp/caring-for-newborns.html.
Accessed 21 January 2021.
Center for Disease Control and Prevention (CDC 2020e). COVID-19 Response Team. Coronavirus disease 2019 in
children - United States, February 12–April 2, 2020. Morb Mortal Wkly Rep 2020;69(14):422–426.
Center for Disease Control and Prevention (CDC 2020g). Multisystem Inflammatory Syndrome in Children (MIS-
C) Associated with Coronavirus Disease 2019 (COVID-19). https://emergency.cdc.gov/han/2020/han00432.asp.
Accessed 21 January 2021.
Center for Disease Control and Prevention (CDC 2020h). Transcript - CDC Media Telebriefing: Update on COVID-
19. https://www.cdc.gov/media/releases/2020/t0309-covid-19-update.html. Accessed 21 January 2021.
Centers for Disease Control and Prevention (CDC 2020i), National Center for Health Statistics. CDC growth charts:
United States. http://www.cdc.gov/growthcharts/. Accessed 21 January 2021.
Center for Disease Control and Prevention (CDC 2020j). Coronavirus Disease 2019 (COVID-19) Symptoms of
Coronavirus. https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html. Accessed 21 January
2021.
Center for Disease Control and Prevention (CDC 2020k). Infographic: Early Cases of MIS-C: Multi-System
Inflammatory Syndrome in U.S. Children. https://www.cdc.gov/coronavirus/2019-ncov/covid-data/infographic-mis-
c.html. Accessed 11 June 2021.
Center for Disease Control and Prevention (CDC 2020l). Multisystem Inflammatory Syndrome in Children (MIS-C)
Associated with Coronavirus Disease 2019 (COVID-19). https://emergency.cdc.gov/han/2020/han00432.asp.
Accessed 18 June 2021.
Centers for Disease Control and Prevention (CDC 2021a). Cases of cerebral venous sinus thrombosis with
thrombocytopenia after receipt of the Johnson & Johnson COVID-19 Vaccine. 13 April 2021.
https://emergency.cdc.gov/han/2021/han00442.asp. Accessed: 27 April 2021.
Centers for Disease Control and Prevention (CDC 2021b). Selected Adverse Events Reported after COVID-19
Vaccination. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/adverse-events.html. Accessed 17 June
2021.
Chen Z (2005), Zhang L, Qin C, et al. Recombinant modified vaccinia virus Ankara expressing the spike
glycoprotein of severe acute respiratory syndrome coronavirus induces protective neutralizing antibodies primarily
targeting the receptor binding region. J Virol. 2005;79(5):2678-2688.
Chen N (2020), Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel
coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507-513.
Chin J (1969), Magoffin RL, Shearer LA, Schieble JH, Lennette EH. Field evaluation of a respiratory syncytial virus
vaccine and a trivalent parainfluenza virus vaccine in a pediatric population. Am J Epidemiol. 1969;89(4);449-463.
Colby DJ (2020), Sarnecki M, Barouch DH, et al. Safety and immunogenicity of Ad26 and MVA vaccines in
acutely treated HIV and effect on viral rebound after antiretroviral therapy interruption. Nat Med. 2020;26(4):498-
501.
Collins JP (2019), Campbell AP, Openo K, et al. Clinical features and outcomes of immunocompromised children
hospitalized with laboratory-confirmed influenza in the United States, 2011–2015. J Pediatric Infect Dis Soc
2019;8:539–49.
Coronaviridae Study Group of the International Committee on Taxonomy of Viruses (2020). The species Severe
acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol.
2020;5(4):536-544.
Deming D (2006), Sheahan T, Heise M, et al. Vaccine efficacy in senescent mice challenged with recombinant
SARS-CoV bearing epidemic and zoonotic spike variants. PLoS Med. 2006;3(12):e525.
Division of Microbiology and Infectious Diseases (DMID) Pediatric Toxicity Tables November 2007 Draft.
https://www.niaid.nih.gov/sites/default/files/dmidpedtox.pdf. Accessed 21 January 2021.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
157
Status: Approved, Date: 15 Aug 2022
Dong Y (2020), Mo X, Hu Y, et al. Epidemiological Characteristics of 2143 Pediatric Patients With 2019
Coronavirus Disease in China. Pediatrics. 2020. Epub ahead of print.
European Centre for Disease Prevention and Control (2020b). Latest evidence on COVID-19.
https://www.ecdc.europa.eu/en/covid-19/latest-evidence. Accessed 21 January 2021.
European Centre for Disease Prevention and Control (2020c). Rapid Risk Assessment: Paediatric inflammatory
multisystem syndrome and SARS-CoV-2 infection in children. https://www.ecdc.europa.eu/en/publications-
data/paediatric-inflammatory-multisystem-syndrome-and-sars-cov-2-rapid-risk-assessment. Accessed 21 January
2021.
European Medicines Agency (EMA) (2017). Ethical considerations for clinical trials on medicinal products
conducted with minors: Recommendations of the expert group on clinical trials for the implementation of
Regulation (EU) No 536/2014 on clinical trials on medicinal products for human use, Revision 1, 18 September
2017. https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-
10/2017 09 18 ethical consid ct with minors.pdf. Accessed 21 January 2021.
European Parliament (EU 2008). Ethical considerations for clinical trials on medicinal products conducted with the
paediatric population. Recommendations of the ad hoc group for the development of implementing guidelines for
Directive 2001/20EC relating to good clinical practice in the conduct of clinical trials on medicinal products for
human use. 2008. http://ec.europa.eu/health//sites/health/files/files/eudralex/vol-10/ethical considerations en.pdf.
Accessed 21 January 2021.
Faber M (2005), Lamirande EW, Roberts A, et al. A single immunization with a rhabdovirus-based vector
expressing severe acute respiratory syndrome coronavirus (SARS-CoV) S protein results in the production of high
levels of SARS-CoV-neutralizing antibodies. J Gen Virol. 2005;86(Pt 5):1435-1440.
Feldstein LR (2020), Rose EB, Horwitz SM, et al. Multisystem Inflammatory Syndrome in U.S. Children and
Adolescents. N Engl J Med. 2020;383(4):334-346.
Fleming S (2011), Thompson M, Stevens R, et al. Normal ranges of heart rate and respiratory rate in children from
birth to 18 years of age: a systematic review of observational studies. Lancet. 2011;377(9770):1011-1018.
Fulginiti VA (1969), Eller JJ, Sieber OF, Joyner JW, Minamitani M, Meiklejohn G. Respiratory virus immunization.
I. A field trial of two inactivated respiratory virus vaccines; an aqueous trivalent parainfluenza virus vaccine and an
alum-precipitated respiratory syncytial virus vaccine. Am J Epidemiol. 1969:89(4);435-448.
Garg S (2020), Kim L, Whitaker M, et al. Hospitalization rates and characteristics of patients hospitalized with
laboratory-confirmed coronavirus disease 2019 — COVID-NET, 14 States. Morb Mortal Wkly Rep.
2020;69(15):458–464.
Golan-Tripto I (2018), Goldbart A, Akel K, Dizitzer Y, Novack V, Tal A. Modified Tal Score: Validated score for
prediction of bronchiolitis severity. Pediatr Pulmonol. 2018;53(6):796-801.
Goldstein B (2005), Giroir B, Randolph A, International Consensus Conference on Pediatric Sepsis. International
pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care
Med. 2005;6(1):2-8.
Goyal MK (2020), Simpson JN, Boyle MD, et al. Racial/Ethnic and Socioeconomic Disparities of SARS-CoV-2
Infection Among Children. Pediatrics. 2020;146(4):e2020009951.
Guan WJ (2020), Ni ZY, Hu Y, et al, for the China Medical Treatment Expert Group for Covid-19. Clinical
Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020;382:1708-1720.
Heald-sargent T (2020), Muller WJ, Zheng X, Rippe J, Patel AB, Kociolek LK. Age-Related Differences in
Nasopharyngeal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Levels in Patients With Mild to
Moderate Coronavirus Disease 2019 (COVID-19). JAMA Pediatr. 2020;174(9):902-903.
Henderson LA (2020), Canna SW, Friedman KG, et al. American College of Rheumatology Clinical Guidance for
Multisystem Inflammatory Syndrome in Children Associated With SARS-CoV-2 and Hyperinflammation in
Pediatric COVID-19: Version 1. Arthritis Rheumatol. 2020 Nov;72(11):1791-1805
Honda-okubo Y (2015), Barnard D, Ong CH, Peng BH, Tseng CT, Petrovsky N. Severe acute respiratory syndrome-
associated coronavirus vaccines formulated with delta inulin adjuvants provide enhanced protection while
ameliorating lung eosinophilic immunopathology. J Virol. 2015;89(6):2995-3007.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
158
Status: Approved, Date: 15 Aug 2022
Houser KV (2017), Broadbent AJ, Gretebeck L, et al. Enhanced inflammation in New Zealand white rabbits when
MERS-CoV reinfection occurs in the absence of neutralizing antibody. PLoS Pathog. 2017;13(8):e1006565.
Howie SR (2011). Blood sample volumes in child health research: review of safe limits. Bull World Health Organ.
2011;89:46-53.
Investigator’s Brochure: Ad26COV2.S (VAC31518), Edition 6.0. Janssen Vaccines & Prevention B.V. (May 2022).
Janssen Vaccines & Prevention B.V. Data on file.
Johns Hopkins CSSE (2021). Coronavirus COVID-19 Global Cases. Available from:
https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6.
Accessed 21 January 2021.
Kapikian AZ (1969), Mitchell RH, Chanock RM, Shvedoff RA, Stewart CE. An epidemiologic study of altered
clinical reactivity to respiratory syncytial (RS) virus infection in children previously vaccinated with an inactivated
RS virus vaccine. Am J Epidemiol. 1969:89(4);405-421.
Kim HW (1969), Canchola JG, Brandt CD, et al. Respiratory syncytial virus disease in infants despite prior
administration of antigenic inactivated vaccine. Am J Epidemiol. 1969:89(4);422-434.
Kim L (2020), Whitaker M, O'Halloran A, et al. Hospitalization Rates and Characteristics of Children Aged <18
Years Hospitalized with Laboratory Confirmed COVID-19 - COVID-NET, 14 States, March 1-July 25, 2020.
Mmwr 2020; 69(32): 1081-1088.
LaRovere KL (2021), Riggs BJ, Poussaint TY, et al. Neurologic Involvement in Children and Adolescents
Hospitalized in the United States for COVID-19 or Multisystem Inflammatory Syndrome. JAMA Neurol.
2021;78(5):536–547.
Letko M (2020), Marzi A, Munster V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and
other lineage B betacoronaviruses. Nat Microbiol. 2020:5:562–569.
Li Q (2020), Guan X, Wu P, et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected
Pneumonia. N Engl J Med. 2020;382(13):1199-1207.
Linton NM (2020), Kobayashi T, Yang Y, et al. Incubation Period and Other Epidemiological Characteristics of
2019 Novel Coronavirus Infections with Right Truncation: A Statistical Analysis of Publicly Available Case Data. J
Clin Med. 2020;9(2):1-9.
Lopez A (2020), Hill M, Antezano J, et al. Transmission Dynamics of COVID-19 Outbreaks Associated with Child
Care Facilities — Salt Lake City, Utah, April–July 2020. MMWR Morb Mortal Wkly Rep. 2020:69(37);1319–1323
Lu R (2020), Zhao X, Li J, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus:
implications for virus origins and receptor binding. Lancet. 2020 Jan 30. pii: S0140-6736(20)30251-30258.
Mantovani A (2020), Rinaldi E, Zusi C, et al. Coronavirus disease 2019 (COVID19) in children and/or adolescents:
a meta-analysis. Pediatr Res. 2020: https://doi.org/10.1038/s41390-020-1015-2. [Epub ahead of print]
Marcy SM (2004), Kohl KS, Dagan R, et al./The Brighton Collaboration Fever Working Group. Fever as an adverse
event following immunization: case definition and guidelines of data collection, analysis, and presentation. Vaccine
2004:22(5-6);551-556.
Meena J (2020), Yadav J, Saini L, Yadav A, Kumar J. Clinical Features and Outcome of SARS-CoV-2 Infection in
Children: A Systematic Review and Meta-analysis. Indian Pediatrics. 2020:57(9):820-826.
Milligan ID (2016), Gibani MM, Sewell R, et al. Safety and immunogenicity of novel adenovirus type 26- and
modified vaccinia ankara-vectored ebola vaccines: a randomized clinical trial. JAMA. 2016:315;1610-1623.
Moghaddam A (2006), Olszewska W, Wang B, et al. A potential molecular mechanism for hypersensitivity caused
by formalin-inactivated vaccines. Nat Med. 2006:12(8);905-907.
Modjarrad K (2019), Roberts CC, Mills KT, et al. Safety and immunogenicity of an anti-Middle East respiratory
syndrome coronavirus DNA vaccine: a phase 1, open-label, single-arm, dose-escalation trial. Lancet Infect Dis.
2019;19(9):1013-1022.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
159
Status: Approved, Date: 15 Aug 2022
Mutua G (2019), Anzala O, Luhn K, et al. Safety and Immunogenicity of a 2-Dose Heterologous Vaccine Regimen
With Ad26.ZEBOV and MVA-BN-Filo Ebola Vaccines: 12-Month Data From a Phase 1 Randomized Clinical Trial
in Nairobi, Kenya. J Infect Dis. 2019;220(1):57-67.
Peplow C (2019), Assfalg R, Beyerlein A, Hasford J, Bonifacio E, Ziegler -G. Blood draws up to 3% of blood
volume in clinical trials are safe in children. Acta Paediatrica 2019;108:940-944.
Sadoff J (2021a), Le Gars M, Shukarev G, et al. Interim Results of a Phase 1-2a Trial of Ad26.COV2.S Covid-19
Vaccine. N Engl J Med. Published online January 13, 2021:NEJMoa2034201.
Salisch NC (2019), Izquierdo gil A, Czapska-casey DN, et al. Adenovectors encoding RSV-F protein induce durable
and mucosal immunity in macaques after two intramuscular administrations. NPJ Vaccines. 2019;4:54.
Smatti MK (2018), Al Thani AA, Yassine HM. Viral-Induced Enhanced Disease Illness. Front Microbiol.
2018;9:2991.
Stephenson KE (2020), Wegmann F, Tomaka F, et al. Comparison of shortened mosaic HIV-1 vaccine schedules: a
randomised, double-blind, placebo-controlled phase 1 trial (IPCAVD010/HP×1002) and a preclinical study in rhesus
monkeys (NHP 17-22). Lancet HIV. 2020; Erratum in: Lancet HIV. 2020 Feb 28.
Subbarao K (2004), Mcauliffe J, Vogel L, et al. Prior infection and passive transfer of neutralizing antibody prevent
replication of severe acute respiratory syndrome coronavirus in the respiratory tract of mice. J Virol.
2004;78(7):3572-3577.
Sui J (2005), Li W, Roberts A, et al. Evaluation of human monoclonal antibody 80R for immunoprophylaxis of
severe acute respiratory syndrome by an animal study, epitope mapping, and analysis of spike variants. J Virol.
2005;79(10):5900-5906.
UC San Diego Health (2020). Coronavirus (COVID-19) updates for UC San Diego Health patients and visitors.
Available at: https://health.ucsd.edu/coronavirus/Pages/FAQ.aspx. Accessed: 18 September 2020.
US Department of Health and Human Services (1998). Office for Human Research Protections - OHRP Expedited
Review Categories. 1998. Available from: https://www.hhs.gov/ohrp/regulations-and-policy/guidance/categories-of-
research-expedited-review-procedure-1998/index.html. Accessed 21 January 2021.
US Department of Health and Human Services (2007), Food and Drug Administration, Center for Biologics
Evaluation and Research. September 2007. Guidance for Industry. Toxicity Grading Scale for Healthy Adult and
Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. Available from:
https://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/V
accines/ucm091977.pdf. Accessed 21 January 2021.
US Food and Drug Administration (1998). Conditions for IRB Use of Expedited Review. Federal Register:
November 9, 1998 (Volume 63, Number 216). Available from: https://www.fda.gov/science-research/clinical-trials-
and-human-subject-protection/categories-research-may-be-reviewed-institutional-review-board-irb-through-
expedited-review. Accessed 21 January 2021.
US Food and Drug Administration (2019). General Clinical Pharmacology Considerations for Neonatal Studies for
Drugs and Biological Products. Guidance for Industry. August 2019. Available from:
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/general-clinical-pharmacology-
considerations-neonatal-studies-drugs-and-biological-products-guidance. Accessed 21 January 2021.
US Food and Drug Administration (2020a). COVID-19: Developing Drug and Biological Products for Treatment or
Prevention. Guidance for Industry. May 2020. Available from: https://www.fda.gov/regulatory-information/search-
fda-guidance-documents/covid-19-developing-drugs-and-biological-products-treatment-or-prevention. Accessed 21
January 2021.
US Food and Drug Administration (2020b). Development and Licensure of Vaccines to Prevent COVID-19.
Guidance for Industry. June 2020. Available from: https://www.fda.gov/media/139638/download. Accessed 21
January 2021.
van der Fits L (2020), Bolder R, Heemskerk-van der Meer M, et al. Adenovector 26 encoded prefusion
conformation stabilized RSV-F protein induces long-lasting Th1-biased immunity in neonatal mice. NPJ Vaccines.
2020;5:49.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
160
Status: Approved, Date: 15 Aug 2022
Veal GJ (2014). Blood volumes in pediatric clinical trials: a review of current regulations and guidance for research
studies. Clin Invest (Lond) 2014;4(11):1005-1011.
Verdoni L (2020), Mazza A, Gervasoni A, Martelli L et al. An outbreak ofsevere Kawasaki-like disease at the
Italian epicenter of the SARS-CoV-2 epidemic: an observational cohort study. The Lancet. 2020;395(10239):1771-
1778.
Verity R (2020), Okell LC, Dorigatti I, et al. Estimates of the severity of coronavirus disease 2019: a model-based
analysis. Lancet Infect Dis. 2020;20(6):669-677.
World Health Organization (2020a). Coronavirus disease 2019 (COVID-19) Situation Report. Available at:
https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports. Accessed: 06 October 2020.
World Health Organization (2020b). Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-
19). 
Available 
at: 
https://www.who.int/emergencies/diseases/novel-coronavirus-
2019?gclid=EAIaIQobChMIvuDQ2ZfM6QIVxPZRCh2DwguUEAAYASAAEgLP6 D BwE. Accessed: 21 January
2021.
World Health Organization (2020c). WHO Director-General's opening remarks at the media briefing on COVID-19.
11 March 2020. Available from: https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-
the-media-briefing-on-covid-19---11-march-2020.Accessed: 21 January 2021.
Widjojoatmodjo MN (2015), Bogaert L, Meek B, et al. Recombinant low-seroprevalent adenoviral vectors Ad26
and Ad35 expressing the respiratory syncytial virus (RSV) fusion protein induce protective immunity against RSV
infection in cotton rats. Vaccine. 2015;33(41):5406-5414.
Wu F (2020), Zhao S, Yu B, et al. A new coronavirus associated with human respiratory disease in China. Nature.
2020;579(7798):265-269.
Yang ZY (2004), Kong WP, Huang Y, et al. A DNA vaccine induces SARS coronavirus neutralization and
protective immunity in mice. Nature. 2004;428(6982):561-564.
Yonker LM (2020), Neilan AM, Bartsch Y, et al. Pediatric SARS-CoV-2: Clinical Presentation, Infectivity, and
Immune Responses. J Pediatr. 2020.
Zahn R (2012), Gillisen G, Roos A, et al. Ad35 and Ad26 vaccine vectors induce potent and cross-reactive antibody
and T-cell responses to multiple filovirus species. PLoS ONE. 2012;7(12):e44115.
Zhang H (2004), Wang G, Li J, et al. Identification of an antigenic determinant on the S2 domain of the severe acute
respiratory syndrome coronavirus spike glycoprotein capable of inducing neutralizing antibodies. J Virol.
2004;78(13):6938-6945.
Zhao J (2017), Alshukairi AN, Baharoon SA, et al. Recovery from the Middle East respiratory syndrome is
associated with antibody and T-cell responses. Sci Immunol. 2017;2(14). pii: eaan5393.
Zhou T (2004), Wang H, Luo D, et al. An exposed domain in the severe acute respiratory syndrome coronavirus
spike protein induces neutralizing antibodies. J Virol. 2004;78(13):7217-7226.
Zhou P (2020), Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat
origin. Nature. 2020;579(7798):270-273.
Zumla A (2016), Chan JF, Azhar EI, Hui DS, Yuen KY. Coronaviruses - drug discovery and therapeutic options.
Nat Rev Drug Discov. 2016;15(5):327-347.
NCT05007080

VAC31518  (JNJ-78436735) 
Clinical Protocol VAC31518COV3006
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
161
Status: Approved, Date: 15 Aug 2022
INVESTIGATOR AGREEMENT
I have read this protocol and agree that it contains all necessary details for carrying out this study. I will
conduct the study as outlined herein and will complete the study within the time designated.
I will provide copies of the protocol and all pertinent information to all individuals responsible to me who
assist in the conduct of this study. I will discuss this material with them to ensure that they are fully informed
regarding the study intervention, the conduct of the study, and the obligations of confidentiality.
Coordinating Investigator (where required):
Name (typed or printed):
Institution and Address:
Signature: 
Date:
(Day Month Year)
Principal (Site) Investigator:
Name (typed or printed):
Institution and Address:
Telephone Number:
Signature: 
Date:
(Day Month Year)
Sponsor's Responsible Medical Officer:
Name (typed or printed): 
Institution: 
Janssen Vaccines & Prevention B.V.
Signature: electronic signature appended at the end of the protocol 
Date:
(Day Month Year)
Note: If the address or telephone number of the investigator changes during the study, written notification will be
provided by the investigator to the sponsor, and a protocol amendment will not be required.
NCT05007080
PPD

Signature
User 
Date 
Reason
 
15-Aug-2022
13:50:47
(GMT)
Document Approval
NCT05007080
PPD