Clinical trial NCT02315703
Conditions: Healthy
Keywords: Healthy Acquired Immuno-Deficiency Syndrome Acquired Immunodeficiency Syndrome Virus adenovirus serotype 26 Ad26.Mos.HIV Modified Vaccinia Ankara Glycoprotein Adjuvant Vaccine Placebo
Sponsor: Janssen Vaccines & Prevention B.V.
Start date: 2014-12-22; Completion date: 2022-03-28
Enrollment: 393 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to assess the safety and tolerability of various regimens containing adenovirus serotype 26-Mosaic -Human Immunodeficiency Virus (Ad26.Mos.HIV), Modified Vaccinia Ankara (MVA)-Mosaic, and/or HIV type 1 Clade C glycoprotein 140 drug product (gp140 DP) components and to compare envelope binding antibody responses between the different vaccine regimens.

Detailed description:
This is a multicenter (more than 1 hospital or medical school team work on a study), randomized (the study drug is assigned by chance), parallel group (each group of participants will be treated at the same time), placebo-controlled (study in which the experimental treatment or procedure is compared to a pretend treatment with no drug in it to test if the drug has a real effect), and double-blind (neither physician nor participant knows the treatment that the participant receives) study. All eligible participants will be randomly assigned to receive 1 of the 8 vaccine regimens. Participants will receive study vaccines (Ad26.Mos.HIV, MVA-Mosaic, gp140 DP, and placebo) 4 times as per assigned regimen. The study comprises a Screening Period (up to 4 weeks), a Vaccination Period (participants will be vaccinated at Baseline (Week 0), Week 12, Week 24 and Week 48), and a Follow-up Period (up to 48 weeks). A long-term follow-up period (approximately 2 years after Week 96) will continue for participants randomized to the regimen subsequently selected for future studies, based on analysis of Week 28 data. If Week 28 data are inconclusive, Week 52 data will be considered for regimen selection. If no clear decision can be made, the extended follow-up period could include participants from more than 1 group for assessing durability of immune responses. Participants' safety will be monitored throughout the study.

Arms: arm 1: Participants will receive adenovirus serotype 26-Mosaic -Human Immunodeficiency Virus (Ad26.Mos.HIV) vaccine at Week 0 and 12; followed by Ad26.Mos.HIV vaccine + HIV type 1 Clade C glycoprotein 140 drug product (gp140 DP) vaccine containing 250 microgram (mcg) of total protein mixed with adjuvant (aluminum phosphate) at Week 24 and 48. arm 2: Participants will receive Ad26.Mos.HIV vaccine at Week 0 and 12; followed by Ad26.Mos.HIV vaccine + gp140 DP vaccine containing 50 mcg of total protein mixed with adjuvant at Week 24 and 48. arm 3: Participants will receive Ad26.Mos.HIV vaccine at Week 0 and 12; followed by Ad26.Mos.HIV vaccine + placebo injection at Week 24 and 48. arm 4: Participants will receive Ad26.Mos.HIV vaccine at Week 0 and 12; followed by modified Vaccinia Ankara (MVA)-Mosaic vaccine + gp140 DP vaccine containing 250 mcg of total protein mixed with adjuvant at Week 24 and 48. arm 5: Participants will receive Ad26.Mos.HIV vaccine at Week 0 and 12; followed by MVA-Mosaic vaccine + gp140 DP vaccine containing 50 mcg of total protein mixed with adjuvant at Week 24 and 48. arm 6: Participants will receive Ad26.Mos.HIV vaccine at Week 0 and 12; followed by MVA-Mosaic vaccine + placebo injection at Week 24 and 48. arm 7: Participants will receive Ad26.Mos.HIV vaccine at Week 0 and 12; followed by gp140 DP vaccine containing 250 mcg of total protein mixed with adjuvant + placebo injection at Week 24 and 48. arm 8: Participants will receive 1 placebo injection at Week 0 and 12; followed by 2 placebo injections at Week 24 and 48.
Interventions: intervention 1: Ad26.Mos.HIV intervention 2: MVA-Mosaic intervention 3: gp140 DP Low-dose intervention 4: gp140 DP High-dose intervention 5: Placebo
Intervention descriptions: intervention 1: Recombinant replication-deficient Ad26 vectored vaccine and consists of 3 Ad26 vectors, one containing a mosaic insert of envelop (Env) sequence, and 2 vectors containing mosaic inserts of Gag and Pol sequences (Ad26.Mos.1.Env + Ad26.Mos1.Gag-Pol + Ad26.Mos2.Gag-Pol). Total dose is 5\*10\^10 viral particle per 0.5 milliliter (mL) injection administered intramuscularly. intervention 2: Recombinant live attenuated MVA virus-vectored vaccine that has been genetically engineered to express 2 mosaic Gag, Pol, and Env sequences (Mosaic 1 and Mosaic 2). Total dose is 10\^8 plaque-forming unit per 0.5 mL injection administered intramuscularly. intervention 3: The gp140 DP vaccine containing 50 mcg of total protein, mixed with aluminum phosphate adjuvant (0.425 mg aluminum), per 0.5 mL injection administered intramuscularly. intervention 4: The gp140 DP vaccine containing 250 mcg of total protein, mixed with aluminum phosphate adjuvant, per 0.5 mL injection administered intramuscularly. intervention 5: Normal saline, 0.5 mL injection administered intramuscularly.

Protocol documents:
Prot_002.pdf: 
1
Status: Approved, Date: 21 December 2016
Janssen Vaccines & Prevention B.V. *
Clinical Protocol
A Phase 1/2a Study to Evaluate the Safety/Tolerability and Immunogenicity of 
Homologous Ad26 Mosaic Vector Vaccine Regimens or Ad26 Mosaic and MVA Mosaic 
Heterologous Vector Vaccine Regimens, with High-Dose, Low-Dose or no Clade C gp140 
Protein Plus Adjuvant for HIV Prevention
Protocol HIV-V-A004 Amendment 5 (IPCAVD009); Phase 1/2a
JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
*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.
This study will be conducted under US Food and Drug Administration IND regulations (21 CFR 
Part 312).
Status:
Approved
Date:
21 December 2016
EDMS number:
EDMS-ERI-102817395, 9.0
GCP Compliance: This study will be conducted in compliance with Good Clinical Practice, and applicable regulatory 
requirements. 
Confidentiality Statement
The information in this document contains trade secrets and commercial information that are privileged or confidential and may 
not be disclosed unless such disclosure is required by applicable law or regulations. In any event, persons to whom the 
information is disclosed must be informed that the information is privileged or confidential and may not be further disclosed by 
them. These restrictions on disclosure will apply equally to all future information supplied to you that is indicated as privileged or 
confidential.
NCT02315703


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
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Approved, Date: 21 December 2016
TABLE OF CONTENTS
TABLE OF CONTENTS ............................................................................................................................... 2
LIST OF ATTACHMENTS............................................................................................................................ 4
LIST OF IN-TEXT TABLES AND FIGURES................................................................................................ 4
PROTOCOL AMENDMENTS....................................................................................................................... 5
SYNOPSIS.................................................................................................................................................. 12
TIME AND EVENTS SCHEDULE .............................................................................................................. 19
ABBREVIATIONS ...................................................................................................................................... 24
1.
INTRODUCTION................................................................................................................................ 26
1.1.
Background .................................................................................................................................... 26
1.2.
Overall Rationale for the Study...................................................................................................... 29
2.
OBJECTIVES AND HYPOTHESIS ................................................................................................... 30
2.1.
Objectives ...................................................................................................................................... 30
2.2.
Hypothesis ..................................................................................................................................... 30
3.
STUDY DESIGN AND RATIONALE ................................................................................................. 30
3.1.
Overview of Study Design.............................................................................................................. 30
3.2.
Study Design Rationale.................................................................................................................. 34
4.
SUBJECT POPULATION.................................................................................................................. 34
4.1.
Inclusion Criteria ............................................................................................................................ 34
4.2.
Exclusion Criteria ........................................................................................................................... 37
4.3.
Prohibitions and Restrictions ......................................................................................................... 39
5.
VACCINE ALLOCATION AND BLINDING....................................................................................... 40
6.
DOSAGE AND ADMINISTRATION .................................................................................................. 41
7.
TREATMENT COMPLIANCE............................................................................................................ 42
8.
PRESTUDY AND CONCOMITANT THERAPY ................................................................................ 42
9.
STUDY EVALUATIONS .................................................................................................................... 43
9.1.
Study Procedures........................................................................................................................... 43
9.1.1.
Overview..................................................................................................................................... 43
9.1.2.
Visit Windows ............................................................................................................................. 43
9.1.3.
Screening Phase (Weeks –4 to 0).............................................................................................. 44
9.1.4.
Vaccination (Weeks 0, 12, 24, and 48)....................................................................................... 45
9.1.5.
Post-vaccination Follow-Up Phase (Weeks 1, 2 and 4; Weeks 14 and 16; Weeks 26, 28 
and 36; Weeks 50 and 52) ......................................................................................................... 47
9.1.6.
Second Year Follow-Up Phase (Weeks 60 to 96)...................................................................... 48
9.1.7.
Early Withdrawal – Early Exit Visit.............................................................................................. 49
9.1.8.
Long-Term Extension Phase ...................................................................................................... 49
9.1.9.
Local Mucosal Sampling............................................................................................................. 49
9.2.
Immunogenicity.............................................................................................................................. 50
9.2.1.
Endpoints.................................................................................................................................... 50
9.2.2.
Evaluations ................................................................................................................................. 50
9.3.
Safety Evaluations ......................................................................................................................... 52
9.3.1.
Endpoints.................................................................................................................................... 52
9.3.2.
Evaluations ................................................................................................................................. 52
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9.4.
HIV Testing and VISP .................................................................................................................... 56
9.4.1.
HIV Testing ................................................................................................................................. 56
9.4.2.
Management of Subjects who Become HIV-infected During the Study..................................... 57
9.4.3.
Vaccine Induced Seropositivity (VISP)....................................................................................... 57
9.4.4.
Social Impact .............................................................................................................................. 58
9.4.5.
Post-Exposure Prophylaxis (PEP).............................................................................................. 58
9.5.
Sample Collection and Handling.................................................................................................... 58
10.
SUBJECT COMPLETION/WITHDRAWAL....................................................................................... 58
10.1.
Completion ..................................................................................................................................... 58
10.2.
Discontinuation of Study Vaccine .................................................................................................. 59
10.3.
Contraindications to Vaccination.................................................................................................... 59
10.4.
Withdrawal from the Study............................................................................................................. 59
11.
STATISTICAL METHODS................................................................................................................. 60
11.1.
Analysis Populations...................................................................................................................... 61
11.2.
Sample Size Determination ........................................................................................................... 61
11.3.
Subject Information ........................................................................................................................ 63
11.4.
Immunogenicity Analyses .............................................................................................................. 63
11.5.
Safety Analyses ............................................................................................................................. 64
11.6.
Interim Analysis.............................................................................................................................. 65
11.7.
Protocol Safety Review Team (PSRT)........................................................................................... 65
11.8.
Data Monitoring Committee (DMC)................................................................................................ 66
11.9.
Study Holding Rules....................................................................................................................... 66
12.
ADVERSE EVENT REPORTING ...................................................................................................... 68
12.1.
Definitions ...................................................................................................................................... 68
12.1.1.
Adverse Event Definitions and Classifications ........................................................................... 68
12.1.2.
Attribution Definitions.................................................................................................................. 69
12.1.3.
Severity Criteria .......................................................................................................................... 70
12.2.
Special Reporting Situations.......................................................................................................... 71
12.3.
Procedures..................................................................................................................................... 71
12.3.1.
All Adverse Events...................................................................................................................... 71
12.3.2.
Serious Adverse Events ............................................................................................................. 72
12.3.3.
HIV Infection ............................................................................................................................... 73
12.3.4.
Pregnancy................................................................................................................................... 73
12.4.
Contacting Sponsor Regarding Safety........................................................................................... 74
13.
PRODUCT QUALITY COMPLAINT HANDLING.............................................................................. 74
13.1.
Procedures..................................................................................................................................... 74
13.2.
Contacting Sponsor Regarding Product Quality ............................................................................ 74
14.
STUDY VACCINE INFORMATION ................................................................................................... 75
14.1.
Physical Description of Study Vaccines......................................................................................... 75
14.2.
Packaging and Labeling................................................................................................................. 76
14.3.
Preparation, Handling, and Storage............................................................................................... 76
14.4.
Vaccine Accountability ................................................................................................................... 78
15.
STUDY-SPECIFIC MATERIALS....................................................................................................... 78
16.
ETHICAL ASPECTS ......................................................................................................................... 79
16.1.
Study-Specific Design Considerations........................................................................................... 79
16.2.
Regulatory Ethics Compliance....................................................................................................... 81
16.2.1.
Investigator Responsibilities ....................................................................................................... 81
16.2.2.
Independent Ethics Committee or Institutional Review Board ................................................... 81
16.2.3.
Informed Consent ....................................................................................................................... 82
16.2.4.
Privacy of Personal Data ............................................................................................................ 83
16.2.5.
Long-Term Retention of Samples for Additional Future Research ............................................ 84
16.2.6.
Country Selection ....................................................................................................................... 84
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16.3.
USAMRMC Volunteer Registry Database ..................................................................................... 84
17.
ADMINISTRATIVE REQUIREMENTS .............................................................................................. 85
17.1.
Protocol Amendments.................................................................................................................... 85
17.2.
Regulatory Documentation ............................................................................................................ 85
17.2.1.
Regulatory Approval/Notification ................................................................................................ 85
17.2.2.
Required Pre-study Documentation ........................................................................................... 85
17.3.
Subject Identification, Enrollment, and Screening Logs ................................................................ 86
17.4.
Source Documentation................................................................................................................... 87
17.5.
Case Report Form Completion ...................................................................................................... 87
17.6.
Data Quality Assurance/Quality Control ........................................................................................ 88
17.7.
Record Retention ........................................................................................................................... 88
17.8.
Monitoring ...................................................................................................................................... 89
17.9.
Study Completion/Termination....................................................................................................... 89
17.9.1.
Study Completion ....................................................................................................................... 89
17.9.2.
Study Termination....................................................................................................................... 89
17.10.
On-Site Audits ................................................................................................................................ 90
17.11.
Use of Information and Publication................................................................................................ 90
REFERENCES............................................................................................................................................ 92
INVESTIGATOR AGREEMENT ............................................................................................................... 116
LAST PAGE.............................................................................................................................................. 116
LIST OF ATTACHMENTS
Attachment 1:
Division of AIDS Tables for Grading the Severity of Adult and Pediatric Adverse 
Events Version 1.0, December, 2004; Clarification August 2009 – Including 
Modifications ............................................................................................................................. 94
Attachment 2:
HIV-Risk Assessment .................................................................................................. 112
Attachment 3:
Test of Understanding.................................................................................................. 114
Attachment 4:
Social Impact Questionnaire........................................................................................ 115
LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1:
Study Design HIV-V-A004 ........................................................................................................ 14
Table 2:
Humoral Immune Response Assays ........................................................................................ 17
Table 3:
T-Cell Immune Response Assays ............................................................................................ 17
Table 4:
Study Design HIV-V-A004 ........................................................................................................ 31
Table 5:
Humoral Immune Response Assays ........................................................................................ 51
Table 6:
T-Cell Immune Response Assays ............................................................................................ 52
Table 7:
Power (%) for two-sided 5% test for difference in breadth of response, if the response 
towards Clade A/B/C in one group is 90%/90%/90% ............................................................... 63
Table 8:
AE Notification and Safety Pause/AE Review Rules1............................................................... 67
FIGURES
Figure 1:
Schematic Overview of the Study............................................................................................. 33
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JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
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Approved, Date: 21 December 2016
PROTOCOL AMENDMENTS
Protocol Version
Issue Date
Original Protocol
26 Sep 2014
Amendment 1
17 Dec 2014
Amendment 2
06 Feb 2015
Amendment 3
15 Apr 2015
Amendment 4
20 Aug 2015
Amendment 5
This document
Amendments are listed beginning with the most recent amendment.
Amendment 5 (This document)
The overall reason for the amendment: This amendment specifies the assessments to be performed in the 
long-term extension phase for the treatment groups selected based on the Week 28 results. 
Rationale: Following results of Week 28, treatment groups 1 and 2 were selected for additional 5 years of follow up 
(Long Term Extension phase) from Week 96 to 336 post-vaccination to assess durability of immunologic responses. 
SYNOPSIS
TIME AND EVENTS SCHEDULE
ABBREVIATIONS
2.1 Objectives
3.1 Overview of Study Design
4.3 Prohibitions and Restrictions
5 VACCINE ALLOCATION AND BLINDING
8 PRESTUDY AND CONCOMITANT THERAPY
9.1.2 Visit Windows
9.1.8 Long-Term
9.2.1 Endpoints
9.2.2 Evaluations
9.3.1 Endpoints
9.3.2 Evaluations
9.4.1 HIV Testing
9.4.4 Social Impact
10.1 Completion
10.2 Discontinuation of Study Vaccine
10.4 Withdrawal from the Study
11 STATISTICAL METHODS
11.6 Interim Analysis
12.1.1 Adverse Event Definitions and Classifications
12.3.1 All Adverse Events
16.2.3 Informed Consent
Rationale: From 1 Jun 2016 onwards, the name of Crucell Holland B.V. has been changed to Janssen Vaccines & 
Prevention B.V.
Title Page
1 INTRODUCTION
14.1 Physical Description of Study Vaccines
INVESTIGATOR AGREEMENT
Rationale: minor corrections.
NCT02315703


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
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Approved, Date: 21 December 2016
Amendment 4 (20 Aug 2015)
The overall reason for the amendment: To avoid unnecessary pausing of vaccination for Data Monitoring 
Committee (DMC) review of certain reactogenicity events, common to most vaccines.
Rationale: As vaccinations in general are expected to cause benign reactogenicity events ranging from Grade 1 to 
Grade 3 and up to about a maximum of 72 hours post-vaccination, it is in the opinion of the clinical team, with full 
support of Protocol Safety Review Team (PSRT) and DMC members, that it would make sense to concentrate the 
in-depth reviews by DMC with mandatory vaccination pauses for the vaccine-related Grade 3 solicited adverse 
events (AEs) as follows: DMC review with immediate pause in case ≥3 subjects experience a similar vaccine-related 
Grade 3 solicited AE that would last longer than 72 hours (Table 8; footnote 3). In addition, redaction of Table 8 has 
been done to enhance readability.
11.9 Study Holding Rules
Rationale: Minor changes.
4.1 Inclusion Criteria
4.2 Exclusion Criteria
Attachment 1
Amendment 3 (15 Apr 2015)
The overall reason for the amendment: A clear distinction has been made between single and double methods of 
contraception.
Rationale: Taking into account the very high effectiveness of long-acting reversible contraceptive methods; a single 
contraceptive method is deemed appropriate when using these methods. A double method should be used for all 
other contraceptive methods. The text has been expanded with the necessary details, and a summary table has been 
added.
4.1 Inclusion Criteria
Rationale: To account for values in peri-menstrual women, the blood urinalysis laboratory criterion for inclusion 
has been set from <1+ to <2+ for women.
4.1 Inclusion Criteria
Rationale: Depending on local collection processes, some variations may exist in blood volumes that will be 
collected. Therefore, the specific daily blood volume for the safety laboratory tests has been removed from the 
protocol. However, indicative blood volumes are included in the Study Procedures Manual. Total approximate blood 
volume per visit is still to be respected.
TIME AND EVENTS SCHEDULE
Rationale: It is clarified that the restriction "the vaccine administrator should have no other study function related to 
safety, study data evaluation, or recording of AEs" is limited to the study functions related to those subjects who 
received a study vaccine on that particular visit.
5 VACCINE ALLOCATION AND BLINDING
7 TREATMENT COMPLIANCE
9.1.4 Vaccination (Weeks 0, 12, 24, and 48)
12.3.2 Serious Adverse Events
16.2.2 Independent Ethics Committee or Institutional 
Review Board
17.5 Case Report Form Completion
Administrative changes
Administrative Changes
Removed statement that all data should be recorded in 
CRF.
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JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
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Approved, Date: 21 December 2016
14.3 Preparation, Handling, and Storage
Rationale: It is clarified that women with a history of toxic shock syndrome are excluded from the cervico-vaginal 
part of mucosal sampling only and that subjects who had surgical sex-reassignment are excluded from 
cervico-vaginal mucosal and semen sampling. It is further clarified that estradiol and progesterone levels are 
measured in serum. In addition, it is clarified that the female hormone tests are only for women who consent to the 
cervico-vaginal mucosal sampling.
TIME AND EVENTS SCHEDULE
9.1.9 Local Mucosal Sampling
Rationale: Clarification on definition of related and not related AEs is provided.
11.9 Study Holding Rules
12.1.2 Attribution Definitions
Rationale: Availability of follow-up VISP testing is extended: "Testing for a particular subject will be available as 
long as VISP is present for this subject".
9.4.3 Vaccine Induced Seropositivity (VISP)
Rationale: For consistency with the HIV-Risk Assessment in Attachment 2, HSV-2 has been added to exclusion 
criterion 2.
ABBREVIATIONS
4.2 Exclusion Criteria
Attachment 2
Rationale: To clarify that in case of the mentioned skin conditions in exclusion criterion 16, systemic 
corticosteroids are not allowed while topical forms are allowed, given that the former could interfere with immune 
outcome, not the latter.
4.2 Exclusion Criteria
Rationale: To clarify the hepatitis B and hepatitis C tests to be performed at screening, the actual tests as mentioned 
in the Study Procedures Manual have been added to exclusion criterion 1. 
ABBREVIATIONS
4.2 Exclusion Criteria
Rationale: Typographical error.
TIME AND EVENTS SCHEDULE
Amendment 2 (06 Feb 2015)
The overall reason for the amendment: The overall reason for the amendment is to add a statement that the 
sponsor will reimburse post-exposure prophylaxis.
Rationale: Added post-exposure prophylaxis.
ABBREVIATIONS
8 PRESTUDY AND CONCOMITANT THERAPY
9.4.5 Post-Exposure Prophylaxis (PEP)
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JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
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Approved, Date: 21 December 2016
Rationale: It is clarified that vaccine administration can be performed by a qualified healthcare provider from the 
study site (including the pharmacist who prepared the study vaccine) who will have no other study function related 
to safety, study data evaluation or recording of AEs. 
5 VACCINE ALLOCATION AND BLINDING
7 TREATMENT COMPLIANCE
9.1.4 Vaccination (Weeks 0, 12, 24, and 48)
14.3 Preparation, Handling, and Storage
Rationale: If the initial laboratory sampling occurred longer than 28 days before the Day 1 visit, this test will not be 
repeated. Instead, this will be considered a screen failure.
TIME AND EVENTS SCHEDULE
9.1.4 Vaccination (Weeks 0, 12, 24, and 48)
Rationale: Broadening of visit windows: For the 2nd, 3rd, and 4th vaccination visit, the window will be –1 week and 
+3 weeks. The 2- to 4-week post-vaccination visits will be determined relative to the actual day of vaccination. For 
the second year follow-up visits, the window will be ±3 weeks.
TIME AND EVENTS SCHEDULE
9.1.2 Visit Windows
10.3 Contraindications to Vaccination
Rationale: It is added that if a subject misses more than one study vaccination, he/she will be withdrawn from 
further study vaccination.
6 DOSAGE AND ADMINISTRATION
9.1.2 Visit Windows
10.2 Discontinuation of Study Vaccine
Rationale: It is added that subjects with major protocol violations are excluded from the per-protocol population, 
only if these violations impact the immunogenicity assessments.
11.1 Analysis Populations
Rationale: Based on updated recruitment projections, efforts will be made to enroll a minimum of 50 subjects per 
region.
SYNOPSIS
3.1 Overview of Study Design
5 VACCINE ALLOCATION AND BLINDING
Rationale: It is clarified that central ECG reading will be used.
4.2 Exclusion Criteria
9.1.3 Screening Phase (Weeks –4 to 0)
9.3.2 Evaluations
11.5 Safety Analyses
Rationale: Clarification on receipt of licensed or experimental vaccines. 
4.2 Exclusion Criteria
4.4 Prohibitions and Restrictions
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JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
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Approved, Date: 21 December 2016
8 PRESTUDY AND CONCOMITANT THERAPY
10.3 Contraindications to Vaccination
Rationale: Addition of prohibition to use any experimental medication during the study.
4.4 Prohibitions and Restrictions
8 PRESTUDY AND CONCOMITANT THERAPY
Rationale: It is clarified that it is disallowed to concomitantly participate in another study without prior sponsor 
approval.
4.2 Exclusion Criteria
4.4 Prohibitions and Restrictions
Rationale: Pregnancy counseling will not only be provided at screening, but at several timepoints throughout the 
study.
TIME AND EVENTS SCHEDULE
9.1.4 Vaccination (Weeks 0, 12, 24, and 48)
9.1.6 Second Year Follow-Up Phase (Weeks 60 to 96)
9.1.7 Early Withdrawal – Early Exit Visit
Rationale: Since storage temperature of the study vaccine will be detailed in the site investigational product manual, 
these details have been removed from the protocol.
14.3 Preparation, Handling, and Storage
Rationale: The maximum time allowed between preparation and administration of the study vaccine is set to 
3 hours.
14.3 Preparation, Handling, and Storage
Rationale: It is added that, in the case of VISP, HIV testing can be performed more frequently than every 3 months, 
if approved by the sponsor.
9.4.3 Vaccine Induced Seropositivity (VISP)
Rationale: It is sufficient for subjects to be observed for reactogenicity for 30 minutes after vaccination, instead of 
60 minutes. It is also clarified that this observation does not necessarily mean a one to one observation. 
SYNOPSIS
TIME AND EVENTS SCHEDULE
3.1 Overview of Study Design
9.1.4 Vaccination (Weeks 0, 12, 24, and 48)
Rationale: Weight will need to be measured at every visit, not only at screening.
TIME AND EVENTS SCHEDULE
9.1.4 Vaccination (Weeks 0, 12, 24, and 48)
9.1.5 Post-vaccination Follow-Up Phase (Weeks 1, 2 and 4; Weeks 14 and 16; Weeks 26, 28 and 36; Weeks 50 and 
52)
9.1.6 Second Year Follow-Up Phase (Weeks 60 to 96)
9.1.7 Early Withdrawal – Early Exit Visit
9.3.2 Evaluations
NCT02315703


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
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Approved, Date: 21 December 2016
Rationale: It is clarified that it is required to use a different deltoid for all study vaccine injections to be 
administered at one and the same visit. For visits with only one injection, either deltoid can be used.
SYNOPSIS
6 DOSAGE AND ADMINISTRATION
14.3 Preparation, Handling, and Storage
Rationale: It is added that adaptations to the Test of Understanding are allowed for local purposes, after IRB and 
sponsor approval.
9.1.3 Screening Phase (Weeks –4 to 0)
Attachment 3
Rationale: Minor Clarifications
SYNOPSIS
It is clarified that temperature should be measured at approximately the 
same time each day.
9.3.2 Evaluations
TIME AND EVENTS SCHEDULE
HLA testing was only mentioned in footnote 18 of the Time and Events 
Schedule. To avoid this being overlooked, wording on HLA testing has 
been added to the first column of the actual schedule instead. HLA test at 
baseline has also been added to Section 9.1.4 to match the Time and 
Events Schedule.
9.1.4 Vaccination (Weeks 0, 12, 24, 
and 48)
9.1.3 Screening Phase (Weeks –4 to 0)
Clarification on pre-screening assessment and use of non-study specific 
consent.
9.1.3 Screening Phase (Weeks –4 to 0)
Clarified that Test of Understanding needs to be performed during 
screening.
9.3.2 Evaluations
A subtitle ‘Cardiac-Related Events’ has been added in order to highlight 
the process to be followed for these events.
The wording 'pre-dose' has been removed from the ECG assessment at 
Week 16. This implies pre-dose to the vaccination at Week 24, but might
cause confusion since there is no vaccination planned at Week 16.
11.5 Safety Analyses
It has been clarified that a supine position is not required for a vital signs 
measurement.
ABBREVIATIONS
Wording on reporting of SUSARs is clarified.
12.1.1 Adverse Event Definitions and 
Classifications
12.3.1 All Adverse Events
10.2 Discontinuation of Study Vaccine
It is clarified that subjects, who need to be withdrawn from study vaccine 
administration, will enter the follow-up phase, starting from Visit 14 
onwards. 
12.3.4 Pregnancy
Rationale: A JNJ-compound number for the combination of gp140 DP and the adjuvant aluminum phosphate has 
been added. 
14.1 Physical Description of Study Vaccines
Rationale: Minor errors were corrected.
ABBREVIATIONS
IVRS will not be used, so it has been removed.
NCT02315703


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
11
Approved, Date: 21 December 2016
5 VACCINE ALLOCATION AND 
BLINDING
15 STUDY-SPECIFIC MATERIALS
TIME AND EVENTS SCHEDULE
'Troponin I' was corrected to 'troponin'.
9.1.3 Screening Phase (Weeks –4 to 0)
9.3.2 Evaluations
9.1.6 Second Year Follow-Up Phase 
(Weeks 60 to 96)
For consistency with the Time and Events Schedule, it is added that urine 
pregnancy test will also be performed at Week 60.
9.1.9 Local Mucosal Sampling
Text already mentions that mucosal sampling will not be performed if 
there are symptoms of active inflammation. Changed wording to: 'signs 
or symptoms'.
9.3.2 Evaluations
There will not be a separate field in the CRF for physical examination 
findings. Clinically relevant physical examination findings need to be 
entered in the CRF as medical history/AE. In section 9.3.2, it is added 
that full physical examination is also performed at the final visit, to match 
the Time and Events schedule.
11.5 Safety Analyses
17.4 Source Documentation
10.2 Discontinuation of Study Vaccine
The text on immunosuppressants was made consistent with text in 
Section 8.
11.7 Protocol Safety Review Team 
(PSRT)
Reference to Table 6 was corrected to reference to Table 8.
15 STUDY-SPECIFIC MATERIALS
Removed incorrect wording ‘pharmacy manual’.
Attachment 1
Correction of page reference to ‘Estimating Severity Grade’
Attachment 1
Added Induration/Swelling as parameter in the AE grading table.
Amendment 1 (17 Dec 2014)
The overall reason for the amendment: Upon request of the FDA, the requirement is included that from the 
baseline visit onwards, all grade 3 and grade 4 laboratory abnormalities, as well as laboratory abnormalities 
accompanied by clinically relevant signs and/or symptoms, will be repeated within 48 hours of receipt.
TIME AND EVENTS SCHEDULE
9.1.1 Overview
9.3.2 Evaluations
11.9 Study Holding Rules
NCT02315703


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
12
Approved, Date: 21 December 2016
SYNOPSIS
A Phase 1/2a Study to Evaluate the Safety/Tolerability and Immunogenicity of Homologous Ad26 
Mosaic Vector Vaccine Regimens or Ad26 Mosaic and MVA Mosaic Heterologous Vector Vaccine 
Regimens, with High-Dose, Low-Dose or no Clade C gp140 Protein Plus Adjuvant for HIV 
Prevention
OVERALL RATIONALE
This study, first-in-human for Ad26.Mos.HIVa, will assess the safety/tolerability and immunogenicity of 
seven prime/boost vaccine regimens. Subjects will receive four doses of study vaccine: Ad26.Mos.HIV or 
placebo will be given at Weeks 0 and 12; Ad.26.Mos.HIV or Modified Vaccinia Ankara (MVA)-Mosaic,
both with or without glycoprotein 140 drug product (gp140 DP [low or high dose]), gp140 DP (high dose) 
or placebo, or placebo only will be given at Weeks 24 and 48. The goal of this study is to select a regimen 
for evaluation in future efficacy studies.
Study vaccines used in this study are Ad26.Mos.HIV, MVA-Mosaic and gp140 DP:
Ad26.Mos.HIV vaccine is made up of the following three drug substances in a 2:1:1 ratio:

Ad26.Mos1.Env

Ad26.Mos1.Gag-Pol

Ad26.Mos2.Gag-Pol
MVA-Mosaic consists of the following two vaccine products supplied in separate vials and administered 
in a 1:1 ratio:

MVA-Mosaic1 = MVA virus expressing Mosaic1 HIV-1 Gag, Pol, and Env proteins

MVA-Mosaic2 = MVA virus expressing Mosaic2 HIV-1 Gag, Pol, and Env proteins
gp140 DP (HIV-1 Clade C glycoprotein 140) contains recombinant trimeric gp140, produced on a 
transformed PER.C6® cell line constructed to produce gp140 DP. In this study, gp140 DP will be dosed 
with aluminum phosphate as adjuvant.
The safety of two injections of high (250 mcg) and low (50 mcg) doses of gp140 DP will be established 
in a Phase 1 study prior to dosing with gp140 DP in the current study.
OBJECTIVES AND HYPOTHESIS
Primary Objectives
The primary objectives are:

To assess the safety/tolerability of various prime/boost regimens containing Ad26.Mos.HIV, 
MVA-Mosaic, and/or gp140 DP components.

