Conditions: HIV Therapeutic Vaccine
Keywords: HIV-MAG pDNA Prime HIV Therapy Therapeutic Vaccine
Allocation: RANDOMIZED | Intervention model: SINGLE_GROUP
Enrollment: 33
Healthy volunteers: no

Brief summary:
Background:

\- In most people who have human immunodeficiency virus (HIV), the immune system cannot control or cure the infection. Antiretroviral therapy drugs can keep the amount of HIV virus low for a long time. However, this treatment does not remove the virus from the body. In the vast majority of patients antiretroviral therapy also will not protect the body from the virus once treatment stops. Researchers want to see if therapeutic vaccination can help people with HIV. Therapeutic vaccination means giving vaccines to treat an infection that someone already has (HIV, in this case). It may help the body's immune system attack the infection. This study will look at different measures of HIV infection after receiving either therapeutic vaccination or a placebo.

Objectives:

\- To see whether therapeutic vaccination is safe and can affect how the body responds to HIV infection.

Eligibility:

\- Individuals between 18 and 65 years of age who have HIV and are taking antiretroviral therapy drugs.

Design:

* Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected.
* During the screening visit and throughout the study until week 56, participants will continue to take their HIV medications.
* Participants will be divided into two groups. One group will have the study vaccines. The other will have a placebo.
* The first study vaccine or placebo will be given in weeks 4, 12, and 36. The second study vaccine or the placebo will be given in weeks 24 and 48. Blood samples and other tests will be given at each visit.
* After the study visit at week 56, participants will stop their HIV medications until week 72. From weeks 58 through 72, they will come in every 2 weeks for study visits; each visit will take about 1 hour to complete. These visits will look at the body s response to the vaccines and their HIV viral load. After week 72, participants will re-start their HIV medications.
* There will be follow-up study visits from weeks 76 to 96, with blood tests and other studies.

Detailed description:
The advent of combination antiretroviral therapy (cART) has dramatically improved the clinical outcome in human immunodeficiency virus (HIV)-infected individuals through sustained reduction in viral replication. However, it has become clear that cART alone cannot eradicate HIV in infected individuals, likely in part due to the persistence of viral reservoirs in peripheral blood and various tissue compartments. Consequently, a major thrust of HIV research over the past several years has been to develop therapeutic strategies that can eliminate persistent viral reservoirs and boost host immunity to control viral replication upon discontinuation of cART. Therapeutic HIV vaccination is one approach that could potentially achieve these goals through vaccine-induced improvement in HIV-specific immune responses and/or by direct reactivation of HIV-specific CD4+ memory T cells that harbor latent HIV. An effective therapeutic vaccine could augment immunologic control of HIV infection and potentially obviate the need for chronic cART.

The current study is an exploratory randomized, 2-arm (1:1), double-blind, placebo-controlled trial evaluating the safety and efficacy of an HIV-1 multiantigen plasmid DNA (HIV-MAG pDNA) vaccine prime in combination with an interleukin-12 plasmid DNA (IL-12 pDNA) adjuvant delivered by in vivo electroporation followed by a recombinant vesicular stomatitis virus vector containing the HIV-1 gag gene (rVSV HIV gag) booster vaccine in subjects on cART who started therapy during acute or early HIV infection.

Subjects will be randomized to receive placebo or the HIV-MAG pDNA (3000 g) vaccine prime and IL-12 pDNA adjuvant (1000 g) at week 0, 4, 12, and 36, and the rVSV HIV gag booster vaccine (1x107 plaque-forming units) at week 24 and 48. The HIV-MAG pDNA vaccine prime and IL-12 pDNA adjuvant will be administered as 2 IM injections, 1 into each deltoid, with electroporation using the Ichor TDS device, while the rVSV HIV gag booster vaccine will be administered as 2 conventional IM injections, 1 into each deltoid. After the week 56 visit, all subjects will undergo an analytical treatment interruption to determine if the vaccination strategy results in an improved immune control of viral replication, as evidenced by a blunted or absent rebound in HIV plasma viremia. All subjects will be followed through week 96 for safety and efficacy parameters.

The study population includes HIV-infected adults who began cART during acute or early infection. Subjects must be receiving an effective cART regimen, with a CD4 cell count of \>450 cells/mm3 at screening, and they must have documented viral suppression below the limit of detection for greater than1 year. The rationale for testing the study vaccine regimen in this subject population is because these individuals may have a relatively preserved immune function, which could be augmented by therapeutic vaccination.

Arms:
arm 1: HIV-MAG pDNA vaccine prime will be administered at a dose of 3000 g (1500 g of the HIV-1 gag/pol plasmid and 1500 g of the HIV-1 net/tat/vif, env plasmid) at week 0, 4, 12, and 36. Each construct of HIV-MAG pDNA vaccine (1500 g each) will be mixed and combined with 1000 g of the IL-12 pDNA adjuvant. The resulting mixture will be divided into 2 IM injections and administered as 0.75 mL IM injection in the left deltoid and 0.75 mL IM injection in the right deltoid with EP using the TDS device. IL-12 pDNA adjuvant will be mixed with the HIV-MAG pDNA vaccine prime, as noted above, and administered at a dose of 1000 g (500 g in each IM injection) at week 0, 4, 12, and 36. rVSV HIV gag booster vaccine--The total dose, 1x107 pfu, will be administered as 1 mL (5x106 pfu) IM injection in the left deltoid and 1 mL (5x106 pfu) IM injection in the right deltoid at week 24 and 48. arm 2: Placebo for the IL-12 pDNA adjuvant and HIV-MAG pDNA vaccine (sodium chloride for injection, USP 0.9%) will be administered as 0.75 mL IM injection in the left deltoid and 0.75 mL IM injection in the right deltoid at weeks 0, 4, 12, and 36 with EP using the TDS device. Placebo for the rVSV HIV gag (sodium chloride for injection, USP 0.9%) will be administered as 1 mL IM injection in the left deltoid and 1 mL IM injection in the right deltoid at week 24 and 48.

Interventions: intervention 1: rVSV intervention 2: IL-12 pDNA adjuvant intervention 3: HIV-Mag pDNA intervention 4: Placebo
Intervention descriptions: intervention 1: Attenuated recombinant vesicular stomatitis virus containing HIV-1 gag gene intervention 2: plasmid DNA containing human IL-12 gene intervention 3: plasmid DNA vaccine containing genes encoding multiple HIV-1 proteins intervention 4: None

Protocol document:
Prot_SAP_000.pdf: 
 
 
 A Phase I Randomized, Double-Blind, Placebo-Controlled Study of a Multi-
Antigen DNA Vaccine Prime Delivered by In Vivo Electroporation, rVSV Booster 
Vaccine in HIV-Infected Patients Who Began Antiretroviral Therapy During 
Acute/Early Infection 
 
 
 
 
 
 
 
Version Number: 
 
 
6.0 
 
NIAID Protocol Number: 
 
13-I-0141 
 
Date:  
 
 
 
August 14, 2015 
 
Principal Investigator:  
 
Michael C. Sneller, MD 
 
Pharmaceutical Support  
Provided by:   
 
 
Profectus Biosciences, Inc. 
 
 
 
 
 
Ichor Medical Systems 
 
Investigational New  
Drug (IND) #:  
 
 
15459 
 
Medical Monitor:  
 
 
Marc Teitelbaum, MD 
 
 
 
 
 
 
 
 
Sponsored by: 
Office of Clinical Research Policy and Regulatory Operations (OCRPRO) 
Division of Clinical Research (DCR), Office of the Director 
National Institute of Allergy and Infectious Diseases (NIAID) 
NIH 


 
 
Study Staff Roster 
 
Principal Investigator: 
 
Michael C. Sneller, MD 
 
 
 
 
 
Laboratory of Immunoregulation (LIR)/NIAID 
 
 
 
 
 
Phone: 301.496.0491 
 
 
 
 
 
E-mail: msneller@niaid.nih.gov 
 
Associate Investigators: 
 
Tae-Wook Chun, PhD 
 
 
 
 
 
LIR/NIAID 
 
 
 
 
 
Phone: 301.496.0890 
 
 
 
 
 
E-mail: twchun@niaid.nih.gov 
 
Richard  Davey, MD 
LIR/NIAID 
Phone: 301.496.8029 
E-mail: rdavey@niaid.nih.gov 
 
Michael A. Egan, PhD 
Profectus Biosciences, Inc. 
777 Saw Mill River Road 
Tarrytown, NY 10591 
Phone: 443.743.1113 
E-mail: eganm@profectusbiosciences.com 
 
John H. Eldridge, PhD 
Profectus Biosciences, Inc.  
777 Saw Mill River Road 
Tarrytown, NY 10591 
Phone: 443.743.1111 
E-mail: eldridge@profectusbiosciences.com 
 
Research Contact/Study  
Coordinator(s): 
 
 
Kathleen Gittens  
 
 
 
 
 
Clinical Center/Critical Care Medicine Department 
 
 
 
 
 
Phone: 301.435.8003 
 
 
 
 
 
E-mail: kathleen.gittens@nih.gov 
 
Statistician:  
Michael Proschan, PhD 
Biostatistics Research Branch/DCR 
Phone: 301.451.5129 
E-mail: proscham@niaid.nih.gov 
 
Sponsor Medical Monitor:  
Marc Teitelbaum, MD [C] 


 
HIV-MAG pDNA vaccine version 6.0 
 
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Leidos Biomedical Research, Inc.  
Frederick National Laboratory 
Phone (301) 228-4707 
Fax (301) 846-6224 
E-mail: RCHSPSafety@mail.NIH.gov 
 
 


 
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Table of Contents 
Study Staff Roster ........................................................................................................... 2 
Protocol Summary ........................................................................................................... 9 
1 
Background Information and Scientific Rationale ................................................... 13 
1.1 
Background Information .................................................................................. 13 
1.1.1 
Description of the Study Agents ............................................................... 15 
1.1.2 
Summary of Previous Pre-Clinical Studies ............................................... 18 
1.1.3 
Summary of Relevant Clinical Studies...................................................... 23 
1.2 
Rationale ......................................................................................................... 31 
2 
Study Objective ..................................................................................................... 32 
2.1 
Primary Objective ............................................................................................ 32 
2.2 
Secondary Objectives ..................................................................................... 32 
2.3 
Exploratory Objectives .................................................................................... 32 
3 
Study Design ......................................................................................................... 32 
3.1 
Description of the Study Design ...................................................................... 32 
3.2 
Study Endpoints .............................................................................................. 33 
3.2.1 
Primary Endpoint ..................................................................................... 33 
3.2.2 
Secondary Endpoint ................................................................................. 34 
3.2.3 
Exploratory Endpoints .............................................................................. 34 
4 
Study Population ................................................................................................... 34 
4.1 
Rationale for Subject Selection ....................................................................... 34 
4.2 
Recruitment Plan............................................................................................. 34 
4.3 
Subject Inclusion Criteria ................................................................................. 34 
4.4 
Subject Exclusion Criteria ............................................................................... 35 
5 
Justification for Exclusion of Women and Children (Special Populations) .............. 37 
6 
Study Agent/Interventions ...................................................................................... 37 
6.1 
Disposition and Dispensation .......................................................................... 37 
6.1.1 
Formulation, Packaging and Labeling ...................................................... 37 
6.2 
Study Agent Storage and Stability ................................................................... 37 
6.3 
Preparation, Administration, and Dosage of Study Agent/Intervention(s) ........ 38 
6.4 
Concomitant Medications and Procedures ...................................................... 40 
6.5 
Prohibited Prescription Medications and Procedures ...................................... 41 
7 
Study Schedule ..................................................................................................... 41 
7.1 
Screening ........................................................................................................ 41 
7.2 
Enrollment/Baseline ........................................................................................ 41 
7.3 
Randomization ................................................................................................ 42 
7.4 
Vaccination Phase .......................................................................................... 42 
7.5 
Post-Vaccination ATI Phase ............................................................................ 43 
7.6 
Post-Vaccination, Post-ATI Phase .................................................................. 44 
8 
Study Procedures/Evaluations ............................................................................... 45 
8.1 
Clinical Evaluations ......................................................................................... 45 
8.2 
Research Evaluations ..................................................................................... 46 
9 
Potential Risks and Benefits .................................................................................. 47 
9.1 
Potential Risks ................................................................................................ 47 
Leukapheresis ....................................................................................................... 50 
9.2 
Potential Benefits ............................................................................................ 50 
10 
Research Use of Stored Human Samples, Specimens or Data.......................... 50 
11 
Remuneration Plan for Subjects ........................................................................ 51 
12 
Assessment of Safety ........................................................................................ 51 
12.1 
Documenting, Recording, and Reporting Adverse Events ........................... 51 


 
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12.2 
Definitions .................................................................................................... 51 
12.3 
Investigator Assessment of Adverse Events ................................................ 53 
12.3.1 
Severity ................................................................................................ 54 
12.3.2 
Causality .............................................................................................. 54 
12.4 
Investigator Reporting Responsibilities to the Sponsor ................................ 55 
12.4.1 
Adverse Events .................................................................................... 55 
12.4.2 
Serious Adverse Events ....................................................................... 55 
12.4.3 
Unanticipated Problems ........................................................................ 56 
12.4.4 
Protocol Specified Events ..................................................................... 56 
12.4.5 
Pregnancy ............................................................................................ 56 
12.5 
Investigator Reporting Responsibilities to the NIAID IRB ............................. 56 
12.5.1 
Expedited Reporting to the NIAID IRB .................................................. 56 
12.5.2 
Annual Reporting to the NIAID IRB ....................................................... 57 
12.6 
Follow-up of Adverse Events and Serious Adverse Events .......................... 57 
12.7 
Sponsor’s Reporting Responsibilities ........................................................... 57 
12.8 
Halting Criteria For The Protocol.................................................................. 58 
12.8.1 
Reporting of Study Halting .................................................................... 58 
12.8.2 
Resumption of a Halted Study .............................................................. 58 
12.9 
Pausing Criteria for a Subject or Group ....................................................... 58 
12.9.1 
Reporting of Pausing for a Subject or Group ........................................ 59 
12.9.2 
Resumption of Pausing for a Subject or Group ..................................... 59 
12.10 
Withdrawal Criteria for an Individual Subject ................................................ 59 
12.11 
Replacement for Withdrawn Subjects .......................................................... 60 
12.12 
Safety Oversight .......................................................................................... 60 
12.12.1 
Safety Review and Communications Plan ............................................ 60 
12.12.2 
Sponsor Medical Monitor ...................................................................... 61 
12.12.3 
Data and Safety Monitoring Board ........................................................ 61 
13 
Clinical Monitoring Structure .............................................................................. 61 
13.1 
Site Monitoring Plan..................................................................................... 61 
13.1.1 
Study Blinding and Unblinding .............................................................. 62 
14 
Compliance With NIH Guidelines for Research Involving Products Containing 
Recombinant DNA ........................................................................................................ 62 
15 
Statistical Considerations ................................................................................... 63 
15.1 
Study Hypotheses ....................................................................................... 63 
15.2 
Sample Size Justification ............................................................................. 63 
16 
Ethics/Protection of Human Subjects ................................................................. 64 
16.1 
Informed Consent Process .......................................................................... 64 
16.2 
Subject Confidentiality ................................................................................. 64 
17 
Data Handling and Record Keeping ................................................................... 64 
17.1 
Data Management Responsibilities .............................................................. 65 
17.2 
Data Capture Methods ................................................................................. 65 
17.3 
Types of Data .............................................................................................. 65 
17.4 
Source documents and Access to Source Data/Documents ........................ 65 
17.5 
Record Retention ......................................................................................... 65 
Appendix A: Scientific References ................................................................................. 67 
Appendix B: Schedule of Evaluations ............................................................................ 70 
Appendix C: AEs of Special Interest .............................................................................. 71 
Appendix D: Vaccine Diary Card ................................................................................... 72 
 
 


 
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List of Tables 
Table 1: Previous clinical use of the HIV-MAG pDNA vaccine,  IL-12 pDNA, TDS device, 
and the rVSV HIV gag vaccine ....................................................................................... 24 
Table 2: Schedule of reactogenicity assessments .......................................................... 46 
Table 3: Probability of observing at least 1 vaccine recipient out of 15 with an AE that has 
probability P of occurring in a given participant ............................................................... 63 
 
List of Figures 
Figure 1: Map of HIV-1gag/pol pDNA (WLV-151M) and HIV-1 nef/tat/vif, env pDNA (WLV-
255M) ............................................................................................................................. 16 
Figure 2: Map of IL-12 pDNA .......................................................................................... 16 
Figure 3: The Ichor TDS device ...................................................................................... 17 
Figure 4: Genomic organization of wild type VSV and the vaccine vector, 
rVSVINN4CT1gag1 ......................................................................................................... 18 
Figure 5: SIV-specific IFN-γ ELISpot responses in immunized SIV-infected rhesus 
macaques ...................................................................................................................... 22 
Figure 6: SIV gag-specific epitope breadth in immunized SIV-infected rhesus macaques23 
Figure 7: HIV-specific CD4+ intracellular cytokine staining responses from the HVTN 080 
study .............................................................................................................................. 27 
Figure 8: HIV-specific CD8+ intracellular cytokine staining responses from the HVTN-080 
study .............................................................................................................................. 28 
Figure 9: HVTN 090: Maximum local reactogenicity by treatment group......................... 30 
Figure 10: HVTN 090: Maximum systemic reactogenicity by treatment group ................ 31 
 
 


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List of Abbreviations 
 
ALT 
 
 
Alanine Aminotransferase 
AE 
 
 
Adverse Event/Adverse Experience 
AR 
 
 
Adverse Reaction 
ART 
 
 
Antiretroviral Therapy  
AST 
 
 
Aspartate Aminotransferase 
ATI 
 
 
Analytical Treatment Interruption 
BGH 
 
 
Bovine Growth Hormone 
bp 
 
 
Base Pair 
cART  
 
Combination Antiretroviral Therapy 
CBC 
 
 
Complete Blood Count 
CFR 
 
 
Code of Federal Regulations 
CPK 
 
 
Creatine Phosphokinase  
CRIMSON 
Clinical Research Information Management System of the NIAID 
CSO 
Clinical Safety Office  
CT 
Cytoplasmic Tail 
DAIDS 
Division of AIDS  
DCR 
 
 
Division of Clinical Research 
DSMB  
 
Data and Safety Monitoring Board 
ECG 
 
 
Electrocardiogram 
EDTA  
 
Ethylenediaminetetraacetic Acid 
EIA 
 
 
Enzyme Immunoassay  
ELISpot 
 
Enzyme-Linked Immunosorbent Spot Assay 
EP 
 
 
Electroporation 
FDA 
 
 
Food and Drug Administration 
GCP 
 
 
Good Clinical Practice 
HBsAg  
 
Hepatitis B Surface Antigen  
HCMV  
 
Human Cytomegalovirus 
HCV 
 
 
Hepatitis C Virus  
HIV-1  
 
Human Immunodeficiency Virus Type 1 
HIV-MAG pDNA 
HIV-1 Multiantigen Plasmid DNA  
ICH 
 
 
International Conference on Harmonization 
ICS 
 
 
Intracellular Cytokine Staining 
IFN 
 
 
Interferon 
IL 
 
 
Interleukin 
IL-12 pDNA   
Interleukin 12 Plasmid DNA 
IM 
 
 
Intramuscular  
IND 
 
 
Investigational New Drug 
IRB 
 
 
Institutional Review Board 
NIAID  
 
National Institute of Allergy and Infectious Diseases  
NIH 
 
 
National Institutes of Health 
NNRTIs 
 
Non-Nucleoside Reverse Transcriptase Inhibitors  
OCRPRO 
 
Office of Clinical Research Policy and Regulatory Operations 


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OHRP  
 
Office for Human Research Protections 
PBMCs 
 
Peripheral Blood Mononuclear Cells 
PCR 
 
 
Polymerase Chain Reaction 
pDNA  
 
Plasmid DNA  
Pfu 
 
 
Plaque-Forming Units  
PolyA  
 
Polyadenylation  
PT 
Prothrombin Time  
PTT 
Partial Thromboplastin Time 
rVSV 
Recombinant Vesicular Stomatitis Virus  
rVSV HIV gag 
Recombinant Vesicular Stomatitis Virus Vector Containing the HIV-
1 Gag Gene 
rVSVIN  
Recombinant Indiana Serotype Vesicular Stomatitis Virus  
SAE 
 
 
Serious Adverse Event/Serious Adverse Experience 
SAR 
 
 
Suspected Adverse Reaction 
SCMV   
 
Simian Cytomegalovirus  
SIV 
 
 
Simian Immunodeficiency Virus 
SLE 
 
 
Systemic Lupus Erythematosis   
SRCP  
 
Safety Review and Communication Plan  
SUSAR 
 
Serious And Unexpected Suspected Adverse Reaction 
SV 
 
 
Simian Virus  
TDS 
 
 
TriGrid® Delivery System 
ULN 
 
 
Upper Limit of Normal  
UP 
 
 
Unanticipated Problem 
VPA 
 
 
Valproic Acid 
VSV 
 
 
Vesicular Stomatitis Virus 
VSVIN   
 
Indiana Serotype Vesicular Stomatitis Virus 


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Protocol Summary 
 
Full Title: 
A Phase I randomized, double-blind, placebo-controlled 
study of a multi-antigen DNA vaccine prime delivered by in 
vivo electroporation, rVSV booster vaccine in HIV-infected 
patients who began antiretroviral therapy during acute/early 
infection. 
Short Title: 
 
 
HIV-MAG pDNA prime, rVSV boost. 
Clinical Phase: 
Phase I. 
IND Sponsor:  
 
OCRPRO 
Conducted by: 
 
LIR/NIAID. 
Principal Investigator: 
Michael C. Sneller, MD. 
Sample Size: 
n=30 subjects with human immunodeficiency virus type 1 
(HIV-1). 
Accrual Ceiling: 
n=50. 
Study Population: 
Adults (18-65 years of age) on combination antiretroviral 
therapy (cART) who started therapy during early or acute 
HIV-1 infection.  
Accrual Period: 
18 months. 
Study Design: 
This is a randomized, 2-arm (1:1), double-blind, placebo-
controlled study evaluating the safety and efficacy of an 
HIV-1 multiantigen plasmid DNA (HIV-MAG pDNA) vaccine 
prime in combination with an interleukin 12 plasmid DNA 
(IL-12 pDNA) adjuvant, delivered by intramuscular (IM) 
electroporation (EP), and a recombinant vesicular stomatitis 
virus vector containing the HIV-1 gag gene (rVSV HIV gag) 
booster vaccine delivered by conventional IM injection. 
Study Duration: 
Start Date: August 2013. 
 
End Date: November 2016. 
Study Agents/  
Intervention Description: 
HIV-MAG pDNA vaccine prime (Profectus Biosciences, 
Inc.; Tarrytown, NY) will be administered at a dose of 3000 
µg (1500 µg of the HIV-1 gag/pol plasmid and 1500 µg of 


HIV-MAG pDNA vaccine version 6.0 
August 14, 2015  
Page 10 of 72 
the HIV-1 net/tat/vif, env plasmid) at week 0, 4, 12, and 36. 
Each construct of HIV-MAG pDNA vaccine (1500 µg each) 
will be mixed and combined with 1000 µg of the IL-12 pDNA 
adjuvant. The resulting mixture will be divided and 
administered as 2 IM injections, 1 into each deltoid, with EP 
using the Ichor Medical Systems (San Diego, CA) TriGrid® 
Delivery System (TDS) device. 
 
IL-12 pDNA adjuvant (GENEVAX®; Profectus Biosciences, 
Inc.; Tarrytown, NY) will be mixed with the HIV MAG pDNA 
vaccine, as noted above, and administered at a dose of 
1000 µg (500 µg in each IM injection) at week 0, 4, 12, and 
36. 
 
rVSV HIV gag booster vaccine (Profectus Biosciences, 
Inc.; Tarrytown, NY) will be administered as 2 conventional 
IM injections (1 mL each), 1 into each deltoid, for a total 
dose of 1x107 plaque-forming units (pfu) at week 24 and 48.  
Primary Objective: 
To evaluate safety and tolerability of the study vaccines in 
subjects who began cART during acute or early HIV-1 
infection. 
  Secondary Objectives: 
To evaluate the efficacy of the study vaccines as 
determined by its effect on rebound viremia following 
analytical treatment interruption (ATI). 
Exploratory Objectives: 
1. To assess the effect of the study vaccines on the rate of 
decay of the HIV-infected, CD4+ T-cell reservoir. 
 
2. To determine the immunogenicity of the study vaccines. 
Primary Endpoint: 
The rate of occurrence of grade 3 or higher AEs, including 
serious adverse events (SAEs) that per standard criteria 
(see safety section) are: 
 
At least possibly related to the test article, and 
 
Definitely NOT related to a factor other than the test 
article. 
Secondary Endpoint:      
 The difference in HIV-1 viral load at the end of the ATI 
between the vaccine and placebo groups. 
Exploratory Endpoints:  
1. The frequency and rate of decay of the infectious HIV 
reservoir between the vaccine and placebo groups.  


HIV-MAG pDNA vaccine version 6.0 
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2. Change from baseline (mean of entry and pre-entry) to post- 
vaccination in the number of interferon (IFN)-γ/ interleukin (IL)-2-
generating  CD8+ and CD4+ T-cells/million peripheral blood 
mononuclear cells (PBMCs); in response to gag, pol, env, nef, tat 
and vif, as measured by intracellular cytokine staining (ICS). 


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Précis 
 
The advent of combination antiretroviral therapy (cART) has dramatically improved the 
clinical outcome in human immunodeficiency virus (HIV)-infected individuals through 
sustained reduction in viral replication. However, it has become clear that cART alone 
cannot eradicate HIV in infected individuals, likely in part due to the persistence of viral 
reservoirs in peripheral blood and various tissue compartments. Consequently, a major 
thrust of HIV research over the past several years has been to develop therapeutic 
strategies that can eliminate persistent viral reservoirs and boost host immunity to control 
viral replication upon discontinuation of cART. Therapeutic HIV vaccination is one 
approach that could potentially achieve these goals through vaccine-induced 
improvement in HIV-specific immune responses and/or by direct reactivation of HIV-
specific CD4+ memory T cells that harbor latent HIV. An effective therapeutic vaccine 
could augment immunologic control of HIV infection and potentially obviate the need for 
chronic cART.  
 
The current study is an exploratory randomized, 2-arm (1:1), double-blind, placebo-
controlled trial evaluating the safety and efficacy of an HIV-1 multiantigen plasmid DNA 
(HIV-MAG pDNA) vaccine prime in combination with an interleukin-12 plasmid DNA (IL-
12 pDNA) adjuvant delivered by in vivo electroporation followed by a recombinant 
vesicular stomatitis virus vector containing the HIV-1 gag gene (rVSV HIV gag) booster 
vaccine in subjects on cART who started therapy during acute or early HIV infection.  
 
Subjects will be randomized to receive placebo or the HIV-MAG pDNA (3000 µg) vaccine 
prime and IL-12 pDNA adjuvant (1000 µg) at week 0, 4, 12, and 36, and the rVSV HIV 
gag booster vaccine (1x107 plaque-forming units) at week 24 and 48. The HIV-MAG 
pDNA vaccine prime and IL-12 pDNA adjuvant will be administered as 2 IM injections, 1 
into each deltoid, with electroporation using the Ichor TDS device, while the rVSV HIV 
gag booster vaccine will be administered as 2 conventional IM injections, 1 into each 
deltoid. After the week 56 visit, all subjects will undergo an analytical treatment 
interruption to determine if the vaccination strategy results in an improved immune control 
of viral replication, as evidenced by a blunted or absent rebound in HIV plasma viremia. 
All subjects will be followed through week 96 for safety and efficacy parameters.  
 
The study population includes HIV-infected adults who began cART during acute or early 
infection. Subjects must be receiving an effective cART regimen, with a CD4 cell count of 
>450 cells/mm3 at screening, and they must have documented viral suppression below 
the limit of detection for >1 year. The rationale for testing the study vaccine regimen in 
this subject population is because  these individuals may have a relatively preserved 
immune function, which could be augmented by therapeutic vaccination.  
 


HIV-MAG pDNA vaccine version 6.0 
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1 Background Information and Scientific Rationale 
1.1 Background Information 
Prolonged suppression of plasma viremia is now achievable in the majority of HIV-
infected individuals receiving cART.1 However, complete eradication of HIV has not 
been possible using cART alone, likely due to the persistence of various viral 
reservoirs.2-4 Previous studies have demonstrated that HIV persists in latently 
infected, CD4+ T cells in the peripheral blood of virtually all infected individuals 
receiving clinically effective doses of cART.5-7 In addition, evidence from a number 
of recent studies has suggested that low levels of HIV replication may persist in 
such individuals in the absence of detectable viremia.8-10 Given that plasma viremia 
rapidly rebounds in virtually all HIV-infected individuals upon cessation of cART, 
regardless of the duration and timing of therapy,11,12 therapeutic strategies aimed at 
destroying persistently infected cells are needed to achieve complete eradication of 
HIV.13 
 
Nearly a decade ago, several clinical studies tested the feasibility of purging latent 
HIV reservoirs in infected individuals receiving cART, with the use of non-specific 
immune-activating agents, such as IL-214 and an anti-CD3 antibody.15 In a non-
randomized study, subjects who received cART plus repeated cycles of intermittent 
IL-2 exhibited a marked diminution of the pool of latently infected, resting CD4+ T 
cells, compared with those receiving cART alone;14 nonetheless, rapid rebound of 
plasma viremia was observed following interruption of cART.12 More recently, 
valproic acid (VPA), a histone deacetylase inhibitor, was tested in humans as a 
potential virus-“purging” agent and was shown in one study to diminish the size of 
the latent viral reservoir in infected individuals receiving ART.16 However, 
subsequent studies demonstrated no appreciable reduction of the latent viral 
reservoir following treatment with VPA.17,18  
 
Other therapeutic strategies aimed at achieving eradication are under investigation. 
These include genetic manipulation of CD4+ T cells (deletion of one of the HIV co-
receptors chemokine receptor type 5)19,20 and stem-cell transplantation.21 Although 
it appears that eradication of HIV was achieved in one individual who underwent 
multiple rounds of chemotherapy and stem-cell transplantation,21 it is unlikely that 
this approach can be safely applied to a substantial proportion of the HIV-infected 
population. Considering the difficulties encountered with these modalities, a more 
realistic approach is needed to explore the therapeutic strategies that harness host 
immunity to control HIV replication in infected individuals in the absence of cART (a 
“functional” cure).4 One such strategy is therapeutic vaccination.  
 
The goal of therapeutic vaccination is to induce or augment virus-specific immune 
responses using a planned exposure to HIV antigens. A successful therapeutic 
vaccination regimen would sufficiently augment the immune response to HIV such 


HIV-MAG pDNA vaccine version 6.0 
August 14, 2015  
Page 14 of 72 
that control of viral replication could be achieved in the absence of cART, thus, 
mimicking the unique immune response of a small portion of HIV-infected 
individuals who are able to control viral replication in the absence of treatment 
(variably termed elite controllers or long-term non-progressors). Early attempts at 
therapeutic vaccination in HIV-1-infected individuals during the pre-cART era were 
largely unsuccessful; however, these results were not unexpected. The 
introduction of a small amount of exogenous antigen in the form of a therapeutic 
vaccine is unlikely to have a significant immunostimulatory effect in chronically 
infected individuals with uncontrolled viral replication and ongoing CD4 cell death. 
 
More recent pre-clinical and clinical studies, performed in the cART era, have 
shown improvement of virus-specific immune responses after therapeutic 
vaccination. The induction of broad T-cell responses was observed in a macaque 
simian immunodeficiency virus (SIV) model using DNA vaccine during suppressive 
cART.22 Vaccination reduced virus burden in the gut and blood, compared with 
unvaccinated controls and provided durable protection from viral rebound and 
disease progression following ART interruption. In the ACTG study 5197, 
vaccination of subjects receiving suppressive cART with an Ad5 HIV gag vector 
induced moderate increases in HIV-specific T-cell responses.23 Vaccinated 
subjects showed a modest decrease in their viral load set point at the end of the 
ATI, compared with unvaccinated controls; however, the decrease did not reach 
the pre-specified level of significance (P <0.025). In a recently published 
randomized controlled study by Garcia et al,24 subjects receiving the active 
dendritic cell vaccine (autologous dendritic cells pulsed with autologous heat 
inactivated virus) had a significant decrease in viral set point following ATI 
compared to controls.  
 
The studies presented above suggest that therapeutic vaccination could become a 
promising immune-based modality for the treatment of HIV-1 infection, if more 
immunogenic vaccination strategies can be developed. Our trial will utilize a pDNA 
prime/live virus vector boost vaccination strategy that has been shown to elicit a 
strong HIV-specific cellular immune response in pre-clinical animal models. This 
vaccination regimen has additional features designed to maximize immunogenicity.  
For example, the HIV-MAG pDNA vaccine prime-IL-12 pDNA adjuvant will be 
administered to study participants via an in vivo EP delivery system. EP is a 
technology in which a transient electric field is applied to enhance the cellular 
uptake of large molecules, such as DNA, and it has been shown to provide an 
efficient method of delivering DNA into the cell.25 Preclinical studies in nonhuman 
primates provide compelling evidence that in vivo EP enhances the potency of the 
HIV-MAG pDNA/IL-12 pDNA vaccine (see Section 1.1.2). In addition, clinical 
studies indicate that EP delivery of pDNA vaccines is safe and well tolerated.26 
Secondly, the vaccine regimen will utilize an IL-12 pDNA adjuvant that, when 
administered by in vivo EP, is designed to enhance the immunogenicity of the 
pDNA vaccine. Thirdly, the booster component of the vaccine utilizes a 


HIV-MAG pDNA vaccine version 6.0 
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Page 15 of 72 
recombinant vesicular stomatitis virus (rVSV)-vector encoding HIV gag. Wild-type 
vesicular stomatitis virus (VSV) rarely causes infections in humans; thus, the use of 
an rVSV vector will minimize any interference of pre-existing immune responses in 
study subjects.  
1.1.1 Description of the Study Agents 
HIV-MAG pDNA vaccine prime 
The HIV-MAG pDNA vaccine consists of 2 DNA expression vectors (HIV-1 
gag/pol [WLV-151M] and HIV-1 nef/tat/vif, env [WLV-255M]) encoding 
multiple HIV-1 clade B antigens (Figure 1). WLV-151M is a 7,487-base pair 
(bp) plasmid expressing an HIV-1 clade B (HIV-1HXb2) Gag/Pol fusion protein 
controlled by the human cytomegalovirus (HCMV) immediate early promoter 
and the bovine growth hormone (BGH) polyadenylation (polyA) signal. WLV-
255M is a dual-promoter plasmid (8,750 bp) expressing an HIV-1 clade B 
primary isolate (HIV-16101) Env gp160 controlled by the simian 
cytomegalovirus (SCMV) promoter and the BGH polyA, and an HIV-1 clade B 
(HIV-1NL43) Nef/Tat/Vif fusion protein utilizing the HCMV promoter and the 
simian virus (SV)40 polyA tail. 
 
IL-12 pDNA adjuvant 
IL-12 pDNA adjuvant is a dual-promoter expression plasmid (Figure 2) that is 
6,259 bp long and consists of 2 genes encoding the human IL-12 proteins 
p35 and p40. Each cistron contains one of the two IL-12 subunits, p35 or p40, 
and each subunit is controlled by independent regulatory elements. The p35 
subunit is controlled by the HCMV promoter/ enhancer and the SV40 polyA 
signal. The p40 subunit is regulated by the SCMV promoter and the BGH 
polyA signal. 
 
 
 
 
 
 
 
 
 
 
 
 


HIV-MAG pDNA vaccine version 6.0 
August 14, 2015  
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Figure 1: Map of HIV-1gag/pol pDNA (WLV-151M) and HIV-1 nef/tat/vif, env pDNA 
(WLV-255M) 
 
WLV151M                                                                         WLV255M 
 
 
 
 
 
 
 
 
Figure 2: Map of IL-12 pDNA 
 
 
WLV151M
(7487 bp)
HCMV pr omot e r
kanamyc i n
Or i  s e que nc e
BGH pol y A
HI V gag/ pol
WLV255M.gcs
(8750 bp)
SV40pol yA
HCMV
SCMV
Ka na myc i n
Or i  s e que nc e
HI V ne f / t a t / vi f
HI V e nv 6101 ( gp160)


HIV-MAG pDNA vaccine version 6.0 
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Ichor TriGrid delivery system device 
The Ichor TDS device is designed for IM administration of DNA. Specifically, 
the device is designed to propagate EP inducing transient electrical fields at 
the site of administration in the presence of DNA, thus, enhancing its cellular 
uptake. The TDS device has been shown to be an efficient method for 
delivering DNA into cell,25 and preclinical studies have suggested that in vivo 
EP enhances the potency of a DNA vaccine.27,28 
 
The TDS device consists of 3 components depicted in Figure 3. They include 
a single-use application cartridge, an integrated applicator, and a pulse 
stimulator. The current configuration of the device is designed for the 
administration of investigational agents in the context of early phase human 
clinical studies. To provide the degree of flexibility necessary to support novel 
product candidates entering the clinical-phase testing, the TDS device has 
been designed to interface with a standard, “off-the-shelf” syringe and can 
accommodate injection volumes of 0.5 mL to 1.2 mL.   
 
Figure 3: The Ichor TDS device 
 
 
rVSV HIV gag booster vaccine 
The rVSV HIV gag booster vaccine preparation contains an attenuated, 
replication-competent form of the lab-adapted recombinant Indiana serotype 
vesicular stomatitis virus (rVSVIN) that expresses the HIV-1 clade B (strain 
HXB2) Gag protein. The vaccine vector was attenuated by translocation of 
the virus N gene from the first position (N1) in the genome to the fourth 
position (N4) and truncation of the virus G protein cytoplasmic tail (CT) from 
29 amino acids to 1 amino acid (CT1). The HIV-1 gag gene was inserted at 


HIV-MAG pDNA vaccine version 6.0 
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the first position (gag1) in the rVSV genome adjacent to the virus messenger 
RNA transcription promoter to maximize Gag protein expression. The vaccine 
vector has been named to reflect the major attenuating mutations, the 
position of the gag gene, and the vector serotype (Figure 4). 
 
Figure 4: Genomic organization of wild type VSV and the vaccine vector, 
rVSVINN4CT1gag1 
 
 
 
 
  
 
 
 
WT=wild type; rVSVIN=recombinant Indiana serotype vesicular stomatitis virus. 
Numbering (e.g. N4, gag1) denotes the relative positions of genes within the viral genomes. The 
subscript IN (Indiana) describes the vector serotype. CT1 indicates that the length of the G 
protein cytoplasmic tail  is a single amino acid.  
 
1.1.2 Summary of Previous Pre-Clinical Studies 
An overview of pharmacokinetic, toxicological, and immunogenicity studies 
relevant to the clinical testing of the HIV-MAG pDNA vaccine alone, or in 
combination with human IL-12 pDNA adjuvant (with or without TDS EP 
injector) and the rVSV HIV gag booster vaccine, is presented below. More 
detailed information can be found in the investigator’s brochure documents. 
Biodistribution and persistence/integration study of the HIV-MAG pDNA 
in combination with the human IL-12 pDNA adjuvant delivered by IM or 
IM EP injection in rats 
A good laboratory practice study was carried out to characterize the systemic 
biodistribution and persistence/integration of the HIV-MAG pDNA vaccine in 
combination with the human IL-12 pDNA adjuvant  in rats. The formulated 
pDNA vaccine was administered bilaterally (tibialis anterior muscles) in 2 
groups of 22 rats each (11 rats/sex/group) at a dose of 80 µg (32 µg HIV-1 
gag/pol, 32 µg HIV-1 nef/tat/vif, env, 16 µg IL-12 pDNA)  by conventional IM 
injection or IM EP delivery using the Ichor TDS device (for a total dose of 160 
µg per animal). Additionally, a group of 12 rats (6 rats/sex) was injected with 
saline using the TDS device. Real-time quantitative polymerase chain 
reaction (PCR) was used to estimate the levels of the vaccine pDNA in tissue 
specimens. The presence of the vaccine pDNA in the total DNA (genomic + 


HIV-MAG pDNA vaccine version 6.0 
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plasmid) isolated from the blood and various tissues was examined in this 
study at day 7 and day 60 post-vaccination. PCR analyses of tissue 
specimens obtained at day 7 showed that the distribution of the vaccine 
pDNA was largely confined to the tissues at the site of administration (muscle 
and skin) following IM or IM EP delivery. On day 60,  the vaccine pDNA was 
detected in tissues at the site of administration in both the IM and IM EP 
delivery groups at levels of <7,000 copies/µg. Plasmid levels decreased by 
approximately 1 to 2 orders of magnitude compared to the levels detected on 
day 7. These analyses indicate that IM and IM EP  delivery of the vaccine 
pDNA resulted in an initial uptake of the plasmid, which was localized to the 
injection site and then  decreased substantially over time. No significant 
differences were observed in the biodistribution or persistence of the vaccine 
pDNA between the IM and IM EP delivery groups.    
Biodistribution and persistence study of the rVSV HIV gag vaccine 
delivered by  IM injection in mice 
A virus biodistribution study has been performed in mice to investigate the 
degree of virus replication and dissemination in a permissive host following 
IM vaccination.29 Mice were inoculated with the rVSVINN4CT9gag1 vaccine at 
a dose of 108 pfu (10 x the anticipated clinical dose); the rVSVINN4CT9gag1 
is a closely related but more competent vector than rVSVINN4CT1gag1 
vector. Vector replication and spread was monitored by assaying the 
infectious virus and by virus- specific quantitative PCR performed on tissue, 
blood, and organ samples collected at different time intervals post-injection 
(day 0-2, 4, 8, and 10). Results from these studies showed that all 
measurable virus replication was localized at the IM injection site  and in the 
major, draining poplilteal lymph node. Viral replication peaked at 1 to 2 days 
post-injection, and there was no evidence of viral gene expression at 10 days 
post-injection. 
Repeat-dose toxicity study of the HIV-MAG pDNA vaccine with or 
without the human IL-12 pDNA adjuvant and the rVSV HIV gag booster 
vaccine delivered by IM or IM EP injection in rabbits 
In a repeat-dose toxicology study, NZW rabbits were administered the HIV-
MAG pDNA vaccine as an IM injection at a dose of 4,000 µg with or without 
the human IL-12 pDNA adjuvant (1,000 µg) on day 1, 22, 43, 64, 85, and 
106. A subgroup of animals treated with the HIV-MAG pDNA vaccine and 
IL-12 pDNA adjuvant also received the rVSV HIV gag booster vaccine on day 
64 and 85 by IM delivery. Animals in all groups exhibited minor changes in 
body weight, food consumption, and clinical and anatomical pathology, 
generally with a complete or partial resolution of these changes by the end of 
the recovery period. Based on these results, it was concluded that the toxicity 
effects were localized or reflective of an inflammatory response targeted at 
the injection/EP sites rather than being systemic in nature.   


HIV-MAG pDNA vaccine version 6.0 
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Toxicology study of the rVSV HIV gag vaccine delivered by IM injection 
in rabbits 
A good manufacturing practice toxicology study was performed in 20 rabbits 
using the rVSV HIV gag vaccine. No AEs were observed either at the 
injection site or systemically following the IM injection of the rVSV HIV gag 
vaccine at a total dose of 108 pfu. Blood chemistry panels remained normal 
throughout the study and tissue/organ histopathology profiles were 
unremarkable in animals treated with the vaccine, compared with those in the 
placebo group. 
 
Immunogenicity study of the HIV-MAG pDNA vaccine plus a rhesus IL-
12 pDNA adjuvant with and without in vivo EP in rhesus macaques 
To determine the effect of EP on the immunogenicity of HIV-MAG pDNA 
vaccination, a preclinical study was conducted in rhesus macaques 
immunized with an HIV-MAG pDNA vaccine (8500 µg)  plus a rhesus IL-12 
pDNA adjuvant (1500 µg) by conventional IM injection or IM EP delivery 
(1200 µg HIV MAG pDNA + 300 µg IL-12 pDNA).30 Animals immunized by IM  
EP delivery exhibited stronger cellular responses, compared with those 
immunized by conventional IM injection. At 8 and 22 weeks after the final 
pDNA immunization, there was a 10- and 45-fold increase, respectively, in 
HIV-specific IFN-γ responses, as measured by an enzyme-linked 
immunosorbent spot (ELISpot) assay, in the IM EP delivery group, compared 
with the IM delivery group. The 10- and 45-fold increase translated into an 
apparent 50- or 225-fold increase in pDNA vaccine potency, respectively. 
Importantly, the IM EP delivery enhanced the immune response against the 
less immunogenic antigens (nef-tat-vif), resulting in a more balanced immune 
response. In addition, antibody responses against the env antigen showed 
that the IM EP delivery led to an ~2.5-log increase in antibody titer, compared 
with the IM delivery group.  
 
Immunogenicity studies of an rVSV SIV or HIV Gag p55 vaccine in 
rhesus macaques 
 
The first non-human primate experiments to evaluate rVSV as a vector 
system for HIV infection were conducted by Rose and colleagues at Yale. In 
a pioneering study, rhesus macaques (n=7) were immunized with a 
combination of 2 prototypic rVSV vectors expressing an HIV-1–89.6 env 
gp160/VSV-G fusion polypeptide and an SIV Gag p55 protein or control 
(n=8).31 In this study, all animals in the combination vaccine group remained 
disease-free after the challenge for >4 years. In contrast, all the macaques in 
the control group progressed to AIDS within an average time of 8 months. 
The protection from AIDS in this study correlated with large differences in 
peak viral loads, low or undetectable viral loads at set point, and the 
preservation of CD4+ T cells in the vaccine recipients relative to controls. 
This encouraging level of post-challenge vaccine efficacy suggested that 


HIV-MAG pDNA vaccine version 6.0 
August 14, 2015  
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rVSV vectors expressing HIV genes might be an effective AIDS vaccine in 
humans. 
In a separate unpublished study conducted by Profectus, groups of rhesus 
macaques were immunized at weeks 0 and 8 with a highly attenuated 
replication competent rVSV vaccine vector encoding the HIV-1 Gag p55 
protein (rVSV HIV gag) at a dose of 1x107 pfu or a much more virulent 
prototypic rVSV vector (rVSV-HIV gag5) vaccine at a dose of 1x107 pfu by 
conventional IM injection; the rVSV-HIV gag5 vaccine was previously shown 
by Rose and colleagues31 to protect macaques against simian-AIDS in a 
pathogenic SHIV (simian/human immunodeficiency virus) challenge model. 
The data demonstrate that the highly attenuated rVSV vector was as good as 
the more virulent vector in eliciting HIV gag-specific IFN-γ ELISpot responses 
following vaccination (rVSVINN4CT1gag1 vaccine Profectus Bioscience 
investigator’s brochure). 
 
Immunogenicity studies of an IL-12-enhanced SIV-MAG pDNA vaccine 
plus an rVSV gag booster vaccine in rhesus macaques 
In a pre-clinical, immunogenicity study conducted by Profectus, rhesus 
macaques were infected with SIV and subsequently placed on cART until 
they reached suppressive viremia. Macaques were then immunized with an 
IL-12-enhanced SIV-MAG pDNA vaccine alone or in combination with a 
heterologous rVSV booster vaccine. Unimmunized control animals exhibited 
SIV-specific immune responses barely detectable by ELISpot and 
polyfunctional ICS assays. Animals vaccinated with the IL-12-enhanced SIV-
MAG pDNA vaccine demonstrated a 5-fold increase in total SIV-specific 
ELISpot responses, compared with control animals.. In contrast, animals 
vaccinated with the IL-12-enhanced SIV-MAG pDNA vaccine plus the rVSV 
booster vaccine demonstrated a 17-fold increase in total SIV-specific ELISpot 
responses, compared with control animals (Figure 5). 
 
 
 


                                                                                    HIV-MAG pDNA vaccine version 5.0 
 
             October 23, 2014 
 
Figure 5: SIV-specific IFN-γ ELISpot responses in immunized SIV-infected rhesus 
macaques  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
DDD=animals vaccinated with an IL-12-enhanced SIV-MAG pDNA vaccine; DDV= animals 
vaccinated with IL-12-enhanced SIV-MAG pDNA vaccine plus an rVSV booster vaccine; 
Con=control animals; SIV=simian immunodeficiency virus; IFN-g=interferon γ; 
ELISpot=enzyme-linked immunospot spot assay; SFC=spot- forming cells; PBMCs= 
peripheral blood mononuclear cells; ART=antiretroviral therapy; Vax=vaccination. 
 
 
In additional studies utilizing a polyfunctional ICS assay, the breadth and 
magnitude of SIV-specific cellular responses returned to pre-cART levels in 
vaccinated animals (data not shown). Furthermore, animals vaccinated with the 
IL-12-enhanced SIV-MAG pDNA vaccine plus the rVSV booster vaccine 
demonstrated de novo SIV-specific immune responses resulting in an increase 
in the epitope breadth of SIV gag-specific immune responses, compared with 
animals vaccinated with the IL-12-enhanced SIV-MAG pDNA vaccine alone 
(Figure 6). These data demonstrate that therapeutic immunization of SIV-
infected rhesus macaques with a cytokine-enhanced pDNA prime, rVSV boost 
vaccination regimen augments virus-specific immunity and elicits de novo 
immune responses. 
  
 
 


HIV-MAG pDNA vaccine version 6.0 
August 14, 2015  
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Figure 6: SIV gag-specific epitope breadth in immunized SIV-infected rhesus 
macaques 
 
DDD=animals vaccinated with an IL-12-enhanced SIV-MAG pDNA vaccine alone; DDV= 
animals vaccinated with IL-12-enhanced SIV-MAG pDNA vaccine plus an rVSV booster 
vaccine; Con=control animals; SIV=simian immunodeficiency virus; ELISpot=enzyme-linked 
immunospot spot assay; ART=antiretroviral therapy; Vax=vaccination. 
1.1.3 Summary of Relevant Clinical Studies 
Table 1 below provides a summary of clinical studies evaluating the HIV-MAG 
pDNA vaccine, IL-12 pDNA vaccine, TDS device, and the rVSV HIV gag 
vaccine. Detailed information about these studies can be found in the 
investigator’s brochure documents.   
 


                                                                                    HIV-MAG pDNA vaccine version 5.0 
 
             October 23, 2014 
 
Table 1: Previous clinical use of the HIV-MAG pDNA vaccine,  IL-12 pDNA, TDS 
device, and the rVSV HIV gag vaccine 
Vaccine 
component 
Previous clinical 
experience 
Notes 
HIV-MAG pDNA 
Healthy adults: 
IAVI B004; ClinicalTrials.gov 
identifier: NCT01496989 
HVTN-087; ClinicalTrials.gov 
identifier: NCT01578889 
To date, approximately 105 healthy adult 
volunteers have received HIV-MAG pDNA 
vaccine delivered by IM EP injection. 
HIV-positive adults: 
ACTG-5281; 
ClinicalTrials.gov identifier: 
NCT01266616 
To date, approximately 50 HIV-positive subjects 
have received the HIV-MAG pDNA vaccine 
delivered by IM EP injection. 
IL-12 pDNA 
Healthy adults: 
HVTN-060; ClinicalTrials.gov 
identifier: NCT00111605 
HVTN-063; ClinicalTrials.gov 
identifier: NCT00115960 
HVTN-070; ClinicalTrials.gov 
identifier: NCT00528489 
HVTN-080; ClinicalTrials.gov 
identifier:NCT00991354 
IAVI B004; ClinicalTrials.gov 
identifier: NCT01496989 
HVTN-087; ClinicalTrials.gov 
identifier: NCT01578889 
To date, approximately 120 healthy adult 
volunteers have received IL-12 pDNA delivered 
by IM injection and approximately 88 have 
received IL-12 pDNA delivered by IM EP 
injection. 
HIV-positive adults: 
ClinicalTrials.gov identifier: 
NCT00195312 
ACTG-
5281;ClinicalTrials.gov 
identifier: NCT01266616 
To date, 10 HIV-positive subjects have received 
IL-12 pDNA delivered by IM injection and 
approximately 50 subjects have received IL-12 
pDNA delivered by IM EP injection. 


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Vaccine 
component 
Previous clinical 
experience 
Notes 
TDS device 
Healthy adults: 
Rockefeller University 
Hospital; ClinicalTrials.gov 
identifier: NCT00545987 
 
 
IAVI B004; ClinicalTrials.gov 
identifier: NCT01496989 
 
 
Emory Vaccine Trials Unit; 
ClinicalTrials.gov identifier: 
NCT01169077 
 
 
 
 
Walter Reed Army Institute 
of Research; 
ClinicalTrials.gov identifier: 
NCT01502345 
24 subjects have been administered a DNA 
vaccine encoding HIV-1 subtype B’/C antigens 
env, gag, pol, nef, and tat via the TDS device. 
Subjects have received up to 3 administrations 
at total DNA doses of up to 4,000 µg. An 
additional 8 subjects received placebo via the 
TDS device. 
 
75 subjects  have been administered the HIV-
MAG pDNA vaccine with or without the IL-12 
pDNA adjuvant via the TDS device. 
 
30 subjects have been administered a DNA 
vaccine encoding epitopes from  P falciparum 
antigens via the TDS device. Subjects have 
received up to 3 administrations at total DNA 
doses of up to 4,000 µg. An additional 9 
subjects received placebo via the TDS device. 
 
30 subjects have been administered a DNA 
vaccine encoding antigens from the Hantaan 
and Puumala viruses via the TDS device. 
Subjects have received up to 3administrations 
at total DNA doses of up to 2,000 µg. 
HIV-positive adults: 
ACTG-5281; 
ClinicalTrials.gov identifier: 
NCT01266616 
To date, approximately 50 HIV-positive subjects 
have received the HIV-MAG pDNA vaccine with 
or without the IL-12 pDNA adjuvant delivered by 
IM injection via the TDS device. 
Stage IIB-IV melanoma 
subjects: 
Memorial Sloan Kettering 
Cancer Center; 
ClinicalTrials.gov identifier: 
NCT00471133 
16 subjects have been administered a DNA 
vaccine encoding epitopes derived from the 
tyrosine-related protein 2 delivered by IM 
injection via the TDS device. Subjects received 
up to 6 administrations at total DNA doses of up 
to 4,000 µg. 
Hepatitis B virus-positive 
adults: 
ClinicalTrials.gov identifier: 
NCT01641536 
To date, 9 subjects with chronic hepatitis B virus 
infection have received an antigen-encoding 
DNA vaccine by IM EP injection. 
rVSV HIV gag 
Healthy adults: 
HVTN-090; ClinicalTrials.gov 
identifier: NCT01438606 
To date, approximately 50 healthy adult 
volunteers have received rVSV HIV gag vaccine 
delivered by IM injection. 
IM=intramuscular; EP= electroporation; HIV-MAG pDNA=HIV-1 multiantigen plasmid DNA; IL-12 


HIV-MAG pDNA vaccine version 6.0 
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pDNA= interleukin 12 plasmid DNA; rVSV HIV gag=recombinant vesicular stomatitis virus vector 
containing the HIV-1 gag gene; TDS=TriGrid delivery system. 
 
The safety and adjuvant activity of the IL-12 pDNA alone, or in combination with 
the HIV-MAG pDNA vaccine has been evaluated in several phase I clinical 
trials. The HVTN-080 phase I study evaluated the safety and immunogenicity of 
the PENNVAX™-B (gag, pol, env) vaccine, with or without an IL-12 pDNA 
adjuvant, delivered by IM EP injection in 48 healthy, HIV-negative adults. 
Participants who received the gag, pol, env vaccine alone (group 1), or in 
combination with the IL-12 pDNA adjuvant (group 2 & 3), developed both HIV-
specific CD4+ (Figure 7) and CD8+ (Figure 8) T-cell responses. After 3 
vaccinations, 44.4% (4/9) of subjects in group 1 and 80.8% (21/26) of subjects 
in group 2 and 3 responded (Figure 7). The latter response rate was higher than 
after 4 vaccinations with the gag, pol, env vaccine with the IL-12 adjuvant 
delivered by IM injection without EP (P=.005; HVTN-070). The response rate for 
the gag, pol, env vaccine with the IL-12 adjuvant IM+EP was still relatively high 
(53.6% 15/28) 6 months after the third vaccination. These findings validate the 
activity of the IL-12 pDNA adjuvant in combination with a DNA plasmid vaccine.  
No serious vaccine-related safety concerns or AEs were reported.  
 
 
 
 


HIV-MAG pDNA vaccine version 6.0 
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Figure 7: HIV-specific CD4+ intracellular cytokine staining responses from the 
HVTN 080 study 
 
IFN=interferon; IL=interleukin; VAC=vaccination. 
 
 
 


HIV-MAG pDNA vaccine version 6.0 
August 14, 2015  
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Figure 8: HIV-specific CD8+ intracellular cytokine staining responses from the HVTN-
080 study 
 
IFN=interferon; IL=interleukin; VAC=vaccination. 
 
 
Several other ongoing clinical studies evaluating the HIV-MAG pDNA vaccine or 
the rVSV HIV gag vaccine provide interim safety data. The IAVI-B004 study is a 
double-blind, randomized, placebo-controlled trial assessing the safety and 
immunogenicity of an HIV-MAG pDNA vaccine with a recombinant IL-12 pDNA 
adjuvant followed or preceded by a recombinant Ad35-GRIN/ENV HIV vaccine 
in healthy, HIV-negative participants. Enrollment is complete and vaccination of 
the first participant occurred in December 2011. To date, no safety concerns 
have been reported. Interim data following the HIV-MAG pDNA vaccine 
revealed a 36% combined response rate, and the full data set is anticipated in 
January 2013. The ongoing ACTG-5281 trial is a placebo-controlled, dose-
escalation study evaluating the safety and immunogenicity study of a cytokine-
enhanced HIV-MAG pDNA vaccine delivered IM or IM EP injection in individuals 
with chronic HIV infection. Interim data show a 30% response rate. Enrollment is 
complete and vaccination of the first subject occurred in April 2011; no grade 3 
or 4 AEs have been observed. 
  


HIV-MAG pDNA vaccine version 6.0 
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The safety and immunogenicity of the rVSV HIV gag vaccine was evaluated in a 
phase I, randomized, double-blind, placebo-controlled, dose-escalation study 
(HVTN-090) of healthy, HIV-negative adults; the study began in October 2011. 
Groups of 12 participants received the rVSV HIV gag vaccine (n=10/group) at 5 
nominal dose levels (104, 105, 106, 107, and 108 pfu) or placebo (n=2/group) 
delivered by IM injection at 0 and 2 months. Reactogenicity over 7 days, AEs, 
and viral cultures from whole blood, urine, saliva, and swabs of oral lesions were 
collected. HIV-1-specific CD4+ and CD8+ T-cell responses to the Gag peptides 
were measured 1 and 2 weeks post-vaccination using an ICS assay. 
  
As of July 31, 2012, all the vaccinations for this study were completed. As of 
September 11, 2012, the study is still ongoing, and the data are blinded. The 
median age for the participants is 24 years; 47% of participants are female and 
37% are nonwhite. Local (Figure 9) and systemic (Figure 10) reactogenicity was 
self-limited, mild-to-moderate in intensity, and increased with the dose; 
headache was the common AE (52%) followed by malaise/fatigue (43%).  
 
At the highest dose, 92% of the subjects reported having systemic symptoms, 
including flu-like syndrome (41%), fever (41%), and moderate chills (33%). Of 
the AEs considered related to the study product and reported by 30% of 
participants, the following were experienced by >1 participant: lymphadenopathy 
(3), decreased neutrophil count (3), mouth ulceration (3), other oral lesions (3), 
presyncope (3), and upper respiratory tract infection (2). Other AEs considered 
related to the study product and reported by 1 person each were asthenia, 
axillary pain, injection-site hematoma, increased levels of AST, myalgia, 
dizziness, hypoesthesia (at the injection site), oropharyngeal pain, and hot 
flushes. No severe reactogenicity, encephalitis, or product-related SAEs were 
reported. Viral-infectivity assays were performed on blood, urine, and saliva 
samples at baseline, 3 days post-vaccinations, and any time symptoms of a viral 
syndrome were reported within 1 week of the vaccination. Saliva samples and 
swabs were collected for all oral ulcerations or oral lesions detected during the 
exam. Cultures of VSV tested negative at all the doses and sites analyzed. Low-
frequency, HIV-specific, CD4+ (9%), and CD8+ (3%) T-cell responses were 
detected post-vaccination in the first 3-dose levels. At the 107 pfu dose level, 
HIV gag-specific cell-mediated immune responses were detected in 6 of the 10 
(60%) vaccine recipients, as measured by IFN-γ ELISpot or IFN-γ/IL-2 ICS 
assay. These data indicate that immunization with an attenuated, replicating 
rVSV HIV gag vaccine has an acceptable reactogenicity and safety profile to 
date.  
 
The safety and immunogenicity of  the HIV-MAG pDNA vaccine in combination 
with the IL-12 adjuvant delivered by IM EP injection and followed by the rVSV 
HIV gag boost vaccine is being evaluated in HVTN 087, an ongoing phase I 
study of HIV-negative participants. Administration of the rVSV HIV gag vaccine 


HIV-MAG pDNA vaccine version 6.0 
August 14, 2015  
Page 30 of 72 
boost began in February 2012. Thirty of the expected 100 subjects  have been 
enrolled to date, and interim data are anticipated in May 2013. No safety-related 
concerns have been reported thus far. In a substudy of innate immunity, 3 
subjects who had blood collected 24 hours after vaccination with rVSV were 
noted to have transient lymphopenia. The lymphopenia was not associated with 
any clinical symptoms and had resolved by the second blood collection 72 hours 
post-vaccination. A similar transient lymphopenia (presumably a result of 
transient changes in lymphocyte migration from blood to lymphoid tissue) has 
been reported following immunization with inactivated influenza virus.32 
  
 
Figure 9: HVTN 090: Maximum local reactogenicity by treatment group 
 
 
 
 
 
 
 
 
 


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Figure 10: HVTN 090: Maximum systemic reactogenicity by treatment group 
 
 
 
1.2 Rationale  
The objectives of this study are to evaluate the safety and efficacy of the HIV-MAG 
pDNA vaccine prime plus the IL-12 pDNA adjuvant delivered by IM injection with EP 
in a prime-boost combination with the rVSV HIV gag booster vaccine. Up to 30 
participants will be enrolled in the study, half of whom will receive the study vaccines 
and the other half will receive placebo. Only study participants who began cART 
during the acute/early phase of HIV infection are eligible to participate. These 
individuals have been shown to have a relatively preserved immune function, with 
smaller numbers of persistently infected CD4+ T cells, compared with those who 
initiated cART during the chronic phase of infection.33-36  
 
The rationale for using the proposed doses of the HIV-MAG pDNA vaccine prime and 
IL-12 pDNA adjuvant is based on the safety and immunogenicity data generated from 
the HVTN-080 and ACTG-5281 trials described in the previous section. Likewise, the 
proposed dose for the rVSV HIV gag vaccine is based on the safety and 
immunogenicity data from HVTN 090 trial. Additionally, the TDS device will be used in 


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the current study for EP of the DNA prime vaccine/placebo. In vivo EP is believed to 
enhance the potency of DNA vaccines by facilitating cellular uptake of DNA.25,27,28 
  
Various assays measuring HIV-specific immune responses have been used to assess 
vaccine immunogenicity. Yet, to date, none of the assays are clinically validated to 
predict vaccine efficacy. Thus, ATI has been used in the past to evaluate the impact 
of therapeutic vaccination on the viral rebound that occurs following cART treatment 
interruption. The use of ATI in the design of this study will allow us to determine if 
vaccination results in a clinically significant improvement of the immunologic control of 
viral replication, as evidenced by a blunted or absent plasma viral rebound following 
ATI in the vaccine recipients, compared with individuals in the control group. Based 
on results from prior therapeutic vaccine studies using ATI,23,24,37,38 as well as a recent 
subgroup analysis of the SMART study,39 we feel that a 16-week ATI, with close 
clinical and laboratory monitoring, is a safe and acceptable strategy to evaluate the 
efficacy of the study vaccination regimen in this population of HIV-infected adults.    
2 Study Objective 
2.1 Primary Objective 
To evaluate the safety and tolerability of the study vaccines in subjects who began 
cART during acute or early HIV-1 infection. 
2.2 Secondary Objectives 
To evaluate the efficacy of the study vaccines as determined by its effect on rebound 
viremia following ATI.  
2.3 Exploratory Objectives  
1. To assess the effect of the study vaccines on the rate of decay of the HIV-infected, 
CD4+ T-cell reservoir. 
2. To determine the immunogenicity of the study vaccines.  
3 Study Design 
3.1 Description of the Study Design 
This is a randomized, 2-arm (1:1), double-blind, placebo-controlled study evaluating 
the safety and efficacy of an HIV-MAG pDNA vaccine prime with EP in combination 
with an IL-12 pDNA adjuvant and an rVSV HIV gag booster vaccine delivered by 
conventional IM injection, in subjects who began cART during acute or early HIV-1 
infection. Efficacy will be measured in terms of the effect of the study vaccinations on 
the plasma viral rebound at 16 weeks following ATI. Because the study is blinded, 
references to active vaccines included below refer EITHER to the active vaccine OR 
matching placebo, unless otherwise specified.  
 


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Vaccination schedule  
Subjects will be randomized to receive placebo or the HIV-MAG pDNA vaccine prime  
(3000 µg) and IL-12 pDNA adjuvant (1000 µg) at week 0, 4, 12, and 36, and the 
rVSV-HIV gag booster vaccine (1x107 pfu) at week 24 and 48 (see Appendix B).  
 
Each construct (HIV-1 gag/pol plasmid or the HIV-1 net/tat/vif, env plasmid) of the 
HIV-MAG pDNA vaccine (1500 µg each) will be mixed with 1000 µg of the IL-12 
pDNA adjuvant and administered as 2 IM injections, 1 into each deltoid, with EP. The 
rVSV HIV gag  booster vaccine will be administered as 2 IM injections (1 mL each), 1 
into each deltoid. 
 
Analytical treatment interruption 
After the week 56 visit, all subjects meeting ATI criteria (described below) will undergo 
an approximately 16-week ATI to determine if the vaccination strategy results in an 
improved immune control of the viral replication, as evidenced by a blunted or absent 
viral rebound in the vaccine recipients, compared with the placebo recipients.   
1. ATI will be initiated only in subjects whose CD4 cell counts are >400 cells/ mm3 
and plasma viral levels are below the limit of detection at week 56. HIV plasma 
viremia and CD4 cell counts will be assessed every 2 weeks during the ATI. 
2. Subjects who do not receive at least one dose of the rVSV HIV gag boost or 
matching placebo will not undergo ATI, but they will continue to be followed for 
safety outcomes.  
3. Any subject who develops oral lesions that are positive for VSV by culture or 
PCR will not undergo ATI until the lesions resolves (for at least 4 weeks). 
4. Individuals taking non-nucleoside reverse transcriptase inhibitors (NNRTIs) will 
be advised to switch to a protease inhibitor or an integrase inhibitor-based 
regimen 2 weeks prior to the discontinuation of cART to ensure that the washout 
period of antiretroviral agents is roughly equal.    
5. Subjects whose plasma viral levels are below the limit of detection at week 72 
(the end of the ATI period) may elect not to restart cART until their viral levels 
rise above the limits of detection.  
6. Subjects will be restarted on cART if they meet any of the following criteria during 
the ATI:  
 
A confirmed >30% decline in baseline CD4 cell count or an absolute CD4 cell 
count <350 cells/mm3. 
 
A sustained (≥4 weeks) HIV RNA level of >50,000 copies/mL.  
 
Any HIV-related symptoms.  
3.2 Study Endpoints 
3.2.1 Primary Endpoint 
The rate of occurrence of grade 3 or higher AEs, including SAEs, that, per 
standard criteria (see safety section) are: 


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 
At least possibly related to the test article, and 
 
Definitely NOT related to a factor other than the test article. 
3.2.2 Secondary Endpoint 
The difference in HIV-1 viral load at the end of the ATI between the vaccine and 
placebo groups. 
3.2.3 Exploratory Endpoints  
1. The frequency and rate of decay of the infectious HIV reservoir between the 
vaccine and placebo groups.  
2. Change from baseline (mean of entry and pre-entry) to post-vaccination in 
the number of IFN-γ/IL-2-generating  CD8+ and CD4+ T-cells/million PBMCs 
in response to gag, pol, env, nef, tat and vif, as measured by ICS. 
4 Study Population 
4.1 Rationale for Subject Selection 
Individuals who begin cART during early/acute HIV infection have been shown to 
have a relatively preserved immune function, with smaller numbers of persistently 
infected CD4+ T cells, compared with those who initiated cART during the chronic 
phase of infection. Limiting enrollment to this pool of subjects maximizes safety, and it 
helps to determine whether therapeutic vaccination can significantly augment HIV-
specific immune responses in a clinically meaningful way.   
4.2 Recruitment Plan  
Subjects will be recruited from known cohorts of individuals who started treatment 
during acute/early HIV infection. Additional local and national recruitment will be done 
using direct mailing to infectious disease physicians, internet ad campaigns, social 
media outlets, and print ads.  
4.3 Subject Inclusion Criteria 
1. Age, 18-65 years. 
2. Institution of cART within 12 weeks of being diagnosed with acute or early HIV-1 
infection.  
Acute HIV-1 infection is defined as:   
a.  Detectable plasma HIV-1 RNA levels of >2000 copies/mL with a negative 
result from an HIV-1 EIA, or  
b.  Positive result from an HIV-1 EIA with a negative or indeterminate result from 
an HIV-1 western blot that subsequently evolves to a confirmed positive 
result, or  
c.  Negative result from an HIV-1 EIA within the past 4 months and HIV-1 RNA 
levels of >400,000 copies/mL, in the setting of a potential exposure to HIV-1.  


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Early HIV-1 infection is defined as: 
a. Negative result from an HIV-1 EIA within 6 months prior to a positive result 
from an HIV-1 EIA and an HIV-1 western blot.   
b. Negative result from a rapid HIV-1 test within 1 month prior to a positive result 
from an HIV-1 EIA and an HIV-1 western blot. 
c. Presence of low level of HIV antibodies as determined by having a positive 
EIA or a positive Western blot with a non-reactive detuned EIA according to a 
serologic testing algorithm for recent infection. 
 
3. CD4+ cell count >450 cells/mm3 at screening. 
4. Documentation of continuous cART treatment with  suppression of plasma viral 
level below the limit of detection for >1 year. Subjects with a single “blip” (i.e., 
detectable viral levels  on cART) prior to randomization may be included provided 
they satisfy the following criteria:  
a. The blips are <400 copies/mL, and  
b. Succeeding viral levels return to levels below the limit of detection on 
subsequent testing. 
5. Willingness to undergo ATI. 
6. Laboratory values within pre-defined limits at screening:  
 Absolute neutrophil count >1,000/mm3. 
 Hemoglobin levels >10.0 g/dL for men and >9.0 g/dL for women. 
 Platelet count >100,000/mm3.  
 Prothrombin time (PT) and partial thromboplastin time (PTT) <1.5 upper limit of 
normal (ULN). 
 Estimated  or a measured creatinine clearance rate of >60 mL/min as 
determined by the NIH Clinical Center laboratory.  
 AST and ALT levels of <2.5 x ULN. 
7. Willingness to have samples stored for future research.  
8. Women of childbearing potential must have a negative pregnancy test result. 
 They must agree to use an adequate form of contraception: 
o Hormonal contraception.  
o Male or female condoms with or without a spermicidal. 
o Diaphragm or cervical cap with a spermicidal.  
o Intrauterine device. 
4.4 Subject Exclusion Criteria 
1. Allergy to amide-type local anesthetics (bupivacaine [Marcaine], lidocaine 
[Xylocaine], Mepivacaine [Polocaine/Carbocaine], etidocaine [Duranest], 
prilocaine [Citanest, EMLA cream]). 
2. Chronic hepatitis B, as evidenced by a positive test for hepatitis B surface antigen 
(HBsAg), or chronic hepatitis C virus (HCV) infection, as evidenced by a positive 
test for HCV RNA. Subjects with a positive test for HCV antibody and a negative 
test for HCV RNA  are eligible.  
3. Changes in cART regimen due to virologic breakthrough. 


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4. HIV immunotherapy or vaccine(s) received within 1 year prior to screening. 
5. Any licensed or experimental non-HIV vaccination (e.g., hepatitis B, influenza, 
pneumococcal polysaccharide) received within 4 weeks prior to study entry.  
6. Interruption of cART for >3 months since its initiation. 
7. Pregnancy or planned pregnancy during the study period or breastfeeding. 
8. Any active malignancy that may require systemic chemotherapy or radiation 
therapy. 
9. Immunosuppressive medications received within 6 months before the first study 
vaccination (Not excluded: [1] corticosteroid nasal spray for allergic rhinitis; [2] 
topical corticosteroids for mild, uncomplicated dermatitis; or [3] oral/parenteral 
corticosteroids administered for non-chronic conditions not expected to recur 
[length of therapy ≤10 days, with completion in ≥30 days prior to enrollment]). 
10. Evidence of hepatic decompensation in subjects with cirrhosis: history of ascites, 
hepatic encephalopathy, or bleeding esophageal varices, or screening laboratory 
results with any of the following: 
a. International normalized ratio of ≥1.5 x ULN. 
b. Serum albumin <3.2 g/dL. 
c. Serum total bilirubin >1.8 x ULN, unless history of Gilbert's disease or deemed 
related to treatment with atazanavir. 
11. History or other clinical evidence of:  
a. Significant or unstable cardiac disease (e.g., angina, congestive heart failure, 
recent myocardial infarction, significant arrhythmia). 
b. Severe illness, malignancy, immunodeficiency other than HIV, or any other 
conditions that, in the opinion of the investigator, would make the subject 
unsuitable for the study. 
c. AIDS-defining condition. 
12. Known allergy or sensitivity to the components of the investigational therapy. 
13. History of significant cardiac arrhythmia (e.g., supraventricular tachycardia, 
ventricular tachycardia, and atrial fibrillation/flutter). 
14. Active drug or alcohol use or any other pattern of behaivor that, in the opinion of 
the investigator, would interfere with adherence to study requirements. 
15. Any active systemic inflammatory or autoimmune disease or condition. 
16. Presence of implanted electronic medical device (e.g., pacemaker, implantable 
cardiac defibrillator) or surgical/traumatic metal implant in the upper limb and/or 
upper torso.  
17. Neurological or neuropsychiatric disorder that may interfere with the assessment 
of safety (e.g., frequent recurring headaches, for example, a pattern of >1 
headache/month affecting activities of daily living/work, frequent or 
severe/complicated migraines, cluster headaches); or history of encephalitis, 
narcolepsy, stroke with sequelae, moderate/severe major depressive disorder, 
moderate/severe bipolar disorder, seizure disorder. 
18. Deltoid skinfold measurements (by caliper) of >40 mm. 
19. Body mass index >40. 
 


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Co-enrollment guidelines: Co-enrollment in other trials is restricted, other than 
enrollment on observational studies or those evaluating the use of a licensed 
medication. Study staff should be notified of co-enrollment, as it may require the 
approval of the principal investigator. 
5 Justification for Exclusion of Women and Children (Special Populations)  
Exclusion of women:   
 
Pregnancy: Pregnant women are excluded from this study because the effects of the 
HIV-MAG pDNA vaccine prime/IL-12 pDNA adjuvant/rVSV HIV gag booster vaccine 
on the developing human fetus are unknown with the potential for teratogenic or 
abortifacient effects.   
 
Breastfeeding: Because there is an unknown but potential risk for AEs in nursing 
infants secondary to the treatment of the mother with the HIV-MAG pDNA vaccine 
prime/IL-12 pDNA adjuvant/rVSV HIV gag booster vaccine, breastfeeding should be 
discontinued if the mother is treated with these study agents. 
Exclusion of children: Because there are insufficient data regarding the dosing or AEs 
available in adults for the study agents to judge the potential risk in children, they are 
excluded from this study. 
6 Study Agent/Interventions  
6.1 Disposition and Dispensation  
The study agents will be distributed by Profectus, Inc. to the NIH Central Pharmacy 
according to standard pharmacy procedures. 
6.1.1 Formulation, Packaging, and Labeling  
Each study product (i.e., HIV-MAG pDNA vaccine prime, IL-12 pDNA adjuvant, 
and rVSV-HIV gag booster vaccine) will be individually vialed and labeled with 
the study product name, lot number, concentration, and recommended storage 
conditions.  
6.2 Study Agent Storage and Stability  
The HIV-MAG pDNA vaccine prime and the IL-12 pDNA adjuvant should be stored 
and refrigerated at 2˚C to 8˚C, if not immediately administered. When constructs are 
mixed and administered in combination, it is recommended that the combined 
formulation be used within 4 hours after mixing. The proposed expiration period for 
the HIV-MAG pDNA vaccine prime and the IL-12 pDNA adjuvant is 12 months from 
the date of formulation. Batches may be evaluated for stability at the expiration time 
point to justify their use passed the expiration date. 
 
Vials containing the rVSV-HIV gag booster vaccine vector should be stored at -80˚C. 
No more than 4 hours prior to use, vaccine vials should be placed at room 


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temperature to thaw the vaccine formulation rapidly. Thawed vaccine can either be 
used immediately for inoculation or be stored at 2˚C-8˚C for up to 4 hours prior to 
inoculation. The proposed expiration period for the booster vaccine is 12 months from 
the date of formulation. Batches may be evaluated for stability at the expiration time 
point to justify their use passed the expiration date. 
Sodium chloride for injection (USP 0.9%) will be used as a control substance for the 
placebo group. The vials must be stored as directed by the manufacturer of the 
product. 
6.3 Preparation, Administration, and Dosage of Study Agent/Intervention(s) 
 
Description 
HIV-MAG pDNA vaccine prime composed of the HIV-1 gag/pol plasmid and HIV-
1 nef/tat/vif, env plasmid  
HIV-MAG pDNA HIV-1 gag/pol plasmid  
The HIV-MAG pDNA HIV-1 gag/pol plasmid is a clear, colorless solution enclosed in 
2-mL single-use vials. Each 2-mL vial contains 0.8±0.04 mL of the HIV-1 gag/pol 
pDNA at a concentration of 3 mg/mL in 30 mM citrate buffer pH 6.5, containing 150 
mM NaCl, 0.015 ethylenediaminetetraacetic acid (EDTA), and 0.25% bupivacaine-
HCl.  
The product is contraindicated in participants with known hypersensitivