A Randomized, Parallel-group, Placebo-controlled, Double-blind Phase 1/2a Study in Healthy HIV Uninfected Adults to Assess Safety/Tolerability and Immunogenicity of 2 Different Prime/Boost Regimens: Priming With Tetravalent Ad26.Mos4.HIV and Boosting With Tetravalent Ad26.Mos4.HIV and Either Clade C gp140 Plus Adjuvant OR a Combination of Mosaic and Clade C gp140 Plus Adjuvant
Phase: PHASE1
Conditions: Healthy
Sponsor: Janssen Vaccines & Prevention B.V.

CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
1
Status: Approved, Date: 27 October 2021
Janssen Vaccines & Prevention B.V.*
Clinical Protocol
A randomized, parallel-group, placebo-controlled, double-blind Phase 1/2a study in
healthy HIV-uninfected adults to assess safety/tolerability and immunogenicity of 2
different prime/boost regimens: priming with tetravalent Ad26.Mos4.HIV and boosting
with tetravalent Ad26.Mos4.HIV and either Clade C gp140 plus adjuvant OR a
combination of Mosaic and Clade C gp140 plus adjuvant
IPCAVD-012/ HVTN 118
Protocol VAC89220HPX2003Amendment 6; Phase 1/2a
JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471585, JNJ-64219324,
JNJ-64219311, JNJ-65184340
These compounds are being investigated in Phase 1/2a clinical studies.
US sites of this study will be conducted under US Food & Drug Administration IND regulations
(21 CFR Part 312).
IND: 016263
* Janssen Vaccines & Prevention B.V. (formerly known as Crucell Holland 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.
Status: 
Approved
Date: 
27 October 2021
EDMS number: 
EDMS-ERI-112499463, 14.0
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.
NCT02935686

JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471585, JNJ-64219324, JNJ-64219311, JNJ-65184340
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Status: Approved, Date: 27 October 2021
TABLE OF CONTENTS
TABLE OF CONTENTS............................................................................................................................... 2
LIST OF ATTACHMENTS............................................................................................................................ 4
LIST OF IN-TEXT TABLES AND FIGURES................................................................................................ 5
PROTOCOL AMENDMENTS....................................................................................................................... 6
SYNOPSIS.................................................................................................................................................. 16
TIME AND EVENTS SCHEDULE .............................................................................................................. 24
TIME AND EVENTS SCHEDULE FOR OPTIONAL VECTOR SHEDDING ASSESSMENT.................... 27
TIME AND EVENTS SCHEDULE FOR THE LONG-TERM EXTENSION PHASE (FROM
WEEK72 ONWARDS, GROUP 1 AND GROUP 2).......................................................................... 28
TIME AND EVENTS SCHEDULE FOR THE LATE BOOST EXTENSION ............................................... 29
ABBREVIATIONS AND DEFINITIONS...................................................................................................... 32
1. 
INTRODUCTION................................................................................................................................ 34
1.1. 
Background.................................................................................................................................... 34
1.1.1. 
Nonclinical Studies..................................................................................................................... 34
1.1.1.1. 
Repetitive gp120/gp140 Vaccinations..................................................................................... 34
1.1.1.2. 
Ad26/gp140 and Ad26/Ad35 Vaccinations.............................................................................. 35
1.1.1.3. 
Ad26/Ad5 and Repetitive gp140 Vaccinations........................................................................ 35
1.1.1.4. 
Tetravalent Ad26 Vaccinations................................................................................................ 35
1.1.1.5. 
Mosaic gp140 Vaccinations..................................................................................................... 35
1.1.2. 
Clinical Studies........................................................................................................................... 36
1.1.2.1. 
Prototypes and Similar Vaccines............................................................................................. 36
1.1.2.2. 
Current Studies........................................................................................................................ 38
1.1.2.3. 
Clinical Safety Experience With the Ad26.COV2.S Vaccine................................................... 40
1.2. 
Benefit/Risk Section....................................................................................................................... 41
1.2.1. 
Known Benefits........................................................................................................................... 41
1.2.2. 
Potential Benefits........................................................................................................................ 41
1.2.3. 
Known Risks............................................................................................................................... 41
1.2.4. 
Potential Risks............................................................................................................................ 42
1.2.5. 
Overall Benefit/Risk Assessment ............................................................................................... 43
1.3. 
Overall Rationale for the Study...................................................................................................... 45
2. 
OBJECTIVES, ENDPOINTS, AND HYPOTHESIS........................................................................... 45
2.1. 
Objectives and Endpoints.............................................................................................................. 45
2.2. 
Hypothesis..................................................................................................................................... 47
3. 
STUDY DESIGN AND RATIONALE................................................................................................. 47
3.1. 
Overview of Study Design.............................................................................................................. 47
3.2. 
Study Design Rationale.................................................................................................................. 50
4. 
SUBJECT POPULATION.................................................................................................................. 52
4.1. 
Inclusion Criteria for the Main Study.............................................................................................. 53
4.2. 
Exclusion Criteria for the Main Study............................................................................................. 55
4.3. 
Prohibitions and Restrictions......................................................................................................... 57
4.4. 
Inclusion and Exclusion Criteria for the Long-term Extension Phase............................................ 58
4.5. 
Inclusion Criteria, Exclusion Criteria and Prohibitions and Restrictions for the Late Boost
Vaccination..................................................................................................................................... 59

JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471585, JNJ-64219324, JNJ-64219311, JNJ-65184340
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Status: Approved, Date: 27 October 2021
5. 
TREATMENT ALLOCATION AND BLINDING................................................................................. 61
6. 
DOSAGE AND ADMINISTRATION .................................................................................................. 63
7. 
TREATMENT COMPLIANCE............................................................................................................ 64
8. 
PRESTUDY AND CONCOMITANT MEDICATION........................................................................... 64
9. 
STUDY EVALUATIONS.................................................................................................................... 66
9.1. 
Study Procedures........................................................................................................................... 66
9.1.1. 
Overview..................................................................................................................................... 66
9.1.2. 
Visit Windows............................................................................................................................. 67
9.1.3. 
Screening Phase (Week -6 to 0)................................................................................................ 68
9.1.4. 
Vaccination ................................................................................................................................. 70
9.1.5. 
Post-vaccination Follow-up Phase ............................................................................................. 71
9.1.6. 
Second Year Follow-up Phase ................................................................................................... 73
9.1.7. 
Early Withdrawal/Exit Visit.......................................................................................................... 73
9.1.8. 
Vector Shedding Evaluations..................................................................................................... 73
9.1.9. 
Long-term Extension Phase ....................................................................................................... 74
9.1.10. 
Late Boost Vaccination............................................................................................................... 74
9.2. 
Immunogenicity Evaluations.......................................................................................................... 77
9.3. 
Safety Evaluations......................................................................................................................... 77
9.4. 
Human Immunodeficiency Virus Testing and Vaccine Induced Seropositivity.............................. 82
9.4.1. 
HIV Testing ................................................................................................................................. 82
9.4.2. 
Management of Subjects who Become HIV-infected During the Study..................................... 82
9.4.3. 
VISP............................................................................................................................................ 82
9.4.4. 
Social Impact .............................................................................................................................. 83
9.5. 
Sample Collection and Handling.................................................................................................... 83
10. SUBJECT COMPLETION/DISCONTINUATION OF STUDY TREATMENT/ WITHDRAWAL
FROM THE STUDY........................................................................................................................... 84
10.1. 
Completion ..................................................................................................................................... 84
10.2. 
Discontinuation of Study Treatment/Withdrawal from the Study ................................................... 84
10.3. 
Contraindications to Vaccination.................................................................................................... 86
10.4. 
Withdrawal From the Use of Samples in Future Research............................................................ 86
11. STATISTICAL METHODS................................................................................................................. 86
11.1. 
Subject Information ........................................................................................................................ 86
11.2. 
Analysis Populations...................................................................................................................... 86
11.3. 
Sample Size Determination ........................................................................................................... 87
11.4. 
Immunogenicity Analyses.............................................................................................................. 87
11.5. 
Safety Analyses............................................................................................................................. 88
11.6. 
Analysis Time Points...................................................................................................................... 89
11.7. 
Protocol Safety Review Team........................................................................................................ 89
11.8. 
Data Review Committee ................................................................................................................ 90
11.9. 
Study Holding Rules....................................................................................................................... 90
12. AE REPORTING................................................................................................................................ 92
12.1. 
Definitions...................................................................................................................................... 93
12.1.1. 
AE Definitions and Classifications.............................................................................................. 93
12.1.2. 
Attribution Definitions.................................................................................................................. 94
12.1.3. 
Severity Criteria .......................................................................................................................... 94
12.2. 
Situations Requiring Special Notification ....................................................................................... 95
12.3. 
Procedures..................................................................................................................................... 96
12.3.1. 
All AEs........................................................................................................................................ 96
12.3.2. 
SAEs........................................................................................................................................... 97
12.3.3. 
Adverse Events of Special Interest............................................................................................. 98
12.3.3.1. 
HIV Infection ............................................................................................................................ 98

JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471585, JNJ-64219324, JNJ-64219311, JNJ-65184340
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Status: Approved, Date: 27 October 2021
12.3.3.2. 
Thrombosis with Thrombocytopenia Syndrome...................................................................... 99
12.3.4. 
Pregnancy................................................................................................................................. 100
12.4. 
Contacting Sponsor Regarding Safety......................................................................................... 100
13. PRODUCT QUALITY COMPLAINT HANDLING............................................................................ 100
13.1. 
Procedures................................................................................................................................... 101
13.2. 
Contacting Sponsor Regarding Product Quality.......................................................................... 101
14. VACCINE INFORMATION .............................................................................................................. 101
14.1. 
Physical Description of Vaccines................................................................................................. 101
14.2. 
Packaging and Labeling............................................................................................................... 103
14.3. 
Preparation, Handling, and Storage............................................................................................. 103
14.4. 
Vaccine Accountability................................................................................................................. 103
15. STUDY-SPECIFIC MATERIALS..................................................................................................... 104
16. ETHICAL ASPECTS....................................................................................................................... 104
16.1. 
Study-specific Design Considerations......................................................................................... 104
16.2. 
Regulatory Ethics Compliance..................................................................................................... 105
16.2.1. 
Investigator Responsibilities..................................................................................................... 105
16.2.2. 
Independent Ethics Committee or Institutional Review Board................................................. 105
16.2.3. 
Informed Consent ..................................................................................................................... 107
16.2.4. 
Privacy of Personal Data .......................................................................................................... 108
16.2.5. 
Long-term Retention of Samples for Additional Future Research............................................ 109
17. ADMINISTRATIVE REQUIREMENTS............................................................................................ 109
17.1. 
Protocol Clarification Communications........................................................................................ 109
17.2. 
Protocol Amendments.................................................................................................................. 109
17.3. 
Regulatory Documentation .......................................................................................................... 110
17.3.1. 
Regulatory Approval/Notification .............................................................................................. 110
17.3.2. 
Required Prestudy Documentation........................................................................................... 110
17.4. 
Subject Identification, Enrollment, and Screening Logs.............................................................. 111
17.5. 
Source Documentation................................................................................................................. 111
17.6. 
Case Report Form Completion .................................................................................................... 112
17.7. 
Data Quality Assurance/Quality Control ...................................................................................... 112
17.8. 
Record Retention ......................................................................................................................... 113
17.9. 
Monitoring .................................................................................................................................... 113
17.10. Study Completion/Termination..................................................................................................... 114
17.10.1. Study Completion/End of Study................................................................................................ 114
17.10.2. Study Termination..................................................................................................................... 114
17.11. On-Site Audits.............................................................................................................................. 114
17.12. Use of Information and Publication .............................................................................................. 115
18. COVID-19 APPENDIX: GUIDANCE ON STUDY CONDUCT DURING THE COVID-19
PANDEMIC...................................................................................................................................... 117
REFERENCES.......................................................................................................................................... 119
INVESTIGATOR AGREEMENT............................................................................................................... 149
LIST OF ATTACHMENTS
Attachment 1: 
Division of Aids Table for Grading the Severity of Adult and Pediatric AEs –
Including Modifications............................................................................................................ 121
Attachment 2: 
HIV-risk Assessment.................................................................................................... 143
Attachment 3: 
Test of Understanding.................................................................................................. 146
Attachment 4: 
Social Impact Questionnaire........................................................................................ 147
Attachment 5: 
Thrombotic Events to be Reported as Potential AESIs............................................... 148

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Status: Approved, Date: 27 October 2021
LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1: 
Schematic Overview of the Main Study.................................................................................... 49
Table 2: 
Schematic Overview of the Late Boost Vaccination ................................................................. 50
Table 3: 
Description of Interventions...................................................................................................... 64
Table 4: 
AE Notification and Safety Pause/AE Review Rules1............................................................... 91
FIGURES
Figure 1: GMR (95% CI) of the Clade C+ Mos gp140 /Clade C gp140 Groups (Pooling
VAC89220HPX2003-VAC89220HPX2004).............................................................................. 52

JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471585, JNJ-64219324, JNJ-64219311, JNJ-65184340
Clinical Protocol Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 27 October 2021
PROTOCOL AMENDMENTS
Protocol Version 
Issue Date
Original Protocol 
29 Feb 2016
Amendment 1 
02 Dec 2016
Amendment 2 
12 Feb 2018
Amendment 3 
6 Feb 2020
Amendment 4 
23 July 2020
Amendment 5 
21 May 2021
Amendment 6 
This document
Amendments below are listed beginning with the most recent amendment.
Amendment 6 (This document)
The overall reason for the amendment: Upon request of the Center for Biologics Evaluation and Research
(CBER), it is specified that a serum sampling for a PF4 antibody ELISA test should be performed in case of a
potential AESI of TTS, if possible, and that a test for anti-PF4 will also be performed on a stored pre-vaccination
sample, if possible. Additional changes are listed below.
Rationale: Upon request of CBER, it is specified that a serum sampling for a PF4 antibody ELISA test should be
performed in case of a potential AESI of TTS, if possible, and that a test for anti-PF4 will also be performed on a
stored pre-vaccination sample, if possible.
TIME AND EVENTS SCHEDULE FOR THE LATE BOOST EXTENSION
9.3 Safety Evaluations
12.3.3.2 Thrombosis with Thrombocytopenia Syndrome
Rationale: Align wording on TTS with changes in TTS wording in the Ad26.Mos(4).HIV Investigator’s Brochure
Edition 8 Addendum 1, dated 19 Oct 2021, that were made on request of CBER:
- The qualitative statement of ‘very rare’ incidences of TTS was replaced by reporting ratios.
- It was added that cases of venous thrombosis have also occurred at more common sites, eg, lower
extremities.
- Onset of symptoms was changed from 1 to 2 weeks to 1 to 4 weeks, and sometimes even  later after
vaccination (up to 42 days as per the American Society of Hematology).
- Added that these events have also occurred in men and in individuals older than 60 years.
- Changed statement that TTS ‘can be fatal’ to ‘has been fatal in some cases’.
- Added that participants should also be instructed to report any leg pain, changes in mental status or the
occurrence of seizures.
ABBREVIATIONS AND DEFINITIONS
1.1.2.3 Clinical Safety Experience With the Ad26.COV2.S Vaccine
12.3.3.2 Thrombosis with Thrombocytopenia Syndrome
REFERENCES
Rationale: For consistency with the definitions of thrombocytopenia of the CDC, Brighton Collaboration and
Medicines and Healthcare products Regulatory Agency, which do not include symptomatology, ‘symptomatic
thrombocytopenia’ was replaced by ‘thrombocytopenia’ in the definition of TTS in this protocol.
SYNOPSIS
1.2.5 Overall Benefit/Risk Assessment
3.1 Overview of Study Design
9.3 Safety Evaluations
12.3.1 All AEs
12.3.3.2 Thrombosis with Thrombocytopenia Syndrome
Rationale: The reference to the Brighton Collaboration case definition of thrombotic events and thrombocytopenia
was updated.
REFERENCES

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Clinical Protocol Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 27 October 2021
Rationale: Clarified that no specific AESI form is present in the eCRF, but rather is a checkbox to indicate if an
AE is a potential AESI.
12.3.3 Adverse Events of Special Interest
Rationale: Clarified that TTS is reported using the SAE form and not a separate or different AESI specific form.
12.3.3.2 Thrombosis with Thrombocytopenia Syndrome
Rationale: For consistency with a request from an ethics committee in one of the other studies of the HIV Vaccine
program, it was clarified that any postnatal sequelae in an infant will be collected if possible.
12.3.4 Pregnancy
Rationale: The background section of the protocol has been updated with a summary of the HPX2008/HVTN 705
results.
1.1.2.2 Current Studies
REFERENCES
Rationale: Clarified that a blood draw will be needed for the central HIV testing. The footnote stating ‘no extra
blood required’ has been removed. As a result, the overall blood volume throughout the late boost extension phase
was updated.
TIME AND EVENTS SCHEDULE FOR THE LATE BOOST EXTENSION
9.1.1 Overview
16.1 Study-specific Design Considerations
Amendment 5 (21 May 2021)
The overall reason for the amendment: This amendment has been created to provide information and guidance
for investigators on signs and symptoms and on medical management should very rare events of thrombosis with
thrombocytopenia syndrome (TTS) occur, as observed in another Ad26-based vaccine program (Ad26.COV2.S,
COVID-19 vaccine). The Ad26.Mos4.HIV vaccine uses the same Ad26 vector as Ad26.COV2.S, but has different
transgene inserts. To date, no cases of TTS have been reported in Janssen’s Ad26.Mos4.HIV clinical studies nor in
any other Ad26-based non-COVID-19 vaccine programs from Janssen. Nonetheless, TTS will be followed in this
protocol as adverse event of special interest (AESI) that needs to be reported to the sponsor within 24 hours of
awareness. Additional changes are listed below.
Rationale: Following observation of very rare events of TTS after vaccination with Janssen’s Ad26-based
COVID-19 vaccine, TTS will be followed as an AESI in this study. A potential TTS/AESI is defined as
thrombotic events or symptomatic thrombocytopenia.
SYNOPSIS
TIME AND EVENTS SCHEDULE
TIME AND EVENTS SCHEDULE FOR THE LONG-TERM EXTENSION PHASE (FROM WEEK72
ONWARDS, GROUP 1 AND GROUP 2)TIME AND EVENTS SCHEDULE FOR THE LONG-TERM
EXTENSION PHASE (FROM WEEK72 ONWARDS, GROUP 1 AND GROUP 2)
TIME AND EVENTS SCHEDULE FOR THE LATE BOOST EXTENSION
ABBREVIATIONS AND DEFINITIONS
1.1.2.3 Clinical Safety Experience With the Ad26.COV2.S Vaccine
1.2.5 Overall Benefit/Risk Assessment
2.1 Objectives and Endpoints
3.1 Overview of Study Design
4.5 Inclusion Criteria, Exclusion Criteria and Prohibitions and Restrictions for the Late Boost Vaccination
8 PRESTUDY AND CONCOMITANT MEDICATION
9.1.4 Vaccination
9.1.5 Post-vaccination Follow-up Phase
9.1.6 Second Year Follow-up Phase

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9.1.7 Early Withdrawal/Exit Visit
9.1.9 Long-term Extension Phase
9.1.10 Late Boost Vaccination
9.3 Safety Evaluations
10.2 Discontinuation of Study Treatment/Withdrawal from the Study
12 AE REPORTING
12.1.1 AE Definitions and Classifications
12.2 Situations Requiring Special Notification
12.3.1 All AEs
12.3.3 Adverse Events of Special Interest
Attachment 5: Thrombotic Events to be reported as Potential AESIs
Rationale: Participants planning to receive the late boost study vaccination are allowed to receive a COVID-19
vaccine that has been either licensed or authorized for emergency use (eg, EUA, EUL or similar program).
However, an exclusion criterion is added for the late boost vaccination that specifies the time interval that should
be respected between late boost study vaccination and COVID-19 vaccination. An exclusion criterion is also
added for the late boost vaccination, specifying that concomitant participation in an interventional study with
COVID-19 vaccines is not allowed.
ABBREVIATIONS AND DEFINITIONS
4.5 Inclusion Criteria, Exclusion Criteria and Prohibitions and Restrictions for the Late Boost Vaccination
8 PRESTUDY AND CONCOMITANT MEDICATION
Rationale: For participants planning to receive the late boost study vaccination, COVID-19 vaccination is to be
recorded as of any time before signing of the ICF addendum until the end of the study for a participant.
TIME AND EVENTS SCHEDULE FOR THE LATE BOOST EXTENSION
8 PRESTUDY AND CONCOMITANT MEDICATION
9.1.10 Late Boost Vaccination
Rationale: To ensure alignment with Janssen internal Standard Operation Procedures, the process for protocol
clarification communications was added.
17.1 Protocol Clarification Communications
Rationale: For clarification, the IND number is added to the title page.
Title page
Amendment 4 (23 July 2020)
The overall reason for the amendment: In this amendment, it is clarified that if a visit of the LTE and late
boost extension phases can’t be scheduled within the allowed window, it will be assessed on a case-by-case basis
whether this visit can still be performed. In addition, all post late boost vaccination visits have been made relative
to the time of the boost vaccination. An appendix has been included to outline temporary measures while access
to the sites is restricted during public health crises such as e.g. COVID-19 outbreak and to provide investigators
with flexibility to conduct study assessments while ensuring the safety and well-being of the subjects and site
staff during the pandemic. These measures will not be described in the body of the protocol but rather outlined in
an appendix (Section 18). Furthermore, the Time and Events Schedule has been updated to reflect all assessments
described for the exit visit as mentioned in the protocol body and the outdated storage conditions of the
Ad26.Mos4.HIV vaccine have been removed.

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Rationale: It is clarified that if a visit of the LTE and late boost extension phases can’t be scheduled within the
allowed window, it will be assessed on a case-by-case basis upon discussion between investigator and sponsor
whether this visit can still be performed. In addition, all post late boost vaccination visits have been made relative
to the time of the boost vaccination for consistency in immunological assessments. A clarification has been added
to interpret 1 month as 30 days, and 1 week as 7 days; hence, the visit window for visit 22a ought to be
interpreted as -28 days/+120 days.
TIME AND EVENTS SCHEDULE FOR THE LONG-TERM EXTENSION PHASE (FROM WEEK72
ONWARDS, GROUP 1 AND GROUP 2)
TIME AND EVENTS SCHEDULE FOR THE LATE BOOST EXTENSION
9.1.2 Visit Windows
9.1.10 Late Boost Vaccination
Rationale: A COVID-19 Appendix has been added to provide guidance to investigators for managing
study-related procedures during the COVID-19 pandemic. For health and safety reasons, subjects may not be able
to come to the study site for scheduled procedures.
TIME AND EVENTS SCHEDULE
3.1 Overview of Study Design
9.1.2 Visit Windows
18 COVID-19 APPENDIX: GUIDANCE ON STUDY CONDUCT DURING THE COVID-19 PANDEMIC
Rationale: The Time and Events Schedule for the late boost extension has been updated to include a
symptom-directed physical examination and vital signs measurements for the exit visit.
TIME AND EVENTS SCHEDULE FOR THE LATE BOOST EXTENSION
Rationale: The storage conditions for Ad26.Mos4.HIV mentioned in the protocol are outdated. Therefore, the
details have been removed from the protocol. A sentence has been added to clarify that the study vaccine storage
conditions are also mentioned on the clinical label.
14.1 Physical Description of Vaccines
14.3 Preparation, Handling, and Storage
Rationale: The Confidentiality Statement was revised and the statement ‘CONFIDENTIAL –FOIA Exemptions
Apply in U.S.’ was added to the running footer, to comply with an update from Janssen’s Legal department.
Title page
Amendment 3(6 Feb 2020)
The overall reason for the amendment: In this amendment, an optional late boost extension to the long term
extension (LTE) phase of the study is introduced to assess the impact of a late boost vaccination administered
approximately 3 years after the 4th  vaccination of the primary vaccination series on the immunologic responses
as well as to assess the safety of such late boost vaccination. Eligible subjects will be randomized (3:1 ratio) to
receive vaccination with Ad26.Mos4.HIV together with Clade C gp140 and Mosaic gp140 or placebo.

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Status: Approved, Date: 27 October 2021
Rationale: The goal of this protocol amendment is to include an optional extension to the LTE phase of the
study. Subjects enrolled in the LTE phase will be offered participation in this extension and ifeligible, consenting
subjects will be randomized (3:1 ratio) in a blinded fashion to receive a late boost vaccination with
Ad26.Mos4.HIV together with a co-formulation of aluminum phosphate-adjuvanted Clade C gp140 and Mosaic
gp140 (gp140 HIV bivalent vaccine, further referred bivalent gp140) or placebo. The late boost vaccination will
be administered at Week 192 (-4 weeks/+4 months [Visit 22a], ie, approximately 3 years after the 4th  vaccination
of the primary vaccination series). The goal is to evaluate the impact of a late boost vaccination on the quantity
(including magnitude and breadth) and quality of the immune response (humoral and cellular) as well as the
safety of such late boost vaccination.
Data from the current clinical study HPX2003 and ongoing study HPX2004 have been added to the protocol
where relevant to demonstrate the acceptable overall benefit/risk profile for the late boost vaccination.
TITLE PAGE
SYNOPSIS
TIME AND EVENTS SCHEDULE FOR THE LONG-TERM EXTENSION PHASE (FROM WEEK 72
ONWARDS, GROUP 1 AND GROUP 2) TIME AND EVENTS SCHEDULE FOR THE LONG-TERM
EXTENSION PHASE (FROM WEEK 72 ONWARDS, GROUP 1 AND GROUP 2)
TIME AND EVENTS SCHEDULE FOR THE LATE BOOST EXTENSION
ABBREVIATIONS AND DEFINITIONS
1 INTRODUCTION
1.1 Background
1.1.2.2 Current Studies
1.2.3 Known Risks
1.2.4 Potential Risks
1.2.5 Overall Benefit/Risk Assessment
1.3 Overall Rationale for the Study
2.1 Objectives and Endpoints
2.2 Hypothesis
3.1 Overview of Study Design
3.2 Study Design Rationale
4.5 Inclusion Criteria, Exclusion Criteria and Prohibitions and Restrictions for the Late Boost Vaccination
5 TREATMENT ALLOCATION AND BLINDING
6 DOSAGE AND ADMINISTRATION
7 TREATMENT COMPLIANCE
8 PRESTUDY AND CONCOMITANT MEDICATION
9.1.1 Overview
9.1.2 Visit Windows
9.1.9 Long-term Extension Phase
9.1.10 Late Boost Vaccination
9.2 Immunogenicity Evaluations
9.3 Safety Evaluations
9.4.1 HIV Testing
9.5 Sample Collection and Handling
10.1 Completion
10.2 Discontinuation of Study Treatment/Withdrawal from the Study
11.6 Analysis Time Points
12.3.1 All AEs
12.3.2 SAEs
12.3.3 HIV Infection
14.1 Physical Description of Vaccines
14.3 Preparation, Handling, and Storage
16.1 Study-specific Design Considerations
16.2.3 Informed Consent
REFERENCES

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Rationale: The section describing the risks related to aluminum has been aligned with updated template
language.
1.2.4 Potential Risks
REFERENCES
Rationale: It is clarified that subjects may be excluded from donating blood following vaccination in the study
due to vaccine induced seropositivity (VISP) for as long as VISP persists, as the screening HIV tests most often
used on donated blood (ELISA) will often be positive.
4.3 Prohibitions and Restrictions
Rationale: Due to a typographical error the HPX2003 protocol amendment 2 states that subjects in Group 3 of
the study will not be informed of their treatment assignment until after the Week 72 eDC database lock.
However, given the three-arm design of the study and the inclusion of both active groups in the LTE, it is
impossible to inform participants if they qualify for the LTE phase (ie, if the subject is randomized to Group 1 or
Group 2) without unblinding those randomized to Group 3 (placebo). Subjects randomized to Group 3 are
informed of their treatment assignment when the subject reaches the Week 72 visit, or as soon as possible
following Week 72 upon sponsor unblinding at the Week 28 analysis. The protocol has been adjusted
accordingly.
5 TREATMENT ALLOCATION AND BLINDING

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Amendment 2 (12 Feb 2018)
The overall reason for the amendment: In this amendment, a Long-term Extension (LTE) phase was
introduced to assess the durability of immunologic responses up to approximately 3 years after the end of the
main study.
Rationale: To assess the durability of the immune responses, an LTE phase of approximately 3 years was
introduced for subjects randomized to Group 1 or Group 2, who have received all 4 vaccinations and are negative
for HIV infection at the end of the main study. The vaccination regimens of Group 1 and Group 2 (including
Ad26.Mos4.HIV and either Clade C gp140 alone or combined with Mosaic gp140) form the basis for the
regimens that will likely be evaluated in future studies.
SYNOPSIS
TIME AND EVENTS SCHEDULE
TIME AND EVENTS SCHEDULE FOR THE LONG-TERM EXTENSION PHASE (FROM WEEK72
ONWARDS, GROUP 1 AND GROUP 2)
ABBREVIATIONS
1.2.4 Potential Risks
1.3 Overall Rationale for the Study
2.1 Objectives and Endpoints
3.1 Overview of Study Design
4.1 Inclusion Criteria for the Main Study
4.2 Exclusion Criteria for the Main Study
4.3 Prohibitions and Restrictions
4.4 Inclusion and Exclusion Criteria for the Long-term Extension Phase
5 TREATMENT ALLOCATION AND BLINDING
8 PRESTUDY AND CONCOMITANT MEDICATION
9.1.1 Overview
9.1.2 Visit Windows
9.1.6 Second Year Follow-up Phase
9.1.7 Early Withdrawal/Exit Visit
9.1.9 Long-term Extension Phase
9.3 Safety Evaluations
9.4.1 HIV Testing
9.4.2 Management of Subjects who Become HIV-infected During the Study
10.1 Completion
10.2 Discontinuation of Study Treatment/Withdrawal from the Study
11.6 Analysis Time Points
12.3.1 All AEs
12.3.2 SAEs
12.3.3 HIV Infection
16.1 Study-specific Design Considerations
16.2.3 Informed Consent

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Rationale: It was clarified that subjects are not eligible for participation in the study if they received an
experimental vaccine (other than a prophylactic or therapeutic HIV vaccine candidate) within the last 12 months
prior to the Day 1 visit (Vaccination 1).
4.2 Exclusion Criteria for the Main Study
8 PRESTUDY AND CONCOMITANT MEDICATION
Rationale: It was indicated that microscopic reflex testing will not be carried out in the event of abnormal
urinalysis tests that are considered by the investigator to have a menstrual origin.
TIME AND EVENTS SCHEDULE
9.3 Safety Evaluations
Rationale: A definition of the per protocol immunogenicity population was added to exclude subjects with major
protocol deviations from the immunogenicity population.
11.2 Analysis Populations
11.4 Immunogenicity Analyses
Rationale: It was clarified that a (remote) safety follow-up communication 24-72 hours post-vaccination is not
required if the vaccination was missed.
TIME AND EVENTS SCHEDULE
9.1.5 Post-vaccination Follow-up Phase
Rationale: It was clarified that subjects who have been prematurely withdrawn from study vaccine
administration will be encouraged to complete the post-vaccination follow-up visits of the last vaccination
received and a 12 and 24 weeks follow-up visit after the last vaccination received.
TIME AND EVENTS SCHEDULE
10.2 Discontinuation of Study Treatment/Withdrawal from the Study
Rationale: For subjects who withdraw from the study, options regarding the use of optional research samples
which were collected are added.
10.2 Discontinuation of Study Treatment/Withdrawal from the Study
Rationale: Minor clarifications and corrections.
1.1.2.1 Prototypes and Similar Vaccines 
A typographical error was corrected.
1.2.4 Potential Risks 
Update of text on risks related to vaccination for consistency
throughout the company’s vaccine studies.
1.2.5 Overall Benefit/Risk Assessment 
9.3 Safety Evaluations
Administrative change.
SYNOPSIS  
3.1 Overview of Study Design  
Duration of the main study has been corrected from 76 to
78 weeks (6-week screening + 72 weeks main study).
5 TREATMENT ALLOCATION AND 
BLINDING
Administrative change.
TIME AND EVENTS SCHEDULE 
9.1.1 Overview
Added clarification on time points for review of diary.
9.3 Safety Evaluations 
12 AE REPORTING
Added clarification of collection of symptoms in diary.
9.4.3 VISP  
It was indicated that the central lab will carry out a follow-up
testing algorithm in response to a positive result in an HIV-Ab
test.

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9.4.4 Social Impact 
It was indicated that more details regarding completion of the
social impact questionnaire can be found in the Study
Procedures Manual.
10.2 Discontinuation of Study 
Treatment/Withdrawal from the Study  
It was clarified that subjects who are vaccinated and who
withdraw will not be replaced.
11.8 Data Review Committee 
It was clarified that DRC reviews blinded data but can request
unblinded data.
11.9 Study Holding Rules 
Clarification of footnote 4 of Table 3.
12 AE REPORTING  
Removal of redundant instructional text.
12.3.2 SAEs 
Administrative change.
12.3.4 Pregnancy  
Administrative change.
Attachment 4 
It was clarified that adaptations to the social impact
questionnaire are allowed for local purposes, after IRB and
sponsor approval.
17.3 Subject Identification, Enrollment, and 
Screening Logs
Administrative change.
17.11 Use of Information and Publication  
Administrative changes.
Amendment 1 (02 Dec 2016)
The overall reason for the amendment: Removal of mucosal sampling from the optional study procedures.
Changes in the inclusion criteria to align with updated company policies regarding standard contraceptive use
in vaccine studies.
Rationale: The optional mucosal sampling assessments have been removed from the protocol. Assessment of
mucosal immune responses will be performed later in the clinical development program.
SYNOPSIS
Time and Events Schedule
1.2.4. Potential Risks
1.2.5. Overall Benefit/Risk Assessment
2.1. Objectives and Endpoints
3.1. Overview of Study Design
9.1.3. Screening Phase (Week -6 to 0)
9.1.4. Vaccination
9.1.5. Post-vaccination Follow-up Phase
9.1.6. Second Year Follow-up Phase
9.2. Immunogenicity Evaluations
9.3. Safety Evaluations
9.5. Sample Collection and Handling
12.3.4. Pregnancy
Rationale: Changes in the contraceptive requirement in the inclusion criteria to align with updated company
policies regarding standard contraceptive use in vaccine studies.
4.1. Inclusion Criteria

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Rationale: Change in the approach for collection of specimens to assess vector shedding (optional procedure).
Frequency of specimen collection has been updated to align with Health Authority guidance. 
Time and Events Schedule
TIME AND EVENTS SCHEDULE FOR OPTIONAL VECTOR SHEDDING ASSESSMENT
3.1. Overview of Study Design
9.1.2 Visit Windows
9.1.3. Screening Phase (Week -6 to 0)
9.1.8. Vector Shedding Evaluations
9.5. Sample Collection and Handling
Rationale: The HIV RNA test at baseline has been deleted, since evaluation of VISP is not relevant at this
timepoint. Clarification of HIV testing to include local and central HIV testing.
ABBREVIATIONS
Time and Events Schedule
9.3. Safety Evaluations
9.4.1. HIV Testing
12.3.3. HIV Infection
Rationale: From 1 Jun 2016 onwards, the name of Crucell Holland B.V. has been changed to Janssen Vaccines
& Prevention B.V.
Title page
Rationale: Subject's diary should be reviewed at the first opportunity to collect the most reliable AE information
and discuss diary data. Therefore diary should be reviewed at Visit 9, one week after third study vaccination.
Visit 9 is an additional safety follow-up after the FIH administration of Mosaic gp140 at Visit 8. If the 7-day
diary observation period is not completed at Visit 9, the diary will be returned at the subsequent Visit 10.
Time and Events Schedule
9.1.5. Post-vaccination Follow-up Phase
Rationale: Minor clarifications
Title page 
Time and Events Schedule 
4.2. Exclusion Criteria 
9.3. Safety Evaluations 
12.2. Situations Requiring Special Notification 
Addition of HVTN study number.
Simplification in TES on weight measurement being predose at
vaccination visits
Corrected reference to Criteria 10 and 12.
Added language that laboratory test ranges will be applied
according to subject’s sex at birth.
Clarification on the process for notifying the sponsor of new
HIV infection.
Rationale: Minor corrections
Time and Events Schedule and 9.1.2. Visit 
Windows 
1.2.5. Overall Benefit/Risk Assessment 
9.3. Safety Evaluations 
9.4.1. HIV Testing, 9.4.3. VISP and 12.3.3. 
HIV Infection
17.5. Case Report Form Completion 
Addition of specification on visit window for the visit one week
post-vaccination.
Aligned inconsistency in review of blinded data in sentinel
group.
Removed redundant reference to Section 12.1.1.
Changed Study Procedures Manual to Laboratory Manual.
Removed statement that all data should be recorded in CRF.

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SYNOPSIS
A randomized, parallel-group, placebo-controlled, double-blind Phase 1/2a study in healthy HIV-
uninfected adults to assess safety/tolerability and immunogenicity of 2 different prime/boost regimens:
priming with tetravalent Ad26.Mos4.HIV and boosting with tetravalent Ad26.Mos4.HIV and either Clade
C gp140 plus adjuvant OR a combination of Mosaic and Clade C gp140 plus adjuvant
The goal of this study is to evaluate if the addition of Mosaic glycoprotein 140 (gp140) to Clade C gp140
improves the breadth of humoral immune responses (defined as immune recognition of diverse
strains/clades of human immunodeficiency virus [HIV]), which will ultimately assist in the selection of the
best regimen(s) for evaluation in future efficacy studies.
Subjects enrolled in the LTE phase will be offered participation in an extension of the LTE phase. Eligible
subjects who consent to participation will be randomized (3:1 ratio) in a blinded fashion to receive a late
boost vaccination with Ad26.Mos4.HIV together with a co-formulation of aluminum phosphate-adjuvanted
Clade C gp140 and Mosaic gp140 (gp140 HIV bivalent vaccine, further referred to as bivalent gp140) or
placebo at Week 192 (-4 weeks/+4 months [Visit 22a], ie, approximately 3 years after the 4th  vaccination
of the primary vaccination series). The goal is to evaluate the impact of a late boost vaccination on the
quantity (including magnitude and breadth) and quality of the immune response (humoral and cellular) as
well as the safety of such late boost vaccination.
OBJECTIVES, ENDPOINTS, AND HYPOTHESIS
Objectives 
Endpoints
Primary
 
To assess safety/tolerability of the different 
vaccine regimens 
 
Solicited local and systemic adverse events (AEs) for 7
days after each vaccination.
 
AEs for 28 days after each vaccination.
 
Discontinuations from vaccination/from study due to
AEs.
 
Serious adverse events (SAEs) and AEs of special
interest (AESIs) of confirmed HIV infection during the
course of the study, including the LTE phase.
 
To assess Envelope (Env)-binding antibody
(Ab) responses of the 2 different vaccine
regimens.
 
Env-specific binding Abs (titers and breadth). 
 
To assess safety/tolerability of a late boost
vaccination.
 
Solicited local and systemic AEs for 7 days after the late
boost vaccination.
 
AEs for 28 days after the late boost vaccination.
 
SAEs and AESIs of confirmed HIV infection until the
end of the study.
 
AESIs of thrombosis with thrombocytopenia syndrome
(TTS) for 6 months after the late boost vaccination.
Secondary (applicable to main study, LTE and late boost vaccination)
 
To assess neutralizing Ab (nAb) responses, 
Ab 
functionality 
(as 
assessed 
by
phagocytosis), and Ab isotyping.
 
Env-specific nAbs (titers and breadth)

Env-specific functional Abs (phagocytosis score and
breadth).
 
Env-specific binding Ab isotypes (immunoglobulin
(Ig)A, IgG1-4) (titers and breadth).

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Objectives 
Endpoints
 
To assess T-cell responses. 
 
Interferon gamma (IFNγ) peripheral blood mononuclear
cell (PBMC) responders to mosaic and potential T-cell
epitopes (PTE) peptide pools of Env/group-specific
antigen (Gag)/polymerase (Pol).
 
Cluster of differentiation (CD)4+ and CD8+ T-cell
functionality (% cells producing ia, IFNγ, interleukin 2
(IL-2), IL-4, tumor necrosis factor α [TNFα]).
 
T-cell development with emphasis on follicular helper T-
cells and memory differentiation.a
Exploratory (applicable to main study, LTE and late boost vaccination)
 
To explore whether the adenovirus serotype 
26 (Ad26) vector is shed after vaccination. 
 
Polymerase chain reaction (PCR) positive for Ad26
sequences (urine and mid-turbinate swab).
 
To explore Ab functionality (other than 
phagocytosis). 
 
Ab functionality evaluation (such as Ab-dependent
cellular 
cytotoxicity 
[ADCC], 
Ab-dependent
complement 
deposition 
[ADCD]; 
excluding
phagocytosis (ie, Ab-dependent cellular phagocytosis
[ADCP]).
 
To explore Ab Fc characterization. 
 
Ab Fc (sub)typing.
 
To explore T-cell and Ab epitope mapping. 
 
Epitope mapping of Ab to Env and T-cell responses to
Gag/Pol/Env (PTE and vaccine peptide pools).
 
To explore gene expression patterns using 
PBMCs. 
 
Regulation of genes (or clusters) that predict specific
immune responses and human leukocyte antigen (HLA)
typing.
 
To explore B-cell responses. 
 
Ab-producing B-cells and characterization of B-cell
memory development.
 
To explore immune responses against the 
viral vector.
 
Ad26 nAbs (titer).
 
To explore the social impact of participation 
in an HIV-vaccine study for subjects via a
social impact questionnaire.
 
Social impact.
 
To explore durability of the immune 
responses to the vaccine regimens in the 
groups selected for the Long-term Extension 
(LTE) phase.
 
Available samples from time points during the LTE
phase will be used for determination of long-term
durability of the immune responses.
In addition, the following exploratory objectives are applicable to the late boost vaccination only:
Objectives 
Endpoints
 
To assess Env-binding Ab responses
following 
late 
boost 
vaccination
approximately 3 years after receiving the 4th
vaccination of the primary vaccination series.
 
Env-specific binding Abs [ELISA] at 3, 7 or 14 daysb
and 28 days post late boost vaccination (titers and
breadth).
a The follicular helper T-cells and memory differentiation was included as secondary objective for the main study. Due to difficulty
qualifying the assay for these specific markers, these T-cell responses will be considered as an exploratory objective for the
late boost vaccination.
b Subjects will be divided into three groups: the first 20 enrolled subjects will have the Visit 22b 7 days post late boost, the next 20
enrolled subjects 3 days post late boost and the remainder of the subjects 14 days post late boost.

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Objectives 
Endpoints
 
To explore the role of Ad26 neutralizing 
antibodies on the immune response to a late 
boost vaccination.
 
Ad26 neutralizing antibodies at the time of vaccination
relative to the immune response as evaluated by ELISA.
 
To compare the immune response to late 
boost vaccination with a vaccine matched to 
the primary vaccination series (Group 2) vs a
closely related vaccine (Group 1).
 
Relative 
ELISA 
magnitudes 
between 
groups
randomized to Group 1 vs Group 2 in the main study.
 
To evaluate whether humoral responses
induced by a late boost vaccination are able to
mediate protection in non-clinical passive
transfer studies.
 
Analysis of protection against HIV-related challenge
viruses, such as simian human immunodeficiency virus
(SHIV), in a suitable animal model, and/or in vitro.
Hypothesis
No formal statistical hypothesis will be tested. The proposed clinical study in healthy HIV uninfected
subjects will evaluate the safety/tolerability and the immunogenicity of 2 different prime/boost regimens:
priming with Ad26.Mos4.HIV and boosting with Ad26.Mos4.HIV and either Clade C gp140 plus adjuvant
or a combination of Clade C and Mosaic gp140 plus adjuvant.
OVERVIEW OF STUDY DESIGN
This is a randomized, double-blind, placebo-controlled, parallel-group, multicenter, Phase 1/2a study in
healthy HIV-uninfected adult men and women between the ages 18 to 50 years, inclusive. A target of
150 subjects will participate in this study with 25 subjects in  Group 1, 100 subjects in Group 2, and
25 subjects in Group 3 (see table below). Group 1 represents the “base-case” regimen which allows bridging
of data from this study to study VAC89220HPX2004. Randomization will be stratified by region. Subjects
will receive intramuscular (IM) doses of study vaccine or placebo at 4 time points: Ad26.Mos4.HIV or
placebo will be given at Weeks 0 and 12; Ad26.Mos4.HIV together with either Clade C gp140 plus adjuvant
or a combination of Mosaic and Clade C gp140 plus adjuvant, or placebo will be given at Weeks 24 and
48.
The main study will be conducted in 3 phases: a 6-week screening period; a 48-week vaccination period
during which subjects will be vaccinated at baseline (Week 0) and at Weeks 12, 24, and 48; and a follow-
up period to the final main study visit at Week 72.
An LTE phase (approximately 3 years after Week 72) will be performed for subjects randomized to Group 1
or Group 2, who have received all 4 vaccinations and are negative for HIV infection at Week 72. The
vaccination regimens of Group 1 and Group 2 (including Ad26.Mos4.HIV and either Clade C gp140 alone
or combined with Mosaic gp140) form the basis for the regimens that will likely be evaluated in future
studies. Subjects enrolled in the LTE phase will be offered participation in an extension to the LTE phase
to investigate the safety and immunogenicity of a late boost vaccination approximately 3 years after the last
vaccination in the main study  (depending on availability of IRB and HA approvals per country/site
regulations). Assessment of participants’ eligibility for the late boost vaccination and vaccination itself will
occur within 4 weeks prior to Week 192 until 4 months after Week 192 (Visit 22a, which can be split over
several visits). Eligible, consenting subjects will be randomly assigned (3:1 ratio, see Table below) in a
blinded fashion to active vaccination with Ad26.Mos4.HIV and bivalent gp140 (Group 1b) or placebo
(0.9% saline) (Group 2b). The aim is to have at least 48 participants enrolled in the late boost extension.
Randomization will be stratified by region (USA, East Africa: assuming sufficient numbers from Rwanda
in the LTE phase agree to participate) and by group randomized to in the main study (Group 1/Group 2).
Upon receipt of the late boost vaccination, participants will be followed up for immunogenicity and safety
for a further 12 months or, if they consent to longer follow-up, 24 months. Unblinded interim data analysis
(sponsor unblinding only) will be performed approximately 4 weeks after the last subject received the late

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boost vaccination. LTE subjects declining participation or not eligible to participate in the late boost
extension will complete the study at Visit 23 of the LTE phase.
The duration of the subject’s participation will be approximately 78 weeks (6-week screening + 72 weeks
main study) for subjects not participating in  the LTE phase, approximately 222 weeks for subjects
participating in the LTE phase but not receiving a late boost vaccination and approximately 246 (12-month
follow-up) or 294 (24-month follow-up) weeks for subjects receiving a late boost vaccination.
After vaccination, subjects will remain under observation at the study site for at least 30 minutes for
presence of any acute reactions and solicited events. In addition, subjects will record solicited events in a
diary for 7 days post-vaccination. Further safety evaluations will include monitoring of AEs, physical
examinations, vital sign measurements, clinical laboratory tests, and pregnancy testing. Blood samples will
be taken at specific clinic visits to assess immune responses. Subjects will complete a social impact
questionnaire at specific clinic visits. Optional urine samples and mid-turbinate swabs will be collected
from consenting subjects to assess vector shedding. A Protocol Safety Review Team (PSRT) and Data
Review Committee (DRC) will be commissioned for this study.
Table: Schematic Overview of the Main Study
Group  
N 
Week 0 
Week 12 
Week 24 
Week 48
1b 
25 
Ad26.Mos4.HIV  
Ad26.Mos4.HIV
Ad26.Mos4.HIV  
+ 
Clade C gp140 (250 
mcg + adjuvant)a 
Ad26.Mos4.HIV
+
Clade C gp140 (250
mcg + adjuvant)a
2b 
100 
Ad26.Mos4.HIV  
Ad26.Mos4.HIV  
Ad26.Mos4.HIV  
+ 
Clade C + Mosaic 
gp140 (250 mcg + 
adjuvant)a 
Ad26.Mos4.HIV
+
Clade C + Mosaic
gp140 (250 mcg +
adjuvant)a
3 
25 
Placebo 
Placebo 
Placebo 
+ 
Placebo 
Placebo
+
Placebo
a250 mcg refers to total protein content (Clade C gp140 [250 mcg] alone or a combination of Mosaic gp140
[125 mcg] and Clade C gp140 [125 mcg]). Sterile aluminum phosphate suspension will be used as adjuvant.
Aluminum content will be 0.425 mg/0.5 mL dose.
bAn LTE phase (approximately 3 years after Week 72) will be performed for subjects randomized to Group 1 or
Group 2, who have received all 4 vaccinations and are negative for HIV infection at Week 72.

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Table: Schematic Overview of the Late Boost Vaccination
Group  
N 
Week 192 (-4 weeks/+4months)
1b 
3*N/41 
Ad26.Mos4.HIV
+
gp140 HIV bivalent vaccine
2b 
1*N/41 
Placebo
+
Placebo
Total dose of Ad26.Mos4.HIV is 5x1010 viral particles (vp)/0.5 mL injection.
gp140 HIV bivalent vaccine: adjuvanted protein co-formulation with a dosage strength of 80 mcg Clade C
protein, 75 mcg Mosaic protein and 425 mcg aluminum (as aluminum phosphate adjuvant). Note: the dose of
Clade C gp140 and/or Mosaic gp140 as separate entities is reported as mcg of glycoprotein: 125 mcg Clade C
gp140 and 125 mcg Mosaic gp140 glycoprotein correspond with 80 mcg and 75 mcg of protein, respectively.
1 
Subjects will be randomly assigned in a 3:1 ratio to active vaccine or placebo. The aim is to have at least 48
subjects enrolled in the late boost extension.
PSRT
A PSRT will review blinded safety data reports on a regular basis (at least 2 times per month) starting from
one week after first vaccination until the last subject has completed the Week 52 visit, and thereafter as
needed.
Since the study is the first-in-human  (FIH) administration of Mosaic gp140, after a sentinel group of
6 subjects receives the third injection, further third injections will be paused until a 1-day safety evaluation
is performed. This evaluation will be performed by the PSRT and the PI(s) of the subjects involved and
will be based on the information received from the investigator(s) by email/telephone.
If a dose of vaccine is considered, by PSRT review, to raise significant safety concerns, all enrollment and
vaccinations will be suspended until recommendations are issued. In specific cases, a DRC meeting will be
triggered.
The PSRT will include, but will not be limited to medical and safety representatives from the sponsor, a
limited number of sites, the Division of Acquired Immune Deficiency Syndrome (DAIDS), Beth Israel
Deaconess Medical Center (BIDMC), HIV Vaccine Trials Network (HVTN), International Acquired
Immune Deficiency Syndrome (AIDS) Vaccine Initiative (IAVI), and Military HIV Research Program
(MHRP). The PSRT responsibilities, authorities, and procedures will be documented in its charter.
DRC
A DRC will be established for this study, which will monitor data to ensure the safety and well-being of
the subjects enrolled. The DRC will review data as indicated below. The conclusions of the DRC will be
communicated to the investigators, the Institutional Review Board (IRB)/Independent Ethics Committee
(IEC), and the national regulatory authorities, as appropriate.
The DRC will specifically review safety data (solicited and unsolicited AEs, SAEs, and available laboratory
assessments) at 2 time points following injections of Mosaic gp140:
 
Review blinded safety data (2 weeks of follow-up) after approximately 25 (15%) of subjects have
received their third injection.
 
Review blinded safety data (2 weeks of follow-up) after approximately 50 (30%) of subjects have
received their third injection.
In addition, ad hoc review may be performed further to the occurrence of any AE/SAE leading to a study
holding situation or at request of the PSRT.

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Status: Approved, Date: 27 October 2021
The DRC will include medical experts in vaccines and at least one statistician. The DRC can include
members from both inside and outside Janssen, but will not include any study team personnel or people
otherwise directly involved in the study conduct, data management, or statistical analysis for the study. The
DRC responsibilities, authorities, and procedures will be documented in its charter.
SUBJECT POPULATION
Screening for eligible subjects will be performed within 6 weeks before the first administration of study
vaccine or placebo at Week 0.
Study subjects must be healthy (on the basis of medical history, physical examination, vital signs
measurement, and laboratory assessments), HIV-uninfected adult men and women, aged ≥18 to ≤50 years,
and assessed by the clinic staff as being at low risk for HIV infection.
For entering the LTE phase, subjects must have been randomized to Group 1 or Group 2 during the main
study, must have received all 4 vaccinations and must be negative for HIV infection at the end of the main
study.
For the late boost extension, eligible subjects must be enrolled in the LTE phase, healthy and HIV-
uninfected.
DOSAGE AND ADMINISTRATION
During the main study, each subject will receive doses of study vaccine or placebo at 4 time points
according to randomization, on Day 1 and Weeks 12, 24, and 48, administered by IM injection into the
deltoid. Subjects eligible and consenting to the late boost vaccination will receive an additional dose of
Ad26.Mos4.HIV in combination with bivalent gp140 or placebo at Week 192 -4 weeks/+ 4 months (ie,
approximately 3 years after the 4th  vaccination of the primary vaccination series), administered by IM
injection into the deltoid. For visits with only one injection (ie, at Week 0 and 12), preferably the deltoid of
the non-dominant upper arm is used. When 2 injections are to be given at one visit (ie, at Week 24 and 48
and at Week 192 [if applicable]), it is required to use a different deltoid for each injection. Two injections
in the same deltoid are allowed only if medically indicated.

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Table: Description of Interventions
Test articles 
Ad26.Mos4. 
HIV  
Clade C gp140 with 
aluminum phosphate 
Clade C gp140 +
Mosaic gp140 
with aluminum 
phosphate*
gp140 HIV
bivalent vaccine*
Placebo
Description  
See Section Vaccine Information.
Dose/delivery 
(0.5 mL 
injection) 
5x1010 
viral 
particle 
(vp) 
250 mcg Clade C
gp140, mixed with
aluminum phosphate 
adjuvant (0.425 mg
aluminum)
125 mcg Clade C 
gp140 + 125 mcg 
Mosaic gp140, 
mixed with 
aluminum 
phosphate 
adjuvant (0.425 
mg aluminum) 
80 mcg Clade C
gp140/75 mcg
Mosaic gp140/
aluminum
phosphate
adjuvant
(425 mcg
aluminum)
0.9% saline
Frequency  
Week 0, 
12, 24, 48, 
and Week 
192** (if 
applicable) 
Week 24 and 48 
Week 24 and 48 
Week 192** (if
applicable)
Week 0, 12,
24, 48, and
Week 192**
(if
applicable)
Delivery 
method 
IM in
deltoid
IM in deltoid 
IM in deltoid 
IM in deltoid 
IM in deltoid
Delivery 
instructions
Refer to the Study Procedures Manual for details.
* The dosage of DP  in the gp140 HIV bivalent vaccine (late boost vaccination) is identical to the dosage of DP in the co-
administered separate gp140 formulations (main study) . However, there has been a change of unit for the reported gp140
concentration from mg/mL glycoprotein to mg/mL protein. This will not impact the dose strength of gp140 in the vial or
administered to the participants in the late boost extension, compared to the main study, but the gp140 concentration will be
expressed in protein instead of glycoprotein in the specification. Consequently, 125 mcg Clade C gp140 and 125 mcg Mosaic
gp140 of glycoprotein correspond with 80 mcg Clade C gp140 and 75 mcg Mosaic gp140 of protein, respectively.
** The late boost vaccination is to be administered at Week 192 -4 weeks/+4 months, ie, approximately 3 years after the 4th
vaccination of the primary vaccination series.
IMMUNOGENICITY EVALUATIONS
Humoral immune response assays will include, but are not limited to Env-Ab-binding assays (ELISA),
virus neutralization assay, and assays for Ab functionality. Additional assays may include binding antibody
assays to evaluate the breadth and isotypes of Ig induced and passive transfer assays.
Cellular immune response assays will include, but are not limited to INFγ enzyme-linked immunospot
(ELISPOT) assay, intracellular cytokine staining (ICS), and multiparameter flow cytometry.
SAFETY EVALUATIONS
All AEs and situations requiring special notification will be reported from the time the signed and dated
study-specific informed consent form (ICF) is obtained until 28 days after first dose of study vaccine, and
thereafter, pre-dose on the day of injection and for 28 days after each subsequent dose of study vaccine or
placebo. From the time of local regulatory approval of protocol amendment 5 onwards, thrombosis with
thrombocytopenia syndrome (TTS) is considered to be an AESI. Thrombotic events and/or
thrombocytopenia are considered to be potential AESIs. Thrombocytopenia is defined as platelet count
below the lower limit of normal (LLN) range for the testing lab. All AESIs of TTS, including potential
AESIs, will be reported to the sponsor from the moment of the late boost vaccination until 6 months after
the late boost vaccination. Each potential AESI will be reviewed to identify a TTS case. All SAEs and AEs
leading to discontinuation from the study vaccination (regardless of the causal relationship) and AESIs of
confirmed HIV infection are to be reported from signing of study-specific ICF onwards for the duration of
the study.

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After each vaccination, subjects will remain under observation at the study site for at least 30 minutes for
presence of any acute reactions and solicited events.
In addition, symptoms of the following solicited AEs will be collected via a diary  for 7 days
post-vaccination (day of vaccination and the subsequent 7 days). The diary will be used as a source
document.
 
Solicited local AEs: erythema, swelling/induration (measured using the ruler supplied) and
pain/tenderness.
 
Solicited systemic AEs: fever (temperature measurement), fatigue, headache, nausea, myalgia, and
chills.
 
Temperature should be measured at approximately the same time each day using the thermometer
supplied.
STATISTICAL METHODS
The sample size in this study is regarded to be appropriate to assess the safety and tolerability of the different
vaccine regimens. Placebo recipients are included for blinding and safety purposes and will provide control
specimens for immunogenicity assays. With 25 individuals in a vaccine regimen, the observation of 0 such
reactions would be associated with a 90% confidence that the true rate is less than 10%. For Group 2 with
Mosaic and Clade C gp140 (n=100), there would be 90% confidence that the true rate is less than 2.5%
when 0 events are observed.
The primary population for the safety analyses will consist of all subjects who received at least 1 dose
(Ad26.Mos4.HIV or placebo).
Anticipating a dropout rate of approximately 10%, the sample sizes will allow detection of approximately
1.85-fold differences in Env-binding Ab titers, generally accepted to be biologically relevant, between the
groups with Mosaic and Clade C gp140 (approximately 90 evaluable subjects) and their corresponding
group with Clade C gp140 only (approximately 22 evaluable subjects); with 80% probability, assuming a
2-sided 5% Type I error and an SD of 0.4 on the log10 scale.
Immunogenicity Analyses
No formal hypothesis on immunogenicity will be tested. Descriptive statistics (actual values and changes
from reference with 95% confidence interval) will be calculated for continuous parameters. Frequency
tabulations will be calculated for discrete parameters. Graphical representations of changes in immunologic
parameters will be made as applicable.
Magnitude and breadth of (neutralizing)Ab responses will be explored graphically through the generation
of individual magnitude-breadth (M-B) curves. The area-under-the M-B curve (AUC) will be compared
between groups.
Safety Analyses
No formal statistical testing of safety data is planned. Safety data will be analyzed descriptively.

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2Complete physical exam will be performed at screening and final main study visit. At all other visits, an abbreviated, symptom-directed exam will be performed as indicated by the
investigator. Weight will be measured at every visit.
3Within 24-72 hours post-vaccination a member of the site staff will have a (remote) safety follow-up communication with the subject (by e-mail, telephone, or visit; according to the
subject’s preference). A (remote) safety follow-up communication 24-72 hours post-vaccination is not required if the vaccination was missed.
4Microscopic reflex testing in the event of abnormal urinalysis, except when the investigator considers the abnormal urinalysis result to be from menstrual origin.
5 If medical status and/or physical examination on Day 1 suggest significant changes may have occurred since screening, the clinically relevant screening assessments will be repeated
and the Day 1 visit rescheduled, provided that the rescheduled visit is within 42 days of the initial screening assessment. In case a Grade 3 or 4 laboratory abnormality, or any laboratory
abnormality accompanied by clinically relevant signs or symptoms, occurs (from the baseline visit onwards), all attempts will be made to perform a confirmatory test within 48 hours
after the results have become available. After that, laboratory tests will be repeated weekly until values are resolved or stable.
6All subjects will be followed up until Week 72 to assess durability of immune response. Subjects who have been prematurely withdrawn from study vaccine administration will be
encouraged to complete the post-vaccination follow-up visits of the last vaccination received and a 12 and 24 weeks follow-up visit after the last vaccination received, specified as
Week 60 and Week 72. Upon sponsor unblinding at the Week 28 analysis, subjects randomized to Group 1 or Group 2 who have received all 4 vaccinations, will be asked to participate
in the LTE phase and sign the ICF appendix for the LTE phase at Week 72. During the first visit of the LTE phase, the remaining eligibility criteria for the LTE phase will be verified.
Subjects who attend their Week 72 visit prior to the sponsor’s unblinding at the Week 28 analysis, will be enrolled in the LTE phase if they consent and sign the ICF appendix for the
LTE phase and meet the eligibility criteria for the LTE phase. When the Week 28 sponsor unblinding subsequently occurs, subjects that started the LTE phase but turn out to have
received placebo in the main study will be withdrawn from the LTE phase. If signing the ICF appendix is not possible at Week 72, signing should be performed at an extra visit
(Visit 17bis) as soon as possible after Week 72 and at the latest before any assessment is done on the first visit of the LTE phase. See TIME AND EVENTS SCHEDULE FOR THE
LONG-TERM EXTENSION PHASE (FROM WEEK72 ONWARDS, GROUP 1 AND GROUP 2)
7For those subjects who are unable to continue participation in the study, an exit visit will be conducted as soon as possible.
8For both male and female subjects.
9For female subjects only. (pregnancy test only for female subjects of childbearing potential)
10Observation at the study site for at least 30 minutes for presence of any acute reactions and solicited events.
11Timings of visits at 1, 2 and 4 weeks post-vaccination will be determined relative to the actual day of vaccination.
12Urine or vaginal swab may be used.
13Only at screening.
14 Must be signed before first study-related activity.
15Minimum criteria for the availability of documentation supporting the eligibility criteria are described in Section 17.5. Check clinical status again before first dose of study vaccine.
16For the sentinel group of 6 subjects, this will need to be an actual visit, 1 day post vaccination.
17Solicited local and systemic events will be recorded for 7 days after each vaccination; AEs will be recorded from signing of the study-specific ICF onwards until 28 days after first
vaccination, and thereafter, pre-dose on the day of injection and for 28 days after each subsequent vaccination; SAEs, AEs leading to treatment discontinuation, and AESIs of confirmed
HIV infection will be recorded from signing of the study-specific ICF onwards throughout the study.
18The test of understanding (TOU) must be completed by all subjects, as the first assessment after signing of the ICF.
19If on Visit 9, the 7-day diary observation period is not complete, the diary will be returned at Visit 10. If the diary card review is missed, the diary card will be reviewed in the
following visit. If a participant misses a vaccination, the diary covering the period after the missed vaccination does not have to be filled in.

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TIME AND EVENTS SCHEDULE FOR THE LONG-TERM EXTENSION PHASE (FROM WEEK72 ONWARDS, GROUP 1
AND GROUP 2)
Phase 
Long-term Extension
Visit # 
17
bis1 
181
19 
20 
21 
223
23/Final
Visit
Visit Week  
961 
120 
144 
168 
1923
216
Visit Day4 
673
± 4 wks
841 
± 4 
wks 
1009 
± 4 
wks 
1177 
± 4 
wks 
1345
-
4wks/+4months
1513
± 4 wks
Informed consent 

Review of inclusion/ exclusion criteria 

HIV-risk assessment 
 
 
 
 
 

Counseling on HIV  
 
 
 
 
 

Concomitant meds2 
 
 
 
 
 

SAE and AESI of confirmed HIV infection recording 
 
 
 
 
 

Social impact questionnaire 
 
 
 
 
 

Central HIV testing 
 
 
 
 
 

Humoral immuno. assays 
 
 
 
 
 

Cellular immuno. assays 
 
 
 
 
 

AESI = adverse event of special interest; HIV = human immunodeficiency virus; SAE = serious adverse event; wks = weeks.
The COVID-19 Appendix in Section 18 provides guidance to investigators for managing study-related procedures during the COVID-19 pandemic.
1This visit only needs to occur if the informed consent form (ICF) appendix for the LTE phase is not signed at Week 72. Visit 17bis should occur as soon as possible
after the Week 72 visit. The ICF appendix for the LTE phase needs to be signed at the latest before any assessment is done on the first visit of the LTE phase.
2Restricted to concomitant therapies given in conjunction with an SAE, any chronic or recurrent use of immunomodulators/suppressors, oral or parenteral
corticosteroids, any allowed vaccination and/or any HIV prevention medication. Subjects will also be asked during all visits whether they are participating in another
clinical study.
3 Subjects will be asked to participate in an extension to the LTE phase in which they will be randomized to receive a late boost vaccination with Ad26.Mos4.HIV in
combination with bivalent gp140 or placebo. Subjects willing to participate should follow the TIME AND EVENTS SCHEDULE FOR THE LATE BOOST
EXTENSION. Subjects not willing to participate in the late boost extension should continue to follow the above visit schedule.
4 If a visit can’t be scheduled within the allowed window, it will be assessed on a case-by-case basis upon discussion between the investigator and the sponsor
whether this visit can still be performed. Note that 1 month should be interpreted as 30 days and 1 week as 7 days; hence, the visit window for visit 22 ought to be
interpreted as -28 days/+120 days.

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10 All concomitant medication should be recorded from day of vaccination until 28 days post-vaccination. At other time points, recording of concomitant medication is restricted to
concomitant therapies given in conjunction with an SAE, an AESI of TTS, any chronic or recurrent use of immunomodulators/suppressors, oral or parenteral corticosteroids, any allowed
vaccination and/or any HIV prevention medication, including any COVID-19 vaccination.
11 Solicited local and systemic signs and symptoms will be recorded by the subject in the diary and solicited local and systemic AEs recorded in the CRF for 7 days after boost vaccination;
unsolicited AEs will be recorded from signing of ICF addendum for boost vaccination onwards until 28 days after boost vaccination; SAEs and AESIs of confirmed HIV infection will be
recorded from signing of the initial ICF of the main study onwards until the end of the study. Applicable from the time of local regulatory approval of protocol amendment 5 onwards:
AESIs of TTS (including potential AESIs) are to be reported to the sponsor until 6 months after the late boost vaccination. In case of a potential AESI of TTS, a serum sample should be
obtained to test for anti-PF4 at the local laboratory or substitute local laboratory, if possible; repeat testing may be requested for confirmation upon sponsor discretion. A test for anti-PF4
will also be performed on a stored pre-vaccination sample, if possible.
12 Observation at the study site for at least 30 minutes for presence of any acute reactions and solicited events.
13 In case the diary was not completed (7 days post-boost) at the time of Visit 22b.
14 Approximately 6 months post Visit 24, the investigator or study-site personnel will have a (remote) follow-up communication with subjects consenting to the 24-month follow-up (by e-
mail, telephone, or visit; according to the subject’s preference) to collect information on occurrence of any SAEs.
15 Visit 25 is an optional visit. Visit 24 and Visit 25 will be the final visit for subjects who, respectively, do not consent and subjects who consent to the 24-month follow-up.
16 For those subjects who are unable to continue participation in the study, an exit visit will be conducted as soon as possible.
17 If a visit can’t be scheduled within the allowed window, it will be assessed on a case-by-case basis upon discussion between the investigator and the sponsor whether this visit can still
be performed. Note that 1 month should be interpreted as 30 days and 1 week as 7 days; hence, the visit window for visit 22a ought to be interpreted as -28 days/+120 days.

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ABBREVIATIONSAND DEFINITIONS
Ab 
antibody
Ad 
adenovirus
Ad5 
adenovirus serotype 5
Ad26 
adenovirus serotype 26
ADCC  
antibody-dependent cellular cytotoxicity
ADCD  
antibody-dependent complement deposition
ADCP  
antibody-dependent cellular phagocytosis
AE 
adverse event
AESI 
adverse event of special interest
AIDS  
acquired immunodeficiency syndrome
ALT  
alanine aminotransferase
API 
active pharmaceutical ingredient
AUC  
area under curve
β-hCG  
β-human chorionic gonadotropin
BIDMC  
Beth Israel Deaconess Medical Center
BMI 
body mass index
CBC  
complete blood count
CD  
cluster of differentiation
CDC  
Centers for Disease Control and Prevention
CRF  
case report form
DAIDS  
Division of Acquired Immunodeficiency Syndrome
DRC  
Data Review Committee
DMC  
Data Monitoring Committee
DNA 
deoxyribonucleic acid
DS  
drug substance
eDC 
electronic data capture
ELISPOT 
enzyme-linked immunospot
Env 
envelope
ENVA 
envelope A
EUA  
Emergency Use Authorization
EUL 
Emergency Use Listing
FDA  
Food and Drug Administration
FIH  
first-in-human
Gag 
group-specific antigen
GCP  
Good Clinical Practice
gp 
glycoprotein
HCV  
hepatitis C virus
HIV  
human immunodeficiency virus
HITT  
heparin-induced thrombocytopenia and thrombosis
HLA  
human leukocyte antigen
HSV-2 
herpes simplex virus type 2
ICF  
informed consent form
ICH  
International Conference on Harmonisation
ICS  
intracellular cytokine staining
IFNγ 
interferon gamma
Ig 
immunoglobulin
IL 
interleukin
IRB  
Institutional Review Board
IM  
intramuscular
IPCAVD  
Integrated preclinical/Clinical AIDS Vaccine Development
IWRS  
interactive web response system
LLN  
lower limit of normal
LTE 
Long-term Extension
M-B 
magnitude-breadth
Mos1 
Mosaic 1

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MVA  
Modified Vaccinia Ankara
nAb 
neutralizing antibody
PBMC  
peripheral blood mononuclear cell
PCR  
polymerase chain reaction
Pol 
polymerase
PQC  
Product quality complaint
PSRT  
Protocol Safety Review Team
PTE 
potential T-cell epitopes
RNA 
ribonucleic acid
SAE 
serious adverse event
SHIV  
simian human immunodeficiency virus
SIV  
simian immunodeficiency virus
SUSAR  
suspected unexpected serious adverse reaction
TNF  
tumor necrosis factor
TOU  
test of understanding
TTS  
thrombosis with thrombocytopenia syndrome
ULN  
upper limit of normal
VISP  
vaccine-induced seropositivity
vp 
viral particle
For the purpose of this protocol following terminology is applied:
Vaccine regimen/primary 
vaccination series
Vaccination 1 through 4
Prime 
Vaccination 1 and 2 (Ad26.Mos4.HIV or placebo at Week 0 and Week 12)
Boost 
Vaccination 3 and 4 (Ad26.Mos4.HIV and adjuvanted Clade C gp140 or a combination of
adjuvanted Clade C gp140 and Mosaic gp140 or placebo at Week 24 and Week 48,
respectively)
Late boost 
Vaccination with Ad26.Mos4.HIV and bivalent gp140 at Week 192 (-4 weeks/+4 months,
ie, approximately 3 years after the 4th  vaccination of the primary vaccination series)

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1. 
INTRODUCTION
A safe and effective HIV vaccine is the presently elusive cornerstone of HIV prevention.28
Optimally, both a robust CD4+ and CD8+ T-cell responses and a potent humoral response with
multiple effectors should be induced by a vaccine. An objective of the HIV-vaccine development
program being pursued by the sponsor and its partners is to optimize a vaccine candidate for
improved potency, where potency is defined as the quantitative response, frequency, and amplitude
of a variety of potent antibody (Ab) and Ab-mediated cellular effector mechanisms, coupled with
appropriate cellular responses. A second objective is to increase the breadth of response, defined
as immune recognition of diverse strains/clades of HIV to include multiple clades.
A successful global prophylactic HIV vaccine will likely need to protect against the diverse strains
and clades of HIV that may be encountered. Improving the magnitude and breadth of epitope
coverage is thought to be key to development of a successful Ab and T-cell based preventive HIV
vaccine. Strategies to accomplish this include the use of vaccines containing immunogens from a
number of prevalent clades and/or using mosaic sequences, ie, proteins assembled from natural
sequences of the different clades by in silico recombination, optimized for potential T-cell
epitopes.10
Vaccines used in this study are Ad26.Mos4.HIV, Clade C gp140, and Mosaic gp140 (for details
see Section 14).
For the most comprehensive nonclinical and clinical information regarding Ad26.Mos4.HIV,
Clade C gp140, and Mosaic gp140, see the latest version of the Investigator's Brochure and
Addenda (if applicable) for Ad26.Mos4.HIV, Clade C gp140, and Mosaic gp140.
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.
Other organizations are also involved in this study, referred to in this protocol as "partners". For
this protocol, the organizations are the DAIDS, BIDMC, HIV Vaccine Trials Network (HVTN),
International AIDS Vaccine Initiative (IAVI), and Military HIV Research Program (MHRP).
1.1. 
Background
Nonclinical and clinical information below summarize data available at the time of the initial
protocol writing (issued date 29 February 2016) 18,19 unless specified otherwise.
1.1.1. 
Nonclinical Studies
1.1.1.1. 
Repetitive gp120/gp140 Vaccinations
In order to mimic the native trimeric structure of the HIV-Env-gp “spike” (gp120/gp41) and induce
native Env-reactive antibodies, trimeric gp140 proteins based on human Clade A and Clade C
sequences were developed and found to induce significantly higher titers of potent nAb responses
for a cross-clade set of tier 1 (Clades A, B, and C) and tier 2 (Clade C) viruses than the
corresponding gp120 monomers in guinea pigs.23 Although tier 1/2 pseudovirus neutralization is

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likely not predictive of neutralization  capacity against circulating HIV-1 viruses, the results
suggest a broader and more avid Ab recognition of native HIV-1 Env.
1.1.1.2. 
Ad26/gp140 and Ad26/Ad35 Vaccinations
The protective efficacy of boosting with gp140 protein following priming with Ad26 vectors was
evaluated in stringent simian immunodeficiency virus (SIV)- and SHIV-challenge models in non-
human primates (Part 1).5 Boosting with adjuvanted SIVMAC32H  gp140 protein afforded 50%
protection against the complete series of 6 heterologous, intrarectal challenges with SIVMAC251 in
animals that were primed with the Ad26 vector expressing SIVSME543 Env/Gag/Pol antigens, which
was significantly higher than in animals that were similarly primed, but boosted with the
corresponding Ad35 vector expressing SIVSME543 Env/Gag/Pol antigens (17% protection). Binding
Ab titers and ADCP responses correlated with protection against acquisition of infection. Cellular
immune responses measured by IFNγ ELISPOT assays in response to SIVMAC239 and SIVSME543
Env/Gag/Pol peptide pools were also detected in all animals after vaccination. By ICS assays,
gp140 boosting primarily expanded Env-specific IFNγ CD4+ T-lymphocyte responses in the
Ad26/gp140 group.
1.1.1.3. 
Ad26/Ad5 and Repetitive gp140 Vaccinations
A similar level of protection (40%) was seen after a series of 6 heterologous, intrarectal challenges
with SHIV-SF162P3 in a first group of animals primed with Ad26 and Ad5HVR48 vectors
expressing mosaic, consensus, or natural Clade C HIV-1 Env/Gag/Pol antigens and boosted six
times 2 years later with HIV-1 Clade C Env gp140 trimer (Part 2).5 A second group of animals
received only the 6 gp140 immunizations. Although the gp140 vaccine afforded only minimal
protection, 40% of Ad/gp140-vaccinated animals were completely protected against this challenge
series. As for Section 1.1.1.2, Ad26/gp140 and Ad26/Ad35 Vaccinations, binding Ab titers and
ADCP responses correlated with protection against acquisition of infection.
1.1.1.4. 
Tetravalent Ad26 Vaccinations
In ongoing clinical trials the trivalent Ad26.Mos.HIV viral vector is being used. But subsequent
non-clinical data in rabbits have shown that the addition of a vector, expressing Mos2S Env
protein, to Ad26.Mos1.Env increases the magnitude of binding Ab titers and neutralizing capacity
for tier 1A Clade C HIV virus in the absence of negative effects on Clade B neutralization capacity.
Thus, addition of Ad26.Mos2S.Env to Ad26.Mos.HIV has the potential to substantially increase
the breadth of humoral immune responses. Therefore, a clinical study (VAC89220HPX2004) is
planned to study safety and immunogenicity of the tetravalent Ad26.Mos4.HIV. In study
VAC89220HPX2004, a DRC will review blinded interim safety results (4 weeks of follow-up)
after 15% of subjects have received their first injection and will allow administration of the first
dose of Ad26.Mos4.HIV/placebo (first injection) in this study (VAC89220HPX2003) only if no
significant safety concerns are identified.
1.1.1.5. 
Mosaic gp140 Vaccinations
In an attempt to possibly broaden the nAb response, a trimeric Mosaic gp140 has recently been
developed.25 In guinea pigs, the Mosaic gp140 induced nAb primarily against Clade B virus

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whereas Clade C gp140 trimer induced nAb primarily against Clade A and C viruses. A mixture
of both proteins elicited nAb responses that were comparable to the better of the 2 individual
immunogens in the cocktail, against each virus tested. There was therefore no loss of potency due
to dilution or competition in the mixture and the overall immunogenicity was superior to and
broader than either immunogen given alone.
1.1.2. 
Clinical Studies
1.1.2.1. 
Prototypes and Similar Vaccines
There is considerable clinical experience with vaccines similar to Ad26.Mos.HIV,
Ad26.Mos4.HIV, and gp140 that demonstrated their class safety and tolerability.
Ad5 and Ad26 Vaccines
In 2 previous HIV-efficacy studies utilizing Ad5, a trend towards increased HIV-1 infection was
observed in vaccine recipients as compared with placebo recipients.7,13 The HVTN 502/Step
(Merck Ad5) study showed no efficacy and a trend towards increased HIV-1 infections in vaccine
recipients as compared with placebos in the subgroup of men who were baseline Ad5 seropositive
and uncircumcised.7 The HVTN 503/Phambili (Merck Ad5, MRKAd5) study was terminated and
unblinded early, but follow-up of these individuals revealed increased HIV-1 infections in vaccine
recipients as compared with placebo, particularly in men, which occurred after approximately 24
months of follow-up during the unblinded period.13 There was also differential dropout of high-
risk placebos during this time period. Additionally, a third study, the HVTN 505 (NIH VRC
deoxyribonucleic acid [DNA]/Ad5) study14, revealed no efficacy at the interim analysis. More
HIV-1 infections were observed in vaccine recipients as compared with placebos in this study,
including after the DNA prime and prior to the Ad5 boost, but these differences were not
statistically meaningful. To clearly understand whether vaccine-associated increase of HIV-1
acquisition has occurred in one or more studies, a meta-analysis was recently conducted using up-
to-date participant-level data from the 3 efficacy trials and three Phase 1-2 studies.15 The meta-
analysis provides evidence for increased risk associated with the MRKAd5 vaccine overall and in
various subgroups except circumcised and Ad5-negative men. While the meta-analysis does not
provide a reliable basis for predicting whether rAd5-vectored vaccines for other pathogens or other
rAd-vectored vaccines for HIV-1 would increase susceptibility to infection in HIV-1 at-risk
populations, for large efficacy trials of such vaccines it provides a rationale for adding monitoring
plans enabling detection of such increased susceptibility.
The mechanism for this possible increase in HIV-1 acquisition risk remains unclear, but a leading
hypothesis involves activation of vector-specific CD4+ T-lymphocytes at mucosal surfaces
following Ad5 vaccination, potentially resulting in increased targets for HIV-1 infection.6,14 This
hypothesis has never been directly evaluated in humans with Ad5 vectors. Nevertheless, to assess
the extent of mucosal CD4+ T-cell activation with Ad26 vectors, a randomized, double-blinded,
placebo-controlled clinical study (Integrated Preclinical/Clinical AIDS Vaccine Development,
IPCAVD-003) was performed to determine whether vaccination of healthy human subjects with
an Ad26 vector expressing HIV-1 Env would result in increased numbers or activation status of
total or vector-specific CD4+ T-lymphocytes in the colorectal mucosa. The findings of this study

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are reassuring in that this vector did not detectably increase the numbers or activation status of
total or vector-specific CD4+ T-cells in colorectal mucosa in humans3.
The rationale to continue clinical development of Ad26 vector-based vaccines for HIV-1 is based
on data showing that: (1) Ad26 is biologically substantially different than Ad5; (2) Ad26-based
vaccines afford superior protective efficacy compared with Ad5-based vaccines against SIVMAC251
challenges in rhesus monkeys; and (3) Ad26 did not increase the number or activation status of
total or vector-specific CD4+ T-lymphocytes at mucosal surfaces in humans following vaccination
in a randomized, double-blind, placebo-controlled clinical study (IPCAVD-003).
In 3 Phase 1 studies (IPCAVD-001, IPCAVD-003, and IPCAVD-0041)18, Ad26.ENVA.01, at IM
doses over the range 109 to 1011 vp, was found to induce Env-specific humoral and cell-mediated
responses when given on up to 3 occasions to more than 200 healthy subjects. Ad26.ENVA.01
was generally well tolerated in these studies. An IM dose of 5x1010 vp was found to provide the
optimal balance of immunogenicity and reactogenicity. Therefore, this is the dose of
Ad26.Mos.HIV chosen for further evaluation in this study.
In IPCAVD-003, 24 HIV-1 negative subjects were randomized 3:1 to receive a single vaccination
with Ad26.ENVA.01 or placebo. Eight of the subjects were Ad26 seropositive at screening. The
T-cell responses by IFNγ ELISPOT assays were slightly lower in the baseline Ad26-seropositive
subjects; ICS and enzyme-linked immunosorbent assay responses proved comparable between
subjects who were Ad26 seropositive and Ad26 seronegative at baseline, both in peripheral blood
and in colorectal mucosa. In addition, systemic and mucosal responses persisted for at least 1 year
in the majority of subjects after a single IM vaccine dose. These data suggest that the impact of
baseline Ad26 nAbs, at the titers observed in that study, on the immunogenicity of this
Ad26 vaccine is modest. Additionally, there were no consistent increases in Ad26-specific CD4+
T-lymphocyte responses at mucosal surfaces following vaccination in either Ad26-seronegative or
Ad26-seropositive subjects.
A subset of volunteers in IPCAVD-001 and IPCAVD-004 was evaluated for shedding in urine and
respiratory secretions after vaccination and during intercurrent illnesses; all shedding samples were
negative for adenovirus.1,4
gp120 Vaccines
A monovalent gp120 protein (AIDSVAX B) was tested in 671 healthy subjects at 3 doses, 100,
300, and 600 mcg.17 The 300-mcg dose was found to be the most effective, inducing a higher Ab
response without significant side effects. In the Thai trial RV14426, the only vaccine study to date
to demonstrate efficacy in prevention of acquisition of HIV, a bivalent gp120 protein (AIDSVAX
B/E; 300-mcg dose) was used as a booster following priming with a recombinant canarypox vector
(ALVAC-HIV) and afforded more than 30% protection from infection in the absence of either
CD8+ T-cells or nAb to primary HIV isolates. Therefore, a similar dose (250 mcg) of Clade C
gp140 was chosen for evaluation in this study.
For subjects who will receive a combination of Clade C and Mosaic gp140, the total dose will be
250 mcg (125 mcg of each protein). The total dose of aluminum phosphate adjuvant and gp140

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protein (Clade C gp140 mixed 1:1 with Mosaic gp140) will not exceed the maximum doses that
were tested in previous GLP toxicity studies (TOX10872 and TOX10873), ie, 250 mcg total gp140
protein + 425 mcg aluminum phosphate adjuvant.
1.1.2.2. 
Current Studies
At the time of initial protocol writing (issued date 29 February 2016), 2 ongoing FIH studies in
healthy HIV-uninfected subjects were evaluating safety/tolerability and immunogenicity of the
following vaccines:
 
Clade C gp140 (HIV-V-A003).
 
Ad26.Mos.HIV, Modified Vaccinia Ankara (MVA)-Mosaic, and Clade C gp140
(HIV-V-A004; FIH for Ad26.Mos.HIV).
One additional study was planned in healthy HIV-uninfected subjects to evaluate
safety/tolerability and immunogenicity of the following vaccines: Ad26.Mos4.HIV and Clade C
gp140 (VAC89220HPX2004; FIH for Ad26.Mos4.HIV).
HIV-V-A00318,19 is a single-center, randomized, placebo-controlled, double-blind, FIH Phase 1
study to evaluate safety/tolerability, and immunogenicity of 2 dose levels (50 and 250 mcg) of
Clade C gp140, with or without aluminum phosphate adjuvant, in healthy HIV-uninfected adult
subjects. The blinded evaluation that was performed by the Data Monitoring Committee (DMC)
at Week 6 (2 weeks after all of the 50 enrolled subjects had received their second and last
vaccination) showed that Clade C gp140, administered as 50 or 250 mcg, with or without
aluminum phosphate adjuvant, was well tolerated and no safety concerns were identified. The
DMC concurred with proceeding with the clinical development as planned and with administration
of Clade C gp140 in HIV-V-A004.
HIV-V-A00418,19 is a multi-center, randomized, parallel-group, placebo-controlled, double-blind
Phase 1/2a study to evaluate safety/tolerability, and immunogenicity of various regimens
containing Ad26.Mos.HIV, MVA-Mosaic, and/or Clade C gp140 (with aluminum phosphate
adjuvant) components in approximately 400 healthy HIV-uninfected adult subjects. As pre-
specified in the protocol, enrollment was paused when approximately 10% of subjects had received
their first injection (Ad26.Mos.HIV/placebo) and the Protocol Safety Review Team (PSRT) has
reviewed blinded safety data of 2 weeks after this first injection of 39 subjects and on 18 June 2015
all members agreed that the study could resume enrollment. The independent DMC also reviewed
the blinded 2 week safety data after 30% of subjects had their first vaccination and unblinded 2
week safety data after 10% of subjects had their third vaccination (Ad26.Mos.HIV/MVA-
Mosaic/placebo and Clade C gp140/placebo). In both instances, they recommended continuing the
study without modification.
VAC89220HPX2004 is a randomized, parallel-group, placebo-controlled, double-blind
Phase 1/2a clinical study to evaluate the safety/tolerability and immunogenicity of a regimen
including tetravalent Ad26.Mos4.HIV and a regimen including trivalent Ad26.Mos.HIV in 198
healthy HIV-uninfected adult men and women aged 18 through 50 years. Better Clade C responses

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are to be expected with the tetravalent Ad26.Mos4.HIV compared to the trivalent Ad26.Mos.HIV.
A Data Review Committee (DRC) will review blinded safety data (4 weeks of follow-up) after
15% of subjects have received their first injection. Administration of the first dose of
Ad26.Mos4.HIV (first injection) in this study, VAC89220HPX2003, will be allowed only if no
significant safety concerns are identified.
At the time of the writing of the HPX2003 protocol amendment 3, safety and immunogenicity data
from study HPX2004 and the current study HPX2003 had become available. A summary of
information relevant to the current study HPX2003 is provided below. Detailed information is
available in the Investigator’s Brochures of Ad26.Mos4.HIV, Clade C gp140, and Mosaic
gp140.36,37
Study VAC89220HPX2004/HVTN 117: In the Week 72 analysis (final analysis of the main
study), both vaccine regimens evaluated in this study were found to be safe and well tolerated,
with no remarkable differences between the vaccine regimens. The most frequently reported
solicited adverse events post any dose were injection site pain/tenderness, fatigue, headache, and
myalgia. No deaths, AESIs (HIV infections), or grade 4 AEs were reported.  Overall, few SAEs
were reported, one of which was considered related to the study vaccination (SUSAR: rheumatoid
arthritis; refer to the Investigator Brochures36,37 for more information). Few Grade 3 related AEs
and AEs leading to discontinuation were reported.
Throughout the vaccination series and the follow-up period to Week 72, the tetravalent
Ad26.Mos4.HIV was significantly more immunogenic than the trivalent Ad26.Mos.HIV. In
general, the tetravalent group had higher and broader immune responses than the trivalent group.
These differences were present in both binding and functional humoral responses as well as
cellular immune responses after the 3rd vaccination and remained consistent through Week 72.
Furthermore, LTE Week 96 and Week 120 immunogenicity data are available for the ELISA and
ELISpot assay (data on file) from participants who received the tetravalent vaccine during the main
study. Data indicated that both binding humoral responses as well as cellular immune responses
were maintained up to Week 120 in all participants.
Study VAC89220HPX2003/HVTN 118: In the Week 72 analysis (final analysis of the main
study), both  vaccine regimens were found to be well tolerated. The most frequently reported
solicited adverse events post any dose were injection site pain/tenderness, fatigue, headache, and
myalgia. No deaths, SAEs, AESIs (HIV infections) or grade 4 AEs were reported. Few Grade 3
related AEs and AEs leading to discontinuation were reported. Overall, both vaccine regimens
were immunogenic and favor the selection of the bivalent regimen (see Section 3.2).
Study VAC89220HPX2008/HVTN 705 (hereafter abbreviated to HPX2008/HVTN 705) is an
ongoing, multicenter, randomized, parallel-group, placebo-controlled, double-blind Phase 2b
proof-of-concept efficacy study in approximately 2,600 HIV-uninfected sexually active women
aged 18 to 35 years. The study is being conducted in approximately 25 sites, with the majority of
these throughout South Africa. Study participants were selected from populations at high risk of
acquiring HIV infection in southern Africa settings with overall moderate to high HIV incidence.

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The predominant circulating HIV-1 is a Clade C virus. The study is investigating the preventive
vaccine efficacy, safety, and tolerability of a heterologous regimen with 4 vaccinations consisting
of tetravalent Ad26.Mos4.HIV and aluminum phosphate-adjuvanted Clade C gp140, with
vaccinations at Months 0, 3, 6, and 12. The primary analysis recently demonstrated that the vaccine
regimen did not provide statistically significant protection against HIV infection. The vaccine
efficacy over Months 7 to 24 in the per-protocol cohort did not differ significantly from zero, with
a point estimate (95% confidence interval) of 25% (-10% to 49%). The regimen did not cause harm
and was generally well-tolerated.20
1.1.2.3. 
Clinical Safety Experience With the Ad26.COV2.SVaccine
Thrombosis in combination with thrombocytopenia (thrombosis with thrombocytopenia syndrome
[TTS]), in some cases accompanied by internal bleeding, has been observed following vaccination
with the Janssen COVID-19 (Ad26.COV2.S) vaccine. As of 31 August 2021, out of 33,584,049
doses of Ad26.COV2.S administered post-marketing, the following spontaneous reported/solicited
reports of probable TTS cases were identified.c
 
A total of 104 post-marketing events that met the Brighton TTS Case Definition Criteria
Level 1 to 3.7 This corresponds to a reporting ratio of 3.1 per million doses overall.
 
A total of 67 post-marketing events that met the Centers for Disease Control and Prevention
(CDC) TTS Case Definition Criteria Tier 1 to 2.27 This corresponds to a reporting ratio 2 per
million doses overall.
Reports include severe cases of venous thrombosis at unusual sites such as cerebral venous sinus
thrombosis (CVST), splanchnic vein thrombosis and arterial thrombosis, in combination with
thrombocytopenia. Venous thrombosis cases have also been reported at more common sites, eg,
in the lower extremities. The onset of associated symptoms has usually been 1 to 4 weeks, but
sometimes even later following vaccination  (up to 42 days as per the American Society of
Hematology 20211). TTS cases have been reported mostly in women under 60 years of age
although some cases of TTS have also been reported in men and in individuals older than 60 years
of age. Thrombosis in combination with thrombocytopenia has been fatal in some cases. The exact
pathophysiology of TTS is unclear. This event has not been observed to date with any other Janssen
Ad26-based vaccines (including Ad26.Mos4.HIV). Participants should be instructed to seek
immediate medical attention if they develop symptoms such as shortness of breath, chest pain, leg
pain or leg swelling, persistent abdominal pain, severe or persistent headaches, blurred vision, skin
bruising or petechiae beyond the site of vaccination, changes in mental status or the occurrence of
seizures.
Knowledge about TTS continues to evolve, and updates will be made as new data become
available.
c 
Probable TTS is defined as a thrombotic/thromboembolic event reported in combination with a low platelet count
(thrombocytopenia).

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1.2. 
Benefit/Risk Section
1.2.1. 
Known Benefits
The clinical benefits of prime-boost combinations of Ad26.Mos.HIV and Clade C/ Mosaic gp140
have yet to be established.
1.2.2. 
Potential Benefits
Subjects may benefit from clinical testing and physical examination; others may benefit from the
knowledge that they may aid in the development of an HIV vaccine. There is no direct individual
benefit from vaccination for the subjects at the current development stage.
1.2.3. 
Known Risks
This is a first in human study of Mosaic gp140 and therefore the safety profile of this vaccine is
unknown. At the time of initial protocol writing (issued date 29 February 2016), there were limited
safety data available from 2 ongoing Phase 1 studies in which Clade C gp140 is given alone (HIV-
V-A003; N= 50 subjects) or in combination with Ad26.Mos.HIV (HIV-V-A004; N=
approximately 400 subjects). Scheduled reviews of safety data in both studies by the DMC have
not identified any significant safety concerns that have required a change of study conduct.
Please refer to Section 1.1.2.2 for further details of these studies.Ad26- and Ad35-based vaccines
with different gene inserts had also been administered to more than 200 human volunteers in
clinical studies. In these studies, local and systemic reactions, typical of injectable vaccines
occurred. No serious safety concerns were identified in study participants.
In addition, there was extensive clinical experience (N= >10,000 subjects) with HIV Env proteins
such as gp120 or gp140 proteins that are structurally-related to Clade C/ Mosaic gp140. In these
studies, local and systemic reactions, typical of injectable vaccines occurred. No serious safety
concerns were identified in study participants. Please refer to Section 1.1.2.1 for further details.
At the time of the writing of HPX2003_Protocol_Amend_3, a total of 3,420 healthy adult
participants had been enrolled in clinical studies, of which 429 participants for whom the treatment
assignment is known (unblinded), received at least 1 vaccination with Ad26.Mos.HIV  and
236 participants received at least one vaccination with Ad26.Mos4.HIV.36 At that time, a total of
3,470 healthy adult participants had been enrolled in clinical studies, of which 563 participants,
for whom the treatment assignment is known (unblinded), received gp140. Of these, 362
participants received 250 mcg glycoprotein of Clade C gp140, 108 participants received 50 mcg
glycoprotein of Clade C gp140, and 93 participants received 250 mcg glycoprotein Clade C gp140
+ Mosaic gp140.37
Clinical data on Ad26.Mos.HIV, Ad26.Mos4.HIV, Clade C gp140 and Mosaic gp140
demonstrated that the vaccine regimens have an acceptable safety profile in HIV-uninfected
participants with no emerging significant safety concerns to date.36,37

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1.2.4. 
Potential Risks
The following potential risks for Ad26.Mos.HIV and Clade C/ Mosaic gp140 will be monitored
during the study and are specified in the protocol:
Risks Related to Vaccination
Subjects may exhibit general signs and symptoms associated with administration of a vaccine, or
vaccination with placebo, including fever, chills, rash, myalgia, nausea/vomiting, headache,
dizziness, arthralgia, general itching, and fatigue. In addition, subjects may  experience local
(injection site) reactions such as local itching, warmth, pain/tenderness, erythema/redness,
induration/swelling, arm discomfort or bruising of the skin at the injection site. These side effects
will be monitored, but are generally short-term and do not require treatment.
Syncope can occur in association with administration of injectable vaccines. Syncope can be
accompanied by falls. Procedures should be in place to avoid falling injury. If syncope develops,
subjects should be observed until the symptoms resolve. Fear of injection might lead to fainting
and fast breathing.
Subjects may have an allergic reaction to the vaccination. An allergic reaction may cause a rash,
urticaria or even anaphylaxis. Severe reactions are rare. Medications must be available in the clinic
to treat severe allergic reactions. Subjects with a known allergy, or history of anaphylaxis or other
serious adverse reactions to vaccines or vaccine excipients will be excluded from the study.
The risks related to vaccine-induced seropositivity (VISP) are discussed in Section 9.4.3.
Based on data with other replication-incompetent adenovirus vector vaccines, the risk of shedding
of the Ad26 vector is considered negligible, if any.4
Risks Related to Aluminum
Aluminum is one of the most common metals found in nature and is present in air, food, and water.
Aluminum salts, such as aluminum hydroxide, aluminum phosphate have been used safely in
vaccines for more than 70 years. A few studies have reported an association between vaccines
containing aluminum adjuvants and persistent nodules at the injection site, at an estimated rate of
0.03% to 0.83%.29,30,31,32 Two studies examining infant exposure to aluminum from both diet and
vaccines concluded that aluminum adjuvants at the levels included in vaccines are well below the
calculated safe body burden.33,34 A 2017 review found that current data do not support a causal
relationship between aluminum-containing vaccines and a variety of autoimmune disorders.35
Pregnancy and Birth Control
The effect of the study vaccines on a fetus or nursing baby is unknown, as well as the effect on
semen, so women of childbearing potential, and men having sexual intercourse with women, are
required to agree to practice adequate birth control measures for sexual intercourse from at least
28 days before the first vaccination (or immediately prior to first vaccination for men) until at least
3 months after the last vaccination (see Section 4.1) of the main study and from at least 28 days

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before the late boost vaccination until 3 months after the late boost vaccination (see Section 4.5).
Women who are pregnant or breast-feeding, or are planning to become pregnant while enrolled in
the main study until 3 months after the last vaccination, will be excluded from enrollment into the
main study. In addition, women who are pregnant, breast-feeding or planning to become pregnant
from screening for the late boost vaccination until 3 months after the vaccination will not be
eligible to receive the late boost vaccination.
Risks from Blood Draws
Blood drawing may cause pain/tenderness, bruising, bleeding, becoming lightheaded, dizziness,
vaso-vagal response, and, rarely, infection at the site where the blood is taken.
Risks from Human Leukocyte Antigen (HLA) Testing
Tests results can be used to provide information about how susceptible subjects are to certain
diseases. Used inappropriately, this information could be discriminatory (for example, by
insurance companies). HLA typing can also be used to determine paternity. However, the blood
samples donated will not be used for this purpose; they will be used only to provide study
investigators information about the immune system. The results will be coded to protect subject
identity.
Unknown Risks
There may be other serious risks that are not known.
Subjects may believe that this vaccine provides protection against acquiring HIV infection, and
therefore practice riskier behavior. They will receive extensive counseling throughout the study to
address this potential problem. It is not known if the study vaccines increase or decrease the chance
of becoming HIV infected when exposed, or if upon becoming HIV infected, the person’s disease
course progresses faster or slower to AIDS.
In previous HIV-efficacy studies utilizing Ad5, a trend towards increased HIV-1 infection was
observed in vaccine recipients as compared with placebo recipients. Ad26 is biologically
substantially different than Ad5 and Ad26-based vaccines afford superior protective efficacy
compared with Ad5-based vaccines against SIVMAC251 challenges in rhesus monkeys. Further,
Ad26 did not increase the number or activation status of total or vector-specific CD4+
T-lymphocytes at mucosal surfaces in humans following vaccination in a randomized,
double-blind, placebo-controlled clinical study.
1.2.5. 
Overall Benefit/Risk Assessment
Based on the available data and proposed safety measures, the overall benefit/risk assessment for
this clinical study is considered acceptable for the following reasons:
Preliminary safety data from the ongoing clinical studies and safety data generated with the
related vaccines containing different inserts revealed no significant safety issues (see
Section 1.1.2.1).

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 Only subjects who meet all inclusion criteria and none of the exclusion criteria (specified in
Section 4) will be allowed to participate in this study. The selection criteria include adequate
provisions to minimize the risk and protect the well-being of subjects in the study.
 Safety will be closely monitored throughout the study:
 After each vaccination, subjects will remain in the clinic and be closely observed by study
staff for at least total 30 minutes post-vaccination, or longer if deemed necessary by the
investigator, to monitor the development of any acute reactions. Any unsolicited, solicited
local or systemic adverse events will be documented during this period. Subjects will use a
diary to document solicited local and systemic AEs in the evening after each vaccination and
then daily for the next 7 days at approximately the same time each day.
 Subjects will undergo safety follow-up by study staff 24-72h after each vaccination in the
main study, by telephone, email or clinic visit.
 The investigator or the designee will document unsolicited AEs, SAEs and (potential)
adverse events for special interest (AESIs) as indicated in section 12.3.1.
 Safety evaluations, including physical examinations, vital sign measurements, clinical safety
laboratory testing (performed at screening, pre-dose, 2 weeks after each dose and at Weeks
36, 60 and 72 of the main study) and pregnancy testing (prior to each vaccination), will be
performed at scheduled visits during the study. In addition, a symptom-directed physical
examination, vital sign measurements and pregnancy testing will be performed at screening
for the late boost vaccination.
 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 a
clinically stable endpoint is reached (see Section 12.3.2).
 Severalsafety measures are included in this protocol to minimize the potential risk to subjects,
including the following:
 Since this is a first in human study of Mosaic gp140, enrolment will be paused after the first
6 subjects have received their third vaccination (first vaccination with Mosaic gp140,
depending on assignment), the Protocol Safety Review Committee (PSRT) and Principal
Investigators have reviewed blinded safety data collected 1 day after vaccination and
established that there are no concerns.
 For all subjects, there are pre-specified rules that would result in pausing of further
vaccinations if predefined conditions occur, preventing exposure of new subjects to study
vaccine until the PSRT and/or DRC reviews all safety data (seeSection 11.9).
 Subjects will discontinue study vaccine for the reasons included in Section 10.2.
 Confirmed HIV infection will be monitored as an AESI.
 From the time of local regulatory approval of protocol amendment 5 onwards, TTS will be
monitored as an AESI. Thrombotic events and/or thrombocytopenia are considered to be
potential AESIs.

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 If acute illness (excluding minor illnesses such as diarrhea or mild upper respiratory tract
infection) or fever (body temperature ≥38.0°C) occur at the scheduled time for vaccination,
the subject may be vaccinated within the window allowed for the scheduled vaccination.
 Contraindications to vaccination are included in Section 10.3.
1.3. 
Overall Rationale for the Study
The proposed clinical study in healthy HIV-uninfected subjects will evaluate the safety/tolerability
and the immunogenicity of 2 different prime/boost regimens: priming with Ad26.Mos4.HIV and
boosting with Ad26.Mos4.HIV and either Clade C gp140 plus adjuvant or a combination of
Clade C and Mosaic gp140 plus adjuvant. The goal of this study is to evaluate if the addition of
Mosaic gp140 to Clade C gp140 improves the breadth of humoral immune responses (defined as
immune recognition ofdiverse strains/clades of HIV), which will ultimately assist in the selection
of the best regimen(s) for evaluation in future efficacy studies.
To assess the durability of the immune responses, a Long-term Extension  (LTE) phase of
approximately 3 years was introduced for subjects randomized to Group 1 or Group 2, who have
received all 4 vaccinations and are negative for HIV infection at the end of the main study. The
vaccination regimens of Group 1 and Group 2 (including Ad26.Mos4.HIV and either Clade C
gp140 alone or combined with Mosaic gp140) form the basis for the regimens that will likely be
evaluated in future studies.
In addition, subjects enrolled in the LTE phase will be offered participation in an extension of the
LTE phase. Eligible subjects who consent to participation will be randomized (3:1 ratio) to receive
a boost vaccination with Ad26.Mos4.HIV together with bivalent gp140 or placebo at Week 192 (-
4 weeks/+4 months [Visit 22a], ie, approximately 3 years after the 4th  vaccination of the primary
vaccination series). The goal is to evaluate the impact of a late boost vaccination on the quantity
(including magnitude and breadth) and quality of the immune response (humoral and cellular) as
well as the safety of such late boost vaccination.
2. 
OBJECTIVES, ENDPOINTS, AND HYPOTHESIS
2.1. 
Objectives and Endpoints
Objectives 
Endpoints
Primary
 
To assess safety/tolerability of the different 
vaccine regimens 
 
Solicited local and systemic adverse events (AEs) for 7
days after each vaccination.
 
AEs for 28 days after each vaccination.
 
Discontinuations from vaccination/from study due to
AEs.
 
Serious adverse events (SAEs) and AEs of special
interest (AESIs) of confirmed HIV infection during the
course of the study, including the LTE phase.

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Objectives 
Endpoints
 
To assess Envelope (Env)-binding antibody 
(Ab) responses of the 2 different vaccine
regimens.
 
Env-specific binding Abs (titers and breadth).
 
To assess safety/tolerability of a late boost 
vaccination. 
 
Solicited local and systemic AEs for 7 days after the late
boost vaccination.
 
AEs for 28 days after each the late boost vaccination.
 
SAEs and AESIs of confirmed HIV infection until the
end of the study.
 
AESIs of TTS  for 6 months after the late boost
vaccination
Secondary (applicable to main study, LTE and late boost vaccination)
 
To assess neutralizing Ab (nAb) responses, 
Ab 
functionality 
(as 
assessed 
by
phagocytosis), and Ab isotyping.
 
Env-specific nAbs (titers and breadth)
 
Env-specific functional Abs (phagocytosis score and
breadth).
 
Env-specific binding Ab isotypes (immunoglobulin
(Ig)A, IgG1-4) (titers and breadth).
 
To assess T-cell responses. 
 
Interferon gamma (IFNγ) peripheral blood mononuclear
cell (PBMC) responders to mosaic and potential T-cell
epitopes (PTE) peptide pools of Env/group-specific
antigen (Gag)/polymerase (Pol).
 
Cluster of differentiation (CD)4+ and CD8+ T-cell
functionality (% cells producing ia, IFNγ, interleukin 2
(IL-2), IL-4, tumor necrosis factor α [TNFα]).
 
T-cell development with emphasis on follicular helper T-
cells and memory differentiation.d
Exploratory (applicable to main study, LTE and late boost vaccination)
 
To explore whether the adenovirus serotype 
26 (Ad26) vector is shed after vaccination. 
 
Polymerase chain reaction (PCR) positive for Ad26
sequences (urine and mid-turbinate swab).
 
To explore Ab functionality (other than 
phagocytosis). 
 
Ab functionality evaluation (such as Ab-dependent
cellular 
cytotoxicity 
[ADCC], 
Ab-dependent
complement 
deposition 
[ADCD]; 
excluding
phagocytosis (ie, Ab-dependent cellular phagocytosis
[ADCP]).
 
To explore Ab Fc characterization. 
 
Ab Fc (sub)typing.
 
To explore T-cell and Ab epitope mapping. 
 
Epitope mapping of Ab to Env and T-cell responses to
Gag/Pol/Env (PTE and vaccine peptide pools).
 
To explore gene expression patterns using 
PBMCs. 
 
Regulation of genes (or clusters) that predict specific
immune responses and human leukocyte antigen (HLA)
typing.
 
To explore B-cell responses. 
 
Ab-producing B-cells and characterization of B-cell
memory development.
 
To explore immune responses against the 
viral vector.
 
Ad26 nAbs (titer).
d The follicular helper T-cells and memory differentiation was included as secondary objective for the main study.
Due to difficulty qualifying the assay for these specific markers, these T-cell responses will be considered as an
exploratory objective for the late boost vaccination.

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Objectives 
Endpoints
 
To explore the social impact of participation 
in an HIV-vaccine study for subjects via a
social impact questionnaire.
 
Social impact.
 
To explore durability of the immune 
responses to the vaccine regimens in the 
groups selected for the Long-term Extension 
(LTE) phase.
 
Available samples from time points during the LTE
phase will be used for determination of long-term
durability of the immune responses.
In addition, following exploratory objectives are applicable to the late boost vaccination only:
Objectives 
Endpoints
 
To assess Env-binding antibody Ab responses
following 
late 
boost 
vaccination
approximately 3 years after receiving the 4th
vaccination of the primary vaccination series.
 
Env-specific binding Abs [ELISA] at 3, 7 or 14e days
and 28 days post late boost vaccination (titers and
breadth).
 
To explore the role of Ad26 neutralizing
antibodies on the immune response to a late
boost vaccination.
 
Ad26 neutralizing antibodies at the time of vaccination
relative to the immune response as evaluated by ELISA.
 
To compare the immune response to late
boost vaccination with a vaccine matched to
the primary vaccination series (Group 2) vs a
closely related vaccine (Group 1).
 
Relative 
ELISA 
magnitudes 
between 
groups
randomized to Group 1 vs Group 2 in the main study.
 
To evaluate whether humoral responses 
induced by a late boost vaccination are able to 
mediate protection in non-clinical passive 
transfer studies.
 
Analysis of protection against HIV-related challenge
viruses, such as simian human immunodeficiency virus
(SHIV), in a suitable animal model, and/or in vitro.
See Section 9 for evaluations related to endpoints.
2.2. 
Hypothesis
No formal statistical hypothesis will be tested. The proposed clinical study in healthy
HIV-uninfected subjects will evaluate the safety/tolerability and the immunogenicity of 2 different
prime/boost regimens: priming with Ad26.Mos4.HIV and boosting with Ad26.Mos4.HIV and
either Clade C gp140 plus adjuvant or a combination of Clade C and Mosaic gp140 plus adjuvant.
In addition, the study will evaluate the immunogenicity (humoral and cellular responses) and
safety of a late boost vaccination with Ad26.Mos4.HIV together with bivalent gp140.
3. 
STUDY DESIGN AND RATIONALE
3.1. 
Overview of Study Design
This is a randomized, double-blind, placebo-controlled, parallel-group, multicenter, Phase 1/2a
study in healthy HIV-uninfected adult men and women between the ages 18 to 50 years, inclusive.
A target of150 subjects will participate in this study with 25 subjects in Group 1, 100 subjects in
e Subjects will be divided into three groups: the first 20 enrolled subjects will have the Visit 22b 7 days post late boost, the next 20
enrolled subjects 3 days post late boost and the remainder of the subjects 14 days post late boost.

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Group 2, and 25 subjects in Group 3. Group 1 represents the “base-case” regimen which allows
bridging of data from this study to study VAC89220HPX2004. A diagram of the study design is
provided in Table 1. Randomization will be stratified by region. Subjects will receive IM doses of
study vaccine or placebo at 4 time points: Ad26.Mos4.HIV or placebo will be given at Weeks 0
and 12; Ad26.Mos4.HIV together with either Clade C gp140 plus adjuvant or a combination of
Mosaic and Clade C gp140 plus adjuvant, or placebo will be given at Weeks 24 and 48.
The main study will be conducted in 3 phases: a 6-week screening period; a 48-week vaccination
period during which subjects will be vaccinated at baseline (Week 0) and at Weeks 12, 24, and 48;
and a follow-up period to the final main study visit at Week 72. An LTE phase (approximately
3 years after Week 72) will be performed for subjects randomized to Group 1 or Group 2, who
have received all 4 vaccinations and are negative for HIV infection at Week 72. The vaccination
regimens of Group 1 and Group 2 (including Ad26.Mos4.HIV and either Clade C gp140 alone or
combined with Mosaic gp140) form the basis for the regimens that will likely be evaluated in
future studies.
Subjects enrolled in the LTE phase will be offered participation in an extension to the LTE phase
to investigate the safety and immunogenicity of a late boost vaccination approximately 3 years
after the last vaccination in the main study (depending on availability of IRB and HA approvals
per country/site regulations). Assessment of participants’ eligibility for the late boost vaccination
and vaccination itself will occur within 4 weeks prior to Week 192 until 4 months after Week 192
(Visit 22a, which can be split over several visits). Eligible, consenting subjects will be randomly
assigned (3:1 ratio, see Table 2 below) in a blinded fashion to active vaccination with
Ad26.Mos4.HIV and bivalent gp140 (Group 1b) or placebo (0.9% saline) (Group 2b). The aim is
to have at least 48 participants enrolled in the late boost extension. Randomization will be stratified
by region (USA, East Africa: assuming sufficient numbers from Rwanda in the LTE phase) and
by group randomized to in the main study (Group 1/Group 2). Upon receipt of the late boost
vaccination, participants will be followed up for immunogenicity and safety for a further 12
months or, if they consent to longer follow-up, 24 months. Unblinded interim data analysis
(sponsor unblinding only) will be performed approximately 4 weeks after the last subject received
the late boost vaccination. LTE subjects declining participation or not eligible for participation in
the late boost extension will complete the study at Visit 23 of the LTE phase.
The duration of the subject's participation will be approximately 78 weeks (6-week screening +
72 weeks main study) for subjects not participating inthe LTE phase and approximately 222 weeks
for subjects participating in  the LTE phase but not receiving a late boost vaccination and
approximately 246 (12-month follow-up) or 294 (24-month follow-up) weeks for subjects
receiving a late boost vaccination.
After vaccination, subjects will remain under observation at the study site for at least 30 minutes
for presence of any acute reactions and solicited events. In addition, subjects will record solicited
events in a diary for 7 days post-vaccination as described in Section 9.1.1. See Section 12.1.3 for
grading of severity of solicited AEs. From the time of local regulatory approval of protocol
amendment 5 onwards, TTS is considered to be an AESI. Thrombotic events and/or

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thrombocytopenia are considered to be potential AESIs. Thrombocytopenia is defined as platelet
count below the lower limit of normal (LLN) range for the testing lab. All AESIs of TTS (including
potential AESIs) will be reported to the sponsor from the moment of the late boost vaccination
until 6 months after the late boost vaccination. Each potential AESI will be reviewed to identify a
TTS case. Further safety evaluations will include monitoring of AEs, physical examinations, vital
sign measurements, clinical laboratory tests, and pregnancy testing. Blood samples will be taken
at specific clinic visits to assess immune responses. Subjects will complete a social impact
questionnaire at specific clinic visits. Optional urine samples and mid-turbinate swabs will be
collected from consenting subjects to assess vector shedding. For details see TIME AND EVENTS
SCHEDULE. A PSRT and DRC will be commissioned for this study. See Sections 11.7 and 11.8
for details.
A DRC will review blinded interim safety results (4 weeks of follow-up) after 15% of subjects
have received their first injection in the VAC89220HPX2004 study (FIH for Ad26.Mos4.HIV)
and will allow administration of the first dose of Ad26.Mos4.HIV/placebo (first injection) in this
study (VAC89220HPX2003) only if no significant safety concerns are identified.
The COVID-19 Appendix in Section 18 provides guidance to investigators for managing
study-related procedures during the COVID-19 pandemic.
Table 1: 
Schematic Overview of the Main Study
Group  
N 
Week 0 
Week 12 
Week 24 
Week 48
1b 
25 
Ad26.Mos4.HIV  Ad26.Mos4.HIV
Ad26.Mos4.HIV  
+ 
Clade C gp140 (250 mcg 
+ adjuvant)a 
Ad26.Mos4.HIV
+
Clade C gp140 (250 mcg +
adjuvant)a
2b 
100 Ad26.Mos4.HIV  Ad26.Mos4.HIV
Ad26.Mos4.HIV  
+ 
Clade C + Mosaic gp140 
(250 mcg + adjuvant)a 
Ad26.Mos4.HIV
+
Clade C + Mosaic gp140
(250 mcg + adjuvant)a
3 
25 
Placebo 
Placebo 
Placebo 
+ 
Placebo 
Placebo
+
Placebo
a250 mcg refers to total protein content (Clade C gp140 [250 mcg] alone or a combination of Mosaic gp140
[125 mcg] and Clade C gp140 [125 mcg]). Sterile aluminum phosphate suspension will be used as adjuvant.
Aluminum content will be 0.425 mg/0.5 mL dose.
bAn LTE phase (approximately 3 years after Week 72) will be performed for subjects randomized to Group 1 or
Group 2, who have received all 4 vaccinations and are negative for HIV infection at Week 72.

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Table 2: 
Schematic Overview of the Late Boost Vaccination
Group  
N 
Week 192 (-4 weeks/+4months)
1b 
3*N/41 
Ad26.Mos4.HIV
+
gp140 HIV bivalent vaccine
2b 
1*N/41 
Placebo
+
Placebo
Total dose of Ad26.Mos4.HIV is 5x1010 viral particles (vp)/0.5 mL injection.
gp140 HIV bivalent vaccine: adjuvanted protein co-formulation with a dosage strength of 80 mcg Clade C
protein, 75 mcg Mosaic protein and 425 mcg aluminum (as aluminum phosphate adjuvant). Note: the dose of
Clade C gp140 and/or Mosaic gp140 as separate entities is reported as mcg of glycoprotein: 125 mcg Clade C
gp140 and 125 mcg Mosaic gp140 glycoprotein correspond with 80 mcg and 75 mcg of protein, respectively. 37
1 
Subjects will be randomly assigned in a 3:1 ratio to active vaccine or placebo. The aim is to have at least 48
subjects enrolled in the late boost extension.
3.2. 
Study Design Rationale
Vaccines and Dose Selection Rationale
The rationale behind selection of study vaccines and doses is described in Section 1.
Blinding, Control, Study Phase/Periods, Treatment Groups
A placebo control will be used to establish the frequency and magnitude of changes in clinical
endpoints that may occur in the absence of active treatment. Randomization will be used to
minimize bias in the assignment of subjects to treatment groups, to increase the likelihood that
known and unknown subject attributes (eg, demographic and baseline characteristics) are evenly
balanced across treatment groups, and to enhance the validity of statistical comparisons across
treatment groups. Blinded treatment will be used to reduce potential bias during data collection
and evaluation of clinical endpoints.
Late Boost Vaccination
A late boost vaccination with Ad26.Mos4.HIV in combination with bivalent gp140 or placebo,
approximately 3 years after the fourth vaccination of the primary vaccination series will allow
evaluation of the effect on quantity (including magnitude and breadth) and quality of the resultant
immune responses (humoral and cellular). Results could inform current and future clinical
development programs with this regimen.
Since there is currently no direct or indirect evidence from preclinical or clinical studies that a late
boost vaccination would be needed to confer protection against HIV infection, the timing of the
late boost vaccination, approximately 3 years after the 4th  vaccination of the primary vaccination
series, was selected because ofthe planned duration of the ongoing LTE phase at the time of the
writing of amendment 3.
Based on the data described below, Ad26.Mos4.HIV in combination with bivalent gp140 was
chosen as late boost vaccination in the current study.

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Based on the primary analysis of HPX2003 and HPX2004, the combination of aluminum
phosphate-adjuvanted Clade C gp140 and Mosaic gp140 was selected for inclusion in the 3rd and
4th  vaccinations over the Clade C gp140 alone for use in Phase 3. In line with the bivalent nature
of the Env and Gag-Pol encoding Ad26 vectors, a bivalent mixture of gp140 proteins, which have
complementary sequences, is anticipated to provide improved immunological coverage of the
circulating strains of HIV-1 globally, than either component alone. The favorable safety profile of
Clade C gp140 was maintained by replacing half of the Clade C gp140 dose with Mosaic gp140,
while maintaining the same total glycoprotein dose of 250 mcg (corresponding to a total protein
dose of 155 mcg). Peak immune responses at Month 7, post 3rd vaccination were highly
comparable between the 2 regimens and similar levels of Clade C specific humoral and cellular
responses were observed, demonstrating that the regimen containing the bivalent protein
formulation is globally relevant. The immune responses induced by the combination of Clade C
gp140 and Mosaic gp140 show broad Env-specific binding and functional humoral responses, as
well as high frequencies of Env-specific T cell responses and improved Clade B Env-binding
antibody responses without compromising Clade C Env-binding antibody responses. In addition,
a combination of Clade C and Mosaic gp140 is preferred due to the efficient manufacturability of
Mosaic gp140, which results in higher yields compared to Clade C gp140.
The Month 13 (Week 52; 4 weeks post 4th vaccination) analysis results of HPX2003 strengthened
the original choice of the combination of aluminum phosphate-adjuvanted Clade C gp140 and
Mosaic gp140 over the Clade C gp140 alone. After completion of the vaccination series, the Clade
C responses were still comparable between regimens while the combination of Clade C gp140 and
Mosaic gp140 improved responses beyond Clade C. The geometric mean ratio (GMR) and 95%
CI of binding antibody levels induced by the bivalent relative to the Clade C alone regimen for
Clade B and Mos1 (2.1 [1.7 - 2.7] and 1.4 [1.1 - 1.9], respectively) after completion of the
vaccination series (Figure 1) significantly improved from the Clade C alone regimen.

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Figure 1: 
GMR (95% CI) of the Clade C+ Mos gp140 /Clade C gp140 Groups (Pooling
VAC89220HPX2003-VAC89220HPX2004)
[GIMHUMCEL99A.RTF]
[/SAS/Z HIVVACCINEPX/Z ADHOC/FILES/RE/POOLED HPX2003 HPX2004 W52/PROGRAMS/GIMHUMCEL99A.SAS]
18JAN2019, 08:14
Although not covered by the available GLP toxicology studies36,37, administration of this late boost
vaccination does not trigger a safety concern, considering the long interval (more than 2 years)
between the 4th  vaccination of the primary vaccination series and the late boost administration. A
similar late boost dose administration will be tested in a nonclinical immunogenicity study in
NHPs that completed the primary 4-dose vaccination series more than 2 years ago. In this study,
clinical observations, body weight, body temperature and injection site effects will be monitored.
Initial results from this study will be available prior to administering a late boost dose to study
participants and will provide supportive nonclinical safety data. In addition, for another Ad26-
based vaccine (Ad26.RSV.preF) a GLP toxicology study has been conducted in NZW rabbits in
which the animals received up to 5 vaccinations (at 1x1011 vp per dose) with a 2-week interval
between the injections (TOX11592). In this study no vaccine-related adverse effects were noted,
indicating that a regimen of 5 respective vaccinations with an Ad26-based vaccine is unlikely to
cause a significant safety signal in human subjects.
4. 
SUBJECT POPULATION
Screening for eligible subjects will be performed within 6 weeks before the first administration of
study vaccine or placebo at Week 0.
The inclusion and exclusion criteria for enrolling subjects in this study are described in the
following 2 subsections. If there is a question about the inclusion or exclusion criteria below, the
investigator must consult with the appropriate sponsor representative and resolve any issues before
enrolling a subject in the study. Waivers are not allowed.
For a discussion of the statistical considerations of subject selection see Section 11.3.

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4.1. 
Inclusion Criteria for the Main Study
Each potential subject must satisfy all of the following criteria to be enrolled in the study:
1. 
Each subject must sign an ICF indicating that he or she understands the purpose of and
procedures required for the study and is voluntarily willing to participate in the study.
2. 
Subjects are ≥18 to ≤50 years old on the day of signing the ICF.
3. 
Subject must be healthy on the basis of medical history, physical examination, and vital
signs measurement performed at screening.
4. 
Subjects must meet following laboratory criteria prior to randomization*:
a) Hemoglobin: Women ≥10.5 g/dL; Men ≥11.0 g/dL
b) White cell count: 2,500 to 11,000 cells/mm3, inclusive
c) Absolute neutrophil count: >1,000 cells/mm3
d) Platelets: 125,000 to 450,000 per mm3, inclusive
e) Urinalysis: protein <1+, blood <1+ (men) and <2+ (women), and glucose negative
f) Alanine aminotransferase (ALT)/aspartate aminotransferase (AST): <1.25x upper
limit of normal (ULN)
g) Creatinine: <1.1x ULN
*If laboratory screening tests are out of range, repeat of screening tests is permitted once.
5. 
Subjects are negative for HIV infection at screeningf.
6. 
All female subjects of childbearing potential must have a negative serum (-human
chorionic gonadotropin [-hCG]) at the screening visit, and a negative urine pregnancy
test pre-dose on Day 1g.
7. Contraceptive requirements for heterosexually active female subjects (from 28 days prior
first vaccination up until 3 months after last vaccination)h:
a) If not of childbearing potential: postmenopausal (>45 years of age with amenorrhea
for at least 2 years, or any age with amenorrhea for at least 6 months and a serum
follicle stimulating hormone [FSH] level >40 IU/L) or surgically sterile: no
additional contraception required.
f If possible, the site should select an assay that is US FDA-approved
g Note: negative urine pregnancy also required prior to the second, third, and fourth vaccinations
h Verbal assurance should be given that adequate birth control measures have been followed for 28 days prior to first
vaccination

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b) If of child-bearing potential, but has a vasectomized partner (after vasectomy:
sperm count below the limit of detection if procedure occurred <1 year agoi): no
additional contraception required.
c) If of child-bearing potential, but has a non-vasectomized partner, or partner had a
positive sperm count after a vasectomy procedure of <1 year agoi, should be
practicing an acceptable effective method of contraception. Acceptable methods for
this study include:
 Hormonal contraception,
 Intrauterine device (IUD),
 Intrauterine hormone-releasing system (IUS),
 Male or female condom with or without spermicide,
 Cap, diaphragm or sponge with vaginal spermicide, or
 Sexual abstinence *
*Sexual abstinence is considered an effective method onlyif defined as refraining from heterosexual intercourse during the entire
period of risk associated with the study vaccine. The reliability of sexual abstinence needs to be evaluated in relation to the duration
of the study and the preferred and usual lifestyle of the subject.
Women who are not heterosexually active at screening, but become sexually active during
the study must agree to utilize an effective method of birth controlas mentioned above.
8. 
Contraceptive requirements for heterosexually active male subjects (from day of first
vaccination until 3 months after last vaccination):
a) If male subject had a vasectomy (after vasectomy: sperm count below the limit of
detection if procedure occurred <1 year agoi): no additional contraception required.
b) If male subject did not have a vasectomy or had a positive sperm count after a
vasectomy procedure of <1 year agoi: contraceptive methods will depend on
child-bearing potential of female partner: same criteria to be followed as for female
subjects in inclusion criterion 7.
9. 
A woman must agree not to donate eggs (ova, oocytes) for the purpose of assisted
reproduction after the first dose until 3 months after receiving the last dose of study vaccine
or placebo. A man must agree not to donate sperm after the first dose until 3 months after
receiving the last dose of study vaccine or placebo.
10. Subjects are willing/able to adhere to the prohibitions and restrictions specified in the
protocol and study procedures.
11. Subjects are amenable to HIV-risk reduction counseling and committed to maintaining
behavior consistent with low risk of HIV exposure through the last required protocol clinic
visit.
i Based on verbal confirmation

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12. Subjects are assessed by the clinic staff as being at low risk for HIV infection (for
guidelines see Attachment 2).
13. Passed the test of understanding (TOU, see Attachment 3). The TOU must be completed
by all subjects, as the first assessment after signing ofthe ICF.
4.2. 
Exclusion Criteria for the Main Study
Any potential subject who meets any of the following criteria will be excluded from participating
in the study:
1. 
Subject has chronic hepatitis B (measured by hepatitis B surface antigen test) or active
hepatitis C (measured by hepatitis C virus [HCV] Ab test; if positive, HCV ribonucleic
acid (RNA) PCR test will be used to confirm active versus past HCV infection), active
syphilis infection, chlamydia, gonorrhea, or trichomonasj. Active syphilis documented by
serology unless positive serology is due to past treated infection.
2. 
In the 12 months prior to randomization, subject has a history of newly acquired herpes
simplex virus type 2 (HSV-2), syphilis, gonorrhea, non-gonococcal urethritis, chlamydia,
pelvic inflammatory disease, trichomonas, mucopurulent cervicitis, epididymitis, proctitis,
lymphogranulomavenereum, chancroid, or hepatitis B.
3. 
Subject has any condition, including any clinically significant acute or chronic medical
condition, for which, in the opinion of the investigator, participation would not be in the
best interest of the subject (eg, compromise the well-being) or that could prevent, limit, or
confound the protocol-specified assessments. In case of questions, the investigator is
encouraged to contact the study responsible physician.
4. 
Subject has had major surgery (eg, requiring general anesthesia) within the 4 weeks before
screening, or will not have fully recovered from surgery, or has surgery planned through
the course of the study.
Note: Subjects with planned surgical procedures to be conducted under local anesthesia
may participate.
5. 
Subject has had a thyroidectomy or active thyroid disease requiring medication during the
last 12 months (not excluded: a stable thyroid supplementation).
6. 
Subject has had major psychiatric illness and/or substance abuse problems during the past
12 months (including hospitalization or periods of work disability) that in the opinion of
the investigator would preclude participation.
7. 
Current or past drug/alcohol use that investigator assesses poses any more than a remotely
increased risk of the ability of the subject to comply with the protocol requirements.
8. 
Subject is a woman who is pregnant, or breast-feeding, or planning to become pregnant
while enrolled in this study, or within 3 months after the last dose of vaccine or placebo.
j Trichomonas testing will only be performed for female subjects

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9. 
Subject is a man who plans to father a child while enrolled in this study, or within 3 months
after the last dose of vaccine or placebo.
10. Subject has been in receipt of any licensed vaccine within 14 days prior to the first dose of
study vaccine or placebo, plans to receive within 14 days after the first study vaccination,
or plans to receive within 14 days before or after the second, third or fourth vaccination.
11. Subject has used experimental therapeutic drugs within 30 days of randomization. For
experimental vaccines see exclusion criterion 12.
12. Subject is a recipient of a prophylactic or therapeutic HIV vaccine candidate at any time,
or a recipient of other experimental vaccine(s) within the last 12 months prior to the Day 1
visit (Vaccination 1). For subjects who received an experimental vaccine (except HIV
vaccine) more than 12 months prior to the Day 1 visit (Vaccination 1), documentation of
the identity of the experimental vaccine must be provided to the sponsor, who will
determine eligibility on a case-by-case basis.
Exceptions: Subjects can be included if the vaccine received was subsequently licensed
(see exclusion criterion 10). Subjects with proof of having received only a placebo vaccine
can also be included.
13. Subject is currently in, or plans participation in, another interventional study during the
study period. Participation in an observational study is allowed with prior approval of the
sponsor.
14. Subject has been in receipt of blood or immunoglobulin products in the past 3 months.
15. Subject has known allergies, hypersensitivity, or intolerance to vaccines or its
excipients.18,19
16. Subject has a history of chronic urticaria (recurrent hives) or a history of chronic or
recurrent 
eczema 
and/or 
atopic 
dermatitis 
that 
requires 
oral/parenteral
immunomodulators/immunosuppressors.
17. Subject has chronic or recurrent use of immunomodulators/suppressors, eg, cancer
chemotherapeutic agents, and oral or parenteral corticosteroids. Inhaled, ocular, and
topical steroids are allowed.
18. Subject who cannot communicate reliably with the investigator.
19. Subject is an employee of the investigator or study site, with direct involvement in the
proposed study or other studies under the direction of that investigator or study site, as well
as family members of the employees or the investigator.
NOTE: Investigators should ensure that all study enrollment criteria have been met at screening.
If a subject'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 subject should be excluded from
participation in the study. Section 9.1.3 describes options for retesting. Section 17.5 describes the
required documentation to support meeting the enrollment criteria.

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4.3. 
Prohibitions and Restrictions
Potential subjects must be willing and able to adhere to the following prohibitions and restrictions
during the course of the study to be eligible for participation:
1. 
Agree to follow the contraceptive requirements as noted in Section 4.1 during the main
study.
2. 
Criterion modified per Amendment 3:
Following vaccination, subjects may be excluded from donating blood products due to
induced vaccine seropositivity (see Section 9.4.3) for as long as VISP persists .
3. 
Male subjects must agree not to donate sperm from the first administration of study
vaccine or placebo until 3 months after the last dose of study vaccine or placebo.
4. 
Female subjects must agree not to donate eggs (ova, oocytes) for the purpose of assisted
reproduction until 3 months after the last dose of study vaccine or placebo.
5. 
See Section 8 for details regarding prohibited and restricted medication  during the
study.
6. 
Current drug/alcohol use that investigator assesses poses any more than a remotely
increased risk of the ability of the subject to comply with the protocol requirements.
7. 
Concurrent participation in another interventional study is disallowed during the main
study. Concurrent participation in an observational study without sponsor approval is
disallowed during the main study. Subjects who enter the LTE phase are allowed to
participate in another clinical study, except for studies with investigational HIV
vaccines or other investigational HIV prevention which could be determined to interfere
with HIV vaccine response in this study (ie, CD4-Ig depleting Env-specific Abs), which
are disallowed and studies with experimental immunomodulators/suppressors which
need prior sponsor approval.
8. 
Subjects should be amenable to HIV-risk reduction counseling and committed to
maintaining behavior consistent with low risk of HIV exposure through the last required
protocol clinic visit.

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4.4. 
Inclusion and Exclusion Criteria for the Long-term Extension Phase
Each potential subject must satisfy all of the following inclusion criteria to be enrolled in the LTE
phase of the study upon completion of the final main study visit at Week 72.
1. 
Each subject must sign an ICF appendix for the LTE phase indicating that he or she
understands the purpose of and procedures required for the LTE phase and is voluntarily
willing to participate in the LTE phase of the study.
2. 
Subject must be randomized to Group 1 or Group 2 of the main study.
Note: Upon sponsor unblinding at the Week 28 analysis, subjects randomized to Group 1
or Group 2 who have received all 4 vaccinations, will be asked to participate in the LTE
phase and sign the ICF appendix for the LTE phase at Week 72. Subjects who attend their
Week 72 visit prior to the sponsor's unblinding at the Week 28 analysis, will be enrolled
in the LTE phase if they consent and sign the ICF appendix for the LTE phase and meet
the eligibility criteria for the LTE phase. When the Week 28 sponsor unblinding
subsequently occurs, subjects that started the LTE phase but turn out to have received
placebo in the main study will be withdrawn from the LTE phase.
3. 
Subject must have received all 4 vaccinations of the main study.
4. 
Subject must be negative for HIV infection at the final main study visit at Week 72.
5. 
Subject must be willing/able to adhere to the prohibitions and restrictions for the LTE
phase, as specified in the protocol and study procedures.
Any potential subject who meets any of the following exclusion criteria at the end of the main
study will be excluded from participating in the LTE phase of the study.
1. 
Subject has any condition for which, in the opinion of the investigator, participation would
not be in the best interest of the subject (eg, compromise the well-being) or that could
prevent, limit, or confound the protocol-specified assessments.
2. 
Subject is planning to participate in an  interventional study during the LTE phase,
concerning studies with investigational HIV vaccines or other investigational HIV
prevention which could be determined to interfere with HIV vaccine response in this study
(ie, CD4-Ig depleting Env-specific Abs), which are disallowed.
3. 
Subject is planning to participate in an  interventional study during the LTE phase,
concerning an experimental immunomodulator/suppressor that is not allowed per the
sponsor. Documentation of the identity of the experimental immunomodulator/suppressor
must be provided to the sponsor, who will determine eligibility on a case-by-case basis.

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4.5. 
Inclusion Criteria, Exclusion Criteria and Prohibitions and Restrictions for
the Late Boost Vaccination
Assessment of participants’ eligibility will be performed within 4-6 weeks before the
administration of the late boost vaccination. Each potential participant must satisfy all of the
following inclusion criteria to be eligible to receive the late boost vaccination.
1. 
Each subject must sign an ICF appendix indicating that he or she understands the
purpose of and procedures required for the late boost vaccination and is voluntarily
willing to receive this vaccination.
2. 
Subject must be enrolled in the LTE phase.
3. 
All female subjects of childbearing potential must have a negative serum (-hCG) at
the screening visit, and a negative urine pregnancy test pre-late boost vaccination.
4. 
Contraceptive requirements for heterosexually active female subjects (from 28 days
prior to the late boost vaccination up until 3 months after the late boost vaccination)k:
a) If not of childbearing potential: postmenopausal (>45 years of age with
amenorrhea for at least 2 years, or any age with amenorrhea for at least 6
months and a serum follicle stimulating hormone [FSH] level >40 IU/L) or
surgically sterile: no additional contraception required.
b) If of child-bearing potential, but has a vasectomized partner (after vasectomy:
sperm count below the limit of detection if procedure occurred <1 year agol):
no additional contraception required.
c) If of child-bearing potential, but has a non-vasectomized partner, or partner had
a positive sperm count after a vasectomy procedure of <1 year agol, should be
practicing an acceptable effective method of contraception. Acceptable
methods for this study include:
 Hormonal contraception,
 IUD,
 IUS,
 Male or female condom with or without spermicide,
 Cap, diaphragm or sponge with vaginal spermicide, or
 Sexual abstinence *
*Sexual abstinence is considered an effective method onlyif defined as refraining from heterosexual intercourse during the
entire period of risk associated with the study vaccine. The reliability of sexual abstinence needs to be evaluated in relation to
the duration of the study and the preferred and usual lifestyle of the subject.
k Verbal assurance should be given that adequate birth control measures have been followed for 28 days prior to the
boost vaccination
l Based on verbal confirmation

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Women who are not heterosexually active at screening, but become sexually active
during the time window indicated above must agree to utilize an effective method of
birth control as mentioned above.
5. 
Subject must be negative for HIV infection.
6. 
Subject must be willing/able to adhere to the prohibitions and restrictions for late boost
vaccination, as specified in the protocol and study procedures.
Any potential participant who meets any of the following exclusion criteria will be excluded from
receiving the late boost vaccination.
1. 
Subject has chronic hepatitis B (measured by hepatitis B surface antigen test) or active
hepatitis C (measured by hepatitis C virus [HCV] Ab test; if positive, HCV ribonucleic
acid (RNA) PCR test will be used to confirm active versus past HCV infection.
2. 
Subject has any condition for which, in the opinion of the investigator, participation would
not be in the best interest of the subject (eg, compromise the well-being) or that could
prevent, limit, or confound the protocol-specified assessments.
3. 
Subject is planning to participate in an interventional study from signing of the ICF
addendum until the end of the study, concerning studies with investigational HIV vaccines
or other investigational HIV prevention which could be determined to interfere with HIV
vaccine response in this study (ie, CD4-Ig depleting Env-specific Abs), which are
disallowed.
4. 
Subject is planning to participate in an interventional study from signing of the ICF
appendix  
until 
the 
end 
of 
the 
study, 
concerning 
an 
experimental
immunomodulator/suppressor that is not allowed per the sponsor. Documentation of the
identity of the experimental immunomodulator/suppressor must be provided to the
sponsor, who will determine eligibility on a case-by-case basis.
5. 
Subject is a woman who is pregnant, or breast-feeding, or planning to become pregnant
within 3 months after the late boost vaccination.
6. 
Potential participant has had a psychiatric condition or alcohol or drug abuse problems
(including hospitalization or periods of work disability) that in the opinion of the
investigator would interfere with protocol compliance and thus would preclude
participation.
7. 
Potential participant has a history of TTS or heparin-induced thrombocytopenia and
thrombosis (HITT)
8 
Potential participant received or plans to receive:
a. Recombinant viral vectored COVID-19 vaccines or live attenuated COVID-19
vaccines, either licensed or authorized for emergency use (eg, Emergency Use
Authorization [EUA], Emergency Use Listing [EUL] or similar program) –within
28 days before or after planned administration of the late boost study vaccination.

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b. Other COVID-19 vaccines than the ones specified in bullet c (eg, mRNA vaccines,
protein-based vaccines) either licensed or authorized for emergency use (eg, EUA,
EUL or similar program) –within 14 days before or after planned administration
of the late boost study vaccination.
9 
Participant is planning to participate in an interventional study with COVID-19 vaccines,
from signing of the ICF appendix until the end of the study.
Potential participants must be willing and able to adhere to the following prohibitions and
restrictions to be eligible to receive the late boost extension:
1. 
Agree to follow the contraceptive requirements as noted in the inclusion criterion 4.
2. 
Following vaccination, subjects may be excluded from donating blood products due to
induced vaccine seropositivity (see Section 9.4.3) for as long as VISP persists
3. 
Male subjects must agree not to donate sperm from the administration of the late boost
until 3 months after the boost vaccination.
4. 
Female subjects must agree not to donate eggs (ova, oocytes) for the purpose of assisted
reproduction from the administration of the late boost until 3 months after the boost
vaccination.
5. 
See Section 8 for details regarding prohibited and restricted medication  during the
study.
6. 
Subjects should be amenable to HIV-risk reduction counseling and committed to
maintaining behavior consistent with low risk of HIV exposure through the last required
protocol clinic visit.
5. 
TREATMENT ALLOCATION AND BLINDING
Treatment Allocation
Procedures for Randomization
Central randomization will be implemented in this study. In the main study, subjects will be
randomly assigned to 1 of 3 treatment 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 stratified by region. Similarly, subjects
eligible for the late boost vaccination will be randomly (3:1 ratio) assigned to active vaccine or
placebo. The randomization will be balanced by using randomly permuted blocks and stratified by
region (USA, East Africa: assuming sufficient numbers from Rwanda in the LTE phase) and by
group randomized to in the main study (Group 1/Group 2).

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The interactive web response system (IWRS) will assign a unique treatment code, which will
dictate the treatment assignment and matching study vaccine for the subject. The requestor must
use his or her own user identification and personal identification number when contacting the
IWRS, and will then give the relevant subject details to uniquely identify the subject.
Blinding
The subjects, study-site personnel (except for those with primary responsibility for study vaccine
preparation and dispensing), and investigator will be blinded to study vaccine allocation of the
main study until Week 72, with the exception of the partial unblinding for the start of the LTE
phase (see below). The sponsor will be blinded to study vaccine allocation until the primary (Week
28) analysis (see Section 11.6).
The pharmacist with primary responsibility for vaccine preparation (see Section 14.3) will not be
blinded to the study vaccine. In order to preserve blinding, he/she will place an overlay on the
syringes. Administration of study vaccine to the subjects can be performed by a qualified
healthcare provider from the study site (including the pharmacist who prepared the study vaccine)
who will have, on the day of administration, no other study function related to safety, study data
evaluation or recording of AEs for those subjects that he/she vaccinated on that day.
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 subject.
Data that may potentially unblind the treatment assignment will be handled with special care to
ensure that the integrity of the blind is maintained and the potential for bias is minimized. This can
include making special provisions, such as segregating the data in question from view by the
investigators, clinical team, or others as appropriate until the time of database lock and unblinding.
Under normal circumstances, the blind to study vaccine allocation of the main study should not be
broken by the investigator until the end of the main study and the Week 72 electronic data capture
(eDC) database is finalized for the subjects, study-site personnel (except for those with primary
responsibility for study vaccine preparation and dispensing), and investigator. However, for the
purpose of the LTE phase, the investigator, the study-site personnel, and the subject will be
informed if the subject qualifies for the LTE phase (ie, subject is randomized to Group 1 or
Group 2: qualifies, subject is randomized to Group 3: does not qualify) when the subject reaches
the Week 72 visit, or as soon as possible following Week 72 upon  sponsor unblinding at the
Week 28 analysis. This will result in the partial unblinding of the investigator, the study-site
personnel, and the subjects, as they will be informed if the subject qualifies for the LTE phase but
will not be informed which qualifying group the subject was randomized to.
The subjects, study-site personnel (except for those with primary responsibility for study vaccine
preparation and dispensing), and investigator will be blinded to study vaccine allocation of the late
boost vaccination until the subject’s last visit. The sponsor will be blinded until the interim data
analysis approximately 4 weeks after the last subject received the late boost vaccination.

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The investigator may in an emergency determine the identity of the treatment by contacting the
IWRS. While the responsibility to break the code in emergency situations resides solely with the
investigator, it is recommended that the investigator contact the sponsor or its designee if possible
to discuss the particular situation, before breaking the blind. Telephone contact with the sponsor
or its designee will be available 24 hours per day, 7 days per week. In the event the blind is broken,
the sponsor must be informed as soon as possible. The date and reason for the unblinding must be
documented by the IWRS, in the appropriate section of the case report form (CRF), and in the
source document. The documentation received from the IWRS indicating the code break must be
retained with the subject's source documents in a secure manner.
Subjects who have had their treatment assignment unblinded should continue to return for safety
and immunogenicity evaluations, but will be withdrawn from study vaccine administration (see
Section 10.2).
6. 
DOSAGE AND ADMINISTRATION
During the main study, each subject will receive doses of study vaccine or placebo at 4 time points
according to randomization, on Weeks 0, 12, 24, and 48, administered by IM injection into the
deltoid. Subjects eligible and consenting for the late boost vaccination will receive an additional
dose of Ad26.Mos4.HIV in combination with bivalent gp140 or placebo at Week 192 -4 weeks/+
4 months (ie, approximately 3 years after the 4th vaccination of the primary vaccination series).
For visits with only one injection (ie, at Week 0 and 12), preferably the deltoid of the non-dominant
upper arm is used. When 2 injections are to be given at one visit (ie, at Week 24, 48 and late boost
vaccination), it is required to use a different deltoid for each injection. Two injections in the same
deltoid are allowed only if medically indicated.
For information on vaccination windows, see Section 9.1.2. If a subject cannot be vaccinated
within the allowed window, then that vaccination should not be administered. However, if the
window is missed due to a study pause (see Section 11.9), vaccination will be assessed on  a
case-by-case basis, upon discussion between sponsor and investigator. If a subject misses more
than one study vaccination, he/she will be withdrawn from further study vaccination (see
Section 10.2).

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Table 3: 
Description of Interventions
Test articles 
Ad26.Mos4.HIV  
Clade C gp140
with aluminum
phosphate
Clade C gp140
+ Mosaic gp140
with aluminum
phosphate*
gp140 HIV
bivalent 
vaccine*
Placebo
Description  
See Section Vaccine Information.
Dose/delivery 
(0.5 mL 
injection) 
5x1010 viral 
particle (vp) 
250 mcg Clade
C gp140, mixed
with aluminum
phosphate 
adjuvant
(0.425 mg
aluminum)
125 mcg Clade 
C gp140 + 125 
mcg Mosaic 
gp140, mixed 
with aluminum 
phosphate 
adjuvant (0.425 
mg aluminum) 
80 mcg Clade C
gp140/75 mcg
Mosaic gp140/
aluminum
phosphate
adjuvant
(425 mcg
aluminum)
0.9% saline
Frequency  
Week 0, 12, 24, 
48, and Week 
192** (if 
applicable) 
Week 24 and 48 Week 24 and 48
Week 192** (if 
applicable) 
Week 0, 12, 24,
48, and Week
192** (if
applicable)
Delivery
method
IM in deltoid 
IM in deltoid 
IM in deltoid 
IM in deltoid 
IM in deltoid
Delivery 
instructions
Refer to the Study Procedures Manual for details.
* The dosage of DP in the gp140 HIV bivalent vaccine (late boost vaccination) is identical to the dosage of DP in the co-
administered separate gp140 formulations (main study) . However, there has been a change of unit for the reported gp140
concentration from mg/mL glycoprotein to mg/mL protein. This will not impact the dose strength of gp140 in the vial or
administered to the participants in the late boost extension, compared to the main study, but the gp140 concentration will be
expressed in protein instead of glycoprotein in the specification. Consequently, 125 mcg Clade C gp140 and 125 mcg Mosaic
gp140 of glycoprotein correspond with 80 mcg Clade C gp140 and 75 mcg Mosaic gp140 of protein, respectively.
** The late boost vaccination is to be administered at Week 192 -4 weeks/+4 months, ie, approximately 3 years after the 4th
vaccination of the primary vaccination series.
7. 
TREATMENT COMPLIANCE
Subjects will receive doses of study vaccine or placebo at 4 or 5 time points administered by IM
injection by qualified study-site personnel at the study sites.
The date and time of each study vaccine administration will be recorded in the CRF.
8. 
PRESTUDY AND CONCOMITANT MEDICATION
Prestudy medication administered up to 30 days before the screening visit will be recorded in the
CRF at screening. In case a subject received an experimental vaccine more than 12 months prior
to the Day 1 visit (Vaccination 1) and is determined to be eligible, administration of this
experimental vaccine will be recorded in the CRF. For participants that consent to receive the late
boost study vaccination, any COVID-19 vaccination must also be recorded at screening, regardless
of how long before screening the vaccination took place.
Concomitant medication must be recorded in the CRF throughout the study from the signing of
the ICF to the final main study visit at Week 72 and from the day of late boost vaccination until
28 days thereafter, if applicable. Beyond these time windows, only concomitant therapies given in
conjunction with an SAE or in conjunction with AESIs of TTS will be collected. In addition, any
chronic or recurrent use of immunomodulators/suppressors, oral or parenteral corticosteroids (see

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below), any allowed vaccination and/or any HIV prevention medication  and any COVID-19
vaccination should be recorded in the CRF.
Use of any experimental medication (including experimental vaccines other than the study
vaccine) during the main study is disallowed. Vaccination with any licensed vaccine within the
14 days prior to or after any dose of study vaccine or placebo is prohibited. However, if a vaccine
is indicated in a post-exposure setting (eg, rabies or tetanus), it must take priority over the study
vaccine. Subjects who enter the LTE phase are allowed to use any experimental medication during
the LTE phase, irrespective of them receiving the late boost vaccination, except for:
- studies with investigational HIV vaccines or other investigational HIV prevention which
could be determined to interfere with HIV vaccine response in this study  (ie, CD4-Ig
depleting Env-specific Abs), which are disallowed and studies with experimental
immunomodulators/suppressors which are disallowed from signing of the ICF appendix
for the late boost vaccination until the end of the study or would need prior sponsor
approval if the subject will not receive the late boost vaccination.
- Vaccination with COVID-19 vaccines that have been either licensed or authorized for
emergency use (eg, EUA, EUL, or similar program) must take priority over the study
vaccine. The interval between late boost study vaccination and administration of a
recombinant viral vectored COVID-19 vaccine or a live attenuated COVID-19 vaccine
should be at least 28 days. The interval between study vaccination and administration of
other types of COVID-19 vaccines (eg, mRNA vaccines, protein-based vaccines) should
be at least 14 days.
- For participants planning to receive the late boost study vaccination, concomitant
participation in an interventional study with COVID-19 vaccines is not allowed.
Study subjects can receive medications, such as acetaminophen, non-steroidal anti-inflammatory
drugs, or antihistamines as needed, although their use must be documented and use of these
medications as routine prophylaxis prior to study vaccination is discouraged.
Chronic or recurrent use of:
 
Immunomodulators/suppressors, eg, cancer chemotherapeutic agents
 
Oral or parenteral corticosteroids, eg, glucocorticoids
is an exclusion criterion for the main study (Section 4.2), and these medications are prohibited
during the main study. During the LTE phase, use of these medications is discouraged, except
when required by the medical condition of the subject, and each use should be reported during
clinical visits. In case a subject uses or is planning to use these medications at the time of the late
boost vaccination, it should be discussed with the sponsor on a case-by-case basis if this subject is
allowed to receive the late boost vaccination. Ocular and topical steroids are allowed, as well as
inhaled steroids for the treatment of pulmonary conditions.

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The sponsor must be notified in advance (or as soon as possible thereafter) of any instances in
which prohibited therapies are administered.
9. 
STUDY EVALUATIONS
9.1. 
Study Procedures
9.1.1. 
Overview
The TIME AND EVENTS SCHEDULE summarizes the frequency and timing of immunogenicity
and safety measurements applicable to the study.
Evaluation of the safety/tolerability and immunogenicity of the vaccine regimens will include
laboratory assessments, physical examinations by clinical staff, and subject reports on signs and
symptoms following vaccinations. Additional unscheduled study visits may be required if in the
investigator’s opinion, further clinical or laboratory evaluation is needed.
Subjects will be provided with a thermometer, ruler, and subject diary to measure and record body
temperature and solicited local (at injection site) and systemic events.
The diary includes instructions how to capture the data and grading scales to assess severity of the
symptoms. The study staff is responsible for providing appropriate training to the subject to avoid
missing or incorrect data. The diary card will be reviewed by the study personnel at visits indicated
on the TIME AND EVENTS SCHEDULE. If the diary card review is missed, the diary card will
be reviewed in the following visit. If a participant misses a vaccination, the diary covering the
period after the missed vaccination does not have to be filled in.
From screening to the final main study visit at Week 72, the total blood volume to be collected
from each subject will be approximately 1,200 mL. The total blood volume to be collected during
the LTE phase (Group 1 and Group 2) in case the subject does not receive the boost vaccination
will be approximately 470 mL over a 3-year period. In case subjects receive the boost vaccination,
the total blood volume collected from the start of the LTE phase until 12 months post late boost
will be approximately 1,201 mL. For subjects followed-up to 24 months post late boost, an
additional 145,5 mL of blood will be collected. The total blood volume to be collected is
considered to be within the US Department of Health and Human Services (HHS) Office for
Human Research Protections (OHRP), and US Food and Drug Administration (FDA) guidelines
of 550 mL in any 8-week period. Volumes for humoral immunogenicity testing will be
approximately 20 to 30 mL/visit and for cellular immunogenicity testing approximately 50-102
mL/visit except for the Visit 22c (subjects who received the late boost vaccination), during which
200 mL of blood will be collected.
Repeat or unscheduled samples may be taken for safety reasons or for technical issues with the
samples.

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9.1.2. 
Visit Windows
The maximum screening period is 6 weeks.
For the study visits, following windows will be allowed as indicated:
 Visit 3: Day 15 ± 5 days
 Visit 4: Day 29 ± 5 days
 Visit 5: Day 85 -1 week, +3 weeks (second vaccination)
 Visit 6*: Visit 5 + 14 days (Day 99) ± 5 days
 Visit 7*: Visit 5 + 28 days (Day 113) ± 5 days
 Visit 8: Day 169 -1 week, +3 weeks (third vaccination)
 Visit 9*: Visit 8 + 7 days (Day 176) ± 1 day
 Visit 10*: Visit 8 + 14 days (Day 183) ± 5 days
 Visit 11*: Visit 8 + 28 days (Day 197) ± 5 days
 Visit 12: Day 253 ± 5 days
 Visit 13: Day 337 -1 week, +3 weeks (fourth vaccination)
 Visit 14*: Visit 13 + 14 days (Day 351) ± 5 days
 Visit 15*: Visit 13 + 28 days (Day 365) ± 5 days
 Visit 16: Day 421 ± 3 weeks
 Visit 17: Day 505 ± 3 weeks
 Visit 18 to 21 inclusive and Visit 23/Visit 23a*: Days 673 (Week 96), 841 (Week 120),
1009 (Week 144), 1177 (Week 168), and 1513 (Week 216) ± 4 weeks
 Visit 22/Visit 22a: Day 1345 (Week 192) -4 weeks/+4 months
 Visit 22b*: Visit 22a + 3, 7 or 14 days** (Day 1348 [-1/+2 days], 1352 [± 3 days] or 1359
[± 3 days]; Week 193)
 Visit 22c*: Day 1373 ± 2 weeks (Week 196)
 Visit 22d*, 24*, and 25* (optional visit): Days 1429 (Week 204), 1513 (Week 216), 1681
(Week 240) and 2017 (Week 288)

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The visit window for the optional vector shedding assessments will be ± 1 day for every visit. For
those vector shedding visits that are also included in the general study schedule (Visit 3 and 4), the
± 1 day window will apply instead of the general ± 5 day window listed above.
*If a subject is not vaccinated on the given day of vaccination, the timings of the visits 1,
2 and 4 weeks post-vaccination of the main study and the Visits 22b, 22c, 22d, 23a, 24, and 25
following late boost vaccination (see TIME AND EVENTS SCHEDULE) will be determined
relative to the actual day of vaccination.
** Subjects will be divided into three groups: the first 20 enrolled subjects will have the Visit 22b
7 days post late boost, the next 20 enrolled subjects 3 days post late boost and the remainder of the
subjects 14 days post late boost.
If a subject cannot be vaccinated within the allowed window, then that vaccination should not be
administered. However, if the window is missed due to a study pause (see Section 11.9) or a special
situation such as a pandemic (see e.g. Section 18, COVID-19 APPENDIX: GUIDANCE ON
STUDY CONDUCT DURING THE COVID-19 PANDEMIC), vaccination will be assessed on a
case-by-case basis upon discussion between investigator and sponsor. If a subject misses more
than 1 study vaccination, he/she will be withdrawn from further study vaccination  (see
Section 10.2).
For the LTE and late boost extension phases (from Week 72 onwards): If a visit can't be scheduled
within the allowed window, it will be assessed on a case-by-case basis upon discussion between
investigator and sponsor whether this visit can still be performed.
9.1.3. 
Screening Phase (Week -6 to 0)
Only healthy subjects negative for HIV infection (if possible, an assay that is FDA-approved
should be selected) and complying with the inclusion and exclusion criteria specified in Section 4,
Subject Population, will be included into the study. The investigator or designee will provide
detailed information on the study to the subjects and will obtain written informed consent prior to
each subject’s participation in the study. All the procedures described in the TIME AND EVENTS
SCHEDULE and TIME AND EVENTS SCHEDULE FOR OPTIONAL VECTOR SHEDDING
ASSESSMENT will only take place after written informed consent has been obtained.
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 6 weeks prior to first vaccination. However, no study
specific procedures, other than screening assessments, will be performed until the subject has
signed the study-specific ICF. The study-specific ICF date and time will be entered into the CRF.
The non-study specific ICF will be considered source data.
During screening, subjects must pass the TOU, a questionnaire provided to the subject to document
his/her understanding of the study (see Section 16.1 and Attachment 3). The TOU must be
completed by all subjects, as the first assessment after signing of the ICF. Adaptations to the TOU
are allowed for local purposes, after IRB/IEC and sponsor approval.

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The following evaluations will be performed to determine eligibility requirements as specified in
the inclusion and exclusion criteria:
 
Medical history
 
Complete physical examination, including weight and height
 
Vital signs measurement
 
Review of pre-study medications
 
HIV-risk assessment (see Attachment 2) and counseling on avoidance of HIV infection, for
both male and female subjects
 
Review of inclusion/exclusion criteria
 
Blood sampling for complete blood count (CBC) with differential and platelets, blood
chemistry, hepatitis B/C serology, and HIV testing (including pre- and post-HIV-test
counseling)
 
Sexually-transmitted infection (STI) testing (syphilis, chlamydia, gonorrhea, trichomonas
[trichomonas for female subjects only; urine or vaginal swab may be used])
 
Contraceptive counseling for both male and female subjects
 
Female subjects of childbearing potential: serum -hCG pregnancy testing
 
Urinalysis
General eligibility for this clinical study will be dependent on results of laboratory tests and the
medical assessment. Study subjects who qualify for inclusion based on the medical history,
physical examination, and laboratory results will be contacted and scheduled for vaccination (Visit
2) within 6 weeks from signing ICF.
Subjects with laboratory values or vital signs not meeting eligibility criteria on the screening visit
may have one repeat testing during the screening period if the abnormality is not clinically
significant and may be a testing aberrancy. The screening visit may be split into multiple
days/visits.
After medical history, physical examination, and laboratory data have been reviewed for
completeness and adherence to inclusion/exclusion criteria, the subject can be deemed to be
eligible for the study.
All AEs will be recorded on the CRF, from signing of the study-specific ICF onwards, together
with information about any concomitant medications.
If a subject is a screen failure, but at some point in the future is expected to meet the subject
eligibility criteria, the subject may be rescreened on one occasion only. Subjects who are
rescreened will be assigned a new subject number, undergo the informed consent process, and then
restart a new screening phase.

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Subjects who consent to the optional vector shedding assessment (see Section 9.1.8) may have
baseline samples taken during screening instead of pre-vaccination on Day 1.
9.1.4. 
Vaccination
Visit 2/Randomization/Vaccination 1
After re-check of inclusion/exclusion criteria (including concomitant medication), abbreviated,
symptom-directed physical examination (including weight measurement), measurement of vital
signs, and a urine pregnancy test (for women of childbearing potential), eligible subjects will be
randomized as described in Section 5.
If medical status and/or physical examination suggest(s) significant changes have occurred since
screening, the clinically relevant screening assessments will be repeated and the Day 1 visit
rescheduled, provided that the rescheduled visit is within 42 days of the initial screening
assessment.
Pre-dose samples for hematology, biochemistry, HIV testing, urinalysis, and immunogenicity will
be collected. HLA will be tested using the baseline blood sample.
Pre- and post-dose AEs (including SAEs, AEs leading to treatment discontinuation, and AESIs of
confirmed HIV infection) will also be collected, together with information about any concomitant
medications.
Study vaccine will be prepared by the site pharmacist, who will place an overlay on the syringes
(to preserve blinding) and will send it to the clinic. Administration of study vaccine to the subject
can be performed by a qualified healthcare provider from the study site (including the pharmacist
who prepared the study vaccine) who will have, on the day of administration, no other study
function related to safety, study data evaluation or recording of AEs for those subjects that he/she
vaccinated on that day.
After each vaccination, subjects will remain under observation at the study site for at least
30 minutes for presence of any acute reactions and solicited events (see Section 9.3), and vital
signs measurement will be repeated.
Subjects will be provided with a thermometer, ruler, and subject diary to measure and record
solicited events for 7 days post-vaccination (day of vaccination and the subsequent 7 days).
In addition to an HIV-risk assessment (see Attachment 2), counseling related to avoidance of HIV
infection, pre- and post-HIV-test counseling, and contraceptive counseling will be provided to all
subjects (men and women).
Optional urine samples and mid-turbinate swabs will be collected for vector shedding assessments
from consenting subjects.

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Visit 5/Vaccination 2
An abbreviated, symptom-directed physical examination  (including weight measurement) and
measurement of vital signs will be performed for all subjects pre-vaccination. A urine pregnancy
test must be performed before vaccination for women of childbearing potential, and results must
be available and negative prior to vaccination. Pre-dose samples for hematology, biochemistry,
HIV testing, and urinalysis will be collected. A pre-dose blood sample for the humoral
immunogenicity assays will be drawn.
Pre- and post-dose AEs (including SAEs, AEs leading to treatment discontinuation, and AESIs of
confirmed HIV infection) will also be collected, together with information about any concomitant
medications.
Study vaccine will be prepared by the site pharmacist, who will place an overlay on the syringes
(to preserve blinding) and will send it to the clinic. Administration of study vaccine to the subject
can be performed by a qualified healthcare provider from the study site (including the pharmacist
who prepared the study vaccine) who will have, on the day of administration, no other study
function related to safety, study data evaluation or recording of AEs for those subjects that he/she
vaccinated on that day.
After each vaccination, subjects will remain under observation at the study site for at least
30 minutes for presence of any acute reactions and solicited events (see Section 9.3), and vital
signs measurement will be repeated.
Subjects will be provided with a thermometer, ruler, and subject diary to measure and record
solicited events for 7 days post-vaccination (day of vaccination and the subsequent 7 days).
In addition to an HIV-risk assessment (see Attachment 2), counseling related to avoidance of HIV
infection, pre- and post-HIV-test counseling, and contraceptive counseling will be provided to all
subjects (men and women).
Subjects will complete a social impact questionnaire (Attachment 4).
Visit 8/Vaccination 3
The procedures for Visit 8 will be the same as at Visit 5 as detailed above. No social impact
questionnaire will be completed.
Visit 13/Vaccination 4
The procedures for Visit 13 will be the same as at Visit 5 as detailed above.
9.1.5. 
Post-vaccination Follow-up Phase
Visits 2a, 3, and 4
At Visit 2a (24-72 hours post-vaccination), a member of the site staff will have a (remote) safety
follow-up communication with the subject (by e-mail, telephone, or visit, according to the
subject’s preference). The subject will be brought in for a clinic visit based on this assessment, if

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deemed necessary by the investigator/sub-investigator or upon request of the subject. A (remote)
safety follow-up communication 24-72 hours post-vaccination is not required if the vaccination
was missed.
Visit 3 is a clinic visit that will include an abbreviated, symptom-directed physical examination
(including weight measurement), vital signs measurement, recording of concomitant medications
and any AEs (including SAEs, AEs leading to treatment discontinuation, and AESIs of confirmed
HIV infection), and review of the diary for 7 days post-vaccination (day of vaccination and the
subsequent 7 days). Samples will be collected for safety laboratory testing (CBC and serum
chemistry) and the humoral immunogenicity assays. In addition to an HIV-risk assessment (see
Attachment 2), counseling related to avoidance of HIV infection will be provided to all subjects.
Optional urine samples and mid-turbinate swabs will be collected for vector shedding assessments
from consenting subjects.
Visit 4 is a clinic visit that will include an abbreviated, symptom-directed physical examination
(including weight measurement), vital signs measurement, recording of concomitant medications
and any AEs (including SAEs, AEs leading to treatment discontinuation, and AESIs of confirmed
HIV infection), and collection of samples for humoral and cellular immunogenicity assays. In
addition to an HIV-risk assessment (see Attachment 2), counseling related to avoidance of HIV
infection will be provided to all subjects.
Visits 5a, 6, and 7
The procedures for Visits 5a, 6, and 7 will be the same as for Visits 2a, 3, and 4, respectively.
Exception: for Visit 6, both cellular and humoral immunogenicity assays will be done.
Visits 8a, 9, 10, and 11
The procedures for Visits 8a, 10, and 11 will be the same as for Visits 2a, 3, and 4, respectively.
Exception: for the sentinel group of 6 subjects, Visit 8a will need to be an actual visit 1 day
post-vaccination (only valid for Visit 8a, not required for Visit 2a, 5a, or 13a). And for Visit 10,
both cellular and humoral immunogenicity assays will be done.
Visit 9 is a clinic visit for safety follow-up only, and will include an abbreviated, symptom-directed
physical examination (including weight measurement), vital signs measurement, and recording of
concomitant medications, AEs (including SAEs, AEs leading to treatment discontinuation, and
AESIs of confirmed HIV infection) and review of the diary for 7 days post-vaccination (day of
vaccination and the subsequent 7 days). In addition to an HIV-risk assessment (see Attachment 2),
counseling related to avoidance of HIV infection will be provided to all subjects. Note: If on Visit
9, the 7-day diary observation period is not complete, the diary will be returned at the subsequent
visit.
Visit 12
Visit 12 is a clinic visit for safety follow-up only, and will include an abbreviated, symptom-
directed physical examination  (including weight measurement), vital signs measurement,
recording of concomitant medication, recording of SAEs, AEs leading to treatment

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discontinuation, and AESIs of confirmed HIV infection, and collection of samples for safety
laboratory testing (CBC and serum chemistry). In addition to an HIV-risk assessment (see
Attachment 2), counseling related to avoidance of HIV infection will be provided to all subjects.
Visits 13a, 14, and 15
The procedures for Visits 13a, 14, and 15 will be the same as at Visits 2a, 3, and 4, respectively.
Exception: no special requirements for the sentinel group for Visit 13a. And for Visit 14, both
cellular and humoral immunogenicity assays will be done.
9.1.6. 
Second Year Follow-up Phase
Follow-up visits will be performed at the clinic at Week 60 and 72 (Visits 16 and 17). Each visit
includes a physical examination (abbreviated at Week 60, full at Week 72, both including weight
measurement), vital signs measurement, recording of concomitant medications, recording of
SAEs, AEs leading to treatment discontinuation, and AESIs of confirmed HIV infection, and
collection of samples for immunogenicity and safety laboratory testing (CBC and serum
chemistry). In addition to an HIV-risk assessment (see Attachment 2), counseling related to
avoidance of HIV infection will be provided to all subjects. Optional urine samples and
mid-turbinate swabs will be collected for vector shedding assessments from consenting subjects.
At the final main study visit (Week 72), samples for HIV testing and urinalysis will be collected.
Pre- and post-HIV-test counseling will be provided to all subjects. Subjects will also complete a
social impact questionnaire (Attachment 4).
9.1.7. 
Early Withdrawal/Exit Visit
In the event of early withdrawal from the main study (ie, before Week 72), an exit visit will be
conducted as soon as possible. The following procedures will be performed: an abbreviated,
symptom-directed physical examination  (including weight measurement), vital signs
measurement, recording of concomitant medications and any AEs (including SAEs, AEs leading
to treatment discontinuation, and AESIs of confirmed HIV infection), and collection of samples
for safety laboratory testing (CBC and serum chemistry), the immunogenicity assays, urinalysis,
and HIV testing. In addition to an HIV-risk assessment (see Attachment 2), counseling related to
avoidance of HIV infection, pre- and post-HIV-test counseling, and contraceptive counseling will
be provided to all subjects (men and women). A urine pregnancy test will be carried out for women
of childbearing potential. Additionally, subjects will complete a social impact questionnaire
(Attachment 4).
9.1.8. 
Vector Shedding Evaluations
Vector shedding sampling is optional. The target is to include approximately 30 subjects. Urine
samples (approximately 5-10 mL) and mid-turbinate swabs (culture swab in universal transport
medium) for vector shedding assessments will be collected at selected sites according to the TIME
AND EVENTS SCHEDULE FOR OPTIONAL VECTOR SHEDDING  ASSESSMENT  from
consenting subjects. Ad26 vector shedding will be analyzed by PCR.

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9.1.9. 
Long-term Extension Phase
An LTE phase (approximately 3 years after Week 72) will be performed for subjects randomized
to Group 1 or Group 2, who have received all 4 vaccinations and are negative for HIV infection at
Week 72.
The sponsor will be unblinded to study treatment at the Week 28 analysis and will notify the
investigator and study-site personnel of subjects randomized to Group 1 or Group 2. At Week 72,
subjects randomized to Group 1 or Group 2 who have received all 4 vaccinations, will be asked to
participate in the LTE phase and sign the ICF appendix for the LTE phase. During the first visit of
the LTE phase, the remaining eligibility criteria for the LTE phase will be verified. Subjects who
attend their Week 72 visit prior to the sponsor’s unblinding at the Week 28 analysis, will be
enrolled in the LTE phase if they consent and sign the ICF appendix for the LTE phase and meet
the eligibility criteria for the LTE phase. When the Week 28 sponsor unblinding subsequently
occurs, subjects that started the LTE phase but turn out to have received placebo in the main study
will be withdrawn from the LTE phase.
If signing the ICF appendix is not possible at Week 72, signing should be performed at an extra
visit (Visit 17bis) as soon as possible after Week 72 and at the latest before any assessment is done
on the first visit of the LTE phase.
Subjects will attend follow-up visits at the clinic from Week 96 until the final visit at Week 216.
Each visit includes recording of any SAEs, AESIs of HIV infection, and concomitant medications
(any medication given in conjunction with an SAE, as well as any recurrent or chronic use of
immunomodulators/suppressors and corticosteroids), and collection of samples for cellular and
humoral immunogenicity assays.
Samples for HIV testing will be collected. In addition to an HIV-risk assessment, counseling
related to avoidance of HIV infection, pre- and post-HIV test counseling will be provided to all
subjects.
Also, at each visit, subjects will complete a social impact questionnaire (Attachment 4).
Approximately at the time of the Visit 22 of the LTE phase, subjects will be informed on the option
to participate in an extension to the LTE phase, including an additional boost vaccination. See
Section 9.1.10 for more information. Subjects not willing to participate will continue the LTE
phase as outlined in the TIME AND EVENTS SCHEDULE FOR THE LONG-TERM
EXTENSION PHASE (FROM WEEK72 ONWARDS, GROUP 1 AND GROUP 2).
9.1.10. 
Late Boost Vaccination
Assessments are summarized in the TIME AND EVENTS SCHEDULE FOR THE LATE BOOST
EXTENSION. Only subjects enrolled in the LTE phase who are complying with the inclusion and
exclusion criteria specified in Section 4.5 will be eligible to receive a late boost vaccination. The
investigator or designee will obtain written informed consent prior to any assessment of the late
boost extension.

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Screening of subjects and vaccination will be performed at Week 192 -4 weeks/+4 months (ie,
approximately 3 years after the 4th  vaccination of the primary vaccination series), ie, Visit 22a,
which may be split into several visits within the specified time window. Screening should occur
within 4-6 weeks before the administration of the late boost vaccination.
No study procedures specific to the late boost vaccination will be performed until the subject has
signed the appendix to the ICF. The ICF date and time will be entered into the CRF.
The following evaluations will be performed to determine eligibility requirements as specified in
the inclusion and exclusion criteria:
 
Abbreviated symptom-directed physical examination, including weight
 
Vital signs measurement
 
Review of pre-boost medications
 
HIV-risk assessment (see Attachment 2) and counseling on avoidance of HIV infection, for
both male and female subjects
 
Review of inclusion/exclusion criteria
 
Blood sampling for hepatitis B/C serology, and HIV testing (including pre- and post-HIV-test
counseling)
 
Contraceptive counseling for both male and female subjects
 
Female subjects of childbearing potential: serum -hCG pregnancy testing
General eligibility for boost vaccination will be dependent on results of the medical assessment.
Study subjects who qualify to receive the late boost vaccination based on this assessment will
receive the vaccination within the -4 week/+ 4 month time window to Visit 22a.
Subjects vital signs not meeting eligibility criteria on the screening visit may have one repeat
testing during the screening period.
Screen failures should continue the LTE phase as outlined in Section 9.1.9.
After re-check of inclusion/exclusion criteria, abbreviated, symptom-directed physical
examination (including weight measurement), measurement of vital signs, and a urine pregnancy
test (for women of childbearing potential), eligible subjects will be randomized as described in
Section 5. If the vaccination occurs on the same day as the screening, the pre dose vital signs
assessment and physical examination do not need to be repeated.
If medical status and/or physical examination suggest(s) significant changes have occurred since
screening, the clinically relevant screening assessments will be repeated and the vaccination visit
rescheduled, provided that the rescheduled visit is within 42 days of the initial screening
assessment and all screening assessments and vaccination are still possible within the -4 week/+4
month time window around Visit 22a (Week 192).
Pre-dose samples for immunogenicity will be collected.

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Pre- and post-dose AEs (including SAEs, AEs leading to treatment discontinuation, and AESIs
[confirmed HIV infection and TTS]) will also be collected, together with information about any
concomitant medications. If the vaccination occurs on the same day as the screening pre-dose AEs
will only be collected once.
Study vaccine will be prepared by the site pharmacist, who will place an overlay on the syringes
(to preserve blinding) and will send it to the clinic. Administration ofstudy vaccine to the subject
can be performed by a qualified healthcare provider from the study site (including the pharmacist
who prepared the study vaccine) who will have, on the day of administration, no other study
function related to safety, study data evaluation or recording of AEs for those subjects that he/she
vaccinated on that day.
After the late boost vaccination, subjects will remain under observation at the study site for at least
30 minutes for presence of any acute reactions and solicited events (see Section 9.3), and vital
signs measurement will be repeated.
Subjects will be provided with a thermometer, ruler, and subject diary to measure and record
solicited events for 7 days post-vaccination (day of vaccination and the subsequent 7 days).
In addition to an HIV-risk assessment (see Attachment 2), counseling related to avoidance of HIV
infection, pre- and post-HIV-test counseling, and contraceptive counseling will be provided to all
subjects (men and women). If the vaccination occurs on the same day as the screening HIV risk
assessment, contraceptive counselling, and pre-dose counselling on HIV will only be performed
once.
Subjects will complete a social impact questionnaire (Attachment 4).
Subjects will have a follow-up clinic visits approximately 3, 7 or 14 days post boost (Visit 22b
[Week 193]; first 20 subjects 7 days post late boost, next 20 subjects 3 days post late boost and the
remainder of the subjects 14 days post late boost). This visit will include the recording of all
concomitant medications and AEs (including SAEs, AEs leading to treatment discontinuation, and
AESIs [confirmed HIV infection and TTS]) and review of the diary for 7 days post-vaccination
(day of vaccination and the subsequent 7 days). Samples will be collected for humoral and cellular
immunogenicity assays.
Subsequent follow-up visits will occur 1 (Visit 22c [Week 196]), 3 (Visit 22d [Week 204]), 6
(Visit 23a), 12 (Visit 24), and, optionally (separate consent to be provided), 24 months post late
boost (Visit 25), calculated from the actual day of vaccination. Assessments during these visits
include the recording of concomitant medications: all concomitant medications until 28 days post
vaccination and from then onwards, concomitant medication given in conjunction with an SAE or
AESI of TTS, any chronic or recurrent use of immunomodulators/suppressors, oral or parenteral
corticosteroids, any allowed vaccination and/or any HIV prevention medication, including any
COVID-19 vaccination. Solicited AEs will be recorded until 7 days post vaccination and
unsolicited AEs until 28 days post vaccination. SAEs and AESIs of confirmed HIV infection will
be recorded until the end of the study. AESIs of TTS will be recorded up to Visit 23a (6 months

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after the late boost vaccination). Each visit will include collection of humoral and cellular
immunogenicity assays. In addition, at Visit 23a, 24 and 25 (if applicable), HIV testing will be
performed, an HIV-risk assessment (see Attachment 2) will be performed and counseling related
to avoidance of HIV infection will be provided to all subjects. At Visit 23 subjects will complete
a social impact questionnaire (Attachment 4).
In the event of early withdrawal from study following the late boost vaccination (ie, before Week
240), an exit visit will be conducted as soon as possible. The following procedures will be
performed: an abbreviated, symptom-directed physical examination (including weight
measurement), vital signs measurement, recording of concomitant medications and any AEs
(including SAEs, AEs leading to treatment discontinuation, and AESIs [confirmed HIV infection
and TTS, if applicable]), the immunogenicity assays, and HIV testing. In addition to an HIV-risk
assessment (see Attachment 2), counseling related to avoidance of HIV infection, and pre- and
post-HIV-test counseling will be provided to all subjects (men and women). Additionally, subjects
will complete a social impact questionnaire (Attachment 4).
9.2. 
Immunogenicity Evaluations
Humoral immune response assays will include, but are not limited to Env-Ab-binding assays
(ELISA), virus neutralization assay, and assays for Ab functionality. Additional assays may
include binding antibody assays to evaluate the breadth and isotypes of Ig induced and passive
transfer assays.
Cellular immune response assays will include, but are not limited to IFNγ ELISPOT assay, ICS,
and multiparameter flow cytometry.
9.3. 
Safety Evaluations
Details regarding the PSRT and DRC are provided in Section 11.7 and 11.8, respectively.
Any clinically significant abnormalities that are considered related to vaccination persisting at the
end of the study/early withdrawal will be followed by the investigator until resolution or until a
clinically stable endpoint is reached (see Section 12.3.2).
The study will include the following evaluations of safety and tolerability according to the time
points provided in the TIME AND EVENTS SCHEDULE.
AEs
All AEs will be reported from the time the signed and dated study-specific ICF is obtained until
28 days after first dose of study vaccine, and thereafter, pre-dose on the day of injection and for
28 days after each subsequent dose of study vaccine. 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 on the CRF AE page. All SAEs and
AEs leading to discontinuation from the study vaccination and AESIs ofconfirmed HIV infection
are to be reported from signing of study-specific ICF onwards for the duration of the study (see
Section 12.3.1 for details). Adverse events will be followed by the investigator as specified in

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Section 12.1.3. From the time of local regulatory approval of protocol amendment 5 onwards, TTS
is considered to be an AESI. Thrombotic events and/or thrombocytopenia are considered to be
potential AESIs. Thrombocytopenia is defined as platelet count below the LLN range for the
testing lab. All AESIs of TTS, including potential AESIs, will be reported to the sponsor from the
moment of the late boost vaccination until 6 months after the late boost vaccination. Each potential
AESI will be reviewed to identify a TTS case.
For solicited AEs, the following applies.
Solicited AEs
After vaccination, subjects will remain under observation at the study site for at least 30 minutes
for presence of any acute reactions and solicited events. In addition, subjects will record solicited
events in a diary for 7 days post-vaccination. All subjects will be provided with a diary and
instructions on how to complete the diary (Section 9.1.1). Diary information will be transcribed
by the study personnel in the appropriate CRF pages. Once a solicited symptom from a diary is
considered to be of severity Grade 1 or above, it will be referred to as a solicited adverse event.
For AE severity criteria, see Section 12.1.3.
Injection Site (Local) AEs
Subjects will be asked to note in the diary occurrences of pain/tenderness, erythema and
induration/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
induration/swelling should be measured (using the ruler supplied) and recorded daily.
 
Injection Site Pain/Tenderness
Injection site pain (eg, stinging, burning) is an unpleasant sensory and emotional experience
associated with actual or potential tissue damage and occurring at the immunization site (with
or without involvement of surrounding tissue). Injection site tenderness is a painful sensation
localized at the injection site upon palpation and/or movement of the limb. Due to subjective
nature of the reaction, the severity assessment of pain/tenderness is self-reported.12
 
Injection Site Erythema
Injection site erythema is a redness of the skin caused by dilatation and congestion of the
capillaries localized at the injection site. It can best be described by observation  and
measuring.

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 
Injection Site Swelling/Induration
Injection site swelling is a visible enlargement of an injected limb. It may be either soft
(typically) or firm (less typical). Injection site induration is a palpable thickening, firmness,
or hardening of soft tissue, usually has well-demarcated palpable borders, can be visible
(raised or sunken compared to surrounding skin), is often ‘woody’ to touch and has a flat
shape. As differentiation between swelling and induration may be difficult without health care
professional’s assessment, both symptoms have been combined to allow self-assessment by
the subjects. Both swelling and induration can best be described by observation  and
measuring.21,22
Note: any other injection site events not meeting the above case definitions should be reported
separately as unsolicited AEs.
Systemic AEs
Subjects will be instructed on how to record daily temperature using a thermometer provided for
home use. Subjects should record the temperature in the diary in the evening of the day of
vaccination, and then daily for the next 7 days approximately at the same time each day. If more
than one measurement is made on any given day, the highest temperature of that day will be used
in the CRF.
Fever is defined as endogenous elevation of body temperature ≥38°C, as recorded in at least one
measurement.24
Subjects will also be instructed on how to note daily in the diary symptoms for 7 days
post-vaccination (day of vaccination and the subsequent 7 days) of the following events: fatigue,
headache, nausea, myalgia, and chills.
The severity of these solicited systemic AEs will be graded according to the criteria presented in
Section 12.1.3.
Clinical Laboratory Tests
Blood samples for serum chemistry and hematology and a urine sample for urinalysis will be
collected (fasting not required). The investigator must review the laboratory results, document this
review, and record any clinically relevant changes occurring during the study in the AE section of
the CRF. The laboratory reports must be filed with the source documents.
In case a Grade 3 or Grade 4 laboratory abnormality, or any laboratory abnormality accompanied
by clinically relevant signs or symptoms occurs (from the baseline visit onwards), all attempts will
be made to perform a confirmatory test within 48 hours after the results have become available.
After that, laboratory tests will be repeated weekly until values are resolved or stable.

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The following tests will be performed by the local laboratory  (*parameters only measured at
screening):
 
Hematology Panel
-hemoglobin  
-platelet count
-hematocrit
-red blood cell (RBC) count
-white blood cell (WBC) count with differential
A WBC evaluation may include any abnormal cells, which will then be reported by the laboratory.
A RBC evaluation may include abnormalities in the RBC count and/or RBC parameters and/or
RBC morphology, which will then be reported by the laboratory.
In addition, any other abnormal cells in a blood smear will also be reported.
 
Serum Chemistry Panel
-creatinine 
-creatine phosphokinase (CPK)*
-glucose* 
-bilirubin*
-AST  
-FSH (post-menopausal women only)*
-ALT
 
Urinalysis
Dipstick  
-protein
-specific gravity  
-blood
-pH  
-ketones
-glucose
Microscopic reflex testing will be carried out in the event of abnormal urinalysis tests,
except when the investigator considers the abnormal urinalysis result to be from menstrual
origin.
In the microscopic examination, observations other than the presence of WBC, RBC, and casts
may also be reported by the laboratory.
Laboratory values will be graded according to a modified version of the Division of Acquired
Immunodeficiency Syndrome (DAIDS) grading table, Version 2.0 (Attachment 1), and, if
clinically significant, reported as AEs. Laboratory reference ranges will be applied according to
the subject’s sex at birth.
Additional clinical laboratory assessments to be performed are as follows:
 
Serum (at screening of the main study and screening for the late boost vaccination) and Urine
(pre-dose at vaccinations, Week 72, and the early Exit visit of the main study) Pregnancy
Testing for women of childbearing potential only.

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 
Serology (hepatitis B surface antigen [HBsAg], hepatitis C virus Ab; at screening of the main
study and screening for the late boost vaccination)
 
HIV testing (at screening of the main study and screening for the late boost vaccination,
vaccinations, Week 72, the early Exit visit, and at each visit of the LTE phase and each post-
late boost vaccination follow-up visit) (see Section 9.4.1)
 
Syphilis, chlamydia, gonorrhea, trichomonas (trichomonoas for female subjects only; urine or
vaginal swab may be used) at screening of the main study
 
In case of a potential AESI of TTS (see Section 12.3.3.2), a serum sample should be obtained
to test for anti-PF4 at the local laboratory or substitute local laboratory, if possible; repeat
testing may be requested for confirmation upon sponsor discretion. A test for anti-PF4 will
also be performed on a stored pre-vaccination sample, if possible.
Vital Signs (oral or tympanic temperature, pulse/heart rate, blood pressure)
Vital sign measurements will be performed at time points specified in the TIME AND EVENTS
SCHEDULE.
Blood pressure and 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.
Blood pressure and pulse/heart rate measurements should be preceded by at least 5 minutes of rest
in a quiet setting without distractions (eg, television, cell phones).
If any clinically significant changes in vital signs are noted, they will be reported as AEs and
followed to resolution, or until reaching a clinically stable endpoint.
Physical Examination
Full physical examination will be carried out at screening of the main study and at the final main
study visit (Week 72). At all other main study visits and at screening of the late boost vaccination,
an abbreviated, symptom-directed exam will be performed as indicated by the investigator based
on any clinically relevant issues, clinically relevant symptoms, and medical history. Symptom-
directed physical examination may be repeated if deemed necessary by the investigator. Height
will be measured at screening of the main study. Weight will be measured at every study visit
including a physical examination.
Physical examinations will be performed by the investigator or designated medically-trained
clinician. Any screening or baseline abnormality should be documented in the medical history
page of the CRF. Any clinically relevant post-baseline abnormality or any clinically relevant
worsening versus baseline conditions should be documented in the AE pages of the CRF.

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9.4. 
Human Immunodeficiency Virus Testing and Vaccine Induced
Seropositivity
9.4.1. 
HIV Testing
HIV testing will be performed as indicated in the TIME AND EVENTS SCHEDULE.
At screening of the main study and baseline, subjects will be tested for HIV infection, and must be
negative to be entered into the study. If possible, an assay that is US FDA-approved should be
selected.
At all other main study visits that include HIV-testing, a study-specific HIV-testing algorithm
(detailed in the Laboratory Manual) will be followed. Information provided to the clinical staff of
the study site will not include the results of specific tests, but will state only the final interpretation
as “HIV infected” or “HIV uninfected”. This system allows timely HIV testing without
compromising the double-blind nature of the study. The algorithm used for HIV testing throughout
the main study aims to differentiate VISP from true HIV infection (see Section 9.4.3).
During the LTE phase, the study-specific HIV-testing algorithm described above will be followed
as long as treatment assignment is blinded. Upon study unblinding (after the week 72 database
lock), unblinded HIV and VISP results will be reported.
At screening for the late boost vaccination and all subsequent visits of the TIME AND EVENTS
SCHEDULE FOR THE LATE BOOST EXTENSIONTIME AND EVENTS SCHEDULE FOR
THE LATE BOOST , the study-specific HIV-testing algorithm as described above for the main
study will be followed. .Information provided to the clinical staff of the study site will not include
the results of specific tests, but will state only the final interpretation as “HIV infected” or “HIV
uninfected”.
9.4.2. 
Management of Subjects who Become HIV-infected During the Study
Test results performed to confirm the diagnosis will be forwarded to the study staff. Subjects who
become HIV infected during the study, including the LTE phase, will be (see Section 12.3.3.1):
 
Excluded from further vaccinations.
 
Provided counseling and referred for medical treatment.
 
Informed about observational studies monitoring subjects with HIV infection.
 
Excluded from initiation of the LTE phase.
9.4.3. 
VISP
In general, HIV-uninfected subjects who participate in preventative HIV-vaccine studies may
develop HIV-specific antibodies as a result of an immune response to the candidate HIV vaccine,
referred to as VISP. These antibodies may be detected in common HIV-serologic tests, causing
the test to appear positive even in the absence of actual HIV infection. Vaccine Induced
Seropositivity may become evident during the study or after the study has been completed.

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Should an HIV-Ab test give a positive result for a particular subject during the study, the central
lab will carry out a follow-up testing algorithm either to exclude or confirm HIV infection. Further
details of this algorithm are given in the Laboratory Manual.
To avoid possible unblinding as a result of positive HIV testing due to VISP, subjects should not
donate blood during the study. Blood donation options for those subjects who wish to resume
blood donation after the study will be explained at the final study follow-up visit.
In the case of VISP, if, either during the study or after the end of the study, a subject requires an
HIV test outside the study (eg, to obtain a travel visa or insurance, or for medical reasons), he/she
should contact the research center. The center can issue a written statement giving details on VISP
and on the testing algorithm to be followed. If requested by a subject, repeat HIV testing will be
available at most every 3 months to confirm their HIV status. It is highly preferable that this repeat
HIV testing will be performed through the research center. More frequent testing is only allowed
after sponsor approval. Testing for a particular subject will be available as long as VISP is present
for this subject.
Depending on the local availability of a follow-up protocol, subjects could join into such a study
that specifically follows the course of VISP. Such a study may not be available at all sites.
However, if such a study is not available, HIV testing will be provided on request as described in
the previous paragraph.
In addition to providing testing, subjects will always receive pre- and post-test HIV counseling.
9.4.4. 
Social Impact
Subjects in preventive HIV-vaccine clinical studies may experience problems with personal
relationships, employment, education, health care, housing, health, disability or life insurance,
travel, and immigration. In relation to a subject’s family, friends, and/or colleagues, the social
impact could manifest in one or more ways, resulting in social conflicts and stigmatization:
1. The investigational vaccine is thought to be harmful to the subject’s health, including a belief
that it might cause HIV infection.
2. The subject is perceived as HIV infected or at high risk.
3. Repercussions from any VISP.
For these reasons, subjects will complete a social impact questionnaire (Attachment 4; at the time
points specified in the TIME AND EVENTS SCHEDULE) to evaluate any potential consequences
of the subject’s participation. For more information, please refer to the Study Procedures Manual.
9.5. 
Sample Collection and Handling
The actual dates and times of sample collection must be recorded in the CRF or laboratory
requisition form.
See the TIME AND EVENTS SCHEDULE for the timing and frequency of all sample collections.

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Instructions for the collection, handling, storage, and shipment of samples are found in the Study
Procedures 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.
10. 
SUBJECT COMPLETION/DISCONTINUATION OF STUDY TREATMENT/
WITHDRAWAL FROM THE STUDY
10.1. Completion
A subject who is not participating in the LTE phase will be considered to have completed the study
if he or she has completed the assessments at Week 72.
A subject who is participating in the LTE phase will be considered to have completed the main
study if he or she has completed the assessments at Week 72 and will be considered to have
completed the LTE phase if he or she has completed the assessments at the last visit of the LTE
phase (Week 216).
Subjects receiving the late boost vaccination will have completed the study if he or she has
completed the assessments at Week 240, if opting for 12 months of follow-up post-boost, or Week
288, if opting for 24 months of follow-up post- late boost.
10.2. Discontinuation of Study Treatment/Withdrawal from the Study
Discontinuation of Study Treatment
Subjects will be withdrawn from study vaccine administration during the main study for the
reasons listed below. These subjects must not receive any additional dose of study vaccine but
should enter the follow-up phase with assessments of safety and immunogenicity. The subject will
be encouraged to complete the post-vaccination follow-up visits of the last vaccination received
and a 12 and 24 weeks follow-up visit after the last vaccination received, specified as Week 60
and Week 72 in the TIME AND EVENTS SCHEDULE. Additional unscheduled visits may be
performed for safety/tolerability reasons, if needed. In case the subject withdraws before receiving
the first vaccination, the subject is not required to attend follow-up visits. In case of questions, the
investigator is encouraged to contact the study responsible physician. Subjects who have been
prematurely withdrawn from study vaccine administration are not eligible for the LTE phase.
 
Unblinding
 
Anaphylactic reaction following vaccination
 
Pregnancy
 
Any related SAE
 
Any related AE, worsening of health status or intercurrent illnesses that, in the opinion of the
investigator, requires discontinuation from study vaccine
 
Confirmed HIV infection
 
Chronic or recurrent use of immunosuppressants (after discussion with the sponsor)

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 
Missing more than 1 study vaccination
Withdrawal From the Study
Each subject has the right to withdraw from the study at any time for any reason without affecting
the right to treatment by the investigator. The investigator should make an attempt to contact
subjects who did not return for scheduled visits or follow-up. Although the subject is not obliged
to give reason(s) for withdrawing prematurely, the investigator should make a reasonable effort to
ascertain the reason(s) while fully respecting the subject’s rights.
A subject will be withdrawn from the study for any of the following reasons:
 
Lost to follow-up
 
Withdrawal of consent
 
Death
 
Repeated failure to comply with protocol requirements
 
Decision by the sponsor or the investigator to stop or cancel the study
 
Decision by local regulatory authorities or IRB/IEC to stop or cancel the study
If a subject is lost to follow-up, every reasonable effort (at least 2 documented attempts to contact
the subject by telephone and at least one documented written attempt) must be made by the study-
site personnel to contact the subject and determine the reason for discontinuation/withdrawal. The
measures taken to follow-up must be documented.
When a subject withdraws before completing the study, the reason for withdrawal is to be
documented in the CRF and in the source document. Study vaccine assigned to the withdrawn
subject may not be assigned to another subject. Subjects who are vaccinated and who withdraw
will not be replaced. If a subject withdraws early from the study, assessments for early withdrawal
should be obtained (see Section 9.1.7).
Subjects who wish to withdraw consent from participation in the study will be offered a single Exit
visit for safety follow-up (prior to formal withdrawal of consent). They have the right to refuse.
The exit visit is only applicable to the main study until Week 72 and for subjects who received the
late boost vaccination.
A subject who withdraws from the study will have the following options regarding the use of
optional research samples which were collected:
 The collected samples will be retained and used in accordance with the subject’s original
informed consent appendix for optional research samples.
 The subject may withdraw consent for optional research samples, in which case the samples
will be destroyed and no further testing will take place. To initiate the sample destruction
process, the investigator must notify the sponsor study site contact of withdrawal of consent

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for the optional research samples and to request sample destruction. If requested, the
investigator will receive written confirmation from the sponsor that the samples have been
destroyed.
10.3. Contraindications to Vaccination
The following events constitute a contraindication to vaccination at that point in time. If any of
these events occur at the scheduled time for vaccination, the vaccination can be rescheduled (as
long as this is in agreement with the allowed windows, see Section 9.1.2):
 
Acute illness at the time of vaccination. This does not include minor illnesses, such as diarrhea
or mild upper-respiratory tract infection.
 
Fever (oral temperature ≥38.0°C) at the planned time of vaccination.
10.4. Withdrawal From the Use of Samples in Future Research
The subject may withdraw consent for use of samples for research (refer to Section 16.2.5,
Long-term Retention of Samples for Additional Future Research). 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 ICF.
11. 
STATISTICAL METHODS
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 safety and immunogenicity data is
outlined below. Specific details will be provided in the Statistical Analysis Plan.
11.1. Subject Information
For all subjects, demographic characteristics (eg, age, height, weight, body mass index [BMI],
race, and gender), and other baseline characteristics (eg, medical history, concomitant diseases)
will be tabulated and summarized with descriptive statistics.
11.2. Analysis Populations
The safety population will consist of all subjects who received at least one dose of study vaccine,
and for whom any post-dose data is available.
The immunogenicity population will consist of all subjects who received at least one dose of study
vaccine, and who have immunogenicity data from at least one evaluable post-dose blood sample.
The per protocol immunogenicity population will consist of all randomized and vaccinated
subjects for whom immunogenicity data are available, excluding subject samples with major
protocol deviations expecting to impact the immunogenicity outcomes (for example missed
vaccinations, natural infections, etc).

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11.3. Sample Size Determination
The sample size in this study is regarded to be appropriate to assess the safety and tolerability of
the different vaccine regimens. Placebo recipients are included for blinding and safety purposes
and will provide control specimens for immunogenicity assays. With 25 individuals in a vaccine
regimen, the observation of 0 such reactions would be associated with a 95% confidence that the
true rate is less than 12%. For Group 2 with Mosaic and Clade C gp140 (n=100), there would be
95% confidence that the true rate is less than 3% when 0 events are observed. The following table
shows the probabilities of observing at least one AE given true AE rates.
True AE Rate 
Probability of Observing at Least One AE in n Subjects
n = 25 
n = 100
0.1% 
2% 
9.5%
0.5% 
12%  
39%
1.0%  
22% 
63%
2.5% 
47% 
92%
5.0% 
72% 
99%
10.0%  
93% 
100%
The primary population for the safety analyses will consist of all subjects who received at
least 1 dose (Ad26.Mos4.HIV or placebo).
Anticipating a dropout rate of approximately 10%, the sample sizes will allow detection of
approximately 1.85-fold differences in Env-binding Ab titers, generally accepted to be biologically
relevant, between the groups with Mosaic and Clade C gp140 (approximately 90 evaluable
subjects) and their corresponding group with Clade C gp140 only (approximately 22 evaluable
subjects); with 80% probability, assuming a 2-sided 5% Type I error and an SD of 0.4 on the log10
scale.
11.4. Immunogenicity Analyses
Descriptive statistics (actual values and changes from reference) will be calculated for continuous
parameters. Frequency tabulations will be calculated for discrete parameters. Graphical
representations of changes in immunologic parameters will be made as applicable.
No formal hypothesis on immunogenicity will be tested. The analysis of immunogenicity will be
done on the (per protocol) immunogenicity population as defined in Section 11.2.
Breadth of the binding Ab response will be summarized as the number of HIV clades to which a
subject shows an Ab response. Magnitude and breadth of (n)Ab responses will be explored
graphically through the generation of individual magnitude-breadth (M-B) curves. The area under
the M-B curve (AUC) provides an overall summary of the M-B profile. The AUCs will be
compared between groups using the Wilcoxon-Mann-Whitney test.
Differences between groups at a specific time point will be tested for exploratory purposes by a 2-
sample t-test if the data appear to be normally distributed. If not, the non-parametric Wilcoxon
rank sum test will be used. If portions of the measurements are censored below the assay

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quantification limit, the Gehan-Wilcoxon test will be employed. All statistical tests will be 2-sided
and will be considered statistically significant if p<0.05.
Frequency tabulations will be calculated for discrete (qualitative) immunologic parameters.
Significant differences between groups will be determined by a 2-sided Fisher’s exact test.
11.5. Safety Analyses
No formal statistical testing of safety data is planned. Safety data will be analyzed descriptively.
Baseline for all safety parameters will be defined as the last evaluation done before the first dose
of study vaccine.
AEs
The verbatim terms used in the CRF by investigators to identify AEs will be coded using the
Medical Dictionary for Regulatory Activities (MedDRA). All reported AEs and events-related
diary information (solicited local at injection site and systemic, and unsolicited) with onset within
28 days after vaccination (ie, treatment-emergent AEs, and AEs that have worsened since baseline)
will be included in the analysis. For each adverse event, the percentage of subjects who experience
at least 1 occurrence of the given event will be summarized by vaccine group.
Treatment-emergent AEs are AEs with onset during the treatment phase or that are a consequence
of a pre-existing condition that has worsened since baseline. All reported AEs will be included in
the analysis. For each AE, the percentage of subjects who experience at least 1 occurrence of the
given event will be summarized by treatment group. In addition, comparisons between treatment
groups will be provided if appropriate.
Summaries, listings, datasets, or subject narratives may be provided, as appropriate, for those
subjects who die, who discontinue treatment due to an adverse event, who experience a severe or
a serious AE or an AESI.
Summaries and listings may be provided separately for AEs with onset outside the above defined
timeframe and that were reported pre-dose at the moment of subsequent vaccinations.
Solicited local (at injection site) and systemic AEs will be summarized descriptively. The overall
frequencies per vaccine group as well as frequencies according to severity and duration will be
calculated for solicited AEs. In addition, the number and percentages of subjects with at least one
solicited local (at injection site) or systemic AE will be presented. Frequencies of solicited and
unsolicited AEs, separately for all and vaccination-related only, will be presented by System Organ
Class and preferred term.
Clinical Laboratory Tests
Laboratory data will be summarized by type of laboratory test. Laboratory abnormalities will be
determined according to a modified version of the DAIDS grading table, Version 2.0 (Attachment
1), and in accordance with the normal ranges of the clinical laboratory. Laboratory abnormalities
will be tabulated per vaccine group and/or treatment group.

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Vital Signs
The percentage of subjects with values beyond pre-specified limits (see Attachment 1) will be
summarized.
Physical Examination
Physical examination findings will not be tabulated separately. Clinically relevant findings will be
reported as AE and will be tabulated and listed as AEs. BMI will be calculated using the recording
of height at screening.
Social Impact Questionnaire
Data from the Social Impact Questionnaire will be summarized using descriptive statistics.
Vector Shedding Analyses
Vector shedding data will be analyzed descriptively.
11.6. Analysis Time Points
The primary analysis (unblinded, see Section  5) will be performed once all subjects have
completed the Week 28 visit (ie, 4 weeks after the third injection) or discontinued earlier. An
additional analysis will be performed once all subjects have completed the Week 52 visit (ie,
4 weeks after the fourth injection) or discontinued earlier. The final analysis of the main study will
be performed once all subjects have completed their final main study visit at Week 72 or
discontinued earlier. The final analysis of the study will be performed once all included subjects
have completed the last visit of the LTE phase (Week 216) or last post late boost follow-up visit
(Week 240 or Week 288), or discontinued earlier. Additional analyses of the immune responses
during the LTE phase may be performed. An interim analysis of the data from the late boost
vaccination will be performed approximately 4 weeks after the last subject received the late boost
vaccination.
11.7. Protocol Safety Review Team
A PSRT will review blinded safety data reports on a regular basis (at least 2 times per month)
starting from one week after first vaccination until the last subject has completed the Week 52
visit, and thereafter as needed.
Since this study is the FIH administration of Mosaic gp140, after a sentinel group of 6 subjects
receives the third injection, further third injections will be paused until a 1-day safety evaluation
is performed. This evaluation will be performed by the PSRT and the PI(s) of the subjects involved
and will be based on the information received from the investigator(s) by email/telephone.
If a dose of vaccine is considered, by PSRT review, to raise significant safety concerns, all
enrollment and vaccinations will be suspended until recommendations are issued (see
Section 11.9). In specific cases, a DRC meeting will be triggered.

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The PSRT will include, but will not be limited to medical and safety representatives from the
sponsor, a limited number of sites, DAIDS, BIDMC, HVTN, IAVI, and MHRP. The PSRT
responsibilities, authorities, and procedures will be documented in its charter.
11.8. Data Review Committee
A DRC will be established for this study, which will monitor data to ensure the safety and
well-being of the subjects enrolled. The DRC will review data as indicated below. The conclusions
of the DRC will be communicated to the investigators, the IRB/IEC, and the national regulatory
authorities, as appropriate.
The DRC will specifically review safety data (solicited and unsolicited AEs, SAEs, and available
laboratory assessments) at 2 time points following injections of Mosaic gp140:
 
Review blinded safety data (2 weeks of follow-up) after approximately 25 (15%) of subjects
have received their third injection.
 
Review blinded safety data (2 weeks of follow-up) after approximately 50 (30%) of subjects
have received their third injection.
In addition, ad hoc review may be performed further to the occurrence of any AE/SAE leading to
a study holding situation as outlined in Section 11.9, or at request of the PSRT.
The DRC will review blinded data first, but is entitled to and has the right to require submission
of unblinded data if deemed necessary.
The DRC will include medical experts in vaccines and at least one statistician. The DRC can
include members from both inside and outside Janssen, but will not include any study team
personnel or people otherwise directly involved in the study conduct, data management, or
statistical analysis for the study. The DRC responsibilities, authorities, and procedures will be
documented in its charter.
11.9. Study Holding Rules
If an administration of vaccine is considered, by the PSRT, to raise significant safety concerns, all
screening and vaccinations will be suspended until recommendations are issued. The AEs that may
lead to a safety pause or prompt PSRT AE review are summarized below in Table 4. These study
holding rules apply to related AEs that occur up to 4 weeks after vaccination and to SAEs occurring
up to 4 weeks after the last vaccination.

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Table 4: 
AE Notification and Safety Pause/AE Review Rules1
(S)AE and 
Relationship2
Severity  
Site Principal Investigator Action 
PSRT/DRC Action3
SAE, related
Any 
grade 
Notify Study Responsible Physician or designee
AND fax or email SAE form to Global Medical 
Safety Office, immediately and no later than 24 h 
after becoming aware of the event
Immediate pause for PSRT
review of safety data
SAE, not 
related 
Grade 5
Notify Study Responsible Physician or designee
AND fax or email SAE form to Global Medical 
Safety Office, immediately and no later than 24 h 
after becoming aware of the event
PSRT review and
consideration of pause
AE4, related
Grade 3 
or 
Grade 4 
Notify Study Responsible Physician immediately
and no later than 24 h after becoming aware of the
event
PSRT review and
consideration of pause
Three subjects 
with a similar 
related AE5 
Grade 3
or 
Grade 4
Not applicable
Immediate pause for DRC
review of safety data
The contact details of the medical team are in the Contact Information page(s). The Study Responsible
Physician (or designee) is responsible for the immediate notification of PSRT/DRC members and coordination
of a PSRT/DRC meeting.
1 
Applicable for AEs/SAEs occurring up to 4 weeks after the last vaccination. For a Grade 3/4 laboratory related
AE, the test must be repeated at least once, within 48 hours of the site becoming aware of the abnormal value.
PSRT evaluation for consideration of a pause will proceed without waiting for repeat testing. Start of DRC review
will require a confirmation of the laboratory test within 48 hours.
2 
Related: suspicion of relationship between the study vaccine and the AE. Not related: no suspicion of relationship
between the study vaccine and the AE. (Relationship as assessed by investigator)
3 
All sites will be notified immediately in case of a safety pause.
4 
For Grade 3 solicited related AEs, immediate PSRT review is mandatory only if the event persists as Grade 3 for
longer than 3 consecutive days. PSRT evaluation for consideration of a pause will proceed for all other cases not
specified in footnote 4.
5 
Applicable for the following related AEs:
- All Grade 4 AEs (regardless of duration)
- Grade 3 unsolicited AEs (regardless of duration)
- Grade 3 solicited AEs (only if persisting for longer than 3 consecutive days)
After each DRC review of a similar AE, the DRC will indicate the conditions under which they require further
notification and/or review of the subsequent similar AEs.
Vaccinations for an individual subject may be suspended for safety concerns other than those
described in the table, at the discretion of the investigator if he/she feels the subject’s safety may
be threatened. The investigator may ask for a PSRT meeting to be held for any single event or
combination of multiple events which, in his/her professional opinion, jeopardize the safety of the
subjects or the reliability of the data.
Vaccinations for the study may be suspended for safety concerns other than those described in the
table, or before pause rules are met, if, in the judgment of the DRC, subject safety may be
threatened.
For events in the table above, the investigator notifies the sponsor’s study responsible physician
(or designee) immediately, and in all cases within 24 hours at the latest after the site observes, or

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is notified of, the AE, and the study responsible physician (or contacted sponsor’s representative)
then notifies the PSRT immediately. If the case(s) is (are) deemed to fulfill the potential holding
rules, the PSRT will convene within one business day to review these AEs. The PSRT will review
and determine disposition, including whether the DRC needs to review the event(s).
If a study pause is triggered by the PSRT, all screening and vaccinations will be held until review
by the PSRT or DRC is complete. Resumption of screening and study treatment may be determined
by the PSRT or DRC (in consultation with the FDA, if required) following a cumulative review of
the available safety data as outlined in the charter. The clinical sites will be allowed to resume
activities upon receipt of a written notification from the sponsor. As needed, the appropriate
regulatory authorities will be informed in writing of the decision by the PSRT and/or DRC to
resume or discontinue study activities. The site is responsible for notifying their IRB/IEC
according to local standards and regulations. The sponsor is responsible for notifying the FDA.
12. 
AE REPORTING
Timely, accurate, and complete reporting and analysis of safety information from clinical studies
are crucial for the protection of subjects, 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.
Method of Detecting AEs, AESIs, and SAEs
Care will be taken not to introduce bias when detecting AEs, AESIs, or SAEs. Open-ended and
nonleading verbal questioning of the subject is the preferred method to inquire about adverse
event occurrence.
Solicited AEs
Solicited AEs are predefined local and systemic events for which the subject is specifically
questioned and symptoms ofwhich are noted by subjects in their diary (see Section 9.1.1).
Unsolicited AEs
Unsolicited AEs are all AEs for which the subject is specifically not questioned in the subject
diary.
AESIs
For details, see section 12.3.3.

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12.1. Definitions
12.1.1. 
AE Definitions and Classifications
AE
An AE is any untoward medical occurrence in a clinical study subject administered a medicinal
(investigational or non-investigational) product. An AE does not necessarily have a causal
relationship with the treatment. 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.
Note: The sponsor collects AEs starting with the signing of the study-specific ICF  (see
Section 12.3.1 for time of last adverse event recording).
SAE
An  SAE based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for
Human Use is any untoward medical occurrence that at any dose:
 
Results in death
 
Is life-threatening
(The subject was at risk of death at the time of the event. It does not refer to an event that
hypothetically might have caused death if it were more severe.)
 
Requires inpatient hospitalization or prolongation of existing hospitalization
 
Results in persistent or significant disability/incapacity
 
Is a congenital anomaly/birth defect
 
Is a suspected transmission of any infectious agent via a medicinal product
 
Is Medically Important*
*Medical and scientific judgment should be exercised in deciding whether expedited reporting is
also appropriate in other situations, such as important medical events that may not be immediately
life threatening or result in death or hospitalization but may jeopardize the subject 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 adverse event occurs for which there is evidence suggesting a causal
relationship between the study vaccine and the event (eg, death from anaphylaxis), the event must

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be reported as a serious and unexpected suspected adverse reaction by the sponsor to the Health
Authorities and by the investigator to the IRB/IEC according to regulatory and local requirements.
Unlisted (Unexpected) AE/Reference Safety Information
An adverse event is considered unlisted if the nature or severity is not consistent with the applicable
product reference safety information. For Ad26.Mos4.HIV, Clade C gp140, and Mosaic gp140,
the expectedness of an adverse event will be determined by whether or not it is listed in the
Investigator's Brochure.
AE Associated With the Use of the Vaccine
An AE is considered associated with the use of the vaccine if the attribution is related by the
definitions listed in Section 12.1.2.
AESI
Confirmed HIV  infection in a subject during the study is considered an AESI. All AESIs,
irrespective if considered serious or not by the investigator, shall be reported to the sponsor
immediately and aggregate analyses performed either at the end of study and possible at interim
time points during the study. For details of the AESI of TTS, see Section 12.3.3.2.
12.1.2. 
Attribution Definitions
Every effort should be made by the investigator to explain any AE and assess its potential causal
relationship, ie, to administration of the study vaccine or to alternative causes (eg, natural history
of the underlying diseases, concomitant medication). This applies to all AEs, whether serious or
non-serious.
Causality of AEs should be assessed by the investigator based on the following:
Related: there is a reasonable possibility that the study vaccine contributed to the AE.
Unrelated: there is no suspicion that there is a relationship between the study vaccine and the AE;
there are other more likely causes and administration of the study vaccine is not suspected to have
contributed to the AE.
By definition, all solicited AEs at the injection site (local) will be considered related to the study
vaccine administration.
12.1.3. 
Severity Criteria
All AEs, laboratory data, and fever will be coded for severity using a modified version of the
DAIDS grading table, Version 2.0 (Attachment 1).
The severity of solicited AEs will be graded in the diary by the subject based on the severity
assessment provided in the diary and then verified by the investigator using the DAIDS grading
table.

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For AEs not identified in the grading table (eg, diagnosis of HIV infection), the following
guidelines will be applied:
Mild  
Grade 1 
Symptoms causing no or minimal interference with usual social and
functional activities
Moderate 
Grade 2 
Symptoms causing greater than minimal interference with usual social
and functional activities
Severe 
Grade 3 
Symptoms causing inability to perform usual social and functional
activities
Potentially 
life- 
threatening 
Grade 4 
Symptoms causing inability to perform basic self-care functions OR
medical or operative intervention indicated to prevent permanent
impairment, persistent disability
Fatal 
Grade 5 
For any AE where the outcome is death, the severity of the AE is
classified as Grade 5
12.2. Situations Requiring Special Notification
Safety events of interest on a sponsor study vaccine that require expedited notification to the
sponsor 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 involving a sponsor product (with or without subject exposure to the sponsor
study vaccine, eg, name confusion)
 
Exposure to a sponsor study vaccine from breastfeeding
 
AESI of confirmed HIV infectionm
 
AESIs of TTS (including potential AESIs), to be reported to the sponsor within 24 hours of
awareness.
Subject-specific situations requiring special notification should be recorded in the CRF. Any
situation requiring special notification that meets the criteria of an SAE should be recorded on the
SAE form. Additional reporting from the sites to IEC/IRB and HA should be performed according
to local regulations.
m New HIV infection has to be notified to the sponsor within 24 hours of awareness, followed by the completed
questionnaire to collect additional information/data.

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12.3. Procedures
12.3.1. 
All AEs
All AEs and situations requiring special notification (see Section 12.2) will be reported from the
time the signed and dated study-specific ICF is obtained until 28 days (including relevant visit
window, if applicable) after first dose of study vaccine, and thereafter, pre-dose on the day of
injection and for 28 days (including relevant visit window, if applicable) after each subsequent
dose of study vaccine. 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 on the CRF AE page.
All SAEs and AEs leading to discontinuation from the study vaccination (regardless of the causal
relationship) and AESIs ofconfirmed HIV infection are to be reported for the duration of the study.
The sponsor will evaluate any safety information that is spontaneously reported by an investigator
beyond the time frame specified in the protocol.
From the time of local regulatory approval of protocol amendment 5 onwards, TTS is considered
to be an AESI. Thrombotic events and/or thrombocytopenia are considered to be potential AESIs.
Thrombocytopenia is defined as platelet count below the LLN range for the testing lab. All AESIs,
including potential AESIs, will be reported to the sponsor from the moment of the late boost
vaccination until 6 months after the late boost vaccination. Each potential AESI will be reviewed
to identify a TTS case.
All events that meet the definition of an SAE will be reported as SAEs, regardless of whether they
are protocol-specific assessments.
The investigator will monitor and analyze study data including all AE and laboratory data as they
become available and will make determinations regarding the severity of the adverse experiences
and their relation to study vaccine. AEs will be deemed eitherrelated to study vaccine or not related
to study vaccine, according to Section 12.1.2. To ensure that all AEs are captured in a timely
manner, CRFs will be entered in real-time, and subjected to review to identify AEs which may
invoke study pausing rules.
The investigator or designee must review both collected solicited events and other AE CRFs to
insure prompt and complete identification of all events that require expedited reporting as SAEs,
invoke study pausing rules or are other serious and unexpected events.
All AEs, regardless of seriousness, severity, or presumed relationship to vaccine, must be recorded
using medical terminology in the source document and the CRF. 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 CRF their opinion concerning the relationship of the AE to the
study vaccine. All measures required for AE management must be recorded in the source document
and reported according to sponsor instructions.

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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.
For all studies with an outpatient phase, including open-label studies, the subject 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 subject 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 staff only)
 
Site number
 
Subject number
 
Any other information that is required to do an emergency breaking of the blind
12.3.2. 
SAEs
All SAEs occurring during the study must be reported to the appropriate sponsor contact person
by study-site personnel within 24 hours of their knowledge of the event.
Information regarding SAEs will be transmitted to the sponsor using the SAE Form, which must
be completed and signed by a physician from the study site, and transmitted to the sponsor within
24 hours of their knowledge of the event. The initial and follow-up reports of an SAE should be
made by facsimile (fax) or email.
All SAEs that have not resolved by the end of the study, or that have not resolved upon
discontinuation of the subject's participation in the study, must be followed until any of the
following occurs:
 
The event resolves
 
The event stabilizes
 
The event returns to baseline, if a baseline value/status is available
 
The event can be attributed to agents other than the vaccine or to factors unrelated to study
conduct
 
It becomes unlikely that any additional information can be obtained (subject or health care
practitioner refusal to provide additional information, lost to follow-up after demonstration of
due diligence with follow-up efforts)

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Suspected transmission of an infectious agent by a medicinal product will be reported as an SAE.
Any event requiring hospitalization (or prolongation of hospitalization) that occurs during the
course of a subject's participation in a study must be reported as an SAE, except hospitalizations
for the following:
 
Hospitalizations not intended to treat an acute illness or AE (eg, social reasons such as pending
placement in long-term care facility)
 
Surgery or procedure planned before entry into the study (must be documented in the CRF).
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 subject in a study during the entire study period, whether or not the event
is expected or associated with the vaccine, is considered an SAE.
12.3.3. 
Adverse Events of Special Interest
Adverse Events of Special Interest (AESIs) (including potential AESIs) are significant AEs that
are judged to be of special interest because of clinical importance, known or suspected class
effects, or based on nonclinical signals. AESIs (including potential AESIs) will be carefully
monitored during the study by the sponsor.
AESIs (including potential AESIs) must be reported to the sponsor within 24 hours of awareness
irrespective of seriousness (ie, serious and nonserious AEs) or causality following the procedure
described above for SAEs.
AESIs (including potential AESIs) must be reported using the AESI checkbox in the eCRF using
the eCRF completion guidelines.
Specific requirements for the AESI are described below.
12.3.3.1. 
HIV Infection
HIV testing will be carried out at times indicated in the TIME AND EVENTS SCHEDULE.
Subjects will be tested for HIV infection at screening of the main study and baseline, and must be
negative to be entered into the study. If possible, an assay that is US FDA-approved should be
selected. At all other main study visits that include HIV testing, a study-specific HIV testing
algorithm (detailed in the Laboratory Manual) will be followed. During the LTE phase, the study-
specific HIV-testing algorithm described above will be followed as long as treatment assignment
is blinded. Upon study unblinding (after the week 72 database lock), unblinded HIV and VISP
results will be reported. In addition, subjects will need to be HIV negative to be eligible to receive
the late boost vaccination and all post late boost visits include HIV testing. The study-specific
HIV-testing algorithm described above for the main study will be followed as long as treatment
assignment is blinded. Any subject with confirmed HIV infection must be discontinued from any
further study vaccine administration, but should remain in the study and be followed up for safety
and immunogenicity until the end of the study.

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Confirmed HIV infection in a subject during the study is considered an AESI. All AESIs,
irrespective if considered serious or not by the investigator, shall be reported to the sponsor
immediately (see Section 12.2). An aggregate analysis will be performed either at the end of study
and possible at interim time points during the study.
Test results performed to confirm the diagnosis will be forwarded to the study staff. Subjects who
become HIV infected during the study, including the LTE phase, will be (see Section 9.4.2):
 
Excluded from further vaccinations.
 
Provided counseling and referred for medical treatment.
 
Informed about observational studies monitoring subjects with HIV infection.
 
Excluded from initiation of the LTE phase.
12.3.3.2. 
Thrombosis with Thrombocytopenia Syndrome
As described in Section 1.1.2.3, TTS has been observed following vaccination with the Janssen
COVID-19 vaccine 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.1,7
Because this syndrome is rare and not completely understood, all cases of thrombosis and/or
thrombocytopenia will be considered a potential case of TTS and should be reported to the sponsor
within 24 hours of awareness using the SAE form (even in cases that are not considered ‘serious’).
Each potential AESI will be reviewed to identify a TTS case. A Charter will describe the roles and
responsibilities of the Committee appointed to perform this review. A potential TTS case is defined
as:
 Thrombotic events: suspected deep vessel venous or arterial thrombotic events as detailed
in Attachment 5,
and/or
 Thrombocytopenia, defined as platelet count below LLN for the testing lab.
Symptoms, signs, or conditions suggestive of a thrombotic event or thrombocytopenia should be
recorded and reported as a potential 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, a serum sample should be obtained to test for
anti-PF4 at the local laboratory or substitute local laboratory, if possible; repeat testing may be
requested for confirmation upon sponsor discretion. A test for anti-PF4 will also be performed on
a stored pre-vaccination sample, if possible.

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AESIs (including potential AESIs) will require enhanced data collection and evaluation. Every
effort should be made to report as much information as possible about the event to the sponsor in
a reasonable timeframe.
If an event meets the criteria for an SAE (Section 12.1.1), it should be reported using the same
process as for other SAEs.
Treatment and Follow-up Recommendation
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, American
Society of Hematology 20211; British Society of Haematology 20218; CDC 202110). The use of
heparin may be harmful and alternative treatments may be needed. Consultation with a
hematologist is strongly recommended.
12.3.4. 
Pregnancy
All initial reports of pregnancy in female subjects or partners of male subjects must be reported to
the sponsor by the study-site personnel within 24 hours of their knowledge of the event using the
appropriate pregnancy notification form. Abnormal pregnancy outcomes (eg, spontaneous
abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy) are considered SAEs and
must be reported using the SAE Form. Any subject who becomes pregnant during the study must
promptly discontinue further vaccinations but should continue participation in the study for follow-
up (see Section 10.2).
Follow-up information regarding the outcome of the pregnancy will be required. Any postnatal
sequelae in the infant will be collected, if possible.
12.4. Contacting Sponsor Regarding Safety
The names (and corresponding telephone numbers) of the individuals who should be contacted
regarding safety issues or questions regarding the study are listed in the Contact Information
page(s), which will be provided as a separate document.
13. 
PRODUCT QUALITY COMPLAINT HANDLING
A product quality complaint (PQC) is defined as any suspicion of a product defect related to
manufacturing, labeling, or packaging, ie, any dissatisfaction relative to the identity, quality,
durability, or reliability of a product, including its labeling or package integrity. A PQC may have
an impact on the safety and efficacy of the product. Timely, accurate, and complete reporting and
analysis of PQC information from studies are crucial for the protection of subjects, investigators,
and the sponsor, and are mandated by regulatory agencies worldwide. The sponsor has established
procedures in conformity with regulatory requirements worldwide to ensure appropriate reporting
of PQC information; all studies conducted by the sponsor or its affiliates will be conducted in
accordance with those procedures.

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13.1. Procedures
All initial PQCs must be reported to the sponsor by the study-site personnel within 24 hours after
being made aware of the event.
If the defect is combined with an SAE, the study-site personnel must report the PQC to the sponsor
according to the SAE reporting timelines (refer to Section 12.3.2). A sample of the suspected
product should be maintained for further investigation if requested by the sponsor.
13.2. Contacting Sponsor Regarding Product Quality
The names (and corresponding telephone numbers) of the individuals who should be contacted
regarding product quality issues are listed in the Contact Information page(s), which will be
provided as a separate document.
14. 
VACCINE INFORMATION
14.1. Physical Description of Vaccines
The Ad26.Mos4.HIV, Clade C gp140, and Mosaic gp140 supplied for this study are formulated
as:
Ad26.Mos4.HIV
Ad26.Mos4.HIV is a tetravalent vaccine containing the following 4 active pharmaceutical
ingredients (APIs) pre-mixed in a 1:1:1:1 vp ratio:
 
Ad26.Mos1.Gag-Pol = recombinant, replication-incompetent Ad26 encoding for Mosaic 1
(Mos1) HIV-1 Gag and Pol proteins, manufactured in PER.C6® cells (JNJ-55471494-AAA).
 
Ad26.Mos2.Gag-Pol = recombinant, replication-incompetent Ad26 encoding Mosaic 2
(Mos2) HIV-1 Gag and Pol proteins, manufactured in PER.C6® cells (JNJ-55471520-AAA).
 
Ad26.Mos1.Env = recombinant, replication-incompetent Ad26 encoding Mos1 HIV-1 Env
protein, manufactured in PER.C6® cells (JNJ-55471468-AAA).
 
Ad26.Mos2S.Env = recombinant, replication-incompetent Ad26 encoding modified
(substitute, 
S) Mos2 
HIV-1 
Env protein, 
manufactured 
in 
PER.C6® 
cells
(JNJ-64219324-AAA).
The Ad26.Mos4.HIV vaccine is formulated as a tetravalent vaccine, as a colorless to slightly
yellowish/brownish solution for IM injection and will be provided in individual dosage vials at a
concentration of 1x1011 vp/mL. Refer to the Investigator's Brochure for a list of excipients.18
Clade C gp140
Clade C gp140 is a monovalent vaccine containing the following API:
 
Clade C gp140 Drug Substance (DS) is a trimeric, recombinant HIV-1 Env gp140 of Clade C,
produced on a PER.C6® cell line. Aluminum phosphate suspension is used as adjuvant
(JNJ-55471585-AAA: Clade C gp140 + aluminum phosphate adjuvant).

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Clade C gp140 is formulated as a colorless to slightly yellowish/brownish solution for IM injection.
Clade C gp140 will be supplied as a frozen liquid in a vial to be thawed prior to use, and will be
practically free from particles. Clade C gp140 will be supplied at a nominal strength of either
1 mg/mL or 0.2 mg/mL. Refer to the Investigator’s Brochure for a list of excipients.19 The
aluminum phosphate adjuvant will be supplied as a formulated refrigerated liquid suspension in a
vial with a nominal aluminum content of 1.7 mg/mL. It will be mixed with Clade C gp140 at the
site pharmacy prior to administration.
Mosaic gp140
Mosaic gp140 is a monovalent vaccine containing the following API:
 
Mosaic gp140 DS is a trimeric, recombinant HIV-1 Env gp140 engineered to contain motifs
of multiple HIV-1 variants, produced on a PER.C6® cell line. Aluminum phosphate
suspension is used as adjuvant (JNJ-64219311-AAA: Mosaic gp140 + aluminum phosphate
adjuvant).
Mosaic gp140 is formulated as a colorless to slightly yellowish/brownish solution for IM injection.
Mosaic gp140 will be supplied as a frozen liquid in a vial to be thawed prior to use, and will be
essentially free from particles. Mosaic gp140 will be supplied at a nominal strength of 1 mg/mL.
Refer to the Investigator’s Brochure for a list of excipients.19 Mosaic gp140 will be mixed with
Clade C gp140 at a 1:1 (volume/volume) ratio. The adjuvant will then be mixed in a 1:1
volume/volume ratio with the protein mixture prior to injection.
Clade C and Mosaic gp140 HIV Bivalent Vaccine, Recombinant
The Clade C and Mosaic gp140 HIV bivalent vaccine, recombinant (JNJ-65184340) contains
following active pharmaceutical ingredients:
 Clade C gp140 drug substance (DS) is a trimeric, recombinant HIV-1 Env gp140 of Clade C,
produced on a PER.C6® cell line.
 Mosaic gp140 DS is a trimeric, recombinant HIV-1 Env gp140 engineered to contain motifs
of multiple HIV-1 variants produced on a PER.6® cell line.
 Aluminum phosphate adjuvant.
The bivalent drug product (DP) is a vaccine with a dosage strength of 80 mcg Clade C protein and
75 mcg Mosaic protein and 425 mcg aluminum (as aluminum phosphate adjuvant) based on
0.5 mL delivery volume. Note: previously the dose of Clade C gp140 and/or Mosaic gp140 was
reported as mcg of glycoprotein: 125 mcg Clade C gp140 and 125 mcg Mosaic gp140 glycoprotein
corresponds with 80 mcg and 75 mcg of protein, respectively. The DP white to off-white
suspension for IM injection (or essential free of foreign particles). The DP is to be stored at 2 to
8°C. Refer to the most recent version ofthe Investigator’s Brochure for a list of excipients.

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Placebo
Placebo consisting of sterile 0.9% Saline for Injection will be supplied (as commercially available).
Study vaccines will be manufactured and provided under the responsibility of the sponsor.
14.2. Packaging and Labeling
All study vaccines were manufactured and packaged in accordance with Current Good
Manufacturing Practice (GMP). All study vaccines will be packaged and labeled under the
responsibility of the sponsor.
No study vaccine can be repacked or relabeled without prior approval from the sponsor.
Further details for study vaccine packaging and labeling can be found in the Site Investigational
Product Procedures Manual.
14.3. Preparation, Handling, and Storage
See the Site Investigational Product Procedures Manual for guidance on study vaccine preparation,
handling, and storage. Study vaccine storage conditions are also mentioned on the clinical label.
Study vaccine must be stored in a secured location at controlled temperature with no access for
unauthorized personnel. The study freezer and refrigerator must be equipped with a continuous
temperature monitor and alarm. Study freezers should be equipped with back-up power systems.
In the event that study vaccine is exposed to temperatures outside the specified temperature ranges,
all relevant data will be sent to the sponsor to determine if the affected study vaccine 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.
A site pharmacist will prepare all doses for administration and will provide it to the clinic. In order
to preserve blinding, the pharmacist will place an overlay on the syringes. Administration of study
vaccine to the subjects can be performed by a qualified healthcare provider from the study site
(including the pharmacist who prepared the study vaccine) who will have, on the day of
administration, no other study function related to safety, study data evaluation or recording of AEs
for those subjects that he/she vaccinated on that day.
14.4. Vaccine 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 subject must be
documented on the vaccine accountability form. All study vaccine will be stored and disposed of
according to the sponsor's instructions.
Study vaccine must be handled in strict accordance with the protocol and the container label, and
must be stored at the study site in a limited-access area or in a locked cabinet under appropriate
environmental conditions. Unused study vaccine must be available for verification by the sponsor's
study site monitor during on-site monitoring visits. The return to the sponsor of unused study

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vaccine will be documented on the vaccine return form. When the study site is an authorized
destruction unit and study vaccine supplies are destroyed on-site, this must also be documented on
the vaccine return form.
Potentially hazardous materials such as used ampules, needles, syringes and vials containing
hazardous liquids, should be disposed of immediately in a safe manner and therefore will not be
retained for accountability purposes.
Study vaccine should be dispensed under the supervision of the investigator or a qualified member
of the study-site personnel, or by a hospital/clinic pharmacist. Study vaccine will be supplied only
to subjects participating in the study. Study vaccine may not be relabeled or reassigned for use by
other subjects. 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.
15. 
STUDY-SPECIFIC MATERIALS
The investigator will be provided with the following supplies:
 
Investigator's Brochure for Ad26.Mos.HIV and Clade C gp140
 
Laboratory Manual, Study Procedures Manual
 
IWRS Manual
 
eDC Manual/electronic CRF completion guidelines and randomization instructions
 
Sample ICF
 
Subject diary
 
TOU
 
Social Impact Questionnaire
 
Ruler (to measure diameter of any erythema and induration/swelling), thermometer
 
Subject wallet cards
 
Recruitment tools, as applicable
16. 
ETHICAL ASPECTS
16.1. Study-specific Design Considerations
Potential subjects will be fully informed of the risks and requirements of the study and, during the
study, subjects will be given any new information that may affect their decision to continue
participation. They will be told that their consent to participate in the study is voluntary and may be
withdrawn at any time with no reason given and without penalty or loss of benefits to which they
would otherwise be entitled. Only subjects who are fully able to understand the risks, benefits, and
potential AEs of the study, and provide their consent voluntarily will be enrolled.
From screening to the final main study visit at Week 72, the total blood volume to be collected
from each subject will be approximately 1,200 mL. The total blood volume to be collected during

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the LTE phase (Group 1 and Group 2) in case the subject does not receive the late boost vaccination
will be approximately 470 mL over a 3-year period. In case subjects receive the late boost
vaccination, the total blood volume collected from the start of the LTE phase until 12 months post
late boost will be approximately 1,201 mL. For subjects followed-up to 24 months post late boost,
an additional 145,5 mL of blood will be collected. The total blood volume to be collected is
considered to be within the US Department of HHS OHRP, and US FDA guidelines of 550 mL in
any 8-week period. Volumes for humoral immunogenicity testing will be approximately 20 to 30
mL/visit and for cellular immunogenicity testing approximately 50-102 mL/visit except for the
Visit 22c (subjects who received the late boost vaccination), during which 200 mL of blood will
be collected.
See Section 1.2 for benefit-risk assessment.
Test of Understanding
The TOU is a short assessment of the subject’s understanding of key aspects of the study. The test
will help the study staff to determine how well subjects understand the study and their requirements
for participation.
The TOU must be completed by all subjects, as the first assessment after signing of the ICF. The
TOU is reviewed one-on-one with the subjects and a member of the study team. Subjects are
allowed to retake the test as many times as necessary to achieve the passing score (≥90%) required
for participation in the study. If a subject fails to achieve the passing score, further information
and counseling will be provided by the study team member.
Any subject not capable of understanding the key aspects of the study, and their requirements for
participation, should not be enrolled.
16.2. Regulatory Ethics Compliance
16.2.1. 
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 subjects.
Compliance with this standard provides public assurance that the rights, safety, and well-being of
study subjects are protected, consistent with the principles that originated in the Declaration of
Helsinki, and that the study data are credible.
16.2.2. 
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

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 
Sponsor-approved ICF (and any other written materials to be provided to the subjects)
 
Investigator's Brochure (or equivalent information) and amendments/addenda
 
Sponsor-approved subject recruiting materials
 
Information on compensation for study-related injuries or payment to subjects 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 subjects
 
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
subjects, data or study conduct, unless required locally), the ICF, applicable recruiting materials,
and subject 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 subjects, data or study conduct)
 
Revision(s) to ICF and any other written materials to be provided to subjects
 
If applicable, new or revised subject recruiting materials approved by the sponsor
 
Revisions to compensation for study-related injuries or payment to subjects for participation
in the study, if applicable
 
New edition(s) of the Investigator's Brochure 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 vaccine
 
New information that may adversely affect the safety of the subjects or the conduct of the
study
 
Deviations from or changes to the protocol to eliminate immediate hazards to the subjects
 
Report of deaths of subjects under the investigator's care
 
Notification if a new investigator is responsible for the study at the site
 
Development Safety Update Report and Line Listings, where applicable
 
Any other requirements of the IEC/IRB

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For all protocol amendments (excluding the ones that are purely administrative, with no
consequences for subjects, data or study conduct), the amendment and applicable ICF revisions
must be submitted promptly to the IEC/IRB for review and approval before implementation of the
change(s).
At least once a year, the IEC/IRB will be asked to review and reapprove this study, where required.
At the end of the study, the investigator (or sponsor where required) will notify the IEC/IRB about
the study completion.
16.2.3. 
Informed Consent
Each subject must give written consent according to local requirements after the nature of the study
has been fully explained. The ICF must be signed before performance of any study-related activity.
The ICF that is used must be approved by both the sponsor and by the reviewing IEC/IRB and be
in a language that the subject can read and understand. The informed consent should be in
accordance with principles that originated in the Declaration of Helsinki, current ICH and GCP
guidelines, applicable regulatory requirements, and sponsor policy.
Before enrollment in the study, the investigator or an authorized member of the study-site
personnel must explain to potential subjects the aims, methods, reasonably anticipated benefits,
and potential hazards of the study, and any discomfort participation in the study may entail.
Subjects will be informed that their participation is voluntary and that they may withdraw consent
to participate at any time. They will be informed that choosing not to participate will not affect the
care the subject will receive. Finally, they will be told that the investigator will maintain a subject
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 subject, to the extent permitted by the applicable law(s) or regulations. By
signing the ICF the subject is authorizing such access, which includes permission to obtain
information about his or her survival status if applicable. It also denotes that the subject agrees to
allow his or her study physician to recontact the subject for the purpose of obtaining consent for
additional safety evaluations and subsequent disease-related treatment, if needed.
The subject 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 shouldbe appropriately recorded by means
of the subject's personally dated signature. After having obtained the consent, a copy of the ICF
must be given to the subject.
Subjects will be asked for consent to provide optional samples for research (where local
regulations permit). Refusal to participate in the optional research will not result in ineligibility for
the study.
If the subject is unable to read or write, an impartial witness should be present for the entire
informed consent process (which includes reading and explaining all written information) and
should personally date and sign the ICF after the oral consent of the subject is obtained.

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For participation in the LTE phase of the study, an ICF appendix will be available. Upon sponsor
unblinding at the Week 28 analysis, subjects randomized to Group 1 or Group 2 who have received
all 4 vaccinations, will be asked to participate in the LTE phase and sign the ICF appendix for the
LTE phase at Week 72. Subjects who attend their Week 72 visit prior to the sponsor’s unblinding
at the Week 28 analysis, will be enrolled in the LTE phase if they consent and sign the ICF
appendix for the LTE phase and meet the eligibility criteria for the LTE phase. When the Week 28
sponsor unblinding subsequently occurs, subjects that started the LTE phase but turn out to have
received placebo in the main study will be withdrawn from the LTE phase. If signing the ICF
appendix is not possible at Week 72, signing should be performed at an extra visit (Visit 17bis) as
soon as possible after Week 72 and at the latest before any assessment is done on the first visit of
the LTE phase.
For participation who are willing to participate in the late boost vaccination extension to the LTE
phase, an ICF appendix will be available. Subjects will be asked to sign the ICF appendix for the
late boost vaccination and for the additional, optional, follow-up visit 24 months post late boost at
the Visit 22a.
16.2.4. 
Privacy of Personal Data
The collection and processing of personal data from subjects enrolled in this study will be limited
to those data that are necessary to fulfill the objectives of the study.
These data must be collected and processed with adequate precautions to ensure confidentiality
and compliance with applicable data privacy protection laws and regulations. Appropriate
technical and organizational measures to protect the personal data against unauthorized disclosures
or access, accidental or unlawful destruction, or accidental loss or alteration must be put in place.
Sponsor personnel whose responsibilities require access to personal data agree to keep the identity
of subjects confidential.
The informed consent obtained from the subject 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 subject 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 DNA, immunogenicity, and social impact questionnaire research is not conducted
under standards appropriate for the return of data to subjects. 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 subjects 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.

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16.2.5. 
Long-term Retention of Samples for Additional Future Research
Each study subject will be asked to consent voluntarily for their blood samples to be stored for
other research studies that may be done after this study is completed. Future testing may involve
deoxyribonucleic acid/ribonucleic acid (DNA/RNA) tests. For subjects unwilling to have their
blood samples stored for future use, they can consent to participate in this study only, without
having their blood samples stored for future testing (see Section 10.4). In this case, their blood
samples will be destroyed after all the tests specified for this study have been concluded.
All samples, for which consent has been obtained and for which additional material is available
after study-specified testing is complete, will be stored for future testing. All applicable approvals
will be sought before any such samples are used for analysis not specified in the protocol or a
protocol amendment approved by the IRB.
Stored samples will be coded throughout the sample storage and analysis process and will not be
labeled with personal identifiers. Subjects may withdraw their consent for their samples to be
stored for research (see Section 10.4).
17. 
ADMINISTRATIVE REQUIREMENTS
17.1. Protocol Clarification Communications
If text within a final approved protocol requires clarification (eg, current wording is unclear or
ambiguous) that does not change any aspect of the current study conduct, a protocol clarification
communication (PCC) may be prepared. The PCC Document will be communicated to the
Investigational Site, Site Monitors, Local Trial Managers (LTMs), Clinical Trial Managers
(CTMs), and/or Contract Research Organizations (CROs) who will ensure that the PCC
explanations are followed by the investigators.
The PCC Document may be shared by the sites with Independent Ethics Committees/Institutional
Review Boards (IECs/IRBs) per local regulations.
The PCC Documents must NOT be used in place of protocol amendments, but the content of the
PCC Document must be included in any future protocol amendments.
17.2. 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 subjects, 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) involves only logistic or administrative aspects of the study, the IRB/IEC (where
required) only needs to be notified.

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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 CRF and source
documents will reflect any departure from the protocol, and the source documents will describe
this departure and the circumstances requiring it.
17.3. Regulatory Documentation
17.3.1. 
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.
17.3.2. 
Required Prestudy Documentation
The following documents must be provided to the sponsor before shipment of vaccine to the study
site:
 
Protocol and amendment(s), if any, signed and dated by the principal investigator
 
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, subject 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 principal investigator, where
required
 
Signed and dated clinical trial agreement, which includes the financial agreement
 
Any other documentation required by local regulations

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The following documents must be provided to the sponsor before enrollment of the first subject:
 
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
17.4. Subject Identification, Enrollment, and Screening Logs
The investigator agrees to complete a subject identification and enrollment log to permit easy
identification of each subject during and after the study. This document will be reviewed by the
sponsor study-site contact for completeness.
The subject identification and enrollment log will be treated as confidential and will be filed by
the investigator in the study file. To ensure subject confidentiality, no copy will be made. All
reports and communications relating to the study will identify subjects by subject identification
and date of birth (as allowed by local regulations). In cases where the subject is not randomized
into the study, the date seen and date ofbirth (as allowed by local regulations) will be used.
The investigator must also complete a subject screening log, which reports on all subjects who
were seen to determine eligibility for inclusion in the study.
17.5. Source Documentation
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:
subject identification, eligibility, and study identification; study discussion and date of signed
informed consent; dates of visits; results of safety parameters as required by the protocol; record
of all AEs and follow-up of AEs; concomitant medication; vaccine receipt/dispensing/return
records; vaccine administration information; and date of study completion and reason for early
discontinuation of vaccine or withdrawal from the study, if applicable.
The author of an entry in the source documents should be identifiable.
Specific details required as source data for the study and source data collection methods will be
reviewed with the investigator before the study and will be described in the monitoring guidelines
(or other equivalent document).
An electronic source 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. Ifthe electronic source system is utilized, references made to the
CRF in the protocol include the electronic source system but information collected through the

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electronic source may not be limited to that found in the CRF. Data in this system may be
considered source documentation.
The subject’s diary used to collect information regarding solicited events after vaccination will be
considered source data.
17.6. Case Report Form Completion
Case report forms are prepared and provided by the sponsor for each subject in electronic format.
All CRF 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 CRF are accurate and correct.
The study data will be transcribed by study-site personnel from the source documents onto an
electronic CRF, 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 CRF. Any such
worksheets will become part of the subject's source documentation. Data must be entered into CRF
in English. The CRF must be completed as soon as possible after a subject visit and the forms
should be available for review at the next scheduled monitoring visit.
All subjective measurements (eg, pain scale information or other questionnaires) will be completed
by the same individual who made the initial baseline determinations whenever possible.
If necessary, queries will be generated in the eDC tool. If corrections to a CRF are needed after the
initial entry into the CRF, this can be done in either of the following ways:
 
Investigator and study-site personnel can make corrections in the eDC tool at their own
initiative or as a response to an auto query (generated by the eDC tool).
 
Sponsor or sponsor delegate can generate a query for resolution by the investigator and study-
site personnel.
17.7. 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 CRF completion will be provided and reviewed with study-site personnel before
the start of the study.
The sponsor will review CRFs for accuracy and completeness during on-site monitoring visits and
after transmission to the sponsor; any discrepancies will be resolved with the investigator or
designee, as appropriate. After upload of the data into the study database they will be verified for
accuracy and consistency with the data sources.

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17.8. Record Retention
In compliance with the ICH/GCP guidelines, the investigator/institution will maintain all CRF and
all source documents that support the data collected from each subject, as well as all study
documents as specified in ICH/GCP Section 8, Essential Documents for the Conduct of a Clinical
Trial, and all study documents as specified by the applicable regulatory requirement(s). The
investigator/institution will take measures to prevent accidental or premature destruction of these
documents.
Essential documents must be retained until at least 2 years after the last approval of a marketing
application in an ICH region and until there are no pending or contemplated marketing applications
in an ICH region or until at least 2 years have elapsed since the formal discontinuation of clinical
development of the investigational product. These documents will be retained for a longer period
if required by the applicable regulatory requirements or by an agreement with the sponsor. It is the
responsibility of the sponsor to inform the investigator/institution as to when these documents no
longer need to be retained.
If the responsible investigator retires, relocates, or for other reasons withdraws from the
responsibility of keeping the study records, custody must be transferred to a person who will accept
the responsibility. The sponsor must be notified in writing of the name and address of the new
custodian. Under no circumstance shall the investigator relocate or dispose of any study documents
before having obtained written approval from the sponsor.
If it becomes necessary for the sponsor or the appropriate regulatory authority to review any
documentation relating to this study, the investigator/institution must permit access to such reports.
17.9. Monitoring
The sponsor may 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 CRF with the source documents (eg,
hospital/clinic/physician's office medical records); a sample may be reviewed. The nature and
location of all source documents will be identified to ensure that all sources of original data
required to complete the CRF are known to the sponsor and study-site personnel and are accessible
for verification by the sponsor study-site contact. If electronic records are maintained at the study
site, the method of verification must be discussed with the study-site personnel.
Direct access to source documents (medical records) must be allowed for the purpose of verifying
that the recorded data are consistent with the original source data. Findings from this review will
be discussed with the study-site personnel. The sponsor expects that, during monitoring visits, the
relevant study-site personnel will be available, the source documents will be accessible, and a
suitable environment will be provided for review of study-related documents. The monitor will

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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.
17.10. Study Completion/Termination
17.10.1. 
Study Completion/End of Study
The study is considered completed with the last visit for the last subject participating in the study.
The final data from the study site will be sent to the sponsor (or designee) after completion of the
final subject visit at that study site, in the time frame specified in the Clinical Trial Agreement.
17.10.2. 
Study Termination
The sponsor reserves the right to close the study site or terminate the study at any time for any
reason at the sole discretion of the sponsor. Study sites will be closed upon study completion. A
study site is considered closed when all required documents and study supplies have been collected
and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time, provided there is reasonable cause and
sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a study site by the sponsor or investigator may include but are not
limited to:
 
Failure of the investigator to comply with the protocol, the requirements of the IEC/IRB or
local health authorities, the sponsor's procedures, or GCP guidelines
 
Inadequate recruitment of subjects by the investigator
 
Discontinuation of further vaccine development
17.11. On-Site Audits
Representatives of the sponsor's clinical quality assurance department may visit the study site at
any time during or after completion of the study to conduct an audit of the study in compliance
with regulatory guidelines and company policy. These audits will require access to all study
records, including source documents, for inspection. Subject 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

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regulatory submission. The investigator should immediately notify the sponsor if he or she has
been contacted by a regulatory agency concerning an upcoming inspection.
17.12. Use of Information and Publication
All information, including but not limited to information regarding Ad26.Mos4.HIV, Clade C
gp140, and Mosaic gp140 or the sponsor's operations (eg, patent application, formulas,
manufacturing processes, basic scientific data, prior clinical data, formulation information)
supplied by the sponsor to the investigator and not previously published, and any data generated
as a result of this study, are considered confidential and remain the sole property of the sponsor
and/or its partners. The investigator agrees to maintain this information in confidence and use this
information only to accomplish this study, and will not use it for other purposes without the
sponsor's prior written consent.
The investigator understands that the information developed in the study will be used by the
sponsor in connection with the continued development of Ad26.Mos4.HIV, Clade C gp140, and
Mosaic gp140, and thus may be disclosed as required to other clinical investigators or regulatory
agencies. To permit the information derived from the clinical studies to be used, the investigator
is obligated to provide the sponsor with all data obtained in the study.
The results of the study will be reported in a Clinical Study Report generated by the sponsor and
will contain data from all study sites that participated in the study as per protocol. Recruitment
performance or specific expertise related to the nature and the key assessment parameters of the
study will be used to determine a coordinating investigator for the study. Results of any 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 subject 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 guidelines, the sponsor with its partners 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 substudy 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

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data derived from the individual study site until the combined results from the completed study
have been submitted for publication, within 18 months after study end date, or the sponsor
confirms there will be no multicenter study publication. Authorship of publications resulting from
this study will be based on the guidelines on authorship, such as those described in the ICMJE
Recommendations for the Conduct, Reporting, Editing and Publication of Scholarly Work in
Medical Journals, which state that the named authors must have made a significant contribution to
the conception or design of the work; or the acquisition, analysis, or interpretation of the data for
the work; and drafted the work or revised it critically for important intellectual content; and given
final approval of the version to be published; and agreed to be accountable for all aspects of the
work in ensuring that questions related to the accuracy or integrity of any part of the work are
appropriately investigated and resolved.
Registration of Clinical Studies and Disclosure of Results
The sponsor will register and disclose the existence of and the results of clinical studies as required
by law.

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18. 
COVID-19 APPENDIX: GUIDANCE ON STUDY CONDUCT DURING THE
COVID-19 PANDEMIC
It is recognized that the Coronavirus Disease 2019 (COVID-19) pandemic may have an impact on
the conduct of this clinical study due to, for example, self-isolation/quarantine by participants and
study-site personnel; travel restrictions/limited access to public places, including hospitals; study
site personnel being reassigned to critical tasks.
In alignment with recent health authority guidance, the sponsor is providing options for study
related participant management in the event of disruption to the conduct of the study. This guidance
does not supersede any local or government requirements or the clinical judgement of the
investigator to protect the health and well-being of participants and site staff and to maintain
oversight of delegated trial activities.
Scheduled visits that cannot be conducted in person at the study site will be performed to the extent
possible as a remote visit, a home visit, or delayed until such time that on-site visits can be
resumed.n At each contact, participants will be interviewed to collect safety data. Key endpoint
assessments should be performed if required and as feasible. Participants will also be questioned
regarding general health status to fulfill any physical examination requirement.
Every effort should be made to adhere to protocol-specified assessments. Modifications to
protocol-required assessments may be permitted via COVID-19 Appendix after consultation with
the participant, investigator, and the sponsor. Missed assessments/visits will be captured in the
clinical trial management system for protocol deviations. Discontinuations of study interventions
and withdrawal from the study should be documented with the prefix “COVID-19-related” in the
case report form (CRF). Any deviations to study procedures occurring due to the COVID-19
pandemic need to be properly captured in the clinical trial management system (or CRF), with the
prefix “COVID-19-related” (including actual visit date) and will be summarized in the clinical
study report.
The sponsor will continue to monitor the conduct and progress of the clinical study, and any
changes will be communicated to the sites and to the health authorities according to applicable
guidance documents and regulations. If a participant has tested positive for SARS-CoV-2, the
investigator should contact the sponsor’s responsible medical officer to discuss plans for study
intervention and follow-up. Modifications made to the study conduct as a result of the COVID-19
pandemic should be summarized in the clinical study report.
n An on-site visit is defined as a visit during which the participant and the qualified site staff are both present in person
at the study site.
A remote visit is defined as a visit during which there is no direct in-person physical presence between the participant
and the qualified site staff (telephone or video call).
A home visit is defined as a visit during which the participant and the qualified site staff are both present at the
participants’ home.

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GUIDANCE SPECIFIC TO THIS PROTOCOL:
The following emergency provisions are meant to ensure participant safety on study while site
capabilities are compromised by COVID-19-related restrictions. When restrictions are lifted, sites
should revert to the original protocol conduct as soon as feasible and in accordance with local
guidance and regulations and in agreement with the institutions and the investigator’s assessment
of the safety of site staff and study participants.
Vaccination Visits
 
For the late boost vaccination, vaccination outside of the window can be assessed on a
case-by-case basis and will ultimately be approved by the sponsor. The out of window
vaccination will be documented as ‘COVID-19-related’.
Other Study Visits and Assessments
 
Participants may have remote visits for reactogenicity and safety assessments until such time
that on-site visits can be resumed. The actual visit date should be captured in the eCRF
according to the eCRF completion guidelines.
Sample Management
 If a site is experiencing a disruption in shipment of specimens from their Site Processing Lab
to the centralized HIV diagnostic testing laboratory(ies) due to the COVID-19
pandemic-related challenges, the Site Processing Lab should hold that specimen at the proper
temperature for later per-protocol testing.
Informed Consent:
 Consenting and re-consenting of participants for the measures taken (including also remote
consenting by phone or video consultation) will be performed as applicable and according to
local guidance for informed consent applicable during the COVID-19 pandemic. The process
is to be documented in the source documents.
Source Data Verification/Monitoring
 
In case on-site monitoring visits are not possible, the site monitor may contact the investigator
to arrange monitoring visits and activities remotely (in accordance with site and local
requirements). Additional on-site monitoring visits may be needed in the future to catch up on
source data verification.
Site Audits
During the COVID-19 pandemic and at the impacted sites, study site GCP audits with direct
impact/engagement from the investigator and study site personnel may not be conducted in order
to comply with national, local, and/or organizational social distancing restrictions. Additional
quality assurance activities such as remote audits or focused review of study related documents
may take place with limited impact/engagement if possible.

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REFERENCES
1. 
American Society of Hematology. COVID-19 resources. Thrombosis with Thrombocytopenia Syndrome (also
termed Vaccine-induced Thrombotic Thrombocytopenia). https://www.hematology.org/covid-19/vaccine-
induced-immune-thrombotic-thrombocytopenia. Accessed: 19 October 2021.
2. 
Baden LR, Karita E, Mutua G, et al. Assessment of the Safety and Immunogenicity of 2 Novel Vaccine Platforms
for HIV-1 Prevention: A Randomized Trial. Ann Intern Med. 2016: doi:10.7326/M15-0880 www.annals.org
3. 
Baden LR, Liu J, Li H, et al. Induction of HIV-1-specific mucosal immune responses following intramuscular
recombinant adenovirus serotype 26 HIV-1 vaccination of humans. J Infect Dis. 2015;211(4):518-528.
4. 
Baden LR, Walsh SR, Seaman MS, et al. First-in-human evaluation of the safety and immunogenicity of a
recombinant adenovirus serotype 26 HIV-1 Env vaccine (IPCAVD-001). J Infect Dis. 2013;207:240-247.
5. 
Barouch D, Alter G, Broge T, et al. Protective efficacy of adenovirus-protein vaccines against SIV challenges in
rhesus monkeys. Science. 2015;349:320-324.
6. 
Benlahrech A, Harris J, Meiser A, et al. Adenovirus vector vaccination induces expansion of memory CD4 T
cells with a mucosal homing phenotype that are readily susceptible to HIV-1. Proc Natl Acad Sci USA.
2009;106:19940-19945.
7. 
Brighton Collaboration. Interim Case Definition of Thrombosis with Thrombocytopenia Syndrome (TTS).
V10.16.3. 18 May 2021.. https://brightoncollaboration.us/thrombosis-with-thrombocytopenia-syndrome-
interim-case-definition/. Accessed: 19 October 2021.
8. 
British Society for Haematology. Guidance produced from the Expert Haematology Panel (EHP) focussed on
Covid-19 Vaccine induced Thrombosis and Thrombocytopenia (VITT). https://b-s-
h.org.uk/media/19530/guidance-version-13-on-mngmt-of-thrombosis-with-thrombocytopenia-occurring-after-
c-19-vaccine_20210407.pdf.  Version 1.3; 7 April 2021. Accessed: 17 May 2021.
9. 
Buchbinder S, Mehrotra D, Duerr A, et al. Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the
Step Study): a double-blind, randomized, placebo-controlled, test-of-concept trial. Lancet. 2008;372:1881-1893.
10. Centers for Disease Control and Prevention (CDC). Cases of cerebral venous sinus thrombosis with
thrombocytopenia after receipt of the Johnson & Johnson COVID-19 Vaccine. 13 April 2021.
https://emergency.cdc.gov/han/2021/han00442.asp.  Accessed: 17 May 2021.
11. Fischer W, Perkins S, Theiler J, et al. Polyvalent vaccines for optimal coverage of potential T-cell epitopes in
global HIV-1 variants. Nat Med. 2007;13:100-106.
12. Gidudu JK, Walco GA, Taddio A, et al. The Brighton Immunization Site Pain Working Group. Immunization
site pain: Case definition and guidelines for collection, analysis, and presentation of immunization safety data.
http://www.sciencedirect.com/science/article/pii/S0264410X12005063. Accessed 11 June 2015.
13. Gray G, Allen M, Moodie Z, et al. Safety and efficacy of the HVTN 503/Phambili study of a clade-B-based
HIV-1 vaccine in South Africa: a double-blind, randomized, placebo-controlled test-of-concept phase 2b study.
Lancet Infect Dis. 2011;11:507-515.
14. Hammer S, Sobieszczyk M, Karuna S, et al. Efficacy trial of a DNA/rAd5 HIV-1 preventive vaccine. N Engl J
Med. 2013;369:2083-2092.
15. Huang Y, Follmann D, Nason M, et al. Effect of rAd5-vector HIV -1 preventive vaccines on HIV-1 acquisition:
a participant-level meta-analysis of randomized trials. PloS One. 2015. DOI:10.1371.
16. Hutnick N, Carnathan D, Dubey S, et al. Baseline Ad5 serostatus does not predict Ad5 HIV vaccine-induced
expansion of adenovirus-specific CD4+ T cells. Nat Med. 2009;15:876-878.
17. Information on Phase 1 clinical studies with monovalent AIDSVAX B conducted by Genentech.
http://www.vaxgen.com/hivaids/10k_p8. Accessed: February 26, 2016).
18. Investigator's Brochure: Ad26.Mos.HIV - Ad26.Mos4.HIV. Edition 3. Crucell Holland B.V. (December 2015).
19. Investigator's Brochure: Clade C gp140 - Mosaic gp140. Edition 3. Crucell Holland B.V. (February 2016).

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20. Johnson & Johnson: Johnson & Johnson and Global Partners Announce Results from Phase 2b Imbokodo HIV
Vaccine Clinical Trial in Young Women in Sub-Saharan Africa. August 31, 2021, News Release. Available at:
https://www.jnj.com/johnson-johnson-and-global-partners-announce-results-from-phase-2b-imbokodo-hiv-
vaccine-clinical-trial-in-young-women-in-sub-saharan-africa. Accessed: 20 October 2021.
21. Kohl KS, Walop W, Gidudu J, et al. The Brighton Collaboration Local Reaction Working Group for Swelling at
or near Injection Site. Swelling at or near injection site: Case definition and guidelines for collection, analysis
and 
presentation 
of 
immunization 
safety 
data.
http://www.sciencedirect.com/science/article/pii/S0264410X07004835. Accessed 11 June 2015.
22. Kohl KS, Walop W, Gidudu J, et al. The Brighton Collaboration Local Reaction Working Group for Induration
at or near Injection Site. Induration at or near injection site: Case definition and guidelines for collection, analysis
and 
presentation 
of 
immunization 
safety 
data.
http://www.sciencedirect.com/science/article/pii/S0264410X07005038. Accessed 11 June 2015.
23. Kovacs J, Nkolola J, Peng H, et al. HIV-1 envelope trimer elicits more potent neutralizing antibody responses
than monomeric gp120. Proc Natl Acad Sci USA. 2012;109:12111-12116.
24. Marcy SM, Kohl KS, Dagan R, et al. The Brighton Collaboration Fever Working Group. Fever as an adverse
event following immunization: case definition and guidelines of data collection, analysis, and presentation.
http://www.sciencedirect.com/science/article/pii/S0264410X03006601. Accessed 11 June 2015.
25. Nkolola JP, Bricault CA, Cheung A, et al. Characterization and immunogenicity of a novel mosaic M HIV-1
gp140 trimer. J Virol. 2014;88:9538-9552.
26. Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, et al. Vaccination with ALVAC and AIDSVAX to prevent HIV-
1 infection in Thailand. N Engl J Med. 2009;361:2209-2220.
27. Shimabukuro T. Update: Thrombosis with thrombocytopenia syndrome (TTS) following COVID-19
vaccination. Centers for Disease Control & Prevention Advisory Committee on Immunization Practices (ACIP)
meeting 12 May 2021. https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-05-12/07-COVID-
Shimabukuro-508.pdf. Accessed 19 October 2021.
28. Vella S. Addressing barriers to the end of AIDS by 2030. The Lancet. 2015;2:e360-e361.
29. Baylor NW, Egan W, Richman P. Aluminum salts in vaccines--US perspective. Vaccine. 2002;20 Suppl
3:S18-23.
30. Bergfors E, Hermansson G, Nyström Kronander U, Falk L, Valter L, Trollfors B. How common are long-
lasting, intensely itching vaccination granulomas and contact allergy to aluminium induced by currently used
pediatric vaccines? A prospective cohort study. Eur J Pediatr. 2014;173(10): 1297–1307.
31. Bergfors E, Trollfors B, Inerot A. Unexpectedly high incidence of persistent itching nodules and delayed
hypersensitivity to aluminium in children after the use of adsorbed vaccines from a single manufacturer.
Vaccine. 2003;22(1):64-69.
32. Netterlid E, Bruze M, Hindsén M, Isaksson M, Olin P. Persistent itching nodules after the fourth dose of
diphtheria-tetanus toxoid vaccines without evidence of delayed hypersensitivity to aluminium. Vaccine.
2004;22(27-28):3698-3706.
33. Keith LS, Jones DE, Chou CH. Aluminum toxicokinetics regarding infant diet and vaccinations. Vaccine.
2002;20 Suppl 3:S13-17.
34. Mitkus RJ, King DB, Hess MA, Forshee RA, Walderhaug MO. Updated aluminum pharmacokinetics
following infant exposures through diet and vaccination. Vaccine. 2011;29(51):9538-9543.
35. Ameratunga R, Gillis D, Gold M, Linneberg A, Elwood JM. Evidence Refuting the Existence of
Autoimmune/Autoinflammatory Syndrome Induced by Adjuvants (ASIA). J Allergy Clin Immunol Pract.
2017;5(6):1551-1555.e1.
36. Investigator's Brochure: Ad26.Mos.HIV - Ad26.Mos4.HIV. Edition 7. Janssen Vaccines & Prevention B.V.
(February 2020).
37. Investigator's Brochure: Clade C gp140 - Mosaic gp140. Edition 7. Janssen Vaccines & Prevention B.V.
(February 2020).

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Attachment 1: Division of Aids Table for Grading the Severity of Adult and Pediatric AEs –Including
Modifications
The Division of AIDS Table for Grading the Severity of Adult and Pediatric AEs (Version 2.0,
November 2014), or ‘DAIDS grading table’, is a descriptive terminology to be utilized for AE
reporting in this study. A grading (severity) scale is provided for each AE term. Modifications
made by the sponsor are footnoted.
General Instructions
Estimating Severity Grade for Parameters Not Identified in the Grading Table
If the need arises to grade a clinical AE that is not identified in the DAIDS grading table, use the
category ‘Estimating Severity Grade’ located at the top of the table on the following page. In
addition, all deaths related to an AE are to be classified as Grade 5.
Grading Adult and Pediatric AEs
The DAIDS grading table includes parameters for grading both adult and pediatric AEs. When a
single set of parameters is not appropriate for grading specific types of AEs for both adult and
pediatric populations, separate sets of parameters for adult and/or pediatric populations (with
specified respective age ranges) are provided. If there is no distinction in the table between adult
and pediatric values for a type of AE, then the single set of parameters listed is to be used for
grading the severity of both adult and pediatric events of that type.
Determining Severity Grade
If the severity of an AE could fall under either 1 of 2 grades (eg, the severity of an AE could be
either Grade 2 or Grade 3), select the higher of the 2 grades for the AE.
Laboratory normal ranges should be taken into consideration to assign gradings to a laboratory
value.
Definitions
Basic Self-care Functions 
Adult Activities such as bathing, dressing, toileting, transfer or
movement, continence, and feeding.
Young Children Activities that are age and culturally
appropriate, such as feeding one’s self with culturally
appropriate eating implements.
Usual Social & Functional 
Activities 
Activities which adults and children perform on a routine basis
and those which are part of regular activities of daily living, for
example:
Adults Adaptive tasks and desirable activities, such as going to
work, shopping, cooking, use of transportation, or pursuing a
hobby.
Young Children Activities that are age and culturally
appropriate, such as social interactions, play activities, or
learning tasks.

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Attachment 2: HIV-risk Assessment
The following are intended as guidelines for the investigator to help identify potential vaccine trial
participants at “low risk” for HIV infection (1) in the US and Switzerland and (2) in South Africa,
respectively. Outside these countries, in addition to minimum requirements specified by the first two criteria
defined below (“Have oral, vaginal or anal intercourse with an HIV-infected partner, or a partner who uses
injection drugs” and “Give or receive money, drugs, gifts or services in exchange for oral, vaginal or anal
sex”), low risk criteria as defined by local standards would be applicable.
HVTN Low Risk Guidelines
August 1, 2013
(1)
The following are intended as guidelines for the investigator to help identify potential vaccine trial
participants at “low risk” for HIV infection in the US and Switzerland. These guidelines are based on
behaviors within the last 6-12 months prior to enrollment; however, it may be appropriate to consider a
person’s behavior over a longer period of time than specified to assess the person’s likelihood of
maintaining low risk behavior. Some volunteers may not be appropriate for enrollment even if they meet
these guidelines. These guidelines should be supplemented and interpreted with local epidemiologic
information about HIV prevalence in your area and community networks. The investigator may review the
risk level of any volunteer with the site PI and/or the Protocol Safety Review Team.
A volunteer may be appropriate for inclusion if he/she meets these guidelines:
1. 
SEXUAL BEHAVIORS
In the last 12 months did not:
 
Have oral, vaginal, or anal intercourse with an HIV-infected partner, or a partner who uses injection
drugs
 
Give or receive money, drugs, gifts, or services in exchange for oral, vaginal, or anal sex
AND
In the last 6 months has abstained from penile/anal or penile/vaginal intercourse, OR
In the last 6 months:
 
Had 4 or fewer partners of the opposite birth sex for vaginal and/or anal intercourse, OR
Is an MSM (person born male with partner(s) born male) who, in the last 12 months:
 
Had 2 or fewer MSM partners for anal intercourse and had no unprotected anal sex with MSM, OR
 
Had unprotected anal intercourse with only 1 MSM partner, within a monogamous relationship lasting
at least 12 months (during which neither partner had any other partners). If the monogamous
relationship ended, the volunteer may then have had protected anal intercourse with 1 other MSM
partner (total 2 or fewer partners in the last 12 months).

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Is a transgender person, regardless of the point on the transition spectrum, having sex with men (born male)
and/or other transgender persons, who in the last 12 months:
 
Had 2 or fewer partners for anal or vaginal intercourse, and had no unprotected anal or vaginal sex,
OR
 
Had unprotected anal or vaginal intercourse sex with 1 partner only within a monogamous relationship
lasting at least 12 months (during which neither partner had any other partners). If the monogamous
relationship ended, may then have had protected anal or vaginal sex with 1 other partner (total 2 or
fewer partners in the last 12 months).
AND
Uses or intends to use condoms in situations which may include penile/anal or penile/vaginal intercourse
with new partners of unknown HIV status, occasional partners, partners outside a primary relationship,
and/or partners known to have other partners.
2. 
NON-SEXUAL BEHAVIORS
In the last 12 months did not:
 
Inject drugs or other substances without a prescription
 
Use cocaine, methamphetamine, or excessive alcohol, which in the investigator’s judgment, rendered
the participant at greater than low risk for acquiring HIV infection
The investigator’s judgment should consider local epidemiologic information about HIV prevalence in the
area and community networks.
A volunteer is NOT appropriate for inclusion if he/she:
Acquired an STI (ie, new infection) in the last 12 months:
 
Syphilis
 
Gonorrhea
 
Non-gonococcal urethritis
 
HSV-2
 
Chlamydia
 
Pelvic inflammatory disease (PID)
 
Trichomonas
 
Mucopurulent cervicitis
 
Epididymitis
 
Proctitis
 
Lymphogranuloma venereum
 
Chancroid
 
Hepatitis B

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(2)
LOW RISK GUIDELINES for SOUTH AFRICAN SITES
September 4, 2012
The following are intended as guidelines for the investigator to help identify potential vaccine trial
participants at “low risk” for HIV infection. These guidelines are based on behaviors within the last
12 months prior to enrollment; however, it may be appropriate to consider a person’s behavior over a longer
period of time than specified to assess the person’s likelihood of maintaining low risk behavior. Some
volunteers may not be appropriate for enrollment even if they meet these guidelines. These guidelines
should be supplemented and interpreted with local epidemiologic information about HIV prevalence in
your area and community networks. The investigator may review the risk level of any volunteer with the
site PI and/or protocol team.
ASSESSMENT OF SEXUAL BEHAVIORS
Consider whether a volunteer would be appropriate for inclusion if, within 12 months prior to enrollment,
the person:
 
Was sexually abstinent, or
 
Was in a mutually monogamous relationship with a partner with a known HIV-uninfected status,
or
 
Had one partner believed to be HIV-uninfected with whom he/she regularly used condoms for
vaginal and anal intercourse.
Exclude a volunteer if:
Within the 12 months prior to enrollment: a history of newly acquired syphilis, gonorrhea, chlamydia,
trichomoniasis, active HSV lesions, chancroid, pelvic inflammatory disease (PID), genital sores or ulcers,
cervicitis, genital warts of the labia minora, vagina, or cervix, or any other symptomatic genital warts.

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Attachment 4: Social Impact Questionnaire
Vaccine Research Center (VRC) Social Impact Case Report Formq
q Adaptations to the social impact questionnaire are allowed for local purposes, after IRB and sponsor approval.

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Attachment 5: Thrombotic Events to be Reported as Potential AESIs
At the time of protocol amendment 5 writing, the list of thrombotic events to be reported to the
sponsor as potential AESIs is provided below. Further guidance may become available on
thrombotic events of interest.
 MedDRA PTs for large vessel thrombosis and embolism
- 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
- 
Axillary vein thrombosis, deep vein thrombosis, pulmonary embolism, MedDRA PTs for
acute myocardial infarction*, MedDRA PTs for stroke*
Source: Shimabukuro T. CDC COVID-19 Vaccine Task Force. Thrombosis with thrombocytopenia syndrome (TTS)
following Janssen COVID-19 vaccine. Advisory Committee on Immunization Practices (ACIP). April 23, 2021.
https://www.cdc.gov/vaccines/acip/meetings/slides-2021-04-23.html.
*Vaccine Adverse Event Reporting System (VAERS) Standard Operating Procedures for COVID-19 (as of 29 January
2021) https://www.cdc.gov/vaccinesafety/pdf/VAERS-v2-SOP.pdf

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

Signature
User 
Date 
Reason
 
28-Oct-2021 
12:46:49
(GMT)
Document Approval
PPD