To compare Env binding antibody responses between the different vaccine regimens.
                                                
a Ad26 = adenovirus serotype 26; Mos = mosaic; HIV-1 = Human Immunodeficiency Virus Type 1
NCT02315703


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
13
Approved, Date: 21 December 2016
Secondary Objectives
The secondary objective is:

To assess other antibody binding, antibody effector function and antibody characterization, and 
cellular responses.
Exploratory Objectives
The exploratory objectives are:

To explore immune responses to the different vaccine regimens in mucosal secretions in a subset of 
subjects.

To explore gene expression patterns between the different vaccine regimens.

To explore neutralization antibodies against the Ad26 vector.

To assess the social impact of participation in an HIV vaccine study for subjects via a social impact 
questionnaire.

To explore durability of the vaccine regimen in the groups selected for the long-term extension 
phase.
Hypothesis
No formal statistical hypothesis will be tested. This study will evaluate whether a prime/boost vaccine 
regimen consisting of Ad26.Mos.HIV with or without gp140 protein plus aluminum phosphate adjuvant, 
or Ad26.Mos.HIV/MVA-Mosaic with or without gp140 protein plus aluminum phosphate adjuvant is 
safe, well-tolerated and immunogenic, providing broad, functional and durable humoral and cellular 
responses.
OVERVIEW OF STUDY DESIGN
This is a multicenter, randomized, parallel group, placebo-controlled, double-blind clinical study in 
healthy HIV-uninfected adult men and women. Subjects will be enrolled regardless of their baseline Ad26 
seropositivity, as data from Study IPCAVD003 suggest that there is little impact of baseline Ad26 
neutralizing antibodies (nAbs) on the immunogenicity of this Ad26 vaccine vector, at the titers observed 
in that study, however regional differences are known to occur. Vaccinations are administered as shown 
in Table 1.
The study comprises a maximum 4-week screening period, a 48-week vaccination period during which 
subjects will be vaccinated at baseline, Week 12 and Week 24, with a booster at Week 48, and a 48-week 
follow-up period to the final visit at Week 96. Based on the analysis of the Week 28 data, a Long Term 
Extension (LTE) phase (approximately 5 years after Week 96) will be performed for subjects randomized 
to Group 1 and Group 2 and having received all 4 vaccinations. These 2 groups (including a gp140 
250 mcg and a gp140 50 mcg dose, respectively) form the basis for the regimens that will be evaluated in 
future studies. The end of the study will be the last subject’s last visit.
NCT02315703


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
14
Approved, Date: 21 December 2016
Table 1:
Study Design HIV-V-A004
Group
N
Week 0
(baseline)
Week 12
Week 24
Week 48
Group 1*
50
Ad26.Mos.HIV
Ad26.Mos.HIV
Ad26.Mos.HIV
+ gp140 DP
(250 mcg + adjuvant)a
Ad26.Mos.HIV
+ gp140 DP
(250 mcg + adjuvant) a
Group 2*
50
Ad26.Mos.HIV
Ad26.Mos.HIV
Ad26.Mos.HIV
+ gp140 DP
(50 mcg + adjuvant) a
Ad26.Mos.HIV
+ gp140 DP
(50 mcg + adjuvant) a
Group 3
50
Ad26.Mos.HIV
Ad26.Mos.HIV
Ad26.Mos.HIV
+ Placebo
Ad26.Mos.HIV
+ Placebo
Group 4
50
Ad26.Mos.HIV
Ad26.Mos.HIV
MVA-Mosaic
+ gp140 DP
(250 mcg + adjuvant) a
MVA-Mosaic
+ gp140 DP
(250 mcg + adjuvant) a
Group 5
50
Ad26.Mos.HIV
Ad26.Mos.HIV
MVA-Mosaic
+ gp140 DP
(50 mcg + adjuvant) a
MVA-Mosaic
+ gp140 DP
(50 mcg + adjuvant) a
Group 6
50
Ad26.Mos.HIV
Ad26.Mos.HIV
MVA-Mosaic
+ Placebo
MVA-Mosaic
+ Placebo
Group 7
50
Ad26.Mos.HIV
Ad26.Mos.HIV
gp140 DP
(250 mcg + adjuvant) a
+ Placebo
gp140 DP
(250 mcg + adjuvant) a
+ Placebo
Group 8
50
Placebo
Placebo
Placebo
+ Placebo
Placebo
+ Placebo
a Aluminum content will be 0.425 mg/0.5 mL dose
50 mcg and 250 mcg refer to total protein content
Sterilized aluminum phosphate wet gel suspension will be used as adjuvant for gp140 DP
*An optional LTE phase (approximately 5 years after Week 96) will be performed for subjects randomized to 
Group 1 and Group 2 and having received all 4 vaccinations.
After vaccination, subjects will remain under observation for at least 30 minutes for any reactogenicity. 
Subjects will use a memory aid to document any local and systemic adverse events (AEs) in the evening 
after each vaccination and then daily for the next 7 days. The investigator or his/her designee will 
document any AEsb, and will collect blood and urine samples for safety laboratory assessment 
(hematology, biochemistry, and urinalysis) at each visit until Week 96. Cardiac safety surveillance 
monitoring will be performed by electrocardiogram (ECG) and measurement of specific cardiac enzymes 
(troponin) if cardiac symptoms appear. Also, subjects will be specifically asked about cardiac symptoms 
at each post-vaccination visit.
Blood samples will be taken at specific clinic visits to assess immune responses.
An independent Data Monitoring Committee (DMC) and an internal Protocol Safety Review Team 
(PSRT), composed of medical and safety representatives of the sponsor and partners will be established 
for this study to evaluate safety and tolerability data.
                                                
b At the visits at 2 weeks after each vaccination, the investigator or his/her designee should discuss information from 
the memory aids with subjects, and complete the relevant parts of the CRF.
NCT02315703


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
15
Approved, Date: 21 December 2016
PSRT and DMC Review of Sentinel Groups
There will be a pause in enrollment after 10% of the target number of subjects have received their first 
injection (ie, approximately 40 subjects). The PSRT will review the blinded Week 2 safety data after first 
injection to determine if enrollment can continue. The PSRT will also review blinded safety data (2 weeks 
of follow up) after 30% of subjects have received their first injection without a pause in enrollment.
To decide whether further dosing can continue, the DMC will review blinded safety data (2 weeks of 
follow up) after 30% of subjects have received their first injection, and unblinded data after 10% of 
subjects have received their third injection, and after 30% of subjects have received their third injection.
DMC Review of gp140 DP Safety in HIV-V-A003
The safety, tolerability and immunogenicity of gp140 DP will be evaluated in a separate safety study 
(HIV-V-A003) with interim safety results available prior to the first subject reaching Week 24 of this 
study, HIV-V-A004 (the time point at which subjects in certain arms will receive gp140 DP). The DMC 
will review the interim safety results of study HIV-V-A003 and will allow administration of the first dose 
of gp140 DP (third injection; Week 24 vaccination) in this HIV-V-A004 protocol only if no safety 
concerns are identified.
Analysis Timepoints
The primary analysis will be performed once all subjects have completed the Week 28 visit (ie, 4 weeks 
after the third injection) or discontinued earlier. The purpose of this analysis is to allow for an early 
conclusion on regimen selection for future studies, based on immunogenicity and safety. 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 study visit at Week 96 (ie, including the second year follow-up period)
or discontinued earlier. The final analysis of the LTE phase (optional and only for a subset of subjects) 
will be performed once all included subjects have completed the last visit of the extension period (Week 
336), or discontinued earlier.
SUBJECT POPULATION
Study subjects must be healthy (on the basis of physical examination, medical history, laboratory 
assessments, ECG and vital signs measurement performed at screening) HIV-uninfected adult men and 
women, aged ≥18 to ≤50 years on the day of signing the informed consent form (ICF), and assessed by 
the clinic staff as being at low risk for HIV infection.
In total, 400 subjects will be randomized equally into one of seven prime/boost vaccine regimens, 
consisting 
of 
Ad26.Mos.HIV
with 
or 
without 
gp140
protein 
(low 
or 
high 
dose), 
Ad26.Mos.HIV/MVA-Mosaic with or without gp140 protein (low or high dose), or placebo (Table 1).
Randomization will be stratified by region (United States [US], Africa, and Asia). Efforts will be made to 
enroll a minimum of 50 subjects per region.
DOSAGE AND ADMINISTRATION
Subjects will receive doses of study vaccine at four timepoints according to randomization, on Day 1, at 
Week 12, and at Week 24, with a booster at Week 48, administered by intramuscular injection into the
deltoid. For visits with only one injection (ie, at Week 0 and 12), either deltoid can be used. When 2 study 
vaccine injections are to be given at one visit (ie, at Week 24 and 48), it is required to use a different
deltoid for both injections. Exceptions are allowed only if medically indicated. Study vaccines are as 
follows:

Ad26.Mos.HIV (Ad26.Mos.1.Env + Ad26.Mos1.Gag-Pol + Ad26.Mos2.Gag-Pol):

Total dose is 5x1010 viral particles (vp) per 0.5 mL injection
NCT02315703


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
16
Approved, Date: 21 December 2016

MVA-Mosaic (MVA-Mosaic1 + MVA-Mosaic2): 

Total dose is 108 plaque-forming units (pfu) per 0.5 mL injection

gp140 DP: 

Low-dose: gp140 DP with 50 mcg total protein, mixed with aluminum phosphate adjuvant 
(0.425 mg aluminum) at the pharmacy, per 0.5 mL injection

High-dose: gp140 DP with 250 mcg total protein, mixed with aluminum phosphate adjuvant 
(0.425 mg aluminum) at the pharmacy, per 0.5 mL injection

Placebo:

0.9% saline, 0.5 mL injection
SAFETY EVALUATIONS
All AEs will be recorded from the time the informed consent is signed until the Week 96 visit of 
the main study. During the optional LTE phase (Group 1 and 2), only SAEs (including HIV 
infection and abnormal pregnancy outcome) will be recorded. 
On a daily basis, for 8 days post-vaccination (day of vaccination and the subsequent 7 days), subjects will 
be asked to record symptoms of the following AEs via a memory aid:

Solicited local AEs: erythema, induration and swelling (measured using the ruler supplied), and 
pain/tenderness, itching, or warmth at the injection sites.

Solicited systemic AEs: fatigue, headache, myalgia, arthralgia, chills, fever, nausea, vomiting, 
rashes, and general itching.

Temperature should be measured at approximately the same time each day using the thermometer 
supplied. Fever will be recorded by the investigator for temperatures equal to or higher than 38.0°C.

Other spontaneously reported AEs (ie, unsolicited AEs).
The investigator or his/her designee should discuss information from the memory aids with subjects, 
document relevant information in the clinic chart (source document) and complete the relevant parts of 
the case report form (CRF).
IMMUNOGENICITY EVALUATIONS
Humoral response assays will include, but are not limited to Env-specific serum binding antibody assay,
nAb assays, and antibody-dependent cellular phagocytosis (ADCP) assay, as well as epitope mapping
(see Table 2).
NCT02315703


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
17
Approved, Date: 21 December 2016
Table 2:
Humoral Immune Response Assays
Objective/
endpoint
System
Assay/Method
Readout
Timepoint
Primary
Serum
Env binding antibody 
(ELISA)
Titer or % responders (Clade C)
and breadth
(Clade A, B, C)
Baseline
1 mo post-vac. 1
0.5, 1 mo post-vac. 2-4
3, 6 mo post-vac. 4
Secondary
Serum
HIV neutralizing 
antibody
Tier 1 and Tier 2a nAbs:
GMT for each isolate,
% responders to each isolate
Breadth: # isolates neutralized
As above
Secondary
Serum
gp120 binding 
antibody
Anti-gp120 titer
(Clade A, B, C)
As above
Secondary
Serum
ADCP
% phagocytosis
As above
Secondary
Serum
Isotyping Env binding 
antibody (ELISA)
Isotyping (Clade C)
(IgA, IgG1, IgG2, IgG3)
As above
Exploratory
Serum
Epitope mapping
Targeted epitopes and diversity 
(including V2)
1 mo post-vac. 1-4
At vac. 2-4
Exploratory
Serum
Ad26 neutralization 
antibodies
Titers of Ad26 neutralization 
antibodies
1 mo post-vac. 1-4
3, 7.5, 12 mo post-vac. 4
At vac. 1-4
ADCP = antibody-dependent cellular phagocytosis; ELISA = enzyme-linked immunosorbent assay; GMT = 
geometric mean titer; Ig = immunoglobulin; mo = month ; nAb = neutralizing antibody; vac = vaccination
a Classification of HIV-1 viruses according to sensitivity to antibody-mediated neutralization: very high (tier 1A), 
above-average (tier 1B), moderate (tier 2), or low (tier 3) 1. Tier 2 will only be assessed if Tier 1 shows 
positive results.
Evaluations of cellular immune responses will include, but are not limited to, the following assays: 
ELISPOT, intra-cellular cytokine staining, and multi-parameter flow cytometry (see Table 3).
Table 3:
T-Cell Immune Response Assays
Objective/
endpoint
System
Assay/ Method
Readout
Timepoint
Secondary
PBMC
ELISPOT
Breadth and depth:
# peptides,
% responders,
median response
Baseline
0.5, 1 mo post-vac. 3 & 4
Exploratory
PBMC
Intracellular cytokine 
staining
% of CD4 and CD8+ T cells 
producing IFNγ, IL-2, TNFα
Baseline
1 mo post-vac. 1
0.5, 1 mo post-vac. 2-4
3, 7.5 mo post-vac. 4
Exploratory
PBMC
Multi-parameter flow 
cytometry
Characterization of memory T-
cell development with emphasis 
on follicular helper T cells
Baseline
1 mo post-vac. 1
0.5, 1 mo post-vac. 2-4
3, 7.5 mo post-vac. 4
Exploratory
PBMC
Gene expression 
analysis
Regulation of genes (clusters) 
that predict specific immune 
responses and HLA typing
Baseline
1 mo post-vac. 1
0.5, 1 mo post-vac. 2-4
3, 7.5 mo post-vac. 4
ELISPOT = enzyme-linked immunospot assay; HLA = human leukocyte antigen; IFNγ = interferon gamma; IL-2 
= interleukin 2; mo = month; PBMC = peripheral blood mononuclear cell; TNFα = tumor necrosis factor alpha; 
vac = vaccination
Note: HLA only tested once (using the baseline blood sample)
NCT02315703


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
18
Approved, Date: 21 December 2016
Exploratory humoral and cellular immunogenicity assessments during the optional long-term extension 
phase (Group 1 and 2 only) may include, but are not limited to, the following assays: Env-specific serum 
binding antibody assay and ELISPOT. Further specification will be based on the Week 52 results.
Exploratory assessments on mucosal samples will include, but are not limited to, characterization of 
Env-specific binding antibodies.
OTHER EVALUATIONS
A social impact questionnaire will be administered at Weeks 24, 48, 96 and at each visit of the LTE
phase.
STATISTICAL METHODS
A sample size of 50 subjects per regimen is regarded to be appropriate to assess the safety and tolerability 
of the different vaccine regimens and also collect sufficient data on immunogenicity. Placebo recipients 
are included to assess safety and will provide control specimens for immunogenicity assays.
While mild to moderate vaccine reactions (local site and systemic responses) are expected, AEs that 
preclude further dose administration or more serious ones that would limit product development are not 
anticipated. With 50 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 6%. For the combined groups with 
Ad26.Mos.HIV (n = 350), there would be 95% confidence that the true rate is <1% when 0 events are 
observed. The following table shows the probabilities of observing at least one AE at given true AE rates:
True AE rate
Probability of observing at 
least one AE in n subjects
n = 50
n = 350
0.1%
5%
30%
0.5%
22%
83%
1%
39%
97%
2.5%
72%
100%
5%
92%
100%
10%
99%
100%
The primary population for the safety analyses will consist of all subjects who received at least one dose
(Ad26.Mos.HIV or placebo).
The immunogenicity population will consist of all subjects who received at least one dose and have at 
least one measured post-dose blood sample collected. Anticipating a dropout rate of approximately 10%, 
45 evaluable subjects per group will allow detection of 2.3-fold differences in Env-binding antibody 
titers, generally accepted to be biologically relevant, between groups with 80% probability, assuming a 
two-sided 5% Type I error and a standard deviation of 0.6 on the log10 scale. 
Interim Safety Review
No formal interim analysis prior to the primary analysis at Week 28 is planned. The PSRT and DMC will 
review interim safety data.
An interim safety review by the PSRT is planned of the blinded Week 2 safety data after 10% of subjects 
(approximately 40 subjects) have received their first injection at which time enrollment is paused. Based 
on the results of this analysis, a decision will be made whether enrollment can continue. The PSRT will 
also review blinded safety data (2 weeks of follow up) after 30% of subjects have received their first 
injection without enrollment pause.
NCT02315703


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
19
Approved, Date: 21 December 2016
The DMC will review safety data (2 weeks of follow up) after:

30% of subjects have received their first injection (blinded)

10% of subjects have received their third injection (unblinded)

30% of subjects have received their third injection (unblinded)
Immunogenicity Analysis
Since the correlate of protection for an HIV vaccine is unknown, regimen selection for future studies will 
be based on several immunogenicity assessments aiming at the regimen that elicits a well-balanced 
immune response as well as broad coverage of Clades A, B, and C. Emphasis will be on strength and 
breadth of Env antibody responses, as co-primary endpoints. In addition, functional antibody responses, 
nAb responses as well as mapping of Env antibodies (including V2 loop region) will be considered. 
Additional consideration will be given to responses to a comprehensive package of immunogenicity
testing including, but not limited to HIV nAb responses, functional antibody responses and cellular 
immune responses. This should be supported by strong responses in magnitude and breadth of CD8 IFNγ 
T-cells, CD4 T cells and functional antibodies.
Descriptive statistics (actual values and changes from reference) will be calculated for continuous 
immunologic parameters. Frequency tabulations will be calculated for discrete immunologic parameters. 
Graphical representations of changes in immunologic parameters will be made as applicable.
Safety Analyses
No formal statistical testing of safety data is planned. Safety data will be analyzed descriptively 
(including 95% confidence intervals).
TIME AND EVENTS SCHEDULE
(see next page)
NCT02315703


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
20
Approved, Date: 21 December 2016
Time and Events Schedule for Treatment Phase and Follow-up Phase until Week 96
Phase
Scr
Vac
Post-vac. FU
Vac
Post-vac. FU
Vac
Post-vac. FU
Vac
Post-vac. FU11
Second Year FU11
Visit #
11
2
2a
3
4
5
6
6a18
718
818
9
9a18
1018
1118
12
13
13a
18
1418
1518
16
17
18
Exit12
Visit Week
-4
to
0
0
1
2
4
12
14
16
24
26
28
36
48
50
52
60
78
9611
Visit Day
-28
to
0
1
2 to 
43
8 
±1
15 
±3
29 
±3
85 -
1/+
3we
eks
86-
883
99 
±3
113
±3
169
-1/+
3we
eks
170
to
1723
183
±3
197
±3
253
±5
337
-1/+
3we
eks
338
to 
3403
351
±3
365
±3
421
±3 
wee
ks
547
±3
wee
ks
673
±3
wee
ks
Visit Type
Screening
VACCINE
1
Safety
Safety
Safety and 
Immuno.
Safety and 
Immuno.
VACCINE
2
Safety
Safety and 
Immuno.
Safety and 
Immuno.
VACCINE
3
Safety
Safety and 
Immuno.
Safety and 
Immuno.
Safety
VACCINE
4
Safety
Safety and 
Immuno.
Safety and 
Immuno.
Safety and 
Immuno.
Safety and 
Immuno.
Safety and 
Immuno.
Early exit
Informed consent

Medical history

Physical exam2



















Vital signs



















HIV-risk assessment



















Counseling on HIV



















Test of Understanding

Cardiac risk assessment



















12-lead ECG


Concomitant meds



















Review of inclusion/ 
exclusion criteria


Enrollment/ 
randomization

Vaccination




Post-vac.reactogenicity 
(30 min)17




AE, SAE recording



















8-day memory aid 
distribution




8-day memory aid 
review by site staff




24-72 hour contact3




Social Impact Q’naire




Mucosal secretions4,6







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JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
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Approved, Date: 21 December 2016
pre-dose; no extra blood required; pre- and post-dose; for subjects who consent to mucosal secretion collection; AEs will be recorded from the signing of the ICF.
1 Screening visit may be split into multiple days/visits.
2 Complete physical exam will be performed at the screening and final visits. At all other visits, an abbreviated, symptom-directed exam will be performed as indicated by the investigator. 
Weight will be measured at every visit.
3 Within 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).
Female hormone 
testing5







Urinalysis7


















Serum pregnancy 
test/pregnancy 
counseling14

Urine pregnancy 
test/pregnancy 
counseling14



6




CBC with differential 
and platelets8,13,19


















Serum chemistry8,13,19


















Troponin9

Hepatitis B/C 
serologies

Syphilis serology















Urine chlamydia/ 
gonorrhea








Trichomonas15








HIV EIA19








HIV RNA10








Ad26 seropositivity












HLA test

Cellular immuno. 
Assays
(approx mL)13,16,18
102
50
50
50
102
102
102
102
50
50
50
50
Humoral immuno. 
assays (approx mL)13
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
Cumulative blood draw 
volumes:
Approx daily blood 
volume (mL)
13
135
0
0
27
77
33
0
77
77
33
0
129
129
7
33
0
129
129
77
83
83
83
Approx cumulative 
blood volume (mL)
13
148
148
148
175
252
285
285
362
439
472
472
601
730
737
770
770
899
1028
1105
1188
1271
AE = adverse event; CBC = complete blood count; ECG = electrocardiogram; EIA = enzyme immunoassay; FU = follow up; HIV = human immunodeficiency virus; HLA = human leukocyte 
antigen; ICF = informed consent form; RNA = ribonucleic acid; SAE = serious adverse event; vac = vaccination
NCT02315703


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
22
Approved, Date: 21 December 2016
4 Baseline mucosal secretion sampling may be done at screening or baseline prior to vaccination. (Note: mucosal secretion procedures for both men and women are optional, and will only 
be performed on a subset of subjects who provide consent.)
5 For female subjects who consent to the cervico-vaginal mucosal sample collection
6 Urine pregnancy test performed prior to mucosal secretion procedure, only for females who consent to mucosal secretion collection.
7 Microscopic reflex testing in the event of positive urinalysis
8 If medical status and physical examination on Day 1 suggests 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 28 days of the initial screening assessment. 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), a confirmatory test should be performed within 48 hours after the results have 
become available. After that, laboratory tests will be repeated weekly until values are resolved or stable.
9 Measurement of specific cardiac enzymes (troponin); will also occur at later timepoints if cardiac symptoms warrant
10 An HIV testing algorithm will be followed (detailed in the Study Procedures Manual)
11 Subjects randomized to Group 1 and 2 who have received all 4 vaccinations will be asked to enter the LTE phase. Signing of ICF for this phase will preferably be done at the Week 96 
visit or at an unscheduled visit as soon as possible after the Week 96 visit. ICF needs to be signed at the latest at Visit 19 (before any assessment is done). See Time and Events Schedule 
for the Long-Term Extension Phase. 
12 For those subjects who are unable to continue participation in the study, an exit visit will be conducted as soon as possible
13 Pre-dose at Visits 2, 6, 9 and 13
14 For both male and female subjects
15 For female subjects only
16 For clinical reasons, eg, anemia, the investigator can decide to draw a smaller volume
17 Observation for at least 30 minutes
18 If a subject is not vaccinated on the given day of vaccination, the timings of visits at 2 and 4 weeks post-vaccination will be determined relative to the actual day of vaccination.
19 Blood volumes may vary upon the local collection process. Indicative volumes are provided in the Study Procedures Manual. Total approximate volume per visit is to be respected.
NCT02315703


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
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Approved, Date: 21 December 2016
Time and Events Schedule for the Long-Term Extension Phase (from Week 96 onwards, Group 1 and 2 only)
Phase
Long Term Extension
Visit #
18 
bis1
191
20
21
22
23
24
25
26
27
28
Visit Week
1201±4
144±4
168±4
192±4
216±4
240±4
264±4
288±4
312±4
336±4
Informed consent

HIV-risk assessment










Counseling on HIV










Concomitant meds2










SAE recording










Social Impact Q’naire










HIV EIA3










HIV RNA3,4










Ad26 seropositivity










Cellular immuno. Assays
(approx mL)5
102
102
102
102
102
102
102
102
102
102
Humoral immuno. assays 
(approx mL)
20
20
20
20
20
20
20
20
20
20
EIA = enzyme immunoassay; HIV = human immunodeficiency virus; RNA = ribonucleic acid; SAE = serious adverse event
1this visit only needs to occur if ICF is not signed at Week 96. Visit 18bis should occur as soon as possible after the Week 96 visit. ICF needs to be signed at the latest at visit 19 (before 
any assessment is done).
2restricted to concomitant therapies given in conjunction with an SAE and any chronic or recurrent use of immunomodulators/suppressors and oral or parenteral corticosteroids.
3Blood volumes may vary upon the local collection process. Indicative volumes are provided in the Study Procedures Manual. Total approximate volume per visit is to be respected.
4An HIV testing algorithm will be followed (detailed in the Study Procedures Manual)
5For clinical reasons, eg, anemia, the investigator can decide to draw a smaller volume
NCT02315703


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
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Approved, Date: 21 December 2016
ABBREVIATIONS
Ad 
adenovirus 
Ad5 
adenovirus serotype 5 
Ad26 
adenovirus serotype 26 
ADCP
antibody-dependent cellular phagocytosis
AE 
adverse event 
AIDS 
Acquired Immunodeficiency Syndrome 
ALT
alanine aminotransferase
API
active pharmaceutical ingredient
AST
aspartate aminotransferase
β-HCG
β-human chorionic gonadotropin
BIDMC
Beth Israel Deaconess Medical Center
BMI
body mass index
CBC
complete blood count
CD4/8
cluster of differentiation 4/8
CMDR
Chiang Mai Double Recombinant
CRF
case report form
DAIDS 
Division of AIDS 
DMC
Data Monitoring Committee
DNA 
deoxyribonucleic acid 
DP
drug product
ECG
electrocardiogram
eDC
electronic data capture
EIA
enzyme immunoassay
ELISA 
enzyme-linked immunosorbent assay 
ELISPOT
enzyme-linked immunospot assay 
Env 
envelope 
ENVA 
envelope A 
FDA
Food and Drug Administration
Gag
group-specific antigen
GCP 
Good Clinical Practice 
gp 
glycoprotein 
GMT
geometric mean titer
HCV
hepatitis C virus
HIV 
human immunodeficiency virus 
HLA
human leukocyte antigen
HSV-2
herpes simplex virus type 2
ICF
informed consent form
ICH
International Conference on Harmonisation
ICS
intracellular cytokine staining
IEC
Independent Ethics Committee
IFNγ 
interferon gamma 
IL-2 
interleukin 2 
ID
intradermal
IM
intramuscular 
Ig
immunoglobulin
NCT02315703


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
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Approved, Date: 21 December 2016
IPCAVD 
Integrated Preclinical/Clinical AIDS Vaccine Development 
IRB
Institutional Review Board
IWRS
LTE
interactive web response system
Long Term Extension
MVA
Modified Vaccinia Ankara
nAb
neutralizing antibody
PBMC 
peripheral blood mononuclear cell 
PEP
post-exposure prophylaxis
pfu
plaque-forming unit
PIR
post-injection reactogenicity
Pol 
polymerase 
PQC
Product Quality Complaint
PSRT
Protocol Safety Review Team
RNA 
ribonucleic acid 
SAE 
serious adverse event 
SUSAR
suspected unexpected serious adverse reaction
TNFα
tumor necrosis factor alpha
TOU
test of understanding
ULN
upper limit of normal
US
United States
USAMRMC US Army Medical Research and Materiel Command
VISP
vaccine induced seropositivity
vp 
viral particle 
NCT02315703


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
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Approved, Date: 21 December 2016
1.
INTRODUCTION
Janssen Vaccines & Prevention B.V. is evaluating the potential of a prophylactic Human 
Immunodeficiency Virus Type 1 (HIV-1) vaccine comprising four candidate HIV-1 vaccine 
products that will be used in different prime-boost regimens. These products are 
Ad26.Mos.HIVc, Modified Vaccinia Ankara (MVA)-Mosaic1, MVA-Mosaic2, and glycoprotein 
140 drug product (gp140 DP).
Ad26.Mos.HIV vaccine is a recombinant replication-deficient Ad26 vectored vaccine and 
consists of three Ad26 vectors, one containing a mosaic insert of Env sequence, and two vectors 
containing mosaic inserts of Gag and Pol sequences.
MVA-Mosaic is a recombinant live attenuated MVA virus-vectored vaccine that has been 
genetically engineered to express two mosaic Gag, Pol, and Env sequences (Mosaic 1 and 
Mosaic 2) optimized for maximal coverage of potential T-cell epitopes.
gp140 DP (HIV-1 Clade C glycoprotein 140) contains recombinant trimeric gp140, produced on 
a transformed PER.C6® cell line constructed to produce gp140 DP. In this study, gp140 DP will 
be dosed with aluminum phosphate as adjuvant.
Funding for the manufacture of the vaccine products came from the National Institute of Allergy 
and Infectious Diseases (NIAID)-sponsored Integrated Preclinical/Clinical AIDS Vaccine 
Development (IPCAVD) program, grants AI078526/ AI096040.
For the most comprehensive nonclinical and clinical information regarding Ad26.Mos.HIV, 
MVA-Mosaic and gp140 DP, refer to the latest versions of the respective Investigator’s 
Brochures 2-4.
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, these organizations are: the U.S. National Institute of Allergy and Infectious 
Diseases Division of AIDS (DAIDS), the U.S. Military HIV Research Program (MHRP), the
Beth Israel Deaconess Medical Center (BIDMC), and the International AIDS Vaccine Initiative 
(IAVI).
1.1.
Background
A safe and effective HIV vaccine is the presently elusive cornerstone of HIV prevention. 
Although the ideal vaccine would prevent infection of persons exposed to the virus, a vaccine 
might also attenuate infection once it has occurred. No presently available immunogen is able to 
induce efficient protection against HIV through neutralizing antibodies (nAbs), the mechanism 
by which licensed vaccines typically confer protection. The results of study RV144, “the Thai 
                                                
c Ad26 = adenovirus serotype 26; Mos = mosaic
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JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
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Approved, Date: 21 December 2016
trial”, which evaluated a recombinant canarypox vector vaccine (ALVAC-HIV [vCP1521]) 
prime and a recombinant gp120 subunit vaccine (AIDSVAX B/E) boost, demonstrated 
approximately 30% protection from infection in the absence of either CD8 or nAb to primary 
HIV isolates 5. A subsequent case-control analysis of RV144 revealed the following correlates of 
activity of vaccines: high V1V2 antibody responses were associated with lower risk of HIV 
infection and high levels of anti-HIV-1 Env plasma immunoglobulin A (IgA) correlated with 
decreased vaccine efficacy 6,7. Optimally, both a robust CD4/CD8 T-cell response and a potent 
humoral response with multiple effectors would be induced by a vaccine.
Recent data have shown that heterologous Ad26/MVA vaccine regimens containing Gag, Pol, 
and Env antigens can establish a per exposure risk reduction against acquisition of infection 
following repetitive, heterologous, intrarectal challenges with a neutralization-resistant virus 
(SIV MAC251) in rhesus monkeys 8. These data also demonstrated that the inclusion of Env 
sequences is required for protection, despite an 18% difference in the Env amino-acid sequences 
between the vaccine and the challenge strains. Moreover, immunological correlates analyses 
suggest that Env-specific antibodies are critical for blocking acquisition of infection, whereas 
multiple cellular and humoral immune responses correlate with virological control, although the 
actual mechanisms of protection remain to be determined 8.
Studies of HIV vaccine subjects and infected patients suggest that a successful HIV vaccine 
program will need to protect against the diverse strains and clades. Recently published data 
demonstrated the capacity of bivalent HIV-1 mosaic antigens expressing Env, Gag, and Pol, as 
part of adenovirus/poxvirus and adenovirus/adenovirus vaccines, to protect rhesus monkeys 
against acquisition of SHIV-SF162P3 9. Improving the magnitude and breadth of epitope
coverage is thought to be key to development of a successful T-cell based preventive HIV 
vaccine. Published data from studies in non-human primates indicate that the number of epitope-
specific responses induced by a vaccine may be an important immune correlate of viral load 
control in the SIV challenge system 10.
Strategies to accomplish this include the use of vaccines containing immunogens from a number 
of prevalent clades or using mosaic sequences, ie, proteins assembled from natural sequences by 
in silico recombination, optimized for potential T-cell epitopes 11. 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, as well as the qualitative complexity of the induced immune response. 
A second objective is to increase the breadth of response, defined as immune recognition of 
diverse strains of HIV to include multiple clades and multiple genes. 
This study proposes to evaluate the safety/tolerability and the immunogenicity of vaccination 
with homologous Ad26.Mos.HIV regimens with high-dose gp140 DP/aluminum phosphate 
adjuvant, low-dose gp140 DP/aluminum phosphate adjuvant or no protein, as well as 
heterologous vector vaccine regimens with Ad26.Mos.HIV and MVA-Mosaic with high or 
low-dose gp140 DP/aluminum phosphate adjuvant or no protein.
NCT02315703


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
28
Approved, Date: 21 December 2016
Both Ad26 and MVA viral vectors with HIV deoxyribonucleic acid (DNA) inserts and HIV 
envelope proteins have been previously studied in clinical studies with no important or 
unexpected safety concerns. In three Phase 1 studies, Ad26.ENVA.01, at intramuscular (IM)
doses over the range 109 to 1011 viral particles (vp), was found to induce Env-specific humoral 
and cell-mediated responses when given on up to three 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 to study further in this study.
In nine completed Phase 1/2 studies in approximately 350 healthy subjects, MVA-CMDR
(Chiang Mai Double Recombinant) was found to be safe and immunogenic when given by either 
the intradermal (ID) or IM routes, either as a single agent, or when administered as a booster 
following appropriate priming 3. At IM doses of 107 and 108 pfu and ID doses of 106 and 107 pfu, 
MVA-CMDR was found to induce robust and durable humoral and cell-mediated immune 
responses when given on up to three occasions, with an IM dose of 108 pfu being optimally 
immunogenic. Therefore, this is the dose of MVA with mosaic inserts to be studied in this study.
A monovalent gp120 protein (AIDSVAX B) was tested in 671 healthy subjects at three doses, 
100 mcg, 300 mcg and 600 mcg. The 300 mcg dose was found to be the most effective, inducing
a higher antibody response without significant side effects. In RV144, the only vaccine study to 
date to demonstrate efficacy in prevention of acquisition of HIV, a bivalent gp120 protein 
(AIDSVAX B/E) was used as a booster following a priming with a recombinant canarypox 
vector (ALVAC-HIV). The gp120 proteins were dosed at 300 mcg. Therefore, a similar dose 
(250 mcg) of trimeric gp140 was chosen for evaluation in this study. Evidence exists indicating 
that there is no clear correlation between dose of envelope protein and antibody response 12. For
this reason, a lower (50 mcg) dose of gp140 will also be tested.
In two previous HIV efficacy studies utilizing Ad5 a trend towards increased HIV-1 infection 
was observed in vaccine recipients as compared with placebo recipients 13,14. 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. The HVTN 503/Phambili (Merck Ad5) 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. There was also differential 
dropout of high-risk placebos during this time period.
Additionally, a third study, the HVTN 505 (NIH VRC DNA/Ad5) study, 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.
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 
NCT02315703


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
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Approved, Date: 21 December 2016
surfaces following Ad5 vaccination, potentially resulting in increased targets for HIV-1 
infection 15,16.
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 IPCAVD003, 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 enrollment. 
The T-cell responses by ELISPOT were slightly lower in the baseline Ad26 seropositive 
subjects, the intracellular cytokine staining (ICS) and enzyme-linked immunosorbent assay 
(ELISA) 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 vector 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.
In this study (HIV-V-A004), Ad26 with mosaic inserts will be used for the first time in a clinical 
study. It is not expected that the DNA insert will alter the safety of the viral vector. However, an 
internal Protocol Safety Review Team (PSRT) and an independent data monitoring committee 
(DMC) will be established and pauses in enrollment, regular safety reviews, and stringent 
vaccine/study pause rules will be included (see Section 11.9).
1.2.
Overall Rationale for the Study
This
study, first-in-human for Ad26.Mos.HIV,
will assess the safety/tolerability and 
immunogenicity of seven prime/boost vaccine regimens. Ad26.Mos.HIV or placebo will be 
given at Weeks 0 and 12. Ad.26.Mos.HIV or MVA-Mosaic, both with or without gp140 DP (low 
or high dose), gp140 DP (high dose) or placebo, or placebo only will be given at Weeks 24 and 
48. The goal of this study is to select a regimen for evaluation in future efficacy studies.
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2.
OBJECTIVES AND HYPOTHESIS
2.1.
Objectives
Primary Objectives
The primary objectives are:

To assess the safety/tolerability of various prime/boost regimens containing Ad26.Mos.HIV, 
MVA-Mosaic, and/or gp140 DP components.

To compare Env binding antibody responses between the different vaccine regimens.
Secondary Objective
The secondary objective is:

To assess other antibody binding, antibody effector function and antibody characterization, 
and cellular responses.
Exploratory Objectives
The exploratory objectives are:

To explore immune responses to the different vaccine regimens in mucosal secretions in a 
subset of subjects.

To explore gene expression patterns between the different vaccine regimens.

To explore neutralization antibodies against the Ad26 vector.

To assess the social impact of participation in an HIV vaccine study for subjects via a social 
impact questionnaire.

To explore durability of the vaccine regimen in the groups selected for the long-term 
extension phase.
2.2.
Hypothesis
No formal statistical hypothesis will be tested. This study will evaluate whether a prime/boost 
vaccine regimen consisting of Ad26.Mos.HIV with or without gp140 protein plus aluminum 
phosphate adjuvant, or Ad26.Mos.HIV/MVA-Mosaic with or without gp140 protein plus 
aluminum phosphate adjuvant is safe, well-tolerated and immunogenic, providing broad, 
functional and durable humoral and cellular responses.
3.
STUDY DESIGN AND RATIONALE
3.1.
Overview of Study Design
This is a multicenter, randomized, parallel group, placebo-controlled, double-blind clinical study
in healthy HIV-uninfected adult men and women. A target of 400 subjects will participate in this 
study, with 50 subjects planned in each one of eight groups. Subjects will be enrolled regardless 
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of their baseline Ad26 seropositivity. Randomization will be stratified by region (US, Africa, and 
Asia). Efforts will be made to enroll a minimum of 50 subjects per region.
Subjects will receive four doses of study vaccine: Ad26.Mos.HIV or placebo will be given at 
Weeks 0 and 12; Ad.26.Mos.HIV or MVA-Mosaic (both with or without gp140 DP [low or high 
dose]), gp140 DP (high dose) or placebo will be given at Weeks 24 and 48, as shown in Table 4.
Table 4:
Study Design HIV-V-A004
Group
N
Week 0 
(baseline)
Week 12
Week 24
Week 48
Group 1*
50
Ad26.Mos.HIV
Ad26.Mos.HIV
Ad26.Mos.HIV
+ gp140 DP
(250 mcg + adjuvant)a
Ad26.Mos.HIV
+ gp140 DP
(250 mcg + adjuvant) a
Group 2*
50
Ad26.Mos.HIV
Ad26.Mos.HIV
Ad26.Mos.HIV
+ gp140 DP
(50 mcg + adjuvant) a
Ad26.Mos.HIV
+ gp140 DP
(50 mcg + adjuvant) a
Group 3
50
Ad26.Mos.HIV
Ad26.Mos.HIV
Ad26.Mos.HIV
+ Placebo
Ad26.Mos.HIV
+ Placebo
Group 4
50
Ad26.Mos.HIV
Ad26.Mos.HIV
MVA-Mosaic
+ gp140 DP
(250 mcg + adjuvant) a
MVA-Mosaic
+ gp140 DP
(250 mcg + adjuvant) a
Group 5
50
Ad26.Mos.HIV
Ad26.Mos.HIV
MVA-Mosaic
+ gp140 DP
(50 mcg + adjuvant) a
MVA-Mosaic
+ gp140 DP
(50 mcg + adjuvant) a
Group 6
50
Ad26.Mos.HIV
Ad26.Mos.HIV
MVA-Mosaic
+ Placebo
MVA-Mosaic
+ Placebo
Group 7
50
Ad26.Mos.HIV
Ad26.Mos.HIV
gp140 DP
(250 mcg + adjuvant) a
+ Placebo
gp140 DP
(250 mcg + adjuvant) a
+ Placebo
Group 8
50
Placebo
Placebo
Placebo
+ Placebo
Placebo
+ Placebo
a Aluminum content will be 0.425 mg/0.5 mL dose 
50 mcg and 250 mcg refer to total protein content
Sterilized aluminum phosphate wet gel suspension will be used as adjuvant for gp140 DP
* An optional LTE phase (approximately 5 years) will be performed for subjects randomized to Group 1 and Group
2 and having received all 4 vaccinations
An internal PSRT and an independent DMC will be established for this study. Refer to 
Sections 11.7 and 11.8, respectively, for details.
The study comprises a maximum 4-week screening period, a 48-week vaccination period during 
which subjects will be vaccinated at baseline, Week 12 and Week 24, with a booster at Week 48, 
and a 48-week follow-up period to the final visit at Week 96. Based on the analysis of the Week 
28 data, a Long Term Extension (LTE) phase (approximately 5 years after Week 96) will be 
performed for subjects randomized to Group 1 and Group 2 and having received all 
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4 vaccinations. These 2 groups (including a gp140 250 mcg and a gp140 50 mcg dose, 
respectively) form the basis for the regimens that will be evaluated in future studies.
After vaccination, subjects will remain under observation for at least 30 minutes for any 
reactogenicity. Subjects will use a memory aid to document local and systemic adverse events 
(AEs) in the evening after each vaccination and then daily for the next 7 days. The investigator 
or his/her designee will document any AEs in the case report form (CRF), and will collect blood 
and urine samples for safety laboratory assessment (hematology, biochemistry, and urinalysis) at 
each visit until Week 96. Cardiac safety surveillance monitoring will be performed by 
electrocardiogram (ECG) and measurement of specific cardiac enzymes (troponin) if cardiac 
symptoms appear. Also, subjects will be specifically asked about cardiac symptoms at each 
post-vaccination visit.
Blood samples will be taken at specific clinic visits to assess immune responses.
PSRT and DMC Review of Sentinel Groups
There will be a pause in enrollment after 10% of the target number of subjects have received 
their first injection (ie, approximately 40 subjects). The PSRT will review the blinded Week 2
safety data after first injection to determine if enrollment can continue. The PSRT will also 
review blinded safety data (2 weeks of follow up) after 30% of subjects have received their first 
injection without a pause in enrollment. See Section 11.9 on study holding rules.
To decide whether further dosing can continue, the DMC will review blinded safety data 
(2 weeks of follow up) after 30% of subjects have received their first injection, and unblinded 
data after 10% of subjects have received their third injection, and after 30% of subjects have 
received their third vaccination.
DMC Review of gp140 DP Safety in HIV-V-A003
The safety, tolerability and immunogenicity of gp140 DP will be evaluated in a separate safety 
study (HIV-V-A003) with interim safety results available prior to the first subject reaching 
Week 24 of this study, HIV-V-A004 (the time point at which subjects in certain arms will 
receive gp140 DP). The DMC will review the interim safety results of study HIV-V-A003 and 
will allow administration of the first dose of gp140 DP (third injection; Week 24 vaccination) in 
this HIV-V-A004 protocol only if no safety concerns are identified.
A diagram of the study design is provided in Figure 1.
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Figure 1:
Schematic Overview of the Study
A long-term Extension Phase (approximately 5 years after Week 96) will continue for subjects randomized to Group 1 and 
Group 2.
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3.2.
Study Design Rationale
The rationale behind selection of study vaccines and doses is described in Section 1.1.
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 study vaccine will be used to reduce potential bias during data 
collection and evaluation of clinical endpoints.
Based on preclinical data, lack of remarkable differences in immunologic responses generated 
between different adjuvants tested, and its well-known safety and tolerability profile, as well as 
the relatively low cost of goods, aluminum phosphate has been chosen as the adjuvant. 
Aluminum-containing vaccines have been in use for more than 70 years and have been rarely 
associated with serious adverse events. However, local reactions such as redness, swelling and/or 
tenderness at the injection are common.
Aluminum-containing vaccines have been associated with severe local reaction such as redness, 
lumps under the skin, contact allergy or irritation, and swelling at the site of injection. There 
have also been reports, especially in patients with impaired renal function, of systemic 
accumulation of aluminum, which has been associated with nervous disorders and bone disease. 
Nonetheless, aluminum is one of the most common metals found in nature and is present in food 
and water. Aluminum intake from vaccines is far less than that received from dietary sources or 
medications such as antacids. Aluminium salts do not cause any serious or long-lasting adverse 
events 20,21.
4.
SUBJECT POPULATION
Screening for eligible subjects will be performed within the 4 weeks before the first 
administration of study vaccine at Week 0.
The inclusion and exclusion criteria for enrolling subjects in this study are described in the 
following two subsections. If there is a question about the inclusion or exclusion criteria below, 
the investigator should consult with the appropriate sponsor representative before enrolling a 
subject in the study.
4.1.
Inclusion Criteria
Each potential subject must satisfy all of the following criteria to be enrolled in the study. 
1.
Each subject must sign an informed consent form (ICF) indicating that he or she 
understands the purpose of and procedures required for the study and is willing to 
participate in the study.
2.
Subjects are ≥18 to ≤50 years old on the day of signing the ICF.
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3.
Subject must be healthy on the basis of physical examination, medical history, ECG and 
vital signs measurement performed at screening.
4.
Laboratory criteria prior to enrollment*:

Hemoglobin: ≥11.0 g/dL, or accompanied by approval from the investigator and 
sponsor’s study responsible physician and above the site’s lower limit of normal 
(LLN)

White cell count: 2,500 to 11,000 cells/mm3, inclusive

Absolute neutrophil count (ANC): >1,300 cells/mm3, or accompanied by approval 
from the investigator and sponsor’s study responsible physician and within the 
site’s normal ranges

Platelets: 125,000 to 450,000 per mm3, inclusive

Urinalysis: protein <1+, blood <1+ (men) and <2+ (women), and glucose negative

Alanine aminotransferase/aspartate aminotransferase (ALT/AST) <1.25 x upper 
limit of normal (ULN)

Creatinine <1.1 x ULN
*If laboratory screening tests are out of range, repeat of screening tests is permitted once. 
5.
Subjects are negative for HIV infection at screeningd.
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 1e.
7.
Contraceptive requirements for heterosexually active female subjectsf:

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); surgically sterile: no additional 
contraception required.

If of child-bearing potential, but has a vasectomized partner (after vasectomy, sperm 
count below the limit of detection must be confirmed if procedure occurred <1 year 
ago): no additional contraception required.

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 ago, should be practicing 
either: 
                                                
d If possible, the site should select an assay that is US FDA-approved
e Note: negative urine pregnancy also required prior to the second, third and fourth vaccinations
f Verbal assurance should be given that adequate birth control measures have been followed for 28 days prior to 
vaccination
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
A long-acting reversible contraceptive method, including contraceptive implants, 
contraceptive injections, or an intrauterine system or device,) or, 

A double method of birth control, including combined contraceptive pills, 
progestogen-only pills, contraceptive patch, vaginal ring, diaphragm, or a cap in 
conjunction with either a male or female condom.
Women, who are not heterosexually active at screening, must agree to utilize an effective 
method of birth control if they become heterosexually active until 3 months after receiving 
the last dose of study vaccine.
Woman not of
Child-bearing 
Potentiala
Woman of
Child-bearing Potential
Man with vasectomyb
NA
NA
Man without 
vasectomy
NA
Single method
Long-acting reversible 
contraceptive method, 
including
contraceptive implants, 
contraceptive injections, or 
an intrauterine system or 
device
Double method
Combined contraceptive 
pills, progestogen-only 
pills, contraceptive patch, 
vaginal ring, diaphragm, or 
a cap
+
male or female condom
a 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 FSH level >40 IU/L); surgically sterile
bSperm count below the limit of detection must be confirmed if procedure occurred <1 year ago
8.
Contraceptive requirements for heterosexually active male subjects:

If male subject had a vasectomy (after vasectomy, sperm count below the limit of 
detection must be confirmed if procedure occurred <1 year ago): no additional 
contraception required.

If male subject did not have a vasectomy or had a positive sperm count after a 
vasectomy procedure of <1 year ago: contraceptive methods will depend on 
child-bearing potential of female partner: same criteria to be followed as for female 
subjects in Criterion 7.
9.
A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted 
reproduction until 3 months after receiving the last dose of study vaccine. A man must 
agree not to donate sperm until 3 months after receiving the last dose of study vaccine.
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.
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12.
Subjects are assessed by the clinic staff as being at low risk for HIV infection (see
Attachment 2).
13.
Passed the test of understanding (TOU) (see Section 16.1 and Attachment 3).
4.2.
Exclusion Criteria
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] antibody test; if positive, HCV RNA 
PCR test will be used to confirm active versus past HCV infection), active syphilis 
infection, chlamydia, gonorrhea, or trichomonasg. Active syphilis documented by exam or 
serology unless positive serology is due to past treated infection.
2.
In the 12 months prior to enrollment, subject has a history of newly acquired herpes 
simplex virus type 2 (HSV-2), syphilis, gonorrhea, non-gonococcal urethritis, chlamydia, 
pelvic inflammatory disease (PID), trichomonas, mucopurulent cervicitis, epididymitis, 
proctitis, lymphogranulomavenereum, chancroid, or hepatitis B.
3.
Subject has any clinically significant acute or chronic medical condition that in the opinion 
of the investigator would preclude participation (eg, history of seizure disorders, 
bleeding/clotting disorder, autoimmune disease, active malignancy, poorly controlled 
asthma, active tuberculosis or other systemic infections).
4.
Subject has had major surgery within the 4 weeks prior to study entry or planned major 
surgery through the course of the study.
5.
Subject has a history of myocarditis, pericarditis, cardiomyopathy, congestive heart failure 
with permanent sequelae, clinically significant arrhythmia (including any arrhythmia 
requiring medication, treatment, or clinical follow up).
6.
Subject has an ECG (per examination and interpretation of a central reading cardiologist)
with clinically significant findings, or features that would interfere with the assessment of 
myo/pericarditis, including any of the following: 
a. Conduction disturbance (complete left or complete right bundle branch block or 
nonspecific intraventricular conduction disturbance with QRS ≥120 ms, PR interval 
≥220 ms, any second or third degree AV block, or QTch prolongation [>450 ms]); 
b. Significant repolarization (ST segment or T wave) abnormality; 
c. Significant atrial or ventricular arrhythmia; frequent atrial or ventricular ectopy (eg,
frequent premature atrial contractions, two premature ventricular contractions in a 
                                                
g Trichonomas testing will only be for female subjects
h According to Bazett's or Fridericia's formula. In the event that the value is reported by both methods, the longer of 
the 2 values will be considered for the exclusion criterion.
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row)
d. ST elevation consistent with ischemia; or evidence of past or evolving myocardial 
infarction.
Note: If screening ECG parameters indicate suspicion of false positive results or user error, 
repeat of the ECG is permitted once
7.
Subject has had a thyroidectomy, or thyroid disease requiring medication during the last 
12 months.
8.
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.
9.
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/placebo.
10.
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/placebo.
11.
Subject has been in receipt of any licensed vaccine within 14 days prior to the first dose of 
study vaccine, 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.
12.
Subject has used experimental therapeutic drugs (excluding investigational vaccines) 
within 30 days of study entry.
13.
Subject is currently in, or plans participation in, another clinical study during the study 
period without prior approval of the sponsori.
14.
Subject has been in receipt of blood or immunoglobulin products in the past 3 months.
15.
Subject has a history of anaphylaxis or other serious adverse reactions to vaccines or 
vaccine products, or neomycin or streptomycin or egg products.
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, oral or parenteral corticosteroids.
18.
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. For subjects who 
received an experimental vaccine (except HIV vaccine) more than 12 months ago, 
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 where the vaccine received was subsequently 
                                                
i For subjects randomized to the regimen that is subsequently selected and who enter the long-term follow-up period, 
this restriction will continue during this period until approximately 2 years after Week 96.
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licensed (see exclusion criterion 11). Subjects with proof of having received only a placebo 
vaccine can also be included.
19.
Subject who cannot communicate reliably with the investigator.
20.
Subject is a study site employee, directly supervised by members of the study team, as well 
as family members of the investigator, employee of the sponsor or partners.
21.
Subject is in the military.
NOTE: Investigators should ensure that all study enrollment criteria have been met at screening. 
If a subject’s status changes (including 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 and considered to be a screen failure. Section 17.4 describes the required documentation to
support meeting the enrollment criteria.
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.
Subjects must continue using an appropriate method of birth control (as described in 
Section 4.1) until 3 months after receiving the last dose of study vaccine.
All female subjects of childbearing potential must have a negative serum pregnancy test at 
screening (-hCG) and negative urine pregnancy tests immediately prior to each 
vaccine/placebo administration, and additionally at Weeks 26 and 60.
Men must use an effective method of birth control as stated in Section 4.1.
2.
Subjects in this study will not be able to donate blood or blood products during the time of 
the study due to the potential confusion with a false-positive HIV test (vaccine induced 
seropositivity) at blood banks. Furthermore, they may be excluded from donating blood in 
the future upon disclosure of their participation in a viral-vectored vaccine study and the 
potential false-positive HIV screening test result. For subjects randomized to the regimen 
that is subsequently selected and who enter the LTE phase, this restriction will continue 
during this period until approximately 5 years after Week 96.
3.
Male subjects must agree not to donate sperm from the first administration of study vaccine 
until 3 months after the last dose of study vaccine.
4.
Female subjects must agree not to donate eggs (ova, oocytes) for the purposes of assisted 
reproduction until 3 months after the last dose of study vaccine.
5.
Use of any experimental medication (including experimental vaccines other than the study 
vaccine) during the study (including the LTE phase) is disallowed. Vaccination with any 
licensed vaccine within 14 days prior to or after any of the study vaccinations is 
disallowed. However, if a vaccine is indicated in a post-exposure setting (eg, rabies or 
tetanus), it must take priority over the study vaccine.
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6.
Chronic or recurrent use of immunomodulators/suppressors, eg, cancer chemotherapeutic 
agents, oral or parenteral corticosteroids is prohibited during the main study and 
discouraged during the optional LTE phase and each use should be reported during clinical 
visits.
7.
Concurrent participation in another clinical study without prior sponsor approval is 
disallowed. For subjects randomized to the regimen that is subsequently selected and who 
enter the LTE phase , this restriction will continue during this period until approximately 5
years after Week 96.
5.
VACCINE ALLOCATION AND BLINDING
Study Vaccine Allocation
Procedures for Randomization 
Central randomization will be implemented in this study. Subjects will be randomly assigned to 
one of eight 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 (US, Africa, and Asia). Efforts will 
be made to enroll a minimum of 50 subjects from each region.
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, clinical staff, and investigator, will be blinded to study vaccine allocation until 
Week 96. The sponsor will be blinded to study vaccine allocation until the Week 28 analysis (see 
Section 11.6). The pharmacist with primary responsibility for vaccine dispensing will not be 
blinded to the study vaccine.
A pharmacist will prepare study vaccine for administration and will provide it to the clinic. 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. More information and details on the 
preparation of vaccine and adjuvant components, as well as details on the holding time and 
storage conditions from the time of preparation to delivery of the study vaccine, are provided in 
Section 14.
The investigator will not be provided with randomization codes. The codes will be maintained
within the interactive web response system (IWRS), which has the functionality to allow the 
investigator to break the blind for an individual subject.
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Under normal circumstances, the blind should not be broken until the Week 96 electronic Data 
Capture (eDC) database is finalized. By participating to the LTE phase of the study, clinical 
staff, the investigator and participating subjects will be partially unblinded to their received 
treatment prior to full unblinding. Otherwise, the blind should be broken only if specific 
emergency treatment/course of action would be dictated by knowing the treatment status of the 
subject. In such cases, the investigator may in an emergency determine the identity of the 
treatment. 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 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.
The sponsor, but not the investigator, will be unblinded at the time of the primary analysis at 
Week 28.
6.
DOSAGE AND ADMINISTRATION
Each subject will receive doses of study vaccine at four timepoints according to randomization, 
on Day 1, at Week 12, and at Week 24, with a booster at Week 48, administered by IM injection 
into the deltoid. For visits with only one injection (ie, at Week 0 and 12), either deltoid can be 
used. When 2 study vaccine injections are to be given at one visit (ie, at Week 24 and 48), it is 
required to use a different deltoid for both injections. Exceptions 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 
1 study vaccination, he/she will be withdrawn from further study vaccination (see Section 10.2).
Study vaccines are as follows:

Ad26.Mos.HIV (Ad26.Mos.1.Env + Ad26.Mos1.Gag-Pol + Ad26.Mos2.Gag-Pol)

Total dose is 5x1010 vp per 0.5 mL injection

MVA-Mosaic (MVA-Mosaic1 + MVA-Mosaic2): 

Total dose is 108 pfu per 0.5 mL injection

gp140 DP:

Low-dose: gp140 DP with 50 mcg total protein, mixed with aluminum phosphate 
adjuvant (0.425 mg aluminum) at the pharmacy, per 0.5 mL injection

High-dose: gp140 DP with 250 mcg total protein, mixed with aluminum phosphate 
adjuvant (0.425 mg aluminum) at the pharmacy, per 0.5 mL injection
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JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
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Approved, Date: 21 December 2016

Placebo:

0.9% saline, 0.5 mL injection
7.
TREATMENT COMPLIANCE
A pharmacist will prepare study vaccine for administration and will provide it to the clinic. 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. More information and details on the 
mixing and diluting of vaccine and adjuvant components, as well as details on the holding time 
and storage conditions from the time of preparation to delivery of the study vaccine, are provided 
in Section 14.3.
The date and time of each study vaccine administration will be recorded in the CRF.
8.
PRESTUDY AND CONCOMITANT THERAPY
Pre-study therapies administered up to 30 days before the screening visit will be recorded in the 
CRF at screening.
All concomitant therapies must be recorded on the CRF throughout the study from the signing of 
the ICF to the final main study visit at Week 96. Beyond Week 96, only concomitant therapies 
given in conjunction with an SAE will be collected, as well as any chronic or recurrent use of
immunomodulators/suppressors and oral or parenteral corticosteroids (see below).
Use of any experimental medication (including experimental vaccines other than the study 
vaccine) during the study is disallowed. Vaccination with any licensed vaccine within the 
14 days prior to or after any dose of study vaccine 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.
Study subjects can receive medications such as acetaminophen, non-steroidal anti-inflammatory 
drugs (NSAIDs), 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 (Section 4.2), and these medications are prohibited during the main 
study and discouraged during the optional LTE phase and each use should be reported during 
clinical visits.
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JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
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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.
For HIV post-exposure prophylaxis (PEP), see Section 9.4.5.
9.
STUDY EVALUATIONS
9.1.
Study Procedures
9.1.1.
Overview
Evaluation of the safety/tolerability of the vaccine regimens will include laboratory assessments, 
physical assessment by clinical staff, and subject reports on signs and symptoms following 
vaccinations. Additional study visits may be required if in the investigator’s opinion, further 
clinical or laboratory evaluation is needed.
From screening to the final visit at Week 96, the total blood volume to be collected from each 
subject will be approximately 1271 mL.
The Time and Events Schedule summarizes the frequency and timing of safety and 
immunogenicity measurements applicable to this study.
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), a confirmatory 
test should be performed within 48 hours after the results have become available. After that, 
laboratory tests will be repeated weekly until values are resolved or stable.
9.1.2.
Visit Windows
For the following visits, windows will be allowed as indicated:

Visit 3: Day 8 ± 1 day

Visit 4: Day 15 ± 3 days

Visit 5: Day 29 ± 3 days

Visit 6: Day 85 -1 week, + 3 weeks (second vaccination)

Visit 7*: Visit 6 + 14 days (Day 99) ± 3 days

Visit 8*: Visit 6 + 28 days (Day 113) ± 3 days

Visit 9: Day 169 ± -1 week, + 3 weeks (third vaccination)

Visit 10*: Visit 9 + 14 days (Day 183) ± 3 days

Visit 11*: Visit 9 + 28 days (Day 197) ± 3 days

Visit 12: Day 253 ± 5 days

Visit 13: Day 337 - 1 week, + 3 weeks (fourth [booster] vaccination)

Visit 14*: Visit 13 + 14 days (Day 351) ± 3 days
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JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
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Approved, Date: 21 December 2016

Visit 15*: Visit 13 + 28 days (Day 365) ± 3 days

Visits 16 to 18, inclusive: Days 421, 547, and 673 ± 3 weeks

Visit 19 to 28 inclusive: Weeks 120, 144, 168, 192, 216, 240, 264, 288, 312, 336 ±4 weeks
*If a subject is not vaccinated on the given day of vaccination, the timings of visits at 2 and 
4 weeks post-vaccination (see Time and Events Schedule) will be determined relative to the 
actual day of vaccination.
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 investigator and
sponsor. If a subject misses more than 1 study vaccination, he/she will be withdrawn from 
further study vaccination.
9.1.3.
Screening Phase (Weeks –4 to 0)
Only healthy subjects negative for HIV infection (if possible, the site should select an assay that 
is US Food and Drug Administration [FDA]-approved) and complying with the inclusion and 
exclusion criteria specified in Section 4 will be included into the study. The investigator 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 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 these pre-screening procedures are identical to the per 
protocol screening tests and are within the 28-day window 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 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 3j). 
The following evaluations will be performed to determine eligibility requirements as specified in 
the inclusion and exclusion criteria:

Physical examination including vital signs measurement

Medical history

Review of pre-study medications

HIV-risk assessment

Cardiac risk assessment

Review of inclusion/exclusion criteria
                                                
j Adaptations to the TOU are allowed for local purposes, after IRB and sponsor approval.
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
Blood sampling for complete blood count (CBC) with differential, blood chemistries, 
hepatitis B and C serologies, troponin, and HIV testing

Sexually-transmitted infection (STI) testing (syphilis, chlamydia, gonorrhea, trichomonask)

12-lead ECG, interpreted by a central reading cardiologist

Pregnancy counseling for all subjects (men and women)

Female subjects of childbearing potential: serum β-human chorionic gonadotrophin 
pregnancy testing

Urinalysis
General eligibility for this clinical study will be dependent on results of laboratory tests and the 
medical assessment. Counseling related to the potential risks of becoming pregnant during this 
study and avoidance of HIV infection will be provided. Pre- and post-HIV test counseling will be 
provided to all subjects. Study subjects who qualify for inclusion based on the medical history, 
physical examination, and laboratory results will be contacted and scheduled for enrollment and 
initial vaccination (Visit 2) within 28 days.
Subjects with laboratory values or vital signs (eg, elevated blood pressure) not meeting eligibility 
criteria on the screening visit may have one repeat testing if the abnormality is not clinically 
significant and may be a testing aberrancy. The screening visit may be split into several visits.
After laboratory data, medical history, physical examination, and ECG have been reviewed for 
completeness and adherence to inclusion and exclusion criteria, the subject can be deemed to be 
eligible for the study.
Subjects who consent to mucosal secretion collection (Section 9.1.9) may have baseline samples
taken at the screening visit instead of pre-vaccination on Day 1.
All AEs will be recorded on CRFs from the signing of the ICF until the subject’s last study visit, 
together with information about any concomitant medications.
9.1.4.
Vaccination (Weeks 0, 12, 24, and 48)
Visit 2: Week 0/Day of Randomization/Vaccination 1
After re-check of inclusion and exclusion criteria, a urine pregnancy test (for women of 
childbearing potential), abbreviated physical examination (including weight measurement), 
measurement of vital signs, and cardiac risk assessment, 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 28 days of 
                                                
k Trichonomas testing will only be for female subjects
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JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
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the initial screening assessments. If the initial laboratory sampling occurred longer than 28 days 
before the Day 1 visit, this will be considered a screen failure.
Pre-dose samples for hematology, biochemistry, urinalysis, and HIV testing will be collected. 
Before the first vaccination, subjects will also have blood drawn for cellular and humoral 
immunogenicity assays, and for assessment of Ad26 seropositivity. HLA will also be tested 
using the baseline blood sample. 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 
vaccination, subjects will remain under observation for at least 30 minutes for reactogenicity, 
and vital signs measurement will be repeated. 
Subjects will be provided with a memory aid, thermometer, and ruler to measure and record local 
solicited AEs and body temperature. Subjects will also note symptoms of unsolicited and 
solicited systemic AEs through the memory aid for 8 days post-vaccination (day of vaccination 
and the subsequent 7 days). Subjects who consent to mucosal secretion collection at this visit 
(Section 9.1.9) will undergo additional testing for syphilis, chlamydia, gonorrhea, and
trichomonas.
In addition to an HIV-risk assessment, counseling related to avoidance of HIV infection, pre- and 
post-HIV test counseling, and pregnancy counseling will be provided to all subjects (men and 
women).
Visit 6: Week 12/Vaccination 2
An abbreviated physical examination (including weight measurement), measurement of vital 
signs, and cardiac risk assessment will be performed for all subjects pre-vaccination. A pre-dose 
blood sample for humoral immunogenicity assessment will be drawn, and for assessment of 
Ad26 seropositivity. 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, urinalysis, and HIV testing will be collected.
After vaccination, subjects will remain under observation for at least 30 minutes for 
reactogenicity, and vital signs measurement will be repeated. 
All AEs will be recorded on the CRFs, together with information about any concomitant 
medications.
Subjects will be provided a memory aid, thermometer, and ruler to measure and record local 
solicited AEs and body temperature. Subjects will also note symptoms of unsolicited and 
solicited systemic AEs through the memory aid for 8 days post-vaccination (day of vaccination 
and the subsequent 7 days).
NCT02315703


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
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Approved, Date: 21 December 2016
In addition to an HIV-risk assessment, counseling related to avoidance of HIV infection, pre- and 
post-HIV test counseling, and pregnancy counseling will be provided to all subjects (men and 
women).
Visit 9: Week 24/Vaccination 3
The procedures for Week 24 will be the same as at Visit 6 as detailed above. Additionally at 
Week 24, subjects will complete a Social Impact Questionnaire (Attachment 4).
Visit 13: Week 48/(Booster) Vaccination 4
The procedures for Week 48 will be the same as at Visit 6 as detailed above. Additionally, at 
Week 48, subjects will complete a Social Impact Questionnaire (Attachment 4).
9.1.5.
Post-vaccination Follow-Up Phase (Weeks 1, 2 and 4; Weeks 14 and 
16; Weeks 26, 28 and 36; Weeks 50 and 52)
Visits 2a, 3, 4, and 5 (Days 2-4, and Weeks 1, 2, and 4)
At Visit 2a (24-72 hour 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 
deemed necessary by the investigator/sub-investigator or upon request of the subject.
Visit 3 is a clinic visit that will include an abbreviated physical examination (including weight 
measurement), vital signs, and cardiac risk assessment, recording of any AEs and concomitant 
medications, and review of the memory aid for 8 days post-vaccination (day of vaccination and 
the subsequent 7 days).
Visit 4 is a clinic visit that will include an abbreviated physical examination (including weight 
measurement), vital signs, and cardiac risk assessment, recording of any AEs and concomitant 
medications, and collection of samples for humoral immunogenicity assay, and for safety 
laboratory testing (CBC, serum chemistry and urinalysis). Subjects who consent to mucosal
secretion collection at this visit (Section 9.1.9) will undergo additional testing for syphilis, 
chlamydia, gonorrhea, and trichomonas.
Visit 5 is a clinic visit that will include an abbreviated physical examination (including weight 
measurement), vital signs, and cardiac risk assessment, recording of any AEs and concomitant 
medications, and collection of samples for cellular and humoral immunogenicity assay, 
assessment of Ad26 seropositivity, and for safety laboratory testing (CBC, serum chemistry and 
urinalysis).
At Visits 3 and 4, in addition to an HIV-risk assessment, counseling related to avoidance of HIV 
infection will be provided to all subjects.
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JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
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Visits 6a, 7, and 8 (Days 86-88, and Weeks 14 and 16)
The procedures for Visits 6a, 7, and 8 will be the same as at Visits 2a, 4, and 5, respectively, as 
detailed above, with the exception that blood samples for cellular and humoral immunogenicity 
assay will be drawn at both Visits 7 and 8. Additionally at Visit 8 only, a 12-lead ECG will be 
carried out.
Visits 9a, 10, and 11 (Days 170-172, and Weeks 26 and 28)
The procedures for Visits 9a, 10, and 11 will be the same as at Visits 6a, 7 and 8, respectively, as 
detailed above. (Note: no ECG at Visit 11.)
Visit 12 (Week 36)
Visit 12 will be for safety follow up only, and will include an abbreviated physical examination
(including weight measurement), vital signs measurement, and cardiac risk assessment, 
recording of any AEs and concomitant medications, and collection of samples for safety 
laboratory testing (CBC, serum chemistry and urinalysis).
In addition to an HIV-risk assessment, counseling related to avoidance of HIV infection will be 
provided to all subjects.
Visits 13a, 14, and 15 (Days 338-340, and Weeks 50 and 52)
The procedures for Visits 13a, 14, and 15 will be the same as at Visits 6a, 7, and 8, respectively,
as detailed above. 
9.1.6.
Second Year Follow-Up Phase (Weeks 60 to 96)
Visits 16, 17, and 18 (Weeks 60, 78, and 96, respectively)
Subjects will make follow-up visits at the clinic from Week 60 until the final visit at Week 96. 
Each visit includes an abbreviated physical examination (including weight measurement), vital 
signs measurement, cardiac risk assessment, recording of any AEs and concomitant medications, 
and collection of samples for cellular and humoral immunogenicity assay, assessment of Ad26 
seropositivity, and for safety laboratory testing (CBC, serum chemistry and urinalysis). Subjects 
who consent to mucosal secretion collection at Visits 16 and 18 (Section 9.1.9) will undergo 
additional testing for syphilis, chlamydia, gonorrhea, and trichomonas at both visits.
At Visits 17 and 18, 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. At Week 60 and Week 96, a urine pregnancy test will be carried 
out for women of childbearing potential and pregnancy counseling will be provide to all subjects 
(men and women).
Also, at Week 96, subjects will complete a Social Impact Questionnaire (Attachment 4).
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JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
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9.1.7.
Early Withdrawal – Early Exit Visit
In the event of early withdrawal from the study (ie, before Week 96), the following procedures 
will be performed: an abbreviated physical examination (including weight measurement), 
measurement of vital signs, and cardiac risk assessment, recording of any AEs/SAEs and 
concomitant medications, and collection of samples for immunogenicity assays, assessment of 
Ad26 seropositivity, and for safety laboratory testing (CBC, serum chemistry and urinalysis). In 
addition to an HIV-risk assessment, counseling related to avoidance of HIV infection, pre- and 
post-HIV test counseling, and pregnancy counseling will be provided to all subjects (men and 
women). A urine pregnancy test will be carried out for women of childbearing potential.
Additionally at the early withdrawal visit, subjects will complete a Social Impact Questionnaire 
(Attachment 4).
9.1.8.
Long-Term Extension Phase
Based on the analysis of the Week 28 data, a LTE phase (approximately 5 years after Week 96) 
will be performed for subjects randomized to Group 1 and Group 2 who have received all 4 
vaccinations. At Week 96, these subjects will be asked to sign the ICF appendix for the LTE 
phase. If signing the ICF appendix is not possible at Week 96, signing should be performed at an 
extra visit (Visit 18bis) as soon as possible after Week 96 and at the very latest at Visit 19, before 
any assessment is performed.
Subjects will make follow-up visits at the clinic from Week 120 until the final visit at Week 336. 
Each visit includes recording of any SAEs and concomitant medications (any medication given 
in conjunction with an SAE, as well as any recurrent or chronic use of immunomodulators and 
corticosteroids), and collection of samples for cellular and humoral immunogenicity assay, and 
assessment of Ad26 seropositivity.
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).
9.1.9.
Local Mucosal Sampling
Cervico-vaginal secretions (women), ano-rectal secretions (men and women), and ejaculate 
(men) will be collected from consenting subjects to assess if desirable mucosal HIV-1-specific 
immune responses are induced, that may be able to block or attenuate infection. These 
collections are optional and will be collected at all participating sites at Day 1 (baseline), 
2 weeks after each vaccination, during the second year follow-up visits and at the final visit for 
both male and female subjects. Subjects who consent to mucosal collection will be tested for 
gonorrhea, chlamydia, syphilis and trichomonas at each visit where mucosal samples are 
collected. Collection will not take place if the woman is menstruating or has signs or symptoms 
of active inflammation or infection of the vagina or cervix. Serum estradiol and progesterone 
levels and last menstrual period will be measured/recorded at each collection visit, for women 
who consent to the cervico-vaginal sample collection. If, during the course of the study, a woman 
becomes pregnant, she will be excluded from further mucosal secretion collections. Women with 
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JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
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a history of toxic shock syndrome will be excluded from cervico-vaginal mucosal sampling. 
Subjects who have had surgical sex-reassignment will be excluded from cervico-vaginal mucosal
and semen sampling. Further details on the collection of mucosal samples are provided in the 
Site Procedures Manual.
9.2.
Immunogenicity
9.2.1.
Endpoints
The primary immunogenicity endpoints will be defined as the Env-C ELISA binding antibody 
titer and breadth of Env-binding antibody response across Clades A, B, and C measured at 
Week 28.
For evaluation of humoral responses:

Env-specific binding antibody titers (ELISA) 4 weeks after the third and fourth vaccinations, 
covering Clades A, B, and C.

HIV nAb titers for Tier 1 and Tier 2 viruses covering Clades A, B, and C; note: Tier 2 will 
be assessed only if Tier 1 shows positive results.

Functional antibodies as assessed by antibody-dependent cellular phagocytosis (ADCP)
assay.
For evaluation of T-cell responses:

Assays of peptide pool sets covering the Gag, Env or Pol will be evaluated by standard 
ELISPOT criteria 17 with additional mapping of positive pools to determine the number of
positive epitopes for each individual, at baseline and at 2 and 4 weeks after the third and 
fourth vaccinations.
For durability of responses:

Immunogenicity assays at 12, 30, and 48 weeks after the last vaccination. Durability of 
responses to be followed approximately 5 years after Week 96 in selected group(s) (see 
Section 9.1.8).
9.2.2.
Evaluations
Venous blood samples of approximately 20 mL will be collected for the determination of 
humoral responses. For the determination of cellular responses, venous blood samples of 
approximately 102 mL will be collected. The Laboratory Manual contains further information 
regarding the collection, handling, labeling, and shipment of blood samples to the central 
laboratory. Sampling for humoral and cellular immunogenicity testing will be performed as 
indicated in the TIME AND EVENTS SCHEDULE.
Humoral response assays will include, but are not limited to Env-specific serum binding 
antibody assay, nAb assays, and antibody-dependent cellular phagocytosis (ADCP) assay, as 
well as epitope mapping (see Table 5).
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JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
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Table 5:
Humoral Immune Response Assays
Objective/
endpoint
System
Assay/Method
Readout
Timepoint
Primary
Serum
Env binding antibody 
(ELISA)
Titer or % responders
(Clade C)
and breadth
(Clade A, B, C)
Baseline
1 mo post-vac. 1
0.5, 1 mo post-vac. 2-4
3, 6 mo post-vac. 4
Secondary
Serum
HIV neutralizing 
antibody
Tier 1 and Tier 2a nAbs:
GMT for each isolate,
% responders to each isolate
Breadth: # isolates neutralized
As above
Secondary
Serum
gp120 binding 
antibody
Anti-gp120 titer
(Clade A, B, C)
As above
Secondary
Serum
ADCP
% phagocytosis
As above
Secondary
Serum
Isotyping Env binding 
antibody (ELISA)
Isotyping (Clade C)
(IgA, IgG1, IgG2, IgG3)
As above
Exploratory
Serum
Epitope mapping
Targeted epitopes and diversity 
(including V2)
1 mo post-vac. 1-4
At vac. 2-4
Exploratory
Serum
Ad26 neutralization 
antibodies
Titers of Ad26 neutralization 
antibodies
1 mo post-vac. 1-4
3, 7.5, 12 mo post-vac. 4
At vac. 1-4
ADCP = antibody-dependent cellular phagocytosis; ELISA = enzyme-linked immunosorbent assay; GMT = 
geometric mean titer; Ig = immunoglobulin; mo = month; nAb = neutralizing antibody; vac = vaccination
a Classification of HIV-1 viruses according to sensitivity to antibody-mediated neutralization: very high (tier 1A), 
above-average (tier 1B), moderate (tier 2), or low (tier 3) 1. Tier 2 will only be assessed if Tier 1 shows 
positive results.
Evaluations of cellular immune responses will include, but are not limited to, the following 
assays: ELISPOT, intra-cellular cytokine staining, and multi-parameter flow cytometry (see 
Table 6).
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JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
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Table 6:
T-Cell Immune Response Assays
Objective/
endpoint
System
Assay/Method
Readout
Timepoint
Secondary
PBMC
ELISPOT
Breadth and depth:
# peptides,
% responders,
median response
Baseline
0.5, 1 mo post-vac. 3 
& 4
Exploratory
PBMC
Intracellular cytokine 
staining
% of CD4 and CD8+ T 
cells producing IFNγ, IL-2, 
TNFα
Baseline
1 mo post-vac. 1
0.5, 1 mo post-vac. 2-4
3, 7.5 mo post-vac. 4
Exploratory
PBMC
Multi-parameter flow 
cytometry
Characterization of 
memory T-cell 
development with emphasis 
on follicular helper T cells
Baseline
1 mo post-vac. 1
0.5, 1 mo post-vac. 2-4
3, 7.5 mo post-vac. 4
Exploratory
PBMC
Gene expression 
analysis
Regulation of genes 
(clusters) that predict 
specific immune responses 
and HLA typing
Baseline
1 mo post-vac. 1
0.5, 1 mo post-vac. 2-4
3, 7.5 mo post-vac. 4
ELISPOT = enzyme-linked immunospot assay; HLA = human leukocyte antigen; IFNγ = interferon gamma; IL-2 = 
interleukin 2; mo = month; PBMC = peripheral blood mononuclear cell; TNFα = tumor necrosis factor alpha; vac 
= vaccination
Note: HLA only tested once (using the baseline blood sample)
Exploratory humoral and cellular immunogenicity assessments during the optional long-term 
extension phase (Group 1 and 2 only) may include, but are not limited to, the following assays: 
Env-specific serum binding antibody assay and ELISPOT. Further specification will be based on 
the Week 52 results. 
Exploratory assessments on mucosal samples will include, but are not limited to, characterization 
of Env-specific binding antibodies.
9.3.
Safety Evaluations
9.3.1.
Endpoints
Safety and tolerability endpoints:

AEs until Week 96 and local and systemic reactogenicity rates for 8 days after each 
vaccination.

Discontinuations from vaccination/from study due to AEs.

SAEs during the course of the study.
9.3.2.
Evaluations
Any clinically relevant safety-related changes that occur during the study must be recorded in the 
CRF.
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JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
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Any clinically significant abnormalities persisting at the end of the study/early withdrawal will 
be followed by the investigator until resolution or until a clinically stable endpoint is reached.
The study will include the following evaluations of safety and tolerability according to the time 
points provided in the Time and Events Schedule:
Adverse Events
AEs will be recorded from signing of ICF until the final visit of the main study (Week 96). SAEs 
(including HIV infection and abnormal pregnancy outcome) will be recorded for the duration of 
the study, including the optional LTE phase (Group 1 and Group 2 only). AEs will be followed 
by the investigator as specified in Section 12.
Details regarding the PSRT and the DMC are provided in Sections 11.7 and 11.8, respectively.
Cardiac-Related Events
At study visits, subjects will be specifically questioned about cardiac-related events, including 
chest pain/pressure, shortness of breath, and peripheral edema. Any suspicion of a cardiac event 
will be evaluated clinically by history and physical examination, ECG (read by a central reading 
cardiologist), and quantitative troponin assay. In the event of an elevation of troponin and/or 
pathologic ECG changes, the subject will be sent for evaluation by a local cardiologist.
Solicited Adverse Events
Solicited AEs are precisely defined events that subjects are specifically asked about and which 
are noted by subjects through the memory aid. The investigator or his/her designee should 
discuss the information from the memory aids with subjects, document relevant information in 
the clinic chart (source document) and complete the relevant parts of the CRF as described in the 
CRF Completion Guidelines.
Injection Site (Local) Reactions
Subjects will be asked to note occurrences of erythema, induration and swelling (measured using 
the ruler supplied), and pain/tenderness, itching, or warmth at the injection site daily for 8 days 
post-vaccination (day of vaccination and the subsequent 7 days). These occurrences should be 
recorded through the memory aid provided to serve as a reminder to the subject for the next 
clinic visit.
Solicited Systemic AEs
Subjects will be instructed on how to record daily temperature using a thermometer provided for 
home use. Subjects should record oral temperature in the evening post-vaccination, and then 
daily for the next 7 days through the memory aid. Temperature should be measured at 
approximately the same time each day. If more than one measurement is made on any given day, 
the highest daily temperature will be used in the CRF. Fever will be recorded by the investigator 
or his/her designee for temperatures equal to or higher than 38.0 °C.
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Subjects will also be instructed on how to note daily symptoms through the memory aid for 
8 days post-vaccination (including the day of vaccination) of the following events:

fatigue

headache

myalgia

arthralgia

chills

fever

nausea

vomiting

rashes

general itching
Clinical Laboratory Tests 
Blood samples for serum chemistry and hematology will be collected at times specified in the 
Time and Event Schedule. The investigator must review the laboratory report, 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), a confirmatory 
test should be performed within 48 hours after the results have become available. After that, 
laboratory tests will be repeated weekly until values are resolved or stable.
The following tests will be performed by a local laboratory (*parameters only measured at 
screening):

Serum chemistry
sodium*
alkaline phosphatase*
potassium*
phosphate*
chloride*
albumin*
calcium*
total protein*
magnesium*
bilirubin*
bicarbonate*
AST
blood urea nitrogen (BUN)*
ALT
glucose*
creatinine
creatine phosphokinase (CPK)* troponin 
FSH (post-menopausal women only)*

Hematology
hemoglobin
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hematocrit
red blood cell (RBC) count
white blood cell (WBC) count with differential
platelet count

Urinalysis – dipstick for
specific gravity
pH
glucose
protein
blood
ketones
Microscopic reflex testing will be carried out in the event of positive urinalysis tests.
Laboratory values will be graded according to a modified version of the DAIDS Table for 
Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), 
Version 1.0 dated December 2004 (Clarification, August 2009) included in Attachment 1, and, if 
clinically significant, reported as AEs.
Additional clinical laboratory assessments to be performed are as follows:

Serum pregnancy testing (-hCG) for women of childbearing potential at screening

Urine pregnancy testing for women of childbearing potential pre-dose on Day 1, Weeks 12, 
24, 48, 60, 96 and at the early exit visit. A urine pregnancy test will also be carried out prior 
to mucosal secretion collection, for those females who have consented to this procedure.

Troponin at screening

Serology: hepatitis B, and hepatitis C at screening

Syphilis, chlamydia, gonorrhea and trichomonas at screening, and additionally at Weeks 2, 
14, 26, 50, 60, and 96 for subjects who consent to mucosal secretion collection

HIV testing at screening, pre-dose on Day 1, Weeks 12, 24, and 48, and additionally at 
Weeks 78 and 96, at the early exit visit and at each visit of LTE phase.
Electrocardiogram (ECG)
Supine 12-lead ECGs will be performed at screening and at Week 16, and only performed again 
during the study if clinically indicated based on signs and symptoms.
For 30 minutes prior to the ECG, subjects should refrain from meals, hot or cold beverages and 
strenuous exercise, and should remain in a room with a comfortable temperature. Each ECG 
should be obtained after the subject has been at rest for at least 5 minutes. ECG 
interpretation/comparison will be provided by a central reading cardiologist.
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Computer-generated interpretations of ECGs should be reviewed for data integrity, 
reasonableness and for immediate safety assessment by the investigator or appropriately 
delegated healthcare provider. Digital ECG data will be transmitted to a centralized ECG 
over-read service provider. Over-read of the ECGs will be transmitted back to the site within 
72 hours. The centralized ECG over-read data will be considered source data. 
Vital Signs
Vital sign measurements will be performed at time points specified in the Time and Events 
Schedule. Blood pressure and pulse/heart rate measurements should be preceded by at least 
5 minutes of rest in a quiet setting without distractions.
The following measurements will be performed:

Heart rate (beats per minutes, bpm), systolic blood pressure (mmHg) and diastolic blood 
pressure (mmHg). Confirmatory vital signs measurement can be performed if inconsistent 
with a prior measurement

Body temperature (oral)
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, including height and weight, will be carried out at screening and at 
the final visit of the main study (Week 96). At all other visits, 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. Weight will be measured at every visit.
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.
9.4.
HIV Testing and VISP
9.4.1.
HIV Testing
At screening, subjects will be tested for HIV infection, and must be negative to be entered into 
the study. If possible, the site should select an assay that is US FDA-approved.
After screening, diagnostic HIV testing will be performed during the study as indicated in the 
Time and Events Schedule. An HIV testing algorithm (detailed in the Study Procedures 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 “infected” or “uninfected”. 
This system allows timely HIV testing without compromising the double-blind nature of the 
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study. The algorithm used for HIV testing throughout the main phase of the study aims to 
differentiate false-positive results (Vaccine Induced Seropositivity [VISP]) from true positives 
(HIV infection). 
If a false-positive HIV test develops during the study, further HIV testing will be offered via 
post-study follow up. (See Section 9.4.3 for more details on VISP).
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 will (see Section 12.3.3):

be excluded from further vaccinations 

be provided counseling and referred for medical treatment

be informed about observational studies monitoring subjects with HIV infection
9.4.3.
Vaccine Induced Seropositivity (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. VISP may become 
evident during the study, or after the study has been completed.
Should a subject receive a positive result in an HIV antibody test during the study, the site will 
carry out a follow-up testing algorithm either to exclude or confirm HIV infection. Further 
details of this algorithm are given in the Site Procedures Manual.
Subjects should not donate blood during the study. Blood donation options for those subjects 
who wish to resume blood donation 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 the site at most every three months, to confirm their HIV-status. 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, the site will provide HIV testing on request as 
described in the previous paragraph.
In addition to providing testing, subjects will always receive pre- and post-test counseling. 
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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 at Weeks 24, 48, 96, and 
at each visit of the LTE phase as specified in the TIME AND EVENTS SCHEDULE to evaluate 
any potential consequences of the subject’s participation.
9.4.5.
Post-Exposure Prophylaxis (PEP)
In case a subject believes he/she might have been exposed to HIV, he/she should contact the 
study site as soon as possible. Treatment will be determined by the investigator or his designee, 
in accordance with local PEP guidelines. The sponsor should be informed as soon as possible. 
PEP medication will be reimbursed by the sponsor during study participation. HIV prevention 
counseling will be provided. In case a subject has recurrent need for PEP, eligibility of the 
subject (with regards to HIV-risk profile) to continue in the study will be re-assessed.
9.5.
Sample Collection and Handling
The actual dates of sample collection must be recorded in the CRF or laboratory requisition 
form. Refer to the Time and Events Schedule for the timing and frequency of all sample 
collections.
Instructions for the collection, handling, storage, and shipment of samples for immunogenicity 
assay are found in the Laboratory Manual that will be provided. Collection, handling, storage, 
and shipment of samples must be under the specified, and where applicable, controlled 
temperature conditions as indicated in the Laboratory Manual.
10.
SUBJECT COMPLETION/WITHDRAWAL
10.1.
Completion
A subject who is not participating in the long-term extension period will be considered to have 
completed the study if he or she has completed the assessments at Week 96. A subject who is 
participating in the long-term extension period will be considered to have completed the main 
study if he or she has completed the assessments at Week 96 and will be considered to have 
completed the LTE phase if he or she has completed the assessments at the last visit of the
extension period (Week 336).
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10.2.
Discontinuation of Study Vaccine
Subjects will be withdrawn from study vaccine administration for the reasons listed below. These 
subjects must not receive any additional dose of study vaccine but should enter the follow-up 
phase, starting from Visit 14 onwards. Additional unscheduled visits may be performed for 
safety/tolerability reasons, if needed. These subjects are not eligible for the LTE phase.

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 (see Section 8) 

Missing more than 1 study vaccination (see Section 6).
*AEs deemed by the investigator to be very likely, probably, or possibly related to study vaccine.
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 time of vaccination.
10.4.
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:

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 and Institutional Review Board/Independent Ethics 
Committee (IRB/IEC) to stop or cancel the study

Lost to follow up
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
Withdrawal of consent

Death
If a subject is lost to follow up, every reasonable effort must be made by the study site personnel 
to contact the subject and determine the reason for discontinuation/withdrawal. The measures 
taken for at least three efforts 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. Enrollment will be stopped when 400 subjects 
have received at least one vaccination. 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 96.
A subject who withdraws from the study will have the following options regarding optional 
research samples:

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 
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.
Withdrawal From the Optional Research Samples While Remaining in the Main Study
The subject may withdraw consent for optional research samples while remaining in the study. In 
such a case, the optional research samples will be destroyed. The sample destruction process will 
proceed as described above.
Withdrawal From the Use of Samples in Future Research
The subject may withdraw consent for use of samples for future research (refer to 
Section 16.2.5). In such a case, samples will be destroyed after they are no longer needed for the
clinical study. Details of the sample retention for research are presented in the main ICF.
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 immunogenicity and safety data is 
outlined below. Specific details will be provided in the Statistical Analysis Plan. 
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The primary analysis will be performed once all subjects have completed the Week 28 visit (ie,
4 weeks after the third injection) or discontinued earlier. The purpose of this analysis is to allow 
for an early conclusion on regimen selection for future studies, based on immunogenicity and 
safety. 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 study visit at Week 96 (ie,
including the second year follow-up period) or discontinued earlier. The final analysis of the 
LTE phase (optional and only for a subset of subjects) will be performed once all included 
subjects have completed the last visit of the extension period (Week 336), or discontinued 
earlier.
11.1.
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 data from at least one post-dose blood sample.
The per-protocol population will consist of all subjects who have received at least the first three 
vaccinations according to the protocol-specified vaccination schedule, have at least one 
measured post-dose blood sample collected, and who have no major protocol violations
impacting immunogenicity assessments.
11.2.
Sample Size Determination
A sample size of 50 subjects per regimen is regarded to be appropriate to assess the safety and 
tolerability of the different vaccine regimens and also collect sufficient data on immunogenicity. 
Placebo recipients are included for blinding and safety purposes and will provide control 
specimens for immunogenicity assays.
While mild to moderate vaccine reactions (local injection site and systemic responses) are 
expected, AEs that preclude further dose administration or more serious ones that would limit 
product development are not anticipated. With 50 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 6%. For the combined groups with Ad26.Mos.HIV (n = 350), there would be 95% 
confidence that the true rate is <1% when 0 events are observed. The following table shows the 
probabilities of observing at least one AE at given true AE rates:
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True AE rate
Probability of observing at 
least one AE in n subjects
n = 50
n = 350
0.1%
5%
30%
0.5%
22%
83%
1%
39%
97%
2.5%
72%
100%
5%
92%
100%
10%
99%
100%
The primary population for the safety analyses will consist of all subjects who received at least 
one dose (Ad26.Mos.HIV or placebo).
The immunogenicity population will consist of all subjects who received at least one dose and 
have at least one measured post-dose blood sample collected. Anticipating a dropout rate of 
approximately 10%, 45 evaluable subjects per group will allow detection of 2.3-fold differences 
in Env-binding antibody titers, generally accepted to be biologically relevant, between groups 
with 80% probability, assuming a two-sided 5% Type I error and a standard deviation of 0.6 on 
the log10 scale.
Groups will be combined to make comparisons between different viral vectors (groups combined 
over the different protein doses, N=135 per group) or between different protein doses (groups 
combined over different viral vectors, N=90 per group). Under the same assumptions as above, 
this will allow detection of 1.6-fold (N=135/group) to 1.8-fold differences (N=90/group) in Env-
binding antibody titers. Potential statistical interactions will be explored by means of the 
appropriate interaction tests.
Breadth of Env-binding antibody response will be summarized as the number of HIV clades 
(ranging 0-3, for Clades A, B, C) to which a subject shows an antibody response. Differences in 
breadth between different regimens will be compared via the Wilcoxon-Mann-Whitney test. 
Assuming 45 evaluable subjects per group, a two-sided 5% Type I error rate, no correlation 
between the different clades, and a 90% response rate for every clade (A/B/C) in one group, 
Table 7 below shows the power to detect a significant difference with various alternative
breadths and (combined) group sizes.
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Table 7:
Power (%) for two-sided 5% test for difference in breadth of response, if the response towards 
Clade A/B/C in one group is 90%/90%/90%
N per group
45
90
135
Lower response for 3 clades
80/80/80
61.9
88.9
97.3
75/75/75
89.0
99.4
>99.9
70/70/70
98.0
>99.9
>99.9
Lower response for 2 clades
90/80/80
36.0
61.6
78.7
90/75/75
63.4
90.0
97.7
90/70/70
84.1
98.6
>99.9
Lower response for 1 clade
90/90/80
13.7
22.7
31.5
90/90/75
24.4
42.9
58.7
90/90/70
38.3
64.9
81.7
11.3.
Subject Information
For all subjects, demographic characteristics (eg, age, height, weight, body mass index [BMI], 
race, and gender), and other baseline characteristics (eg, physical examination, medical history, 
concomitant diseases) will be tabulated and summarized with descriptive statistics.
11.4.
Immunogenicity Analyses
No formal hypothesis on immunogenicity will be tested. The analysis of immunogenicity will be 
done on the immunogenicity and per-protocol populations as defined in Section 11.1.
Descriptive statistics (actual values and changes from reference) will be calculated for 
continuous immunologic parameters at all time points. Graphical representations of changes in 
immunologic parameters will be made as applicable. 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 quantification limit, the Gehan-Wilcoxon test 
will be employed. All statistical tests will be two-sided and will be considered statistically 
significant if p<0.05.
Frequency tabulations will be calculated for discrete (qualitative) immunologic parameters at all 
time points. Significant differences between groups will be determined by a 2-sided Fisher’s 
exact test. 
Magnitude and breadth of (neutralizing) antibody 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. 
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11.5.
Safety Analyses
No formal statistical testing of safety data is planned. Safety data will be analyzed descriptively 
(including 95% confidence interval).
Baseline for all safety parameters will be defined as the last evaluation done before the first dose 
of study vaccine.
Adverse Events and Reactogenicity
The verbatim terms used in the CRF by investigators to report AEs will be coded using the 
Medical Dictionary for Regulatory Activities (MedDRA). All reported AEs (local and systemic, 
solicited and unsolicited) with onset during the treatment period (ie, treatment-emergent AEs, 
and AEs that have worsened since baseline) will be included in the analysis. For each AE, the 
number and percentage of subjects who experience at least one occurrence of the given event 
will be summarized by group, including exact 95% confidence intervals. Summaries, listings, 
datasets, or subject narratives may be provided, as appropriate, for those subjects who die, who 
discontinue vaccinations due to an AE, or who experience a severe AE or an SAE. The analysis 
for solicited AEs will be done on those subjects in the safety population for whom reactogenicity 
assessments are available in the database. The analysis of unsolicited AEs will be done based on 
the safety population.
Clinical Laboratory Tests
Laboratory data will be summarized by type of laboratory test. Descriptive statistics (actual 
values and changes from reference) will be calculated for each laboratory analyte at baseline and 
at each scheduled time point. Graphical presentation of changes in laboratory tests will be made 
as applicable. Baseline refers to the pre-dose value on Day 1. If this value is not available, the 
value at screening will be used as baseline value. Laboratory abnormalities will be determined 
according to a modified version of the DAIDS Table for Grading the Severity of Adult and 
Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0 dated December 2004 
(Clarification, August 2009) included in Attachment 1, and in accordance with the normal ranges 
of the clinical laboratory. Laboratory abnormalities will be tabulated per treatment group.
Electrocardiogram (ECG)
All statistical analyses of ECG variables will use the centralized ECG over-read data.
The effects on cardiovascular variables will be evaluated by means of descriptive statistics and 
frequency tabulations.
Vital Signs
Descriptive statistics of pulse rate and blood pressure (systolic and diastolic) values and changes 
from baseline will be summarized at each scheduled time point. The percentage of subjects with 
values beyond pre-specified limits will be summarized.
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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. Body weight and BMI results will be tabulated and summarized 
descriptively.
Social Impact Questionnaire
Data from the Social Impact Questionnaire will be summarized using descriptive statistics.
11.6.
Interim Analysis
Interim safety data will be reviewed by the PSRT (see Section 11.7) and the DMC (See 
Section 11.8)
No formal interim analysis is planned prior to the primary analysis. The primary analysis will be 
performed once all subjects have completed the Week 28 visit (ie, 4 weeks after the third 
injection) or discontinued earlier. The purpose of this analysis is to allow for an early conclusion 
on regimen selection for future studies, based on immunogenicity and safety. 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 study visit at Week 96 (ie, including the 
second year follow-up period) or discontinued earlier. The final analysis of the LTE phase 
(optional and only for a subset of subjects) will be performed once all included subjects have 
completed the last visit of the extension period (Week 336), or discontinued earlier.
11.7.
Protocol Safety Review Team (PSRT)
The internal PSRT will review all AEs on a regular basis as needed. The PSRT will also review 
safety data reports on a regular basis until the last subject has completed the Week 52 visit, and 
thereafter as needed. In addition to regular reviews of safety information, the PSRT will perform 
a cumulative review of blinded safety data.
The PSRT will review safety data at two specific timepoints to ensure the safety of the subjects:

Following a pause in enrollment after 10% of the target number of subjects have received 
their first injection, the PSRT will review blinded Week 2 safety data of these subjects to 
determine if enrollment can continue.

Review blinded safety data (2 weeks of follow up) after 30% of subjects have received their 
first injection (without enrollment pause).
The occurrence of any AE/SAE leading to a study holding situation may trigger a DMC meeting 
as outlined in Section 11.9, and the PSRT will decide by consensus whether any other AE/SAE 
should also be reviewed by the DMC. As per Section 11.9, any AE/SAE will be handled as 
indicated in Table 8, be it for a DMC meeting or for a PSRT review and consideration for a
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DMC meeting. As described below, the DMC will operate according to a charter and will 
evaluate safety and tolerability data.
The PSRT will include, but will not be limited to, medical and safety representatives from the 
sponsor, site, DAIDS and BIDMC.
11.8.
Data Monitoring Committee (DMC)
An independent DMC will be appointed by the sponsor before the start of the study and will 
operate according to its charter. The DMC may review an individual SAE or it may choose to 
review AEs, SAEs, and laboratory and vital sign data. The conclusions of the DMC will be 
communicated to the investigators and the IRB/IEC and the national regulatory authorities as 
appropriate. The sponsor agrees to abide by the decision of the DMC and any directives issued 
by the national regulatory authorities, the IRBs or IECs.
In general, the DMC may unblind any amount of safety information needed to conduct their 
assessment.
The DMC will review safety data at three specific timepoints to ensure the safety of the subjects:

Review blinded safety data (2 weeks of follow up) after 30% of subjects have received their 
first injection to decide whether further dosing can continue;

Review unblinded safety data (2 weeks of follow up) after 10% of subjects have received 
their third injection to decide whether further dosing can continue;

Review unblinded safety data (2 weeks of follow up) after 30% of subjects have received 
their third injection to decide whether further dosing can continue.
The occurrence of any AE/SAE leading to a study holding situation may trigger a DMC meeting, 
as outlined in Section 11.9 .
The DMC will consist of at least one medical expert in the relevant therapeutic area and at least 
one statistician. The DMC responsibilities, authorities, and procedures will be documented in its 
charter.
11.9.
Study Holding Rules
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. The AEs that 
may lead to a safety pause or prompt PSRT AE review are summarized below in Table 8. These 
study holding rules apply to AEs/SAEs occurring up to 4 weeks after the last vaccination.
Related AEs are defined as AEs deemed to be very likely, probably, or possibly related to study 
vaccine; not related AEs are defined as AEs deemed to be doubtful or not related to the study 
vaccine.
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Table 8:
AE Notification and Safety Pause/AE Review Rules1
(S)AE and 
Relationship2
Severity
Site Principal Investigator Action
PSRT/DMC Action
SAE, related
Any 
grade
Phone Study Responsible Physician or designee 
AND fax SAE form to Global Medical Safety 
Officer, immediately and within 24 h
Immediate vaccination pause 
for PSRT review of safety 
data
SAE, not 
related
Grade 5
Phone Study Responsible Physician or designee 
AND fax SAE form to Global Medical Safety 
Officer, immediately and within 24 h
PSRT review and 
consideration of pause
AE, related
Grade 3
or
Grade 4
Phone Study Responsible Physician immediately 
and within 24 h
PSRT review and 
consideration of pause
≥3 subjects with 
a similar related 
AE3
Grade 3 
or
Grade 4
Not applicable
Immediate vaccination pause 
for DMC review of safety data
The telephone number of the Study Responsible Physician (and designee) is in the Contact Information 
page(s). The Study Responsible Physician (or designee) is responsible for the immediate notification of 
PSRT/DMC members and coordination of a PSRT/DMC 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. Conduct of DMC 
review will require a confirmation of the laboratory test within 48 hours.
2
Related: very likely, probably, or possibly related to the study vaccine; not related: doubtful or not related to 
the study vaccine. 
3
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 72 hours)
After each DMC review of a similar AE, the DMC 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, pending DMC review, if, in the judgment of the PSRT, 
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 
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, as specified in Table 8, the PSRT will convene within one business day to review these 
AEs. The PSRT will review and determine disposition, including whether the DMC needs to 
review the event(s).
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If a study pause is triggered by the PSRT, all enrollment and vaccinations will be held until 
review by the PSRT or DMC is complete. Resumption of enrollment and study treatment may be 
determined by the PSRT or DMC (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 DMC 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.
ADVERSE EVENT 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.
12.1.
Definitions
12.1.1.
Adverse Event Definitions and Classifications
Adverse Event
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 ICF to the final visit of the main 
study (Week 96). During the optional LTE phase (Group 1 and 2), only SAEs will be recorded.
Serious Adverse Event
An SAE based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for 
Human Use is any untoward medical occurrence that at any dose:

Results in death
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
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 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.
Confirmed HIV infection in a subject during the study is considered an SAE (see Section 12.3.3).
A suspected transmission of any infectious agent via a medicinal product is always considered as 
an important medical event, ie, an SAE.
If a serious and unexpected AE occurs for which there is evidence suggesting a causal 
relationship between the study vaccine and the event (eg, death from anaphylaxis), the event will 
be reported as a suspected unexpected serious adverse reaction (SUSAR) by the sponsor to 
Health Authorities and by the investigator to the IRB/IEC according to regulatory and local 
requirements.
Unlisted (Unexpected) Adverse Event/Reference Safety Information
An AE is considered unlisted if the nature or severity is not consistent with the applicable 
product reference safety information. For Ad26.Mos.HIV, MVA-Mosaic and gp140 DP, the 
expectedness of an AE will be determined by whether or not it is listed in the respective 
Investigator’s Brochures 2-4.
Adverse Event Associated With the Use of Study Vaccine
An AE is considered associated with study vaccine if the attribution is possibly, probably, or 
very likely related by the definitions listed in Section 12.1.2.
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 therapy). This applies to all AEs, whether serious or 
non-serious.
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The investigator will use the following guidelines to assess the causal relationship of an AE to 
study vaccine:
Not related:
An AE that is not related to the use of study vaccine.
Doubtfully 
related:
An AE for which an alternative explanation is more likely, eg,
concomitant drug(s), concomitant disease(s), or the relationship in time 
suggests that a causal relationship is unlikely.
Possibly related:
An AE that might be due to the use of study vaccine. An alternative 
explanation, eg, concomitant drug(s), concomitant disease(s), is 
inconclusive. The relationship in time is reasonable; therefore, the causal 
relationship cannot be excluded.
Probably related:
An AE that might be due to the use of study vaccine. The relationship in 
time is suggestive (eg, confirmed by dechallenge). An alternative 
explanation is less likely, eg,
concomitant drug(s), concomitant 
disease(s).
Very likely
related:
An AE that is listed as a possible adverse reaction and cannot be 
reasonably explained by an alternative explanation, eg, concomitant 
drug(s), concomitant disease(s). The relationship in time is very 
suggestive (eg, it is confirmed by dechallenge and rechallenge).
Related AEs are defined as AEs deemed to be very likely, probably, or possibly related to study 
vaccine; not related AEs are defined as AEs deemed to be doubtful or not related to the study 
vaccine.
12.1.3.
Severity Criteria
All AE and laboratory data will be coded for severity using a modified version of the DAIDS 
Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading 
Table), Version 1.0 dated December 2004 (Clarification, August 2009) included in 
Attachment 1.
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
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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.
Special Reporting Situations
Safety events of interest about a sponsor study vaccine that may require expedited reporting 
and/or safety evaluation include, but are not limited to:

Overdose of a sponsor study vaccine

Suspected abuse/misuse of a sponsor study vaccine

Inadvertent or accidental exposure to a sponsor study vaccine

Medication error involving a sponsor product (with or without subject/patient exposure to 
the sponsor study vaccine, eg, name confusion)
Special reporting situations should be recorded in the CRF. Any special reporting situation that 
meets the criteria of an SAE should be recorded on the SAE page of the CRF.
12.3.
Procedures
12.3.1.
All Adverse Events
All AEs and special reporting situations, whether serious or non-serious, will be reported from 
the time a signed and dated ICF is obtained until completion of the subject’s last procedure of the 
main study (which may include contact for follow-up of safety). During the optional LTE phase 
(Group 1 and 2), only SAEs will be recorded.
All SAEs, must be reported to the sponsor during the entire study period (including the optional 
LTE phase for Group 1 and 2) using the SAE Form. Suspected unexpected serious adverse 
reactions (SUSARs) are reported even after the study is over, if the sponsor, DMC or investigator 
becomes aware of them. The sponsor will evaluate any safety information that is spontaneously 
reported by the investigator beyond the time frame specified in the protocol.
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 either related to study vaccine or not 
related to study vaccine, according to Section 12.1.1. 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.
Post-injection reactogenicity (PIR) includes solicited AEs related to study vaccine and therefore 
must be reported as such. The investigator or designee must review both PIR and other AE CRFs 
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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 study 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 study vaccine. All measures required for AE management must be recorded in the source 
document and reported according to sponsor instructions.
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 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.
Subjects will 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

Information about who should be contacted in case of emergency
12.3.2.
Serious Adverse Events
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. The initial and follow-up reports of a SAE should be made by facsimile (fax)
and/or e-mail.
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:
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
The event resolves

The event stabilizes

The event returns to baseline, if a baseline value/status is available

The event can be attributed to agents other than the study vaccine or to factors unrelated to 
study conduct

It becomes unlikely that any additional information can be obtained (subject or health care 
practitioner refusal to provide additional information, lost to follow up after demonstration 
of due diligence with follow-up efforts)
Any event requiring hospitalization (or prolongation of hospitalization) that occurs during 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 during the entire study period, whether or not the event is 
expected or associated with the study vaccine, is considered an SAE and must be reported.
12.3.3.
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, and must be negative to be entered into the study. If 
possible, the site should select an assay that is US FDA-approved. After screening, an HIV 
testing algorithm (detailed in the Study Procedures Manual) will be followed. 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. Confirmed HIV infection in a subject during the study is considered an SAE and must 
be reported using the Serious Adverse Event Form.
12.3.4.
Pregnancy
All initial reports of pregnancy 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, stillbirth, and congenital 
anomaly) are considered SAEs and must be reported using the Serious Adverse Event Form.
Any subject who becomes pregnant during the study must be promptly withdrawn from further 
study vaccination but should continue participation in the study for follow up (see Section 10.2).
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Because the effect of the study vaccine on sperm is unknown, pregnancies in partners of male 
subjects included in the study will be reported by the study-site personnel within 24 hours of their 
knowledge of the event using the appropriate pregnancy notification form.
Follow-up information regarding the outcome of the pregnancy and any postnatal sequelae in the 
infant will be required to be sent to the sponsor.
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 on 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.
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 on the Contact Information page(s), which will be 
provided as a separate document.
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14.
STUDY VACCINE INFORMATION
14.1.
Physical Description of Study Vaccines
Ad26.Mos.HIV
Ad26.Mos.HIV vaccine is made up of the following three drug substances in a 2:1:1 ratio:

Ad26.Mos1.Env (JNJ-55471468-AAA)

Ad26.Mos1.Gag-Pol (JNJ-55471494-AAA)

Ad26.Mos2.Gag-Pol (JNJ-55471520-AAA)
The Ad26.Mos.HIV vaccine, manufactured by Janssen Vaccines & Prevention B.V., Leiden, The 
Netherlands, that will be supplied for this study is formulated as a trivalent vaccine as a clear to 
slightly opalescent solution for IM injection. The vaccine will be supplied as a frozen liquid to be 
thawed prior to use, and will be essentially free from particles. The vaccine will be provided in 
individual dosage vials at a concentration of 1 x 1011 vp/mL. Each stoppered and sealed glass vial 
contains a volume of approximately 0.7 mL. Refer to the Investigator’s Brochure for a list of 
excipients 2.
MVA-Mosaic
MVA-Mosaic consists of the following two vaccine products supplied in separate vials and 
administered in a 1:1 ratio:

MVA-Mosaic1 = MVA virus expressing Mosaic1 HIV-1 Gag, Pol, and Env proteins 
(JNJ 55471533-AAA)

MVA-Mosaic2 = MVA virus expressing Mosaic2 HIV-1 Gag, Pol, and Env proteins 
(JNJ 55471572-AAA)
The MVA-Mosaic vaccine, manufactured by Advanced BioScience Laboratories, Inc., Rockville, 
MD, USA, that will be supplied for this study is formulated for IM injection as a white to opaque, 
slightly to moderately cloudy solution that may contain white particles. MVA-Mosaic vaccine
will be supplied as frozen liquids to be thawed prior to use. Separate MVA-Mosaic1 (MVA virus 
expressing Mosaic1 HIV-1 Gag, Pol and Env proteins) and MVA-Mosaic2 (MVA virus 
expressing Mosaic2 HIV-1 Gag, Pol and Env proteins) components will be provided in 
individual dosage vials at a concentration of 2x108 pfu/mL. Each stoppered and sealed glass vial 
contains a volume of approximately 0.8 mL. Refer to the Investigator’s Brochure for a list of 
excipients 3.
gp140 DP
The gp140 DP, manufactured by Gallus, Princeton, NJ, USA, that will be supplied for this study 
is formulated as a solution for IM injection. The drug product (DP) will be supplied as a 
colorless frozen liquid to be thawed prior to use, and will be essentially free from particles. The 
DP will be supplied as a 0.5 mL fill in a glass vial at a nominal strength of either 1 mg/mL or 
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0.2 mg/mL based on total protein content. Refer to the Investigator’s Brochure for details of the 
components of the DP and a list of excipients 4.
Adjuvant
In this study, gp140 DP will be adjuvanted, using a commercially available aluminum salt-based 
adjuvant, aluminum phosphate. The adjuvant will be supplied as a formulated refrigerated liquid 
suspension. As supplied, the adjuvant will have a nominal aluminum content of 1.7 mg/mL. It 
will be mixed with gp140 DP at the site pharmacy prior to administration (JNJ-55471585-AAA: 
gp140 DP + aluminum phosphate adjuvant).
Placebo
Placebo consisting of sterile 0.9% Saline for Injection will be supplied (as commercially 
available).
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
Study vaccine must be stored at controlled temperatures. Guidance on storage temperature is 
provided in the site investigational product manual.
Vials must be stored in a secured location with no access for unauthorized personnel. The study 
freezer 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.
All injections should be administered in the deltoid. For visits with only one injection (ie, at 
Week 0 and 12), either deltoid can be used. When 2 study vaccine injections are to be given at 
one visit (ie, at Week 24 and 48), it is required to use a different deltoid for both injections. 
Exceptions are allowed only if medically indicated. No local or topical anesthetic will be used prior 
to the injection. To account for the product with the shortest stability time, the maximum time 
allowed between preparation and administration of the study vaccine will be 3 hours.
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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.
Ad26.Mos.HIV Preparation
Each vial must be thawed to room temperature.
Full details on the holding time and storage conditions from the time of preparation to delivery of 
Ad26.Mos.HIV, are provided in the Site Investigational Product Procedures Manual.
MVA-Mosaic Preparation
Each MVA-Mosaic
vial must be thawed to room temperature.
MVA-Mosaic1 and 
MVA-Mosaic2 are intended to be mixed prior to injection. Equal volumes of MVA-Mosaic1 and 
MVA-Mosaic2 are transferred by syringe into an empty sterile 2 mL Type 1 glass vial with a 
butyl rubber stopper with a final MVA dose of 108. The vial is vortexed at high-speed for 
60 seconds prior to withdrawal of the vaccine into the syringe. 
More information the mixing of the two vaccine components, as well as full details on the 
holding time and storage conditions from the time of preparation to delivery of MVA-Mosaic, 
are provided in the Site Investigational Product Procedures Manual.
gp140 DP Preparation
The gp140 DP active pharmaceutical ingredient (API) vial must be removed from the freezer 
storage location and thawed with occasional gentle swirling by hand at ambient room 
temperature.
For the preparation of the adjuvanted high (250 mcg/0.5 mL) dose, the gp140 DP API with a 
nominal total protein concentration of 1 mg/mL must be diluted 1:1, by mixing 0.5 mL of the 
aluminum adjuvant as supplied with 0.5 mL of gp140 DP. The aluminum content in the 
gp140 DP-adjuvant mix will be 0.85 mg/mL (ie, 0.425 mg aluminum/0.5 mL dose).
For the preparation of the adjuvanted low (50 mcg/0.5 mL) dose, the gp140 DP API with a 
nominal total protein concentration of 0.2 mg/mL must be diluted 1:1, by mixing 0.5 mL of the 
aluminum adjuvant as supplied with 0.5 mL of gp140 DP. The aluminum content in the gp140 
DP-adjuvant mix will be 0.85 mg/mL (ie, 0.425 mg aluminum/0.5 mL dose).
More information and full details on the mixing and diluting of vaccine and adjuvant 
components, as well as full details on the holding time and storage conditions from the time of 
preparation to delivery of gp140 DP, are provided in the Site Investigational Product Procedures 
Manual.
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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 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. Returned study vaccine must not be 
dispensed again, even to the same subject. 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 Brochures for Ad26.Mos.HIV, MVA-Mosaic, and gp140 DP

Site Investigational Product Procedures Manual/Study Procedures Manual

Laboratory Manual

IWRS Manual

Electronic Data Capture (eDC) Manual/electronic CRF completion guidelines and 
randomization instructions

Sample ICF

Memory aids

Test of Understanding

Social Impact Questionnaire

Rulers, thermometers
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
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.
The total blood volume drawn from each subject will not exceed the US Department of Health 
and Human Services (HHS) Office for Human Research Protections (OHRP), and US FDA 
guidelines of 550 mL in any eight-week period.
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, prior to enrollment in the study. 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.
Risks Related to Vaccines
Subjects may exhibit general signs and symptoms associated with administration of a vaccine, or 
vaccination with placebo, including fever, chills, rash, aches and pains, nausea, headache, 
dizziness and fatigue. These side effects will be monitored, but are generally short-term and do 
not require treatment.
Subjects may have an allergic reaction to the vaccination. An allergic reaction may cause a rash, 
hives or even difficulty breathing. Severe reactions are rare. Medications must be available in the 
clinic to treat serious allergic reactions.
The effect of this vaccine on a fetus or nursing baby is unknown, as well as the effect on semen, 
so female subjects of child bearing potential, and male subjects having sexual intercourse with 
females, will be required to agree to use birth control for sexual intercourse beginning prior to 
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the first vaccination and through 3 months after the last vaccination. Women who are pregnant or 
nursing will be excluded from the study.
Risks related to VISP are discussed in Section 9.4.3.
Risk of Myo/Pericarditis
The MVA vaccine used in this study is related to the vaccine to prevent smallpox. A very small 
number of people who received the smallpox vaccine developed myocarditis or pericarditis. The 
number of people who had these problems was very small (96 people out of >650,000 who 
received the vaccine)18. These side effects are not expected from the MVA vaccine because it is
an attenuated virus and it cannot replicate. Myocarditis has not been reported with previous 
MVA use and has not been seen in Phase I/II clinical studies cited in this protocol. Subjects will 
be actively screened to exclude pre-existing cardiac concerns and followed-up for symptoms 
related to cardiac complications. The management of subjects who develop cardiac symptoms is 
detailed in Section 9.3.2.
Risks from Blood Draws
Blood drawing may cause pain, bruising, 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.
Participants 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.
Potential Benefits
There is no direct medical benefit to the subject for participation in this clinical study. Although 
study subjects may benefit from clinical testing and physical examination, they may receive no 
direct benefit from participation. Others may benefit from knowledge gained in this study that 
may aid in the development of an HIV vaccine.
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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

Sponsor-approved ICFs (and any other written materials to be provided to the subjects)

Investigator’s Brochure (or equivalent information) and amendments/addenda

TOU

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:
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
Protocol amendments (excluding the ones that are purely administrative, with no 
consequences for subjects, data or study conduct)

Revision(s) to ICFs 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 study 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
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, 
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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, and agrees to 
allow his or her study physician to recontact the subject for the purpose of obtaining consent for 
additional safety evaluations, 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 should be 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). After informed consent for the study is appropriately obtained, the subject 
will be asked to sign and personally date the ICF appendix indicating agreement to participate in 
the optional research component. Refusal to participate in the optional research will not result in 
ineligibility for the study. A copy of this signed ICF appendix will be given to the subject.
Subjects from Group 1 and Group 2 who received all 4 vaccinations will be asked to sign an ICF 
addendum for the optional LTE phase.
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 
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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.
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 (refer to 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.
16.2.6.
Country Selection
This study will only be conducted in those countries where the intent is to launch or otherwise 
help ensure access to the developed product, unless explicitly addressed as a specific ethical 
consideration in Section 16.1.
16.3.
USAMRMC Volunteer Registry Database
For sites with a direct affiliation with the US Army Military HIV Research Program, it is the 
policy of the US Army Medical Research and Materiel Command (USAMRMC) that volunteer 
registry data sheets are collected on all volunteers participating in this greater than minimal risk 
research for entry into the Command’s Volunteer Registry Database (VRDS). The Volunteer 
Registry Database will collect the following data on volunteers:

Names (first and last name)

Date of birth

Contact information, both permanent and local

Study name and study dates, and dates of individual’s participation
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
SAE and unexpected AEs related to the vaccine experienced during study participation

Details of the product received
The intent of the database is two-fold: firstly, to readily answer questions concerning an 
individual’s participation in research supported by the USAMRMC; and secondly, to ensure that 
the USAMRMC can exercise its obligation to ensure research volunteers are adequately warned 
(duty to warn) of risks and to provide new information as it becomes available. The information 
will be stored for a minimum of 75 years at USAMRMC.
17.
ADMINISTRATIVE REQUIREMENTS
17.1.
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 (and IEC where required) only needs to be notified.
During the course of the study, in situations where a departure from the protocol is unavoidable, 
the investigator or other physician in attendance will contact the appropriate sponsor 
representative (see Contact Information page(s) provided separately). 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.
17.2.
Regulatory Documentation
17.2.1.
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 site may not be initiated until all local 
regulatory requirements are met.
17.2.2.
Required Pre-study Documentation
The following documents must be provided to the sponsor before shipment of study vaccine to 
the study site:

Protocol and amendment(s), if any, signed and dated by the principal investigator
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
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 the 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
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
17.3.
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. In cases where the subject is not randomized into the study, the date seen and 
date of birth will be used.
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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.
17.4.
Source Documentation
At a minimum, source documentation must be available for the following to confirm data 
collected in the CRF: subject identification, eligibility, and study identification; study discussion 
and date of signed informed consent; dates of visits; safety parameters as required by the 
protocol; record of all AEs and follow up of AEs; concomitant medication; vaccine 
receipt/dispensing/return records; study vaccine administration information; and date of study 
completion and reason for early discontinuation of study vaccine or withdrawal from the study, if 
applicable. 
In addition, the author of an entry in the source documents should be identifiable.
At a minimum, the type and level of detail of source data available for a subject should be 
consistent with that commonly recorded at the study site as a basis for standard medical care. 
Specific details required as source data for the study will be reviewed with the investigator 
before the study and will be described in the monitoring guidelines (or other equivalent 
document).
The following data can be recorded directly into the CRF and will be considered source data: 

Race

Blood pressure and pulse/heart rate

Height and weight
Information from the memory aid, given to subjects to note symptoms of unsolicited and 
solicited local and systemic AEs for 8 days after each vaccination, will be reviewed by the 
investigator or his/her designee at Visits 3, 7, 10 and 14, to complete the relevant parts of the 
CRF as described in the CRF Completion Guidelines.
17.5.
Case Report Form Completion
CRFs are provided for each subject in electronic format.
eDC will be used for this study. The study data will be transcribed by study-site personnel from 
the source documents onto an electronic CRF, and transmitted in a secure manner to the sponsor 
within the timeframe agreed upon between the sponsor and the study site. The electronic file will 
be considered to be the CRF.
Data must be entered into CRFs in English. Study site personnel must complete the CRF as soon 
as possible after a subject visit, and the forms should be available for review at the next 
scheduled monitoring visit. The investigator must verify that all data entries in the CRFs are 
accurate and correct.
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All CRF entries, corrections, and alterations must be made by the investigator or other authorized 
study-site personnel. If necessary, queries will be generated in the eDC tool. The investigator or 
study-site personnel must adjust the CRF (if applicable) and complete the query.
If corrections to a CRF are needed after the initial entry into the CRF, this can be done in three 
different ways:

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).

Study site manager can generate a query for resolution by the study-site personnel.

Clinical data manager can generate a query for resolution by the study-site personnel.
17.6.
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.
17.7.
Record Retention
In compliance with the ICH/GCP guidelines, the investigator/institution will maintain all CRFs 
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 
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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.
17.8.
Monitoring
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 CRFs with the hospital or clinic records (source 
documents). 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 documentation (medical records) must be allowed for the purpose of 
verifying that the data recorded in the CRF are consistent with the original source data. Findings 
from this review of CRFs and source documents 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 documentation will be accessible, and a suitable environment will be 
provided for review of study-related documents. The monitor will meet with the investigator on a 
regular basis during the study to provide feedback on the study conduct.
In addition to on-site monitoring visits, remote contacts can occur. It is expected that during 
these remote contacts, study-site personnel will be available to be provide an update on the 
progress of the study at the site.
17.9.
Study Completion/Termination
17.9.1.
Study Completion
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.
17.9.2.
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.
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The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to:

Failure of the investigator to comply with the protocol, the requirements of the IEC/IRB or 
local health authorities, the sponsor’s procedures, or GCP guidelines

Inadequate recruitment of subjects by the investigator

Discontinuation of further study vaccine development
17.10. 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 and comparison with the CRFs. 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 
regulatory submission. The investigator should immediately notify the sponsor if he or she has 
been contacted by a regulatory agency concerning an upcoming inspection.
17.11. Use of Information and Publication
All information, including but not limited to information regarding Ad26.Mos.HIV, MVA-
Mosaic and gp140 DP
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.Mos.HIV, MVA-Mosaic and 
gp140 DP, 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 CRF data from all study sites that participated in the study. Recruitment 
performance or specific expertise related to the nature and the key assessment parameters of the 
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study will be used to determine a coordinating investigator. 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, upon agreement 
with the sponsor. 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 data derived 
from the individual study site until the combined results from the completed study have been 
submitted for publication, within 12 months of the availability of the final data (tables, listings, 
graphs), 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 Uniform Requirements for Manuscripts Submitted to Biomedical Journals, 
which state that the named authors must have made a significant contribution to the design of the 
study or analysis and interpretation of the data, provided critical review of the paper, and given 
final approval of the final version.
Registration of Clinical Studies and Disclosure of Results
The sponsor will register and/or disclose the existence of and the results of clinical studies as 
required by law.
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REFERENCES
1.
Seaman MS, Janes H, Hawkins N, et al. Tiered categorization of a diverse panel of HIV-1 Env 
pseudoviruses for assessment of neutralizing antibodies. J Virol 2010;84:1439-52.
2.
Investigator’s Brochure: Ad26.Mos.HIV. Edition 1. Crucell Holland B.V.
3.
Investigator’s Brochure: MVA-Natural and MVA-Mosaic HIV Vaccines. Edition 2. Walter Reed 
Army Institute of Research. 23 June 2014.
4.
Investigator’s Brochure: gp140. Edition 1. Crucell Holland B.V. 
5.
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;361:2209-20.
6.
Haynes BF, Gilbert PB, McElrath MJ, et al. Immune-correlates analysis of an HIV-1 vaccine 
efficacy trial. N Engl J Med 2012;366:1275-86.
7.
Tomaras GD, Ferrari G, Shen X, et al. Vaccine-induced plasma IgA specific for the C1 region of the 
HIV-1 envelope blocks binding and effector function of IgG. Proc Natl Acad Sci U S A 
2013;110:9019-24.
8.
Barouch DH, Liu J, Li H, et al. Vaccine protection against acquisition of neutralization-resistant SIV 
challenges in rhesus monkeys. Nature 2012;482:89-93.
9.
Barouch D, Stephenson K, Borducchi E, et al. Protective efficacy of a global HIV-1 mosaic vaccine 
against heterologous SHIV challenges in rhesus monkeys Cell 2013;155:531-9.
10. Chen X, Scala G, Quinto I, et al. Protection of rhesus macaques against disease progression from 
pathogenic SHIV-89.6PD by vaccination with phage-displayed HIV-1 epitopes. Nat Med 
2001;7:1225-31.
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;13:100-6.
12. McFarland EJ, Borkowsky W, Fenton T, et al. Human immunodeficiency virus type 1 (HIV-1) 
gp120-specific antibodies in neonates receiving an HIV-1 recombinant gp120 vaccine. J Infect Dis 
2001;184:1331-5.
13. Buchbinder SP, Mehrotra DV, Duerr A, et al. Efficacy assessment of a cell-mediated immunity HIV-
1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial. 
Lancet 2008;372:1881-93.
14. Gray GE, 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, randomised, placebo-controlled test-of-
concept phase 2b study. Lancet Infect Dis 2011;11:507-15.
15. 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 U S A 2009;106:19940-5.
16. Hutnick NA, Carnathan DG, Dubey SA, et al. Baseline Ad5 serostatus does not predict Ad5 HIV 
vaccine-induced expansion of adenovirus-specific CD4+ T cells. Nat Med 2009;15:876-8.
17. Barouch DH. Novel adenovirus vector-based vaccines for HIV-1. Curr Opin HIV AIDS 2010;5:386-
90.
18. Neff J, Modlin J, Birkhead GS, et al. Monitoring the safety of a smallpox vaccination program in the 
United States: report of the joint Smallpox Vaccine Safety Working Group of the advisory 
committee on immunization practices and the Armed Forces Epidemiological Board. Clin Infect Dis 
2008;46 Suppl 3:S258-70.
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19. Allen M, Lau CY. Social impact of preventive HIV vaccine clinical trial participation: a model of 
prevention, assessment and intervention. Soc Sci Med 2008;66:945-51.
20. Eickhoff TC, Myers M. Workshop summary. Aluminum in vaccines. Vaccine 2002;20 Suppl 3:S1-4.
21. Jefferson T, Rudin M, Di Pietrantonj C. Adverse events after immunisation with aluminium-
containing DTP vaccines: systematic review of the evidence. Lancet Infect Dis 2004;4:84-90.
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Attachment 1:
Division of AIDS Tables for Grading the Severity of Adult and Pediatric Adverse Events
Version 1.0, December, 2004; Clarification August 2009 – Including Modifications
Division of AIDS table for grading the severity of 
ADULT AND PEDIATRIC adverse Events
Version 1.0, December, 2004; clarification AUGUST 2009
The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events 
(“DAIDS AE Grading Table”) is a descriptive terminology which can be utilized for Adverse 
Event (AE) reporting. A grading (severity) scale is provided for each AE term.
This clarification of the DAIDS Table for Grading the Severity of Adult and Pediatric AE’s 
provides additional explanation of the DAIDS AE Grading Table and clarifies some of the 
parameters. 
I.
Instructions and Clarifications
Grading Adult and Pediatric AEs
The DAIDS AE 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 given in the Table. 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.
Note: In the classification of adverse events, the term “severe” is not the same as 
“serious.” Severity is an indication of the intensity of a specific event (as in mild, 
moderate, or severe chest pain). The term “serious” relates to a participant/event 
outcome or action criteria, usually associated with events that pose a threat to a 
participant’s life or functioning. 
Addenda 1-3 Grading Tables for Microbicide Studies
For protocols involving topical application of products to the female genital tract, male genital 
area or rectum, strong consideration should be given to using Appendices I-III as the primary 
grading scales for these areas. The protocol would need to specifically state that one or more of 
the Appendices would be primary (and thus take precedence over the main Grading Table) for 
items that are listed in both the Appendix and the main Grading Table.
Addendum 1 - Female Genital Grading Table for Use in Microbicide Studies - PDF
Addendum 2 - Male Genital Grading Table for Use in Microbicide Studies - PDF
Addendum 3 - Rectal Grading Table for Use in Microbicide Studies - PDF
Grade 5
For any AE where the outcome is death, the severity of the AE is classified as Grade 5. 
Estimating Severity Grade for Parameters Not Identified in the Table
In order to grade a clinical AE that is not identified in the DAIDS AE grading table, use the 
category “Estimating Severity Grade” located on top of the table on Page 96.
Determining Severity Grade for Parameters “Between Grades”
If the severity of a clinical AE could fall under either one of two grades (eg, the severity of an AE 
could be either Grade 2 or Grade 3), select the higher of the two grades for the AE. If a 
laboratory value that is graded as a multiple of the ULN or LLN falls between two grades, select 
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the higher of the two grades for the AE. For example, Grade 1 is 2.5 x ULN and Grade 2 is 2.6 x 
ULN for a parameter. If the lab value is 2.53 x ULN (which is between the two grades), the 
severity of this AE would be Grade 2, the higher of the two grades.
Values Below Grade 1
Any laboratory value that is between either the LLN or ULN and Grade 1 should not be graded.
Determining Severity Grade when Local Laboratory Normal Values Overlap with Grade 1 
Ranges 
In these situations, the severity grading is based on the ranges in the DAIDS AE Grading Table, 
even when there is a reference to the local lab LLN.
For example: Phosphate, Serum, Low, Adult and Pediatric > 14 years (Page 20) Grade 1 range 
is 2.50 mg/dL - < LLN. A particular laboratory’s normal range for Phosphate is 2.1 – 3.8 mg/dL.
A participant’s actual lab value is 2.5. In this case, the value of 2.5 exceeds the LLN for the local 
lab, but will be graded as Grade 1 per DAIDS AE Grading Table.
II.
Definitions of terms used in the Table:
Basic Self-care Functions
Adult
Activities such as bathing, dressing, toileting, transfer/movement, 
continence, and feeding.
Young Children
Activities that are age and culturally appropriate (eg, feeding self with 
culturally appropriate eating implement).
LLN
Lower limit of normal
Medical Intervention
Use of pharmacologic or biologic agent(s) for treatment of an AE.
NA
Not Applicable
Operative Intervention
Surgical OR other invasive mechanical procedures.
ULN
Upper limit of normal
Usual Social and Functional 
Activities
Adult
Adaptive tasks and desirable activities, such as going to work, 
shopping, cooking, use of transportation, pursuing a hobby, etc.
Young Children
Activities that are age and culturally appropriate (eg, social 
interactions, play activities, learning tasks, etc.).
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PARAMETER
GRADE 1
MILD
GRADE 2
MODERATE
GRADE 3
SEVERE
GRADE 4
POTENTIALLY
LIFE-THREATENING
ESTIMATING SEVERITY GRADE
Clinical adverse event 
NOT identified 
elsewhere in this 
DAIDS AE Grading 
Table 
Symptoms causing 
no or minimal 
interference with 
usual social & 
functional activities
Symptoms causing 
greater than minimal 
interference with 
usual social & 
functional activities
Symptoms causing 
inability to perform 
usual social & 
functional activities
Symptoms causing 
inability to perform basic 
self-care functions OR 
Medical or operative 
intervention indicated to 
prevent permanent 
impairment, persistent 
disability, or death 
SYSTEMIC
Acute systemic 
allergic reaction 
Localized urticaria 
(wheals) with no 
medical intervention 
indicated
Localized urticaria 
with medical 
intervention indicated 
OR Mild angioedema 
with no medical 
intervention indicated
Generalized urticaria 
OR Angioedema with 
medical intervention 
indicated OR 
Symptomatic mild 
bronchospasm
Acute anaphylaxis OR 
Life-threatening 
bronchospasm OR 
laryngeal edema
Chills
Symptoms causing 
no or minimal 
interference with 
usual social & 
functional activities
Symptoms causing 
greater than minimal 
interference with 
usual social & 
functional activities 
Symptoms causing 
inability to perform 
usual social & 
functional activities
NA
Fatigue
Malaise
Symptoms causing 
no or minimal 
interference with 
usual social & 
functional activities
Symptoms causing 
greater than minimal 
interference with 
usual social & 
functional activities
Symptoms causing 
inability to perform 
usual social & 
functional activities
Incapacitating fatigue/ 
malaise symptoms 
causing inability to 
perform basic self-care 
functions
Fever (nonaxillary)l
37.7 
38.6 ºC
38.7 
39.3 ºC
39.4 
40.5 ºC
>40.5 ºC 
Feverl
38.0 – 38.4 C
100.4 – 101.1 F
38.5 – 38.9 C
101.2 – 102.0 F
39.0 – 40.0 C
102.1 – 104 F
> 40.0 C 
> 104 F
Pain (indicate body 
site)
DO NOT use for pain 
due to injection (See 
Injection Site 
Reactions: Injection 
site pain)
See also Headache, 
Arthralgia, and 
Myalgia
Pain causing no or 
minimal interference 
with usual social & 
functional activities
Pain causing greater 
than minimal 
interference with 
usual social & 
functional activities
Pain causing inability to 
perform usual social & 
functional activities
Disabling pain causing 
inability to perform basic 
self-care functions; OR 
Hospitalization (other 
than emergency room 
visit) indicated
Unintentional weight 
loss
NA
5 – 9% loss in body 
weight from baseline
10 – 19% loss in body 
weight from baseline
20% loss in body 
weight from baseline OR 
Aggressive intervention 
indicated [eg, tube 
feeding or total parenteral 
nutrition (TPN)]
                                                
l Modification of DAIDS toxicity table consistent with FDA guidance “Toxicity Grading Scale for Healthy Adult 
and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials, September 2007 – strike-through text 
replaced by grey-highlighted text
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PARAMETER
GRADE 1
MILD
GRADE 2
MODERATE
GRADE 3
SEVERE
GRADE 4
POTENTIALLY
LIFE-THREATENING
INFECTION
Infection (any other 
than HIV infection)
Localized, no 
systemic antimicrobial 
treatment indicated 
AND Symptoms 
causing no or minimal 
interference with 
usual social & 
functional activities
Systemic 
antimicrobial 
treatment indicated 
OR Symptoms 
causing greater than 
minimal interference 
with usual social & 
functional activities
Systemic antimicrobial 
treatment indicated 
AND Symptoms 
causing inability to 
perform usual social & 
functional activities OR 
Operative intervention 
(other than simple 
incision and drainage) 
indicated
Life-threatening 
consequences (eg, septic 
shock)
INJECTION SITE REACTIONS
Injection site pain 
(pain without 
touching)
Or
Tenderness (pain 
when area is 
touched)m
Pain/tenderness 
causing no or minimal 
limitation of use of 
limb
Pain/tenderness 
limiting use of limb 
OR Pain/tenderness 
causing greater than 
minimal interference 
with usual social & 
functional activities
Pain/tenderness 
causing inability to 
perform usual social & 
functional activities
Pain/tenderness causing 
inability to perform basic 
self-care function OR 
Hospitalization (other 
than emergency room 
visit) indicated for 
management of 
pain/tenderness
Injection site reaction (localized)m
Adult >15 yearsm
Erythema OR 
Induration
of 5x5 cm 
9x9 cm 
(or 25 cm2
81cm2)
Erythema OR 
Induration OR Edema 
>9 cm any diameter
(or >81 cm2)
Ulceration OR 
Secondary infection OR 
Phlebitis OR Sterile 
abscess OR Drainage
Necrosis (involving 
dermis and deeper 
tissue)
Pediatric 15 
yearsm
Erythema OR 
Induration OR Edema 
present but 2.5 cm 
diameter
Erythema OR 
Induration OR Edema 
>2.5 cm diameter but 
<50% surface area of 
the extremity 
segment (eg, upper 
arm/thigh)
Erythema OR
Induration OR Edema 
involving 
50% surface area of 
the extremity segment 
(eg, upper arm/thigh) 
OR Ulceration OR 
Secondary infection OR 
Phlebitis OR Sterile 
abscess OR Drainage
Necrosis (involving 
dermis and deeper 
tissue)
Pain (without 
touching) m
Does not interfere 
with activity 
Repeated use of non-
narcotic pain reliever 
> 24 hours or 
interferes with activity 
Any use of narcotic 
pain reliever or 
prevents daily activity 
Emergency room (ER) 
visit or hospitalization 
Tenderness (pain 
when area is touched)
m
Mild discomfort to 
touch 
Discomfort with 
movement 
Significant discomfort 
at rest 
ER visit or hospitalization 
                                                
m Modification of DAIDS toxicity table consistent with FDA guidance “Toxicity Grading Scale for Healthy Adult 
and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials, September 2007 – strike-through text 
replaced by grey-highlighted text
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PARAMETER
GRADE 1
MILD
GRADE 2
MODERATE
GRADE 3
SEVERE
GRADE 4
POTENTIALLY
LIFE-THREATENING
Erythema/
Rednessm
2.5 cm – 5 cm 
5.1 cm – 10 cm
> 10 cm
Necrosis or exfoliative 
dermatitis
Induration/Swellingm
2.5 cm – 5 cm and 
does not interfere 
with activity
5.1 cm – 10 cm or 
interferes with activity
> 10 cm or prevents 
daily activity
Necrosis
Pruritis associated 
with injection 
See also Skin: Pruritis 
(itching - no skin 
lesions)
Itching localized to 
injection site AND 
Relieved 
spontaneously or with 
<48 hours treatment 
Itching beyond the 
injection site but not 
generalized OR 
Itching localized to 
injection site requiring 
48 hours treatment 
Generalized itching 
causing inability to 
perform usual social & 
functional activities
NA
SKIN – DERMATOLOGICAL
Alopecia
Thinning detectable 
by study participant 
(or by caregiver for 
young children and 
disabled adults)
Thinning or patchy 
hair loss detectable 
by health care 
provider
Complete hair loss
NA
Cutaneous reaction –
rash
Localized macular 
rash 
Diffuse macular, 
maculopapular, or 
morbilliform rash OR 
Target lesions 
Diffuse macular, 
maculopapular, or 
morbilliform rash with 
vesicles or limited 
number of bullae OR 
Superficial ulcerations 
of mucous membrane 
limited to one site
Extensive or generalized 
bullous lesions OR 
Stevens-Johnson 
syndrome OR Ulceration 
of mucous membrane 
involving two or more 
distinct mucosal sites OR 
Toxic epidermal
necrolysis (TEN)
Hyperpigmentation
Slight or localized
Marked or 
generalized
NA
NA
Hypopigmentation
Slight or localized 
Marked or 
generalized
NA
NA
Pruritis (itching – no 
skin lesions) 
(See also Injection 
Site Reactions: 
Pruritis associated 
with injection)
Itching causing no or 
minimal interference 
with usual social & 
functional activities
Itching causing 
greater than minimal 
interference with 
usual social & 
functional activities
Itching causing inability 
to perform usual social 
& functional activities 
NA
CARDIOVASCULAR
Cardiac arrhythmia 
(general)
(By ECG or physical 
exam)
Asymptomatic AND 
No intervention 
indicated
Asymptomatic AND 
Non-urgent medical 
intervention indicated
Symptomatic, non-life-
threatening AND Non-
urgent medical 
intervention indicated 
Life-threatening 
arrhythmia OR Urgent 
intervention indicated
Cardiac-
ischemia/infarction
NA
NA
Symptomatic ischemia 
(stable angina) OR 
Testing consistent with 
ischemia 
Unstable angina OR 
Acute myocardial 
infarction
NCT02315703


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
99
Approved, Date: 21 December 2016
PARAMETER
GRADE 1
MILD
GRADE 2
MODERATE
GRADE 3
SEVERE
GRADE 4
POTENTIALLY
LIFE-THREATENING
Hemorrhage 
(significant acute 
blood loss)
NA
Symptomatic AND No 
transfusion indicated
Symptomatic AND 
Transfusion of 2 units 
packed RBCs (for 
children 10 cc/kg) 
indicated 
Life-threatening 
hypotension OR 
Transfusion of >2 units 
packed RBCs (for 
children >10 cc/kg) 
indicated
Hypertension
Adult >17 years
(with repeat testing at 
same visit)
140 – 159 mmHg 
systolic
OR
90 – 99 mmHg 
diastolic
160 – 179 mmHg 
systolic
OR
100 – 109 mmHg 
diastolic
≥180 mmHg systolic
OR
≥110 mmHg diastolic
Life-threatening 
consequences (eg,
malignant hypertension) 
OR Hospitalization 
indicated (other than 
emergency room visit)
Correction: in Grade 2 to 160 - 179 from >160-179 (systolic) and to 100 -109 from >100-109 (diastolic) and 
in Grade 3 to 180 from >180 (systolic) and to 110 from >110 (diastolic).
Pediatric 17 years
(with repeat testing at 
same visit)
NA
91st – 94th percentile 
adjusted for age, 
height, and gender 
(systolic and/or 
diastolic)
≥95th percentile 
adjusted for age, 
height, and gender 
(systolic and/or 
diastolic)
Life-threatening 
consequences (eg,
malignant hypertension) 
OR Hospitalization 
indicated (other than 
emergency room visit)
Hypotension
NA
Symptomatic, 
corrected with oral 
fluid replacement
Symptomatic, IV fluids 
indicated
Shock requiring use of 
vasopressors or 
mechanical assistance to 
maintain blood pressure
Pericardial effusion
Asymptomatic, small 
effusion requiring no 
intervention
Asymptomatic, 
moderate or larger 
effusion requiring no 
intervention
Effusion with non-life 
threatening physiologic 
consequences OR 
Effusion with non-
urgent intervention 
indicated
Life-threatening 
consequences (eg,
tamponade) OR Urgent 
intervention indicated
Prolonged PR interval
Adult >16 years
PR interval 
0.21 – 0.25 sec
PR interval
>0.25 sec
Type II 2nd degree AV 
block OR Ventricular 
pause >3.0 sec
Complete AV block 
Pediatric ≤16 years
1st degree AV block
(PR >normal for age 
and rate)
Type I 2nd degree AV 
block 
Type II 2nd degree AV 
block 
Complete AV block
Prolonged QTcn
Adult >16 years
Asymptomatic, QTc 
interval 0.45 – 0.47 
sec OR Increase 
interval <0.03 sec 
above baseline
Asymptomatic, QTc 
interval 0.48 – 0.49 
sec OR Increase in 
interval 0.03 – 0.05 
sec above baseline
Asymptomatic, QTc 
interval 0.50 sec OR 
Increase in interval 
0.06 sec above 
baseline
Life-threatening 
consequences, eg, 
Torsade de pointes or 
other associated serious 
ventricular dysrhythmia
                                                
n According to Bazett's or Fridericia's formula. In the event that the value is reported by both methods, the longer of 
the 2 values will be considered for the exclusion criterion.
NCT02315703


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
100
Approved, Date: 21 December 2016
PARAMETER
GRADE 1
MILD
GRADE 2
MODERATE
GRADE 3
SEVERE
GRADE 4
POTENTIALLY
LIFE-THREATENING
Pediatric ≤16 years
Asymptomatic, QTc 
interval 0.450 –
0.464 sec 
Asymptomatic, QTc 
interval 0.465 –
0.479 sec 
Asymptomatic, QTc 
interval 0.480 sec 
Life-threatening 
consequences, eg, 
Torsade de pointes or 
other associated serious 
ventricular dysrhythmia
Thrombosis/
embolism
NA
Deep vein thrombosis 
AND No intervention 
indicated (eg, 
anticoagulation, lysis 
filter, invasive 
procedure) 
Deep vein thrombosis 
AND Intervention 
indicated (eg, 
anticoagulation, lysis 
filter, invasive 
procedure) 
Embolic event (eg, 
pulmonary embolism, life-
threatening thrombus) 
Vasovagal episode 
(associated with a 
procedure of any kind)
Present without loss 
of consciousness 
Present with transient 
loss of consciousness
NA 
NA
Ventricular 
dysfunction 
(congestive heart 
failure)
NA
Asymptomatic 
diagnostic finding 
AND intervention 
indicated
New onset with 
symptoms OR 
Worsening 
symptomatic 
congestive heart failure
Life-threatening 
congestive heart failure
GASTROINTESTINAL
Anorexia
Loss of appetite 
without decreased 
oral intake
Loss of appetite 
associated with 
decreased oral intake 
without significant 
weight loss
Loss of appetite 
associated with 
significant weight loss
Life-threatening 
consequences OR 
Aggressive intervention 
indicated [eg, tube 
feeding or total parenteral 
nutrition (TPN)]
Comment: Please note that, while the grading scale provided for Unintentional Weight Loss may be used as a guideline when 
grading anorexia, this is not a requirement and should not be used as a substitute for clinical judgment. 
Ascites
Asymptomatic
Symptomatic AND 
Intervention indicated 
(eg, diuretics or 
therapeutic 
paracentesis)
Symptomatic despite 
intervention
Life-threatening 
consequences
Cholecystitis
NA
Symptomatic AND 
Medical intervention 
indicated
Radiologic, endoscopic, 
or operative 
intervention indicated
Life-threatening 
consequences (eg, 
sepsis or perforation) 
Constipation 
NA
Persistent 
constipation requiring 
regular use of dietary 
modifications, 
laxatives, or enemas 
Obstipation with 
manual evacuation 
indicated
Life-threatening 
consequences (eg,
obstruction)
Diarrhea
Adult and Pediatric 
1 year
Transient or 
intermittent episodes 
of unformed stools 
OR Increase of ≤3 
stools over baseline 
per 24-hour period
Persistent episodes 
of unformed to watery 
stools OR Increase of 
4 – 6 stools over 
baseline per 24-hour 
period
Bloody diarrhea OR 
Increase of ≥7 stools 
per 24-hour period OR 
IV fluid replacement 
indicated
Life-threatening 
consequences (eg, 
hypotensive shock)
NCT02315703


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
101
Approved, Date: 21 December 2016
PARAMETER
GRADE 1
MILD
GRADE 2
MODERATE
GRADE 3
SEVERE
GRADE 4
POTENTIALLY
LIFE-THREATENING
Pediatric <1 year
Liquid stools (more 
unformed than usual) 
but usual number of 
stools
Liquid stools with 
increased number of 
stools OR Mild 
dehydration
Liquid stools with 
moderate dehydration
Liquid stools resulting in 
severe dehydration with 
aggressive rehydration 
indicated OR 
Hypotensive shock
Dysphagia-
Odynophagia 
Symptomatic but able 
to eat usual diet
Symptoms causing 
altered dietary intake 
without medical 
intervention indicated
Symptoms causing 
severely altered dietary 
intake with medical 
intervention indicated
Life-threatening reduction 
in oral intake
Mucositis/stomatitis 
(clinical exam)
Indicate site (eg, 
larynx, oral)
See Genitourinary for 
Vulvovaginitis 
See also Dysphagia-
Odynophagia and 
Proctitis
Erythema of the 
mucosa
Patchy 
pseudomembranes or 
ulcerations 
Confluent 
pseudomembranes or 
ulcerations OR 
Mucosal bleeding with 
minor trauma
Tissue necrosis OR 
Diffuse spontaneous 
mucosal bleeding OR 
Life-threatening 
consequences (eg, 
aspiration, choking)
Nausea 
Transient (<24 hours) 
or intermittent nausea 
with no or minimal 
interference with oral 
intake
Persistent nausea 
resulting in decreased 
oral intake for 24 – 48 
hours
Persistent nausea 
resulting in minimal oral 
intake for >48 hours 
OR Aggressive 
rehydration indicated 
(eg, IV fluids)
Life-threatening 
consequences (eg, 
hypotensive shock)
Pancreatitis
NA
Symptomatic AND 
Hospitalization not 
indicated (other than 
emergency room 
visit)
Symptomatic AND 
Hospitalization 
indicated (other than 
emergency room visit)
Life-threatening 
consequences (eg, 
circulatory failure, 
hemorrhage, sepsis)
Proctitis (functional-
symptomatic)
Also see 
Mucositis/stomatitis 
for clinical exam
Rectal discomfort 
AND No intervention 
indicated
Symptoms causing 
greater than minimal 
interference with 
usual social & 
functional activities 
OR Medical 
intervention indicated 
Symptoms causing 
inability to perform 
usual social & 
functional activities OR 
Operative intervention 
indicated 
Life-threatening 
consequences (eg,
perforation)
Vomiting
Transient or 
intermittent vomiting 
with no or minimal 
interference with oral 
intake
Frequent episodes of 
vomiting with no or 
mild dehydration
Persistent vomiting 
resulting in orthostatic 
hypotension OR 
Aggressive rehydration 
indicated (eg, IV fluids)
Life-threatening 
consequences (eg, 
hypotensive shock)
NEUROLOGIC
Alteration in 
personality-behavior 
or in mood (eg, 
agitation, anxiety, 
depression, mania, 
psychosis)
Alteration causing no 
or minimal 
interference with 
usual social & 
functional activities 
Alteration causing 
greater than minimal 
interference with 
usual social & 
functional activities 
Alteration causing 
inability to perform 
usual social & 
functional activities 
Behavior potentially 
harmful to self or others 
(eg, suicidal and 
homicidal ideation or 
attempt, acute psychosis) 
OR Causing inability to 
perform basic self-care 
functions 
NCT02315703


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
102
Approved, Date: 21 December 2016
PARAMETER
GRADE 1
MILD
GRADE 2
MODERATE
GRADE 3
SEVERE
GRADE 4
POTENTIALLY
LIFE-THREATENING
Altered Mental Status 
For Dementia, see 
Cognitive and 
behavioral/attentional 
disturbance (including 
dementia and 
attention deficit 
disorder)
Changes causing no 
or minimal 
interference with 
usual social & 
functional activities
Mild lethargy or 
somnolence causing 
greater than minimal 
interference with 
usual social & 
functional activities
Confusion, memory 
impairment, lethargy, or 
somnolence causing 
inability to perform 
usual social & 
functional activities
Delirium OR obtundation, 
OR coma
Ataxia 
Asymptomatic ataxia 
detectable on exam 
OR Minimal ataxia 
causing no or minimal 
interference with 
usual social & 
functional activities
Symptomatic ataxia 
causing greater than 
minimal interference 
with usual social & 
functional activities
Symptomatic ataxia
causing inability to 
perform usual social & 
functional activities 
Disabling ataxia causing 
inability to perform basic 
self-care functions
Cognitive and 
behavioral/attentional 
disturbance (including 
dementia and 
attention deficit 
disorder) 
Disability causing no 
or minimal 
interference with 
usual social & 
functional activities 
OR Specialized 
resources not 
indicated
Disability causing 
greater than minimal 
interference with 
usual social & 
functional activities 
OR Specialized 
resources on part-
time basis indicated
Disability causing 
inability to perform 
usual social & 
functional activities OR 
Specialized resources 
on a full-time basis 
indicated
Disability causing inability 
to perform basic self-care 
functions OR 
Institutionalization 
indicated
CNS ischemia
(acute)
NA
NA
Transient ischemic 
attack
Cerebral vascular 
accident (CVA, stroke) 
with neurological deficit 
Developmental delay 
– Pediatric 16 
years
Mild developmental 
delay, either motor or 
cognitive, as 
determined by 
comparison with a 
developmental 
screening tool 
appropriate for the 
setting 
Moderate 
developmental delay, 
either motor or 
cognitive, as 
determined by 
comparison with a 
developmental 
screening tool 
appropriate for the 
setting 
Severe developmental 
delay, either motor or 
cognitive, as 
determined by 
comparison with a 
developmental 
screening tool 
appropriate for the 
setting 
Developmental 
regression, either motor 
or cognitive, as 
determined by 
comparison with a 
developmental screening 
tool appropriate for the 
setting
Headache 
Symptoms causing
no or minimal 
interference with 
usual social & 
functional activities
Symptoms causing 
greater than minimal 
interference with 
usual social & 
functional activities
Symptoms causing 
inability to perform 
usual social & 
functional activities
Symptoms causing 
inability to perform basic 
self-care functions OR 
Hospitalization indicated 
(other than emergency 
room visit) OR Headache 
with significant 
impairment of alertness 
or other neurologic 
function 
Insomnia
NA
Difficulty sleeping 
causing greater than 
minimal interference 
with usual social & 
functional activities
Difficulty sleeping 
causing inability to 
perform usual social & 
functional activities
Disabling insomnia 
causing inability to 
perform basic self-care 
functions
NCT02315703


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
103
Approved, Date: 21 December 2016
PARAMETER
GRADE 1
MILD
GRADE 2
MODERATE
GRADE 3
SEVERE
GRADE 4
POTENTIALLY
LIFE-THREATENING
Neuromuscular 
weakness 
(including myopathy & 
neuropathy) 
Asymptomatic with 
decreased strength 
on exam OR Minimal 
muscle weakness 
causing no or minimal 
interference with 
usual social & 
functional activities
Muscle weakness 
causing greater than 
minimal interference 
with usual social & 
functional activities
Muscle weakness 
causing inability to 
perform usual social & 
functional activities 
Disabling muscle 
weakness causing 
inability to perform basic 
self-care functions OR 
Respiratory muscle 
weakness impairing 
ventilation
Neurosensory 
alteration (including 
paresthesia and 
painful neuropathy)
Asymptomatic with 
sensory alteration on 
exam or minimal 
paresthesia causing 
no or minimal 
interference with 
usual social & 
functional activities 
Sensory alteration or 
paresthesia causing 
greater than minimal 
interference with 
usual social & 
functional activities 
Sensory alteration or 
paresthesia causing 
inability to perform 
usual social & 
functional activities
Disabling sensory 
alteration or paresthesia 
causing inability to 
perform basic self-care 
functions
Seizure: (new onset) –
Adult ≥18 years
See also Seizure: 
(known pre-existing 
seizure disorder)
NA
1 seizure 
2 – 4 seizures 
Seizures of any kind 
which are prolonged, 
repetitive (eg, status 
epilepticus), or difficult to 
control (eg, refractory 
epilepsy)
Seizure: (known pre-
existing seizure 
disorder) 
– Adult ≥18 years
For worsening of 
existing epilepsy the 
grades should be 
based on an increase 
from previous level of 
control to any of these 
levels.
NA
Increased frequency 
of pre-existing 
seizures (non-
repetitive) without 
change in seizure 
character OR 
Infrequent break-
through seizures 
while on stable 
medication in a 
previously controlled 
seizure disorder
Change in seizure 
character from baseline 
either in duration or 
quality (eg, severity or 
focality) 
Seizures of any kind 
which are prolonged, 
repetitive (eg, status 
epilepticus), or difficult to 
control (eg, refractory 
epilepsy)
Seizure 
– Pediatric <18 years
Seizure, generalized 
onset with or without 
secondary 
generalization, lasting 
<5 minutes with <24 
hours post-ictal state
Seizure, generalized 
onset with or without 
secondary 
generalization, lasting 
5 – 20 minutes with 
<24 hours post-ictal 
state
Seizure, generalized 
onset with or without 
secondary 
generalization, lasting 
>20 minutes 
Seizure, generalized
onset with or without 
secondary generalization, 
requiring intubation and 
sedation
Syncope (not 
associated with a 
procedure)
NA
Present
NA
NA
Vertigo
Vertigo causing no or 
minimal interference 
with usual social & 
functional activities
Vertigo causing 
greater than minimal 
interference with 
usual social & 
functional activities 
Vertigo causing inability 
to perform usual social 
& functional activities
Disabling vertigo causing 
inability to perform basic 
self-care functions
NCT02315703


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
104
Approved, Date: 21 December 2016
PARAMETER
GRADE 1
MILD
GRADE 2
MODERATE
GRADE 3
SEVERE
GRADE 4
POTENTIALLY
LIFE-THREATENING
RESPIRATORY
Bronchospasm 
(acute)
FEV1 or peak flow 
reduced to 
70 – 80%
FEV1 or peak flow 
50 – 69%
FEV1 or peak flow 
25 – 49% 
Cyanosis OR FEV1 or 
peak flow <25% OR 
Intubation
Dyspnea or respiratory distress
Adult ≥14 years
Dyspnea on exertion 
with no or minimal 
interference with 
usual social & 
functional activities 
Dyspnea on exertion 
causing greater than 
minimal interference 
with usual social & 
functional activities 
Dyspnea at rest 
causing inability to 
perform usual social & 
functional activities 
Respiratory failure with 
ventilatory support 
indicated
Pediatric <14 years
Wheezing OR 
minimal increase in 
respiratory rate for 
age
Nasal flaring OR 
Intercostal retractions 
OR Pulse oximetry 90 
– 95%
Dyspnea at rest 
causing inability to 
perform usual social & 
functional activities OR 
Pulse oximetry <90%
Respiratory failure with 
ventilatory support 
indicated
MUSCULOSKELETAL
Arthralgia
See also Arthritis
Joint pain causing no 
or minimal 
interference with 
usual social & 
functional activities
Joint pain causing 
greater than minimal 
interference with 
usual social & 
functional activities
Joint pain causing 
inability to perform 
usual social & 
functional activities
Disabling joint pain 
causing inability to 
perform basic self-care 
functions
Arthritis
See also Arthralgia
Stiffness or joint 
swelling causing no 
or minimal 
interference with 
usual social & 
functional activities
Stiffness or joint 
swelling causing 
greater than minimal 
interference with 
usual social & 
functional activities
Stiffness or joint 
swelling causing 
inability to perform 
usual social & 
functional activities
Disabling joint stiffness or 
swelling causing inability 
to perform basic self-care 
functions 
Bone Mineral Loss
Adult ≥21 years
BMD t-score 
-2.5 to -1.0 
BMD t-score <-2.5
Pathological fracture 
(including loss of 
vertebral height)
Pathologic fracture 
causing life-threatening 
consequences 
Pediatric <21 years
BMD z-score 
-2.5 to -1.0
BMD z-score <-2.5
Pathological fracture 
(including loss of 
vertebral height)
Pathologic fracture 
causing life-threatening 
consequences 
Myalgia
(non-injection site)
Muscle pain causing 
no or minimal 
interference with 
usual social & 
functional activities
Muscle pain causing 
greater than minimal 
interference with 
usual social & 
functional activities
Muscle pain causing 
inability to perform 
usual social & 
functional activities
Disabling muscle pain 
causing inability to 
perform basic self-care 
functions
Osteonecrosis
NA
Asymptomatic with 
radiographic findings 
AND No operative 
intervention indicated
Symptomatic bone pain 
with radiographic 
findings OR Operative 
intervention indicated
Disabling bone pain with 
radiographic findings 
causing inability to 
perform basic self-care 
functions
NCT02315703


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
105
Approved, Date: 21 December 2016
PARAMETER
GRADE 1
MILD
GRADE 2
MODERATE
GRADE 3
SEVERE
GRADE 4
POTENTIALLY
LIFE-THREATENING
GENITOURINARY
Cervicitis 
(symptoms)
(For use in studies 
evaluating topical 
study agents) 
For other cervicitis 
see Infection: Infection 
(any other than HIV 
infection) 
Symptoms causing 
no or minimal 
interference with 
usual social & 
functional activities 
Symptoms causing 
greater than minimal 
interference with 
usual social & 
functional activities 
Symptoms causing 
inability to perform 
usual social & 
functional activities 
Symptoms causing 
inability to perform basic 
self-care functions 
Cervicitis 
(clinical exam)
(For use in studies 
evaluating topical 
study agents) 
For other cervicitis 
see Infection: Infection 
(any other than HIV 
infection) 
Minimal cervical 
abnormalities on 
examination 
(erythema, 
mucopurulent 
discharge, or friability) 
OR Epithelial 
disruption 
<25% of total surface
Moderate cervical 
abnormalities on 
examination 
(erythema, 
mucopurulent 
discharge, or friability) 
OR Epithelial 
disruption of 25 –
49% total surface
Severe cervical 
abnormalities on 
examination (erythema, 
mucopurulent 
discharge, or friability) 
OR Epithelial disruption 
50 – 75% total surface
Epithelial disruption 
>75% total surface
Inter-menstrual 
bleeding (IMB)
Spotting observed by 
participant OR 
Minimal blood 
observed during 
clinical or colposcopic 
examination
Inter-menstrual 
bleeding not greater 
in duration or amount 
than usual menstrual 
cycle
Inter-menstrual 
bleeding greater in 
duration or amount 
than usual menstrual 
cycle
Hemorrhage with life-
threatening hypotension 
OR Operative 
intervention indicated
Urinary tract 
obstruction (eg, stone)
NA
Signs or symptoms of 
urinary tract 
obstruction without 
hydronephrosis or 
renal dysfunction
Signs or symptoms of 
urinary tract obstruction 
with hydronephrosis or 
renal dysfunction
Obstruction causing life-
threatening 
consequences
Vulvovaginitis 
(symptoms)
(Use in studies 
evaluating topical 
study agents) 
For other 
vulvovaginitis see 
Infection: Infection 
(any other than HIV 
infection)
Symptoms causing 
no or minimal 
interference with 
usual social & 
functional activities 
Symptoms causing 
greater than minimal 
interference with 
usual social & 
functional activities 
Symptoms causing 
inability to perform 
usual social & 
functional activities 
Symptoms causing 
inability to perform basic 
self-care functions 
Vulvovaginitis 
(clinical exam)
(Use in studies 
evaluating topical 
study agents) 
For other 
vulvovaginitis see 
Infection: Infection 
(any other than HIV 
infection)
Minimal vaginal 
abnormalities on 
examination OR 
Epithelial disruption 
<25% of total surface
Moderate vaginal 
abnormalities on 
examination OR 
Epithelial disruption of 
25 - 49% total surface
Severe vaginal 
abnormalities on 
examination OR 
Epithelial disruption 
50 - 75% total surface
Vaginal perforation OR 
Epithelial disruption
>75% total surface
OCULAR/VISUAL
NCT02315703


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
106
Approved, Date: 21 December 2016
PARAMETER
GRADE 1
MILD
GRADE 2
MODERATE
GRADE 3
SEVERE
GRADE 4
POTENTIALLY
LIFE-THREATENING
Uveitis
Asymptomatic but 
detectable on exam
Symptomatic anterior 
uveitis OR Medical 
intervention indicated
Posterior or pan-uveitis 
OR Operative 
intervention indicated
Disabling visual loss in 
affected eye(s) 
Visual changes (from 
baseline)
Visual changes 
causing no or minimal 
interference with 
usual social & 
functional activities
Visual changes 
causing greater than 
minimal interference 
with usual social & 
functional activities
Visual changes causing 
inability to perform 
usual social & 
functional activities
Disabling visual loss in 
affected eye(s)
ENDOCRINE/METABOLIC
Abnormal fat 
accumulation
(eg, back of neck, 
breasts, abdomen)
Detectable by study 
participant (or by 
caregiver for young 
children and disabled 
adults)
Detectable on 
physical exam by 
health care provider
Disfiguring OR Obvious 
changes on casual 
visual inspection
NA
Diabetes mellitus
NA
New onset without 
need to initiate 
medication OR 
Modification of 
current medications 
to regain glucose 
control
New onset with 
initiation of medication 
indicated OR Diabetes 
uncontrolled despite 
treatment modification
Life-threatening 
consequences (eg, 
ketoacidosis, 
hyperosmolar non-ketotic 
coma) 
Gynecomastia
Detectable by study 
participant or 
caregiver (for young 
children and disabled 
adults)
Detectable on 
physical exam by 
health care provider
Disfiguring OR Obvious 
on casual visual 
inspection
NA
Hyperthyroidism 
Asymptomatic
Symptomatic causing 
greater than minimal 
interference with 
usual social & 
functional activities 
OR Thyroid 
suppression therapy 
indicated
Symptoms causing 
inability to perform 
usual social & 
functional activities OR 
Uncontrolled despite 
treatment modification 
Life-threatening 
consequences (eg, 
thyroid storm)
Hypothyroidism
Asymptomatic
Symptomatic causing 
greater than minimal 
interference with 
usual social & 
functional activities 
OR Thyroid 
replacement therapy 
indicated
Symptoms causing 
inability to perform 
usual social & 
functional activities OR 
Uncontrolled despite 
treatment modification 
Life-threatening 
consequences (eg,
myxedema coma)
Lipoatrophy
(eg, fat loss from the 
face, extremities, 
buttocks)
Detectable by study 
participant (or by 
caregiver for young 
children and disabled 
adults)
Detectable on 
physical exam by 
health care provider
Disfiguring OR Obvious 
on casual visual 
inspection
NA
NCT02315703


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
107
Approved, Date: 21 December 2016
LABORATORY
PARAMETER
GRADE 1
MILD
GRADE 2
MODERATE
GRADE 3
SEVERE
GRADE 4
POTENTIALLY
LIFE-THREATENING
HEMATOLOGY
Standard International Units are listed in italics
Absolute CD4+ count
– Adult and Pediatric 
>13 years
(HIV NEGATIVE ONLY)
300 – 400/mm3
300 – 400/µL
200 – 299/mm3
200 – 299/µL
100 – 199/mm3
100 – 199/µL
<100/mm3
<100/µL
Absolute lymphocyte 
count 
– Adult and Pediatric
>13 years
(HIV NEGATIVE ONLY)
600 – 650/mm3
0.600 x 109 –
0.650 x 109/L
500 – 599/mm3
0.500 x 109 –
0.599 x 109/L
350 – 499/mm3
0.350 x 109 –
0.499 x 109/L
<350/mm3
<0.350 x 109/L
Comment: Values in children ≤13 years are not given for the two parameters above because the absolute counts are variable.
Absolute neutrophil count (ANC) 
Adult and Pediatric, 
>7 days
1,000 – 1,300/mm3
1.000 x 109 –
1.300 x 109/L
750 – 999/mm3
0.750 x 109 –
0.999 x 109/L
500 – 749/mm3
0.500 x 109 –
0.749 x 109/L 
<500/mm3
<0.500 x 109/L
Infant†, 2 – 7 days
1,250 – 1,500/mm3
1.250 x 109 –
1.500 x 109/L
1,000 – 1,249/mm3
1.000 x 109 –
1.249 x 109/L
750 – 999/mm3
0.750 x 109 –
0.999 x 109/L
<750/mm3
<0.750 x 109/L
Infant†, ≤1 day
4,000 – 5,000/mm3
4.000 x 109 –
5.000 x 109/L
3,000 – 3,999/mm3
3.000 x 109 –
3.999 x 109/L
1,500 – 2,999/mm3
1.500 x 109 –
2.999 x 109/L
<1,500/mm3
<1.500 x 109/L
Comment: Parameter changed from “Infant, <1 day” to “Infant, ≤1 day”
Fibrinogen, decreased
100 – 200 mg/dL
1.00 – 2.00 g/L
OR
0.75 – 0.99 x LLN
75 – 99 mg/dL
0.75 – 0.99 g/L
OR
0.50 – 0.74 x LLN
50 – 74 mg/dL
0.50 – 0.74 g/L
OR
0.25 – 0.49 x LLN
<50 mg/dL 
<0.50 g/L
OR
<0.25 x LLN
OR 
Associated with gross 
bleeding 
Hemoglobin (Hgb)
Comment: The Hgb values in mmol/L have changed because the conversion factor used to convert g/dL to mmol/L has been 
changed from 0.155 to 0.6206 (the most commonly used conversion factor). For grading Hgb results obtained by an analytic 
method with a conversion factor other than 0.6206, the result must be converted to g/dL using the appropriate conversion factor 
for that lab.
Adult and Pediatric
57 days
(HIV POSITIVE ONLY)
8.5 – 10.0 g/dL
5.24 – 6.23 mmol/L
7.5 – 8.4 g/dL
4.62–5.23 mmol/L
6.50 – 7.4 g/dL
4.03–4.61 mmol/L
<6.5 g/dL
<4.03 mmol/L
Adult and Pediatric 
57 days 
(HIV NEGATIVE ONLY) 
10.0 – 10.9 g/dL
6.18 – 6.79 mmol/L
OR
Any decrease 
2.5 – 3.4 g/dL
1.58 – 2.13 mmol/L
9.0 – 9.9 g/dL
5.55 - 6.17 mmol/L
OR
Any decrease 
3.5 – 4.4 g/dL
2.14 – 2.78 mmol/L
7.0 – 8.9 g/dL
4.34 - 5.54 mmol/L
OR
Any decrease 
4.5 g/dL
>2.79 mmol/L
<7.0 g/dL
<4.34 mmol/L
Comment: The decrease is a decrease from baseline
Infant†, 36 – 56 days
(HIV POSITIVE OR
NEGATIVE)
8.5 – 9.4 g/dL
5.24 – 5.86 mmol/L
7.0 – 8.4 g/dL
4.31 – 5.23 mmol/L
6.0 – 6.9 g/dL
3.72 – 4.30 mmol/L
<6.00 g/dL
<3.72 mmol/L
NCT02315703


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
108
Approved, Date: 21 December 2016
LABORATORY
PARAMETER
GRADE 1
MILD
GRADE 2
MODERATE
GRADE 3
SEVERE
GRADE 4
POTENTIALLY
LIFE-THREATENING
Infant†, 22 – 35 days
(HIV POSITIVE OR
NEGATIVE)
9.5 – 10.5 g/dL
5.87 - 6.54 mmol/L
8.0 – 9.4 g/dL
4.93 – 5.86 mmol/L
7.0 – 7.9 g/dL
4.34 – 4.92 mmol/L
<7.00 g/dL
<4.34 mmol/L
Infant†, ≤21 days
(HIV POSITIVE OR
NEGATIVE)
12.0 – 13.0 g/dL
7.42 – 8.09 mmol/L
10.0 – 11.9 g/dL
6.18 – 7.41 mmol/L
9.0 – 9.9 g/dL
5.59- 6.17 mmol/L
<9.0 g/dL
<5.59 mmol/L
Correction: Parameter changed from “Infant <21 days” to “Infant ≤21 days”
International Normalized 
Ratio of prothrombin time 
(INR)
1.1 – 1.5 x ULN
1.6 – 2.0 x ULN
2.1 – 3.0 x ULN
>3.0 x ULN
Methemoglobin
5.0 – 10.0%
10.1 – 15.0%
15.1 – 20.0%
>20.0%
Prothrombin Time (PT)
1.1 – 1.25 x ULN
1.26 – 1.50 x ULN
1.51 – 3.00 x ULN
>3.00 x ULN
Partial Thromboplastin 
Time (PTT)
1.1 – 1.66 x ULN
1.67 – 2.33 x ULN
2.34 – 3.00 x ULN
>3.00 x ULN
Platelets, decreased
100,000 –
124,999/mm3
100.000 x 109 –
124.999 x 109/L
50,000 –
99,999/mm3
50.000 x 109 –
99.999 x 109/L
25,000 –
49,999/mm3
25.000 x 109 –
49.999 x 109/L
<25,000/mm3
<25.000 x 109/L
WBC, decreased
2,000 – 2,500/mm3
2.000 x 109 –
2.500 x 109/L
1,500 – 1,999/mm3
1.500 x 109 –
1.999 x 109/L
1,000 – 1,499/mm3
1.000 x 109 –
1.499 x 109/L
<1,000/mm3
<1.000 x 109/L
NCT02315703


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
109
Approved, Date: 21 December 2016
CHEMISTRIES
Standard International Units are listed in italics
Acidosis
NA
pH <normal, but 7.3
pH <7.3 without life-
threatening 
consequences
pH <7.3 with life-
threatening 
consequences
Albumin, serum, low
3.0 g/dL – <LLN
30 g/L – <LLN
2.0 – 2.9 g/dL
20 – 29 g/L
<2.0 g/dL
<20 g/L
NA
Alkaline Phosphatase
1.25 – 2.5 x ULN†
2.6 – 5.0 x ULN†
5.1 – 10.0 x ULN†
>10.0 x ULN†
Alkalosis
NA
pH >normal, but 7.5
pH >7.5 without life-
threatening 
consequences
pH >7.5 with life-
threatening 
consequences 
ALT (SGPT)
1.25 – 2.5 x ULN
2.6 – 5.0 x ULN
5.1 – 10.0 x ULN
>10.0 x ULN
AST (SGOT)
1.25 – 2.5 x ULN
2.6 – 5.0 x ULN
5.1 – 10.0 x ULN
>10.0 x ULN
Bicarbonate, serum, low
16.0 mEq/L – <LLN
16.0 mmol/L – <LLN
11.0 – 15.9 mEq/L
11.0 – 15.9 mmol/L
8.0 – 10.9 mEq/L
8.0 – 10.9 mmol/L
<8.0 mEq/L
<8.0 mmol/L
Comment: Some laboratories will report this value as Bicarbonate (HCO3) and others as Total Carbon Dioxide (CO2). These 
are the same tests; values should be graded according to the ranges for Bicarbonate as listed above.
Bilirubin (Total)
Adult and Pediatric >14 
days
1.1 – 1.5 x ULN
1.6 – 2.5 x ULN
2.6 – 5.0 x ULN
>5.0 x ULN
Infant†, ≤14 days
(non-hemolytic)
NA
20.0 – 25.0 mg/dL
342 – 428 µmol/L
25.1 – 30.0 mg/dL
429 – 513 µmol/L
>30.0 mg/dL
>513.0 µmol/L
Infant†, ≤14 days
(hemolytic)
NA
NA
20.0 – 25.0 mg/dL
342 – 428 µmol/L
>25.0 mg/dL
>428 µmol/L
Calcium, serum, high
Adult and Pediatric 
≥7 days
10.6 – 11.5 mg/dL
2.65 – 2.88 mmol/L
11.6 – 12.5 mg/dL
2.89 – 3.13 mmol/L
12.6 – 13.5 mg/dL
3.14 – 3.38 mmol/L
>13.5 mg/dL
>3.38 mmol/L
Infant†, <7 days
11.5 – 12.4 mg/dL
2.88 – 3.10 mmol/L
12.5 – 12.9 mg/dL
3.11 – 3.23 mmol/L
13.0 – 13.5 mg/dL
3.245 – 3.38 mmol/L
>13.5 mg/dL
>3.38 mmol/L
Calcium, serum, low 
Adult and Pediatric 
≥7 days
7.8 – 8.4 mg/dL
1.95 – 2.10 mmol/L
7.0 – 7.7 mg/dL
1.75 – 1.94 mmol/L
6.1 – 6.9 mg/dL
1.53 – 1.74 mmol/L
<6.1 mg/dL
<1.53 mmol/L
Infant†, <7 days
6.5 – 7.5 mg/dL
1.63 – 1.88 mmol/L
6.0 – 6.4 mg/dL
1.50 – 1.62 mmol/L
5.50 – 5.90 mg/dL
1.38 – 1.51 mmol/L
<5.50 mg/dL
<1.38 mmol/L
Comment: Do not adjust Calcium, serum, low or Calcium, serum, high for albumin
Cardiac troponin I (cTnI)
NA
NA
NA
Levels consistent 
with myocardial 
infarction or unstable 
angina as defined by 
the manufacturer
Cardiac troponin T (cTnT)
NA
NA
NA
0.20 ng/mL
OR
Levels consistent 
with myocardial 
infarction or unstable 
angina as defined by 
the manufacturer
NCT02315703


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
110
Approved, Date: 21 December 2016
CHEMISTRIES
Standard International Units are listed in italics
Cholesterol (fasting)
Adult ≥18 years
200 – 239 mg/dL
5.18 – 6.19 mmol/L
240 – 300 mg/dL
6.20 – 7.77 mmol/L
>300 mg/dL
>7.77 mmol/L
NA
Pediatric <18 years
170 – 199 mg/dL
4.40 – 5.15 mmol/L
200 – 300 mg/dL
5.16 – 7.77 mmol/L
>300 mg/dL
>7.77 mmol/L
NA
Creatine Kinase
3.0 – 5.9 x ULN†
6.0 – 9.9 x ULN†
10.0 – 19.9 x ULN†
20.0 x ULN†
Creatinine
1.1 – 1.3 x ULN†
1.4 – 1.8 x ULN†
1.9 – 3.4 x ULN†
3.5 x ULN†
Glucose, serum, high 
Nonfasting
116 – 160 mg/dL
6.44 – 8.88 mmol/L
161 – 250 mg/dL
8.89 – 13.88 mmol/L
251 – 500 mg/dL
13.89 – 27.75 mmol/L
>500 mg/dL
>27.75 mmol/L
Fasting
110 – 125 mg/dL
6.11 – 6.94 mmol/L
126 – 250 mg/dL
6.95 – 13.88 mmol/L
251 – 500 mg/dL
13.89 – 27.75 mmol/L
>500 mg/dL
>27.75 mmol/L
Glucose, serum, low
Adult and Pediatric 
≥1 month
55 – 64 mg/dL
3.05 – 3.55 mmol/L
40 – 54 mg/dL
2.22 – 3.06 mmol/L
30 – 39 mg/dL
1.67 – 2.23 mmol/L
<30 mg/dL
<1.67 mmol/L
Infant†, <1 month
50 – 54 mg/dL
2.78 – 3.00 mmol/L
40 – 49 mg/dL
2.22 – 2.77 mmol/L
30 – 39 mg/dL
1.67 – 2.21 mmol/L
<30 mg/dL
<1.67 mmol/L
Lactate
ULN - <2.0 x ULN 
without acidosis
2.0 x ULN without 
acidosis
Increased lactate with 
pH <7.3 without life-
threatening 
consequences 
Increased lactate 
with pH <7.3 with 
life-threatening 
consequences 
Comment: Added ULN to Grade 1 parameter 
LDL cholesterol (fasting)
Adult ≥18 years
130 – 159 mg/dL
3.37 – 4.12 mmol/L
160 – 190 mg/dL
4.13 – 4.90 mmol/L
190 mg/dL
4.91 mmol/L
NA
Pediatric >2 - <18 years
110 – 129 mg/dL 
2.85 – 3.34 mmol/L
130 – 189 mg/dL
3.35 – 4.90 mmol/L
≥190 mg/dL
≥4.91 mmol/L
NA
Lipase
1.1 – 1.5 x ULN
1.6 – 3.0 x ULN
3.1 – 5.0 x ULN
>5.0 x ULN
Magnesium, serum, low
1.2 – 1.4 mEq/L
0.60 – 0.70 mmol/L
0.9 – 1.1 mEq/L
0.45 – 0.59 mmol/L
0.6 – 0.8 mEq/L
0.30 – 0.44 mmol/L
<0.60 mEq/L
<0.30 mmol/L
Pancreatic amylase
1.1 – 1.5 x ULN
1.6 – 2.0 x ULN
2.1 – 5.0 x ULN
>5.0 x ULN
Phosphate, serum, low
Adult and Pediatric 
>14 years
2.5 mg/dL – <LLN
0.81 mmol/L – <LLN
2.0 – 2.4 mg/dL
0.65 – 0.80 mmol/L
1.0 – 1.9 mg/dL
0.32 – 0.64 mmol/L
<1.00 mg/dL
<0.32 mmol/L
Pediatric 1 year – 14 
years 
3.0 – 3.5 mg/dL
0.97 – 1.13 mmol/L
2.5 – 2.9 mg/dL
0.81 – 0.96 mmol/L
1.5 – 2.4 mg/dL
0.48 – 0.80 mmol/L
<1.50 mg/dL
<0.48 mmol/L
Pediatric <1 year
3.5 – 4.5 mg/dL
1.13 – 1.45 mmol/L
2.5 – 3.4 mg/dL
0.81 – 1.12 mmol/L
1.5 – 2.4 mg/dL
0.48 – 0.80 mmol/L
<1.50 mg/dL
<0.48 mmol/L
Potassium, serum, high
5.6 – 6.0 mEq/L
5.6 – 6.0 mmol/L
6.1 – 6.5 mEq/L
6.1 – 6.5 mmol/L
6.6 – 7.0 mEq/L
6.6 – 7.0 mmol/L
>7.0 mEq/L
>7.0 mmol/L
Potassium, serum, low
3.0 – 3.4 mEq/L
3.0 – 3.4 mmol/L
2.5 – 2.9 mEq/L
2.5 – 2.9 mmol/L
2.0 – 2.4 mEq/L
2.0 – 2.4 mmol/L
<2.0 mEq/L
<2.0 mmol/L
Sodium, serum, high
146 – 150 mEq/L
146 – 150 mmol/L
151 – 154 mEq/L
151 – 154 mmol/L
155 – 159 mEq/L
155 – 159 mmol/L
160 mEq/L
160 mmol/L
NCT02315703


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
111
Approved, Date: 21 December 2016
CHEMISTRIES
Standard International Units are listed in italics
Sodium, serum, low
130 – 135 mEq/L
130 – 135 mmol/L
125 – 129 mEq/L
125 – 129 mmol/L
121 – 124 mEq/L
121 – 124 mmol/L
120 mEq/L
120 mmol/L
Triglycerides (fasting)
NA
500 – 750 mg/dL
5.65 – 8.48 mmol/L
751 – 1,200 mg/dL
8.49 – 13.56 mmol/L
>1,200 mg/dL
>13.56 mmol/L
Uric acid
7.5 – 10.0 mg/dL
0.45 – 0.59 mmol/L
10.1 – 12.0 mg/dL
0.60 – 0.71 mmol/L
12.1 – 15.0 mg/dL
0.72 – 0.89 mmol/L
>15.0 mg/dL
>0.89 mmol/L
URINALYSIS
Standard International Units are listed in italics
Hematuria (microscopic)
6 – 10 RBC/HPF
>10 RBC/HPF
Gross, with or without 
clots OR with RBC 
casts
Transfusion indicated
Proteinuria, random 
collection
1 +
2 – 3 +
4 +
NA
Proteinuria, 24 hour collection
Adult and Pediatric 
10 years
200 – 999 mg/24 h
0.200 – 0.999 g/d
1,000 – 1,999 mg/24 
h
1.000 – 1.999 g/d
2,000 – 3,500 mg/24 h
2.000 – 3.500 g/d
>3,500 mg/24 h
>3.500 g/d
Pediatric >3 mo -
<10 years
201 – 499 mg/m2/24 
h
0.201 – 0.499 g/d
500 – 799 mg/m2/24 h
0.500 – 0.799 g/d
800 – 1,000 
mg/m2/24 h
0.800 – 1.000 g/d
>1,000 mg/ m2/24 h
>1.000 g/d
NCT02315703


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
112
Approved, Date: 21 December 2016
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 in the US and Switzerland. 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
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 
NCT02315703


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
113
Approved, Date: 21 December 2016
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).
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
NCT02315703




JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
115
Approved, Date: 21 December 2016
Attachment 4:
Social Impact Questionnaire
Vaccine Research Center (VRC) Social Impact Case Report Form 19
NCT02315703


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004 Amendment 5
116
Approved, Date: 21 December 2016
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 drug, 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 US (an affiliate of Janssen Vaccines & Prevention
B.V.)
Signature:
[electronic signature appended at the end of the protocol]
Date:
(Day Month Year)
Note: If the address or telephone number of the investigator changes during the course of the study, written 
notification will be provided by the investigator to the sponsor, and a protocol amendment will not be required.
LAST PAGE
NCT02315703
PPD


 
 
SIGNATURES 
 
 
 
 
Signed by  
Date  
 
Justification  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
21Dec2016, 17:50:49 PM, UTC
Document Approval
NCT02315703
PPD


CONFIDENTIAL – FOIA Exemptions Apply in U.S.
1
Status: Approved,  Date: 16 July 2020
Janssen Vaccines & Prevention B.V. *
Clinical Protocol
COVID-19 Appendix
Protocol Title
A Phase 1/2a Study to Evaluate the Safety/Tolerability and Immunogenicity of 
Homologous Ad26 Mosaic Vector Vaccine Regimens or Ad26 Mosaic and MVA Mosaic 
Heterologous Vector Vaccine Regimens, with High-Dose, Low-Dose or no Clade C gp140 
Protein Plus Adjuvant for HIV Prevention
Protocol HIV-V-A004 (IPCAVD009); Phase 1/2a
JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585  
*Janssen Research & Development is a global organization that operates through different legal entities in
various countries. Therefore, the legal entity acting as the sponsor for Janssen Research & Development
studies may vary, such as, but not limited to Janssen Biotech, Inc.; Janssen Products, LP; Janssen Biologics,
BV; Janssen-Cilag International NV; Janssen, Inc; Janssen Pharmaceutica NV; Janssen Sciences Ireland
UC; Janssen Biopharma Inc.; or Janssen Research & Development, LLC. The term “sponsor” is used
throughout the protocol to represent these various legal entities; the sponsor is identified on the Contact
Information page that accompanies the protocol.
United States (US) sites of this study will be conducted under US Food & Drug Administration
Investigational New Drug (IND) regulations (21 CFR Part 312).
Status:
Approved  
Date:
16 July 2020
EDMS number:
EDMS-RIM-80643, 1.0
THIS APPENDIX APPLIES TO ALL CURRENT APPROVED VERSIONS OF PROTOCOL
HIV-V-A004 (EDMS-ERI-102817395 and EDMS-ERI-100065253)
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.
NCT02315703


COVID-19 Appendix
JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
2
Status: Approved,  Date: 16 July 2020
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.a 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. Modifications made to the study conduct as a result of the 
COVID-19 pandemic will be summarized in the clinical study report.
                                                
a 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.


COVID-19 Appendix
JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Clinical Protocol HIV-V-A004
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
3
Status: Approved,  Date: 16 July 2020
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.
Study Visits and Assessments: 
!
When site visits are not possible, sites should collect the assessments via remote visits, or via 
home visits (if possible and if the participant allows and provides consent to it). The actual 
visit date and the type of visit (i.e., remote or home visit) should be captured in the eCRF 
according to the eCRF completion guidelines. 
!
Procedures that can’t be performed in case of remote visits (e.g., blood sampling for 
immunogenicity and HIV testing), should be documented as protocol deviations and labelled 
as “missed due to COVID-19”. The protocol deviations need to be captured in the source 
document.
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.



SAP_003.pdf: 
1
Approved, Date: 22 April 2022
Janssen Vaccines & Prevention B.V.
Statistical Analysis Plan
A Phase 1/2a Study to Evaluate the Safety/Tolerability and Immunogenicity of Homologous Ad26 Mosaic 
Vector Vaccine Regimens or Ad26 Mosaic and MVA Mosaic Heterologous Vector Vaccine Regimens, with 
High-Dose, Low-Dose or no Clade C gp140Protein Plus Adjuvant for HIV Prevention
Protocol HIV-V-A004 (IPCAVD009); Phase 1/2a
JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585
Status:
Approved  - V2.0
Date:
22 April 2022
Prepared by:
Janssen Infectious Diseases BVBA
Document No.:
EDMS-ERI-162126788
Compliance: The study described in this report was performed according to the principles of Good Clinical 
Practice (GCP). 
Confidentiality Statement
The information in this document contains trade secrets and commercial information that are privileged or confidential and may not be disclosed 
unless such disclosure is required by applicable law or regulations. In any event, persons to whom the information is disclosed must be informed 
that the information is privileged or confidential and may not be further disclosed by them. These restrictions on disclosure will apply equally to 
all future information supplied to you that is indicated as privileged or confidential.
NCT02315703


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585  
Statistical Analysis Plan
HIV-V-A004 (IPCAVD009)
2
Approved, Date: 22 April 2022
TABLE OF CONTENTS
AMENDMENT HISTORY ............................................................................................................................ 4
ABBREVIATIONS ........................................................................................................................................ 4
DEFINITION OF TERMS............................................................................................................................. 5
1.
INTRODUCTION ................................................................................................................................ 6
1.1.
Trial Objectives.................................................................................................................................. 6
1.2.
Trial Design ....................................................................................................................................... 6
1.3.
Statistical Hypotheses for Trial Objectives............................................................................................ 6
1.4.
Sample Size Justification..................................................................................................................... 6
1.5.
Randomization and Blinding................................................................................................................ 6
2.
GENERAL ANALYSIS DEFINITIONS ............................................................................................... 6
2.1.
Analysis Windows.............................................................................................................................. 6
2.2.
Pooling Algorithm for Analysis Centers ............................................................................................... 8
2.3.
Analysis Sets...................................................................................................................................... 8
2.3.1.
Full Analysis Set ............................................................................................................................. 8
2.3.2.
Per-Protocol Immunogenicity Analysis Set........................................................................................ 8
2.3.1.
LTE Analysis Set ............................................................................................................................ 8
2.4.
Definition of Subgroups ...................................................................................................................... 8
3.
INTERIM ANALYSIS AND DATA REVIEW COMMITTEE.............................................................. 9
4.
SUBJECT INFORMATION ................................................................................................................. 9
4.1.
Demographics and Baseline Characteristics .......................................................................................... 9
4.2.
Disposition Information ...................................................................................................................... 9
4.3.
Concomitant Medications.................................................................................................................... 9
4.4.
Exposure.......................................................................................................................................... 10
4.5.
Protocol Deviations........................................................................................................................... 10
4.6.
Medical History................................................................................................................................ 10
5.
SAFETY............................................................................................................................................. 10
5.1.
Adverse Events................................................................................................................................. 11
5.1.1.
Definitions.................................................................................................................................... 11
5.1.2.
Analysis of Adverse Events............................................................................................................ 11
5.1.3.
Period Allocation of Adverse Events............................................................................................... 12
5.1.4.
Handling of Missing Data for Adverse Events ................................................................................. 12
5.1.5.
Solicited Local (Injection Site) Reactions ........................................................................................ 12
5.1.6.
Solicited Systemic Adverse Events ................................................................................................. 13
5.2.
Clinical Laboratory Tests .................................................................................................................. 13
5.2.1.
Analysis methodology ................................................................................................................... 13
5.3.
Vital Signs and ECG......................................................................................................................... 14
5.3.1.
Definitions.................................................................................................................................... 14
5.3.2.
Analysis methodology ................................................................................................................... 14
6.
IMMUNOGENICITY......................................................................................................................... 14
6.1.
Analysis specifications...................................................................................................................... 14
6.2.
Immune Response Parameters............................................................................................................ 14
6.3.
Immune Response Analysis............................................................................................................... 14
6.4.
Handling of Missing and/or Invalid Immune Response Data................................................................. 16
6.5.
Immune response assays: details ........................................................................................................ 17
7.
VISP ................................................................................................................................................... 23


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Statistical Analysis Plan
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3
Approved, Date: 22 April 2022
8.
SOCIAL IMPACT QUESTIONNAIRE .............................................................................................. 23
APPENDIX 1: LABORATORY, VITAL SIGNS AND ECG ABNORMALITY GRADINGS ........................ 24


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Statistical Analysis Plan
HIV-V-A004 (IPCAVD009)
4
Approved, Date: 22 April 2022
AMENDMENT HISTORY
V1.0 15 May 2018
First version 
V2.0 22 April 2022
Updated version to include long term extension data up 
to week 336
ABBREVIATIONS
ADCP
antibody dependent cellular phagocytosis
AE
adverse event
ALT
alanine aminotransferase
ANC
absolute neutrophil count
AST
aspartate aminotransferase
BAMA
binding antibody multiplex assay
BIDMC
Beth Israel Deaconess Medical Center
BMI
body mass index
CRF
case report form 
CTP
clinical trial protocol
DAIDS
Division of AIDS 
DP
drug product
dTA
data transfer agreement
EDC 
electronic data capture
ELISA
enzyme-linked immunosorbent assay
ELISPOT
Enzyme-Linked ImmunoSpot
ENV
envelope
FHCRC
Fred Hutchinson Cancer Research Center
GCP
Good Clinical Practice
HD
high dose
HIV
human immunodeficiency virus
ICS
intracellular cytokine staining
IG
immunogenicity 
LD
low dose
LLOQ
lower limit of quantification
LOD
limit of detection
LTE
long term extension
SAE
serious adverse event
ULN
upper limit of normal
VISP
vaccine induced seropositivity
VISR
vaccine induced seroreactivity
VRC
Vaccine Research Center
WBC
white blood cell


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585  
Statistical Analysis Plan
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5
Approved, Date: 22 April 2022
DEFINITION OF TERMS
Randomization
1:1:1:1:1:1:1:1 ratio
Study vaccine
-
Ad26.Mos.HIV (Ad26.Mos.1.Env + Ad26.Mos1.Gag-Pol + Ad26.Mos2.Gag-Pol): Total 
dose is 5x1010 viral particles (vp) per 0.5 mL injection
-
MVA-Mosaic (MVA-Mosaic1 + MVA-Mosaic2): Total dose is 108 plaque-forming units 
(pfu) per 0.5 mL injection
-
gp140 DP: 
-
Low-dose: gp140 DP with 50 mcg total protein, mixed with aluminum phosphate 
adjuvant (0.425 mg aluminum) at the pharmacy, per 0.5 mL injection
-
High-dose: gp140 DP with 250 mcg total protein, mixed with aluminum phosphate 
adjuvant (0.425 mg aluminum) at the pharmacy, per 0.5 mL injection
-
Placebo: 0.9% saline, 0.5 mL injection
Vaccination 
compliance
Each vaccine administered (if applicable) according to planned schedule
Vaccine regimen
Group 
Planned N
Day 1, Week 12
Week 24, Week 48
1
50
Ad26.Mos.HIV
Ad26.Mos.HIV + gp140 (250mcg+adjuvant)
2
50
Ad26.Mos.HIV
Ad26.Mos.HIV + gp140 (50mcg+adjuvant)
3
50
Ad26.Mos.HIV
Ad26.Mos.HIV + Placebo
4
50
Ad26.Mos.HIV
MVA-Mosaic + gp140 (250mcg+adjuvant)
5
50
Ad26.Mos.HIV
MVA-Mosaic + gp140 (50mcg+adjuvant)
6
50
Ad26.Mos.HIV
MVA-Mosaic + Placebo
7
50
Ad26.Mos.HIV
gp140 (250mcg+adjuvant) + Placebo
8
50
Placebo
Placebo + Placebo






JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585  
Statistical Analysis Plan
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8
Approved, Date: 22 April 2022
For subjects that received a first dose, but did not receive a 2nd dose while still continuing their planned visit 
schedule, the measurements after the planned but not administered 2nd dose will not be included in graphs and tables 
showing descriptive statistics over time.  Those measurements will be shown in listings but it will be indicated that 
these are not used in the analysis.  Moreover, the vaccinations done after a missed one will be not be shifted to the 
previous one but will be considered as planned: in the example above if the 2nd is missed, the 3rd vaccination will 
still be reported as post-dose 3.
2.2.
Pooling Algorithm for Analysis Centers
Not planned, subgroups analyses by region are described in section 2.4. 
2.3.
Analysis Sets
2.3.1.
Full Analysis Set
The Full Analysis Set (FA) will consist of all subjects who were randomized and who received at least one dose of 
study vaccine. This will be the primary population for all analyses (except immunogenicity, see below) described in 
this document.
2.3.2.
Per-Protocol Immunogenicity Analysis Set
The per protocol immunogenicity (PPI) population consist of all subjects who have received at least the first three 
vaccinations, according to the protocol-specified vaccination schedule (+/- 2 weeks), have at least one measured 
post-dose blood sample collected and were not diagnosed with HIV during the study. Samples taken after Week 48 
from subjects in the PPI population who missed the 4th vaccination or did not receive the 4th vaccination in the 
protocol-specified time window (+/- 2 weeks) will be excluded from the analysis.
The analysis of the immune responses will be performed on the per protocol immunogenicity population.
2.3.1.
LTE Analysis Set
The Long Term Extension (LTE) population consists of all subjects in the Per-Protocol Immunogenicity Analysis 
Set, randomized in group 1 or 2 who had at least one visits in the long term extension part of the study. 
2.4.
Definition of Subgroups
The following subgroups will be investigated for safety (AE, Lab):
⁻
Sex (Female, Male)
⁻
Race (Caucasian, Black or African American, Asian, Othera)
⁻
Region (East Africa, South Africa, Thailand, USA)
⁻
BMI [<25; 25-<30; ≥30]
⁻
The following subgroups will be investigated for immunogenicity:
⁻
Region (East Africa, South Africa, Thailand, USA)
⁻
AD26 VNA at baseline (<LLOQ, >=LLOQ)
The following subgroups will be investigated for the social impact questionnaire:  
⁻
Region (East Africa, South Africa, Thailand, USA)
⁻
Sex (Female, Male)
                                                
a Subgroup “Other” should contain all remaining categories: Other, Multiple, American Indian or Alaska Native, etc.


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Statistical Analysis Plan
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9
Approved, Date: 22 April 2022
3.
INTERIM ANALYSIS AND DATA REVIEW COMMITTEE
A Data Monitoring Committee (DMC) was planned to specifically review the safety data at three specific time 
points to ensure safety of the subjects:
-
Review blinded safety data (2 weeks of follow up) after 30% of subjects have received their first injection 
to decide whether further dosing can continue;
-
Review unblinded safety data (2 weeks of follow up) after 10% of subjects have received their third 
injection to decide whether further dosing can continue;
-
Review unblinded safety data (2 weeks of follow up) after 30% of subjects have received their third 
injection to decide whether further dosing can continue.
These analyses are described in a separate document DMC Charter and DMC SAP. 
4.
SUBJECT INFORMATION
Subject information will be analyzed based on the FA analysis set unless otherwise specified.
Continuous variables will be summarized using the following statistics, as appropriate: number of observations, 
arithmetic mean (mean), 95% confidence interval (CI) for the mean, standard deviation (SD), standard error (SE), 
median, quartiles (Q1 and Q3), minimum and maximum. The minimum and maximum will be presented to the same 
number of decimal places as the original data. The mean and median will be rounded to one more decimal place than 
the original data, while the SD, SE and 95% CI to two more decimal places.
4.1.
Demographics and Baseline Characteristics
The following demographic and baseline characteristics will be summarized.

Sexa (Female/Male)   

Age (years)

Race

Ethnicity

Region

Country

Height (cm)

Weight (kg)

BMI (kg/m2), calculated from the recording of baseline height and weight. 
4.2.
Disposition Information
Number and percentage of subjects that were 1) screened, 2) screening failures, 3) subjects meeting eligibility 
criteria 4) randomized and vaccinated, 5) randomized not vaccinated and 6) vaccinated but not randomized will be 
tabulated. 
Number and percentage of subjects that completed and those who discontinued together with the reason(s) for 
discontinuation will be tabulated. This will be done for completion/vaccine discontinuation from further vaccination 
and from the trial at Week 96 , at the end of LTE.  Number and percentage of subjects at each planned LTE visit will 
also be tabulated.
4.3.
Concomitant Medications
The analysis of concomitant medications will be using the WHO drug dictionary as provided in the clinical 
database.
                                                
a At screening


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585  
Statistical Analysis Plan
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10
Approved, Date: 22 April 2022
Based on their start and stop date, concomitant therapies will be reported in each period during which they were 
applied.
If a concomitant therapy record misses components of its start and/or stop dates (Day and/or month and/or year): 
-
In case of partial start or stop dates, the concomitant therapy records will be allocated to periods using the 
available partial information, without imputations. If, for example, only month and year are available, these 
will be compared to the month and the year of the periods, and the concomitant therapy record will be 
allocated to the period(s) where these date parts match.  
-
In case of a completely missing start date, the concomitant therapy will be considered as having started 
before the trial. 
-
In case of a completely missing end date, the concomitant therapy will be considered as ongoing at the end 
of the trial/cut-off date.
Concomitant therapies will be tabulated. There will be special attention to Acetaminophen, NSAIDS or 
Antihistamines to identify medication that can mask local or systemic solicited events in the 8 days after the 
vaccinations and to Glucocorticosteroids for possible influence on immunogenicity results. Glucocorticosteroids will 
be flagged in the overall CM listing.After Week 96 only specific CM were to be collected (CTP Section 8) thus the 
reporting for the LTE will be limited to those as required by CTP.
4.4.
Exposure
Number and percentage of subjects by number of received vaccinations will be tabulated.
Tabulation of vaccine administered within and outside the protocol-specified time windows (-1/+3 weeks of the 
planned vaccination and additional 2 weeks) will be provided as well.
4.5.
Protocol Deviations
All major protocol deviations will be listed.
4.6.
Medical History
Medical history data will be listed.
5.
SAFETY
The safety and tolerability endpoints are:

Unsolicited AEs 28 days following each vaccination 

Solicited local and systemic AEs (reactogenicity), collected daily from day of vaccination for 7 days post-
vaccination (day of vaccination and the subsequent 7 days).
The safety and tolerability analysis will be performed on the FA set.  Specifically, the analysis for solicited adverse 
events will be done on those subjects in the FA set for whom reactogenicity assessments are available in the 
database (either via on-site assessments or via the diary pages of the CRF). 
Safety data will be tabulated per period by regimen.  Only the active periods will be shown in the tables (AE, Lab, 
VS and ECG), except for SAEs and HIV infections.  In addition, for a selection of tables (AE, Lab), tabulations per 
subject by vaccine and per dose by vaccine will be provided. During the LTE only for SAEs and HIV infections will 
be collected. 
In the ‘per subject by vaccine’ analysis, the safety will be presented per periods (post-dose 1, 2, 3, 4) by vaccine 
rather than by regimen.  A ‘post any dose’ period (= regimen phase in section 2.1) will be added, that summarizes 
the safety after all administered doses of a vaccine. The post-any-dose period allows determining how many subjects 
reported events after administration of a certain vaccine regardless the number of doses.  Each subject is counted 
only once.  In case a subject has the same event after more than one dose, it is counted only once (and in case of 
showing attributes, the worst corresponding attribute is shown) in the post-any dose period.  The denominator is the 
number of subjects that received the considered vaccine in the considered period.
In the ‘per dose by vaccine’ analysis, the safety will also be presented by vaccine.  This table allows determining the 
incidence of events per administered dose of a certain vaccine.  For example, if a subject has the same event at least 


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585  
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11
Approved, Date: 22 April 2022
once after dose 1 and at least once after dose 2 of the same vaccine, it is counted 2 times (so the numerator is the 
sum of post-dose 1, 2, 3 and 4 events in the “per subject by vaccine” table).  In case of showing attributes, the worst 
corresponding attribute of each period are shown. The denominator is the total number of doses administered of the 
considered vaccine over all subjects.
At the 3th and 4th vaccination timepoint two vaccines should be administered at two different injection sites 
(left/right deltoid).  The local solicited events should be linked to the medication injected in that specific injection 
site. However for some subjects the link between local AE and injection site might be unavailable, so the AE will be 
attributed to both medications received by the subject (e.g. if a subject receiving Ad26 + gp140 HD with AE 
“Erythema”: Erythema will be counted for Ad26 and for gp140 HD). Systemic solicited and unsolicited AE will be 
reported under both the administered medications. 
5.1.
Adverse Events
The analysis of AEs will be based on the MedDRA coded terms as provided in the clinical database. 
5.1.1.
Definitions
Emerging adverse events will be defined as any AE starting or worsening on or after the start of the first vaccination 
on Day 1.
Solicited AEs are precisely defined events (local and systemic) that subjects are specifically asked about and which 
are noted by subjects in the memory aid. Unsolicited AEs are all AEs that a subject experienced, but were not 
specifically asked about. 
Both systemic solicited and unsolicited AEs will be considered to be related to the use of the study vaccine if the 
attribution is possibly, probably or very likely. An AE will be considered not related with the use of the study 
vaccine if the attribution is not related or doubtful. 
Relationship of all AEs (systemic solicited and unsolicited) to the study vaccine will be assessed by the investigator. 
Local solicited AEs will always be considered as related to the injection.
The severity of the AEs will be classified as Mild, Moderate, Severe, Life-threatening or Fatal. 
The grading of the adverse events will occur according to the DAIDS grading list (see CTP appendix 1).
Period allocation of AEs is defined in Section 5.1.3.
5.1.2.
Analysis of Adverse Events
AEs (unsolicited and solicited AEs) will be tabulated by presenting the number and percentage of subjects having at 
least one of the observed AEs. 
The unsolicited AEs will be summarized by System Organ Class and Preferred Term. The solicited AEs will be 
summarized by class (local, systemic) and solicited term.  For solicited as well as unsolicited AEs, tables focusing 
on severity, relatedness and both grade 3 severity and relatedness to vaccine will be created.  SAEs, AEs with fatal 
outcome and AEs leading to permanent stop will also be tabulated.  Separate summary tables for the solicited and
the unsolicited events will be produced. 
Events of interest (confirmed HIV infection) will be tabulated.
For the solicited local and systemic AEs, the duration and time to first onset of the events may also be summarized. 
If a subject experiences more than one occurrence of a solicited event, the maximum duration of the events will be 
used.  The time to first onset is defined as (date of first onset – reference date + 1). The reference date is the date of 
the respective vaccination.
AEs summary tables for solicited and unsolicited AEs, tabulation of AEs by worst severity for the solicited AEs and 
overall incidence tabulation will be provided by subgroups (section 2.4) per period by regimen. 


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5.1.3.
Period Allocation of Adverse Events
The analysis of AEs consists of two steps: first, AEs are allocated to periods; second, overlapping/consecutive AEs 
within a period are combined. 
Unless otherwise specified, only emerging AEs are presented and are allocated to the periods as described below.
Solicited AEs will always be considered as emergent, and will be allocated to the respective post-dose x periods.
In the below text active periods refer to the post-dose x (x=1,2,3,4) and the regimen period. The post-dose 1 period
(and the regimen period) are considered as first active period.
STEP 1: allocation of events to the periods
Adverse events present in the SDTM database are allocated to periods based on their start date. If the start date of an 
event falls between (or on) the start and stop date of a period, the AE is attributed to that period.
Incomplete dates (i.e. day and/or month and/or year missing):
-
In case of partial start or stop dates, the events are allocated to the periods using the available partial 
information on start and end date, no imputation is done. If, for instance, for the AE start date only month 
and year is available, these data are compared with the month and year info of the periods. This rule may 
lead to multiplication of the event as a consequence of its assignment to multiple periods.
-
In case of a completely missing end date, the date is imputed by the cut-off date of the analysis for subjects 
still ongoing in the study, and by the end date of the last period for subjects who discontinued or completed 
the trial.
STEP 2: combining events
Overlapping/consecutive events are defined as events in the same subject with the same preferred term which have 
at least 1 day in overlap or for which the start date of an event is 1 day after the end date of the preceding event. 
Overlapping/consecutive events may be combined into one AE or not, according to the following rules:
1)
In case a non-active period (e.g. Screening) is followed by an active period, and the 
overlapping/consecutive events start in both periods, they are allocated to their respective period and are 
considered as separate events.
2)
In case overlapping/consecutive events start within a single period, they are considered as one and the same 
AE. The individual events that contribute to this AE are retained as individual records in the ADAM 
database but are assigned the same onset, period, and total duration. 
3)
In case an active period is followed by a non-active period (e.g. Follow-Up), and the 
overlapping/consecutive events start in both periods, they are allocated to the active period and are 
considered as one and the same AE. The individual events that contribute to this AE are retained as 
individual records in the ADAM database but are assigned the same duration, onset and active period.
4)
In case an active period is followed by an active period, and the overlapping/consecutive events start in 
both periods, they are allocated to their respective period and are considered as separate AEs. The same 
rule applies for 2 non-active periods. 
Remarks: 
1.
Events can only be combined into one and the same AE if their start and stop dates are complete.
2.
In case the completely missing end date is imputed (for phase allocation), this date is also considered as a 
complete date.
3.
Time during the day is not considered when determining overlap of events.
4.
Solicited AEs will never be attributed to the Screening Phase
5.1.4.
Handling of Missing Data for Adverse Events
Missing data will not be imputed. If the severity is missing for a solicited AE, then it is considered as unknown and 
not taken into account for the analysis.
5.1.5.
Solicited Local (Injection Site) Reactions
The analysis of local solicited adverse events will include:
1.
Pain
2.
Erythema
3.
Induration


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585  
Statistical Analysis Plan
HIV-V-A004 (IPCAVD009)
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Approved, Date: 22 April 2022
4.
Swelling
5.
Itching
6.
Warmth
5.1.6.
Solicited Systemic Adverse Events 
The analysis of systemic solicited adverse events will include:
1.
Fever (defined as body temperature of 38.0°C or higher)
2.
Headache
3.
Fatigue
4.
Myalgia
5.
Nausea
6.
Vomiting
7.
Arthralgia
8.
General Itching
9.
Chills
10. Rash
5.2.
Clinical Laboratory Tests
The data will be summarized by the type of laboratory test.
In case a laboratory test result is censored (no numeric value is available, but only a verbatim term) then a numeric 
value will be imputed by a value preceding or exceeding the cut-off value with one unit. (<x: subtract 1 unit from x, 
>x: add 1 unit to x)
Toxicity grades will be determined according to the DAIDS Grading list (See also Appendix 1). In case no toxicity 
grades are defined for a test, the abnormalities (above/below normal range) will be used.  In determining toxicity 
grades, the following rules are applied:
-
worst grades/abnormalities are determined over the whole observational period for each trial phase 
separately, including all post-baseline measurements of that phase.
-
The abnormalities ‘abnormally low’ and ‘abnormally high’ are considered equally important, i.e. if a 
subject has as well an abnormally low as an abnormally high value post-baseline, both abnormalities are 
shown in the tables. (This means that the sum of the percentages can be more than 100%)
-
Note: as the grading scale for some parameters in the grading table has some gaps (zones where no toxicity 
grade definition exists), laboratory results falling in these zones will be allocated to the adjacent worst-case 
grade.
-
If a lab value falls within the grading as specified in the grading table but also within the (local) lab normal 
limits, the value is considered as normal
Definition emergent: An abnormality (toxicity grade or abnormality based on normal ranges) will be considered 
emergent in a particular phase if it is worse than the baseline (baseline  = prior very first vaccination). If the baseline 
is missing, the abnormality is always considered as emergent.  A shift from ‘abnormally low’ at baseline to 
‘abnormally high’ post baseline (or vice versa) is also emergent.
5.2.1.
Analysis methodology
Laboratory data will be analyzed based on the full analysis set.  Unless specified otherwise, percentages are 
calculated versus the number of subjects in the analysis set with non-missing data for the parameter, period (if 
applicable) and treatment group under evaluation. 
Tabulations of the worst graded abnormalities per period following vaccination will be provided. Grade 3 and 4 
toxicities developed following vaccination will be listed. Tabulations of the worst emerging abnormalities (below/ 
above) will be performed for tests that have no grading.


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585  
Statistical Analysis Plan
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14
Approved, Date: 22 April 2022
5.3.
Vital Signs and ECG
5.3.1.
Definitions
Vital sign and ECG measurements will be performed at the time points indicated in the Time and Events Schedule 
(see CTP). Following parameters will be summarized: 

Temperature (°C)

Blood Pressure: systolic/diastolic (mmHg)

Pulse rate (bpm)

PR (ms)

QTc (ms) 
For definition of emergent refer to section 5.2.
5.3.2.
Analysis methodology
Any clinically relevant vital signs and ECG abnormalities occurring from signing of the ICF onwards must be 
recorded on the adverse event page of the CRF and are analyzed as AEs. Tabulations of the parameters per period 
following vaccination will be provided.  All findings will be listed by subject and by time point. Tabulations of the 
worst emerging abnormalities will be performed for parameters if applicable (see grading on Appendix 1).
Listings of all the ECG results and ECG abnormalities reported by the ECG reader will be provided.
Physical examination data will only be listed.
6.
IMMUNOGENICITY
6.1.
Analysis specifications
The analysis of immunogenicity will be done on the PPI analysis set (Section 2.3). 
6.2.
Immune Response Parameters
Humoral and cellular immune responses as measured by the following immune assays will be analyzed:
Humoral response
-
Env ELISA IgG-t gp140
-
ELISA IgG 1-4
-
TZM-BL
-
ADCP gp140
-
BAMA
-
AD26 VNA
Cellular response
-
ELISpot
-
ICS
6.3.
Immune Response Analysis
No formal hypothesis on immunogenicity will be tested. 
Humoral assays
For all the humoral assays the immune response values will be log10-transformed before any further handling. The 
log10-transformed values will be used throughout the analysis. In the graphs, original values will be displayed on 
the log10 scale.  
For each assay and at each time point geometric mean of actual values, geometric mean increases and percentage of 
responders, all with corresponding 95%Cis will be provided in the tables. The definition of responders is defined in 


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585  
Statistical Analysis Plan
HIV-V-A004 (IPCAVD009)
15
Approved, Date: 22 April 2022
section 6.4. for each assay. Graphical presentations will be provided displaying dots for the subject values and 
including the geometric mean and the percentage of responders. If available, baseline values will be summarized 
pooling the 8 groups and will be displayed on the left of each graph. Week 28 and Week 52 timepoints will be 
plotted next to each other for each group, a line will link the geometric mean (or the median) of the 2 different time 
points within the same group.
In the graphs the actual values will be shown and the LLOQ cut-off will be visualized, the values below LLOQ or 
below LOD will be visualized with the value imputed as described in section 6.3. 
Vaccine durability will be shown by linear plots of the GM/median for each group. 
Reverse distribution curves of the actual values will be provided for selected assays.
For BAMA the median will be reported instead of the geometric mean. Cumulative number of responses across the 
IgG/antigen classes will be tabulated.
Magnitude-breadth (MB) plots for the BAMA assay will be provided at each timepoint to explore the magnitude 
(MFI of IgG3 and of IgG breadth binding antibodies) and breadth (number antigens at a given MFI) of each 
individual serum sample assayed. MB curves will show, for each possible MFI threshold, the fraction of antigens
with MFI greater than this threshold. 
The group-specific curve obtained as the average MB across all subjects in that group will be displayed. The AUC-
MB is calculated as the average of the MFI over the panel of antigens.
Cellular response
For Elispot and for each peptide: n, median, quartile range, min, max of actual values, percentage of responders 
above a predefined threshold (see section 6.4) and corresponding 95% CI  will be tabulated. 
Graphical presentations will be provided displaying dots for the subject values and including the median and the 
percentage of responders. In the graphs the actual values will be shown and the LLOQ cut-off will be visualized, the 
values below LLOQ will be visualized with the value imputed as described in section 6.3. 
Reverse distribution curves of the actual values will be provided.
In the graphs, original values will be displayed on the log10 scale.  
ICS 
1) T cells: CD4+, CD8+
Antigen: Combined pools and separated pools 
Cytokine counts: Marginal, Boolean AND (co-expression) counts, Boolean OR (and/or)
For CD4+ and CD8+ and for each antigen (combined and separated pools): n, median, quartile range, min, max, 
percentage of responders (see section 6.4) and corresponding 95% CI  will be tabulated for each available cytokine 
count listed below. 
Cytokine  (ISSCAT)
Description
CD154+
Marginal
GzB+
Marginal
ICOS+
Marginal
IFNg+
Marginal
IL2+
Marginal
IL17a+
Marginal
IL4+
Marginal
TNFa+
Marginal
IFNg+/IL2+
Boolean AND (co-expression)
IFNg+/IL2+/TNFa+
Boolean AND (co-expression)
IFNg+/TNFa+
Boolean AND (co-expression)
IL2+/TNFa+
Boolean AND (co-expression)
IFNg+ or IL2+
Boolean OR (and/or)
IFNg+ or IL2+ or TNFa+
Boolean OR (and/or)
Graphical presentations will be provided displaying dots for the subject values and including the median and the 
percentage of responders. In the graphs the actual values will be shown and the LLOQ cut-off will be visualized, the 
values below LLOQ will be visualized with the value imputed as LLOQ/2. 
In the graphs, original values will be displayed on the log10 scale.  


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585  
Statistical Analysis Plan
HIV-V-A004 (IPCAVD009)
16
Approved, Date: 22 April 2022
The technical details for the calculation of the cytokine background adjusted percentages to be displayed in the 
above described outputs will be outlined in the DPS. 
Additional timepoints between and tests within one of the above listed assays may be investigated for exploratory 
purposes. These data and data from timepoints belonging to the long term extension part of the study will be 
analyzed using the approaches described above.
6.4.
Handling of Missing and/or Invalid Immune Response Data  
Analysis will be carried out on the available data, no imputation will be done for missing samples.
BAMA and ICS unreliable values should be excluded from the analysis: those records will be flagged in the SDTM 
dataset. 
LLOQs by assay/test are listed in Table 1. Values below LLOQ or LOD will be handled as follows:  
-
Calculation of Geomean (humoral response) and median (cellular response): 
o
values < LLOQ are imputed =LLOQ/2
o
values = LOD are not imputed unless no LLOQ is available. In that case LOD will handled 
similarly to  LLOQ (see ADCP)
-
Calculation of fold increases from baseline: 
o
values <LLOQ are imputed =LLOQ
o
values =LOD are imputed = LLOQ when LLOQ is available


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585  
Statistical Analysis Plan HIV-V-A004 (IPCAVD009)
17
Approved, Date: 22 April 2022
6.5.
Immune response assays: details 
The details for each immune response assay are listed in following table. Final values of LLOQ/LOD might deviate from the table below, the dTA approved by the lab 
will be taken as source. 
Assay
Test 
Lab
Time Points
LLOQ
LOD
Unit
Responder 
definition (R)
Fold increase 
(FI) calculation
ELISA
AD26 VNA
Janssen 
Vaccines 
and Prevention
Wk0
17
NA
IC90
>LLOQ
NA
Env 
ELISA 
IgG-t 
gp140
Clade A (92UG037.1)
Clade B (1990a)
Clade C (Con C)
Clade C (C97ZA.012)*
Mos1
Janssen 
Vaccines
and Prevention
Wk0
Wk 28
Wk 52
Wk78
Wk96
625
156.25
625
156.25
78.125
0
EU/ml
1) if baseline 
<LLOQ or missing, 
R>LLOQ 
2) if baseline 
>=LLOQ, R=3-fold 
increase from 
baseline 
1) if baseline 
>LLOQ, 
FI=Value post-
baseline/Value 
wk0
2) if 
baseline<LLOQ, 
FI=value post-
baseline/LLOQ
Env 
ELISA 
IgG1-4
Clade C (C97ZA.012) IgG1
Clade C (C97ZA.012) IgG2
Clade C (C97ZA.012) IgG3
Clade C (C97ZA.012) IgG4
BIDMC
Wk0
Wk 28
Wk 52
Wk78
Wk96
12.3
28.7
12.4
13.2
4
EC50
Env 
ADCP 
gp140
Clade A (92UG037.1)
Clade B (1990a)
Clade C (Con C)
Clade C (C97ZA.012)*
Mos1
Ragon
Wk0
Wk 16 (n=72) 
Wk 28
Wk 52
Wk78
Wk96
NA
5.16
6.43
6.49
4.32
4.28
PS 
1) if baseline 
<LOD, R>LOD 
2) if baseline 
>=LOD, R=3-fold 
increase from 
baseline
1) if baseline 
>LOD, FI=Value 
post-
baseline/Value 
wk0
2) if 
baseline<LOD, 
FI=value post-
baseline/LOD
TZM-bl
Tier1
Clade C (MW965.26) 
Duke U
Wk28
Wk52
20
NA
ID50
>LLOQ
NA
Tier 2
Clade A (398F1) n
Clade AC (246F3) n Ab
Clade AE (CNE55) nAb
Clade AE (CNE8) nAb
Clade B (TRO11) nAb
Clade B (X2278) nAb
Clade BC (BJOX2000) nAb
Clade BC (CH119) nAb
Wk28 (n=72)
10


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585  
Statistical Analysis Plan HIV-V-A004 (IPCAVD009)
18
Approved, Date: 22 April 2022
Assay
Test 
Lab
Time Points
LLOQ
LOD
Unit
Responder 
definition (R)
Fold increase 
(FI) calculation
Clade C ( Ce1176) nAb
Clade C (25710) nAb
Clade C (Ce0217 ) nAb
Clade G (X1632) nAb
BAMA 
IgG3
HIV ENV Con S gp140 CFI 
(Clade M) HIV ENV Con 6 
gp120/B (Clade M) 
HIV ENV gp41  
HIV ENV 1086C_D7gp120  
(Clade C) 
HIV ENV 1086C gp140 (Clade 
C) 
HIV ENV 1086C_V1V2 (Clade 
C) 
HIV ENV 
gp70_B.CaseA_V1V2 (Clade B) 
Duke U
Wk0
Wk 28
Wk 52
Wk78
Wk96
100a
NA
MFI
BAMA 
interpretation= 1
1) if baseline 
>LLOQ, 
FI=Value post 
baseline/Value 
wk0
2) if 
baseline<LLOQ, 
FI=value post 
baseline/LLOQ
BAMA
IgGA
Con S gp140 CFI
Con 6 gp120/B
gp41
1086C_D7gp120.avi/293F 
A1.con.env03 140 CF
00MSA 4076 gp140
Wk0
Wk 28
Wk 52
Wk78
BAMA 
IgG1
Con S gp140 CFI
Con 6 gp120/B
gp41
1086C_D7gp120.avi/293F 
1086C gp140C_avi 
C.1086C_V1_V2 Tags
gp70_B.CaseA_V1_V2
                                                
a This is not LLOQ but positivity cutoff as provided by the lab applied and is based on the 3 response call criteria which include the 95% of baseline responses per 
antigen


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585  
Statistical Analysis Plan HIV-V-A004 (IPCAVD009)
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Approved, Date: 22 April 2022
Assay
Test 
Lab
Time Points
LLOQ
LOD
Unit
Responder 
definition (R)
Fold increase 
(FI) calculation
BAMA 
Breadth
HIV ENV gp120 
Clade A (51802) IgG-t Ab
Clade AE (254008) IgG-t Ab
Clade AE (A244) IgG-t Ab
Clade B (B.6240) IgG-t Ab
Clade B (BORI) IgG-t Ab
Clade B (TT31P) IgG-t Ab
Clade BC (CNE20) IgG-t Ab
Clade BC(BJOX002) IgG-t Ab
Clade C(1086C_D7) IgG-t Ab
B Clade M (Con 6) IgG-t Ab
HIV ENV gp140
Clade B (SC42261) IgG-t Ab
Clade C (CH505TF) IgG-t Ab
C Clade A (9004S) IgG-t Ab
C Clade B (RHPA) IgG-t Ab
C Clade B (WITO)IgG-t Ab
C Clade C (1086C) IgG-t Ab
C Clade C (BF1266) IgG-t Ab
CF Clade AE (conAE) IgG-t Ab
CFI Clade M(Con S) IgG-t Ab
HIV ENV gp41
IgG-t Ab
HIV ENV gp70 
Clade A (191084)IgG-t Ab
Clade AE (C2101) IgG-t Ab
Clade AE (CM244) IgG-t Ab
Clade B (62357.14) IgG-t Ab
Clade B (CaseA) IgG-t Ab
Clade B (RHPA4259) IgG-t Ab
Clade B (TT31P) IgG-t Ab
Clade B(700010058) IgG-t Ab
Clade BC (BJOX) IgG-t Ab
Clade C (96ZM651) IgG-t Ab
Clade C (BF1266) IgG-t Ab
Wk0
Wk 28
Wk 52
Wk78
Wk96


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585  
Statistical Analysis Plan HIV-V-A004 (IPCAVD009)
20
Approved, Date: 22 April 2022
Assay
Test 
Lab
Time Points
LLOQ
LOD
Unit
Responder 
definition (R)
Fold increase 
(FI) calculation
Clade C (CAP210) IgG-t Ab
Clade C(Ce1086) IgG-t Ab
Clade C(TV1.21)IgG-t Ab
Clade C (001428)IgG-t Ab
Clade C (7060101641)IgG-t Ab
BAMA 
IgG2
HIV ENV gp41 IgG2 Ab
HIV ENV gp70 Clade C 
(Ce1086) IgG2 Ab
HIV ENV gp70 Clade B 
(CaseA) IgG2 Ab
HIV ENV gp140CFI Clade M 
(Con S) IgG2 Ab
HIV ENV gp140 Clade C 
(1086C) IgG2 Ab
HIV ENV gp120/B Clade M 
(Con 6) IgG2 Ab  
HIV ENV gp120 Clade C 
(1086C_D7) IgG2 Ab
Wk0
Wk 28
BAMA
IgG4
HIV ENV gp70 Clade C 
(Ce1086) IgG4 Ab
HIV ENV gp70 Clade B 
(CaseA) IgG4 Ab
HIV ENV gp41 IgG4 Ab
HIV ENV gp140CFI Clade M 
(Con S) IgG4 Ab
HIV ENV gp140 Clade C 
(1086C) IgG4 Ab
HIV ENV gp120/B Clade M 
(Con 6) IgG4 Ab
HIV ENV gp120 Clade C 
(1086C_D7) IgG4 Ab
Wk0
Wk 28
ELISpot
Env peptide pool Mos1
Pol peptide pool Mos1
Gag peptide pool Mos1
Env peptide pool Mos2
BIDMC
Wk0
Wk26
Wk 50
Wk78
55
0
SFC/106
PBMC 
1) if baseline 
<threshold, 
R>threshold 
2) if baseline 
73b
112
87
70
NA


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585  
Statistical Analysis Plan HIV-V-A004 (IPCAVD009)
21
Approved, Date: 22 April 2022
Assay
Test 
Lab
Time Points
LLOQ
LOD
Unit
Responder 
definition (R)
Fold increase 
(FI) calculation
Pol peptide pool Mos2
Gag peptide pool Mos2
Env peptide pool PTEa (Env 
peptide pool 1 PTE,
Env peptide pool 2 PTE, Env 
peptide pool 3 PTE)
Pol peptide pool PTE
Gag peptide pool PTE
Wk96
>=threshold, 
R=3-fold 
increase 
from 
baseline
63
55
100
105
181
ICS 
(CD4+, 
CD8+)
Combined pools
HIV Gag pep pool (Mos1) 
HIV Pol pep pool (Mos1)
HIV ENV pep pool (Mos1) 
HIV ENV pep pool clade C 
(C97ZA.012)
HIV ENV pep pool (Clinical 
PTE)
Separated pools
HIV Pol RT pep pool (Mos1)*
HIV Pol RNAseInt pep pool 1 
(Mos1)
HIV ENV gp120 pep pool 1 
(Mos1)* 
HIV ENV gp41 pep pool 1 
(Mos1) 
HIV ENV gp120 pep pool clade 
C (C97ZA.012)
HIV ENV gp41 pep pool clade 
C (C97ZA.012)
HIV ENV pep pool 1 (Clinical 
PTE)a
FHCRC
Wk26
Wk 50
Wk78
Wk96
NA
NA
% of 
CD4+/C
D8+ T 
cells
ICS 
interpretation=1
NA
                                                                                                                                                                                                                                  
a ENV pep pool (PTE) will be provided split in pool 1,2,3: for the purpose of the Week 28 PA they will be reported only as sum of the 3: HIV ENV pep pool. The ADAM should however 
contain also the 3 separated pools.
b Threshold for ELISpot test is based on the 95 percentile from the baseline values of about 350 subjects on that test in the HIV-V-A004 study


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585  
Statistical Analysis Plan HIV-V-A004 (IPCAVD009)
22
Approved, Date: 22 April 2022
Assay
Test 
Lab
Time Points
LLOQ
LOD
Unit
Responder 
definition (R)
Fold increase 
(FI) calculation
HIV ENV pep pool 2 (Clinical 
PTE)a
HIV ENV pep pool 3 (Clinical 
PTE)a
NA: not applicable: PS: phagocytic score; SFC: spot forming cells, PBMC: peripheral blood mononuclear cell, MFI: median fluorescent intensities
* Clade C (C97ZA.012) for Elisa and ADCP, ENV gp120 Mos1 and Pol RT Mos1 for ICS will be available for group 1 at additional intermediate timepoints: 
exploratory scatterplots with timepoint on the x-axis  will be provided.
                                                                                                                                                                                                                                  
a ENV pep pool 1,2,3 (PTE Clinical): calculation of the pure cytokine count cannot be obtained from the combined HIV ENV pep pool (only Boolean OR data will be available) so it will 
be derived from the 3 separated pools.


JNJ-55471468, JNJ-55471494, JNJ-55471520, JNJ-55471533, JNJ-55471572, JNJ55471585  
Statistical Analysis Plan HIV-V-A004 (IPCAVD009)
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Approved, Date: 22 April 2022
7.
VISP
VISP data was collected throughout the study outside of the EDC database. An overview of the results (Reactive, 
Indeterminate, Not Reactive) of the HIV Ag/Ab Combo 4th generation assays will be provided by visit and by brand 
name.
8.
SOCIAL IMPACT QUESTIONNAIRE
Data from the Vaccine Research Center (VRC) Social Impact Questionnaire will be listed and summarized using 
descriptive statistics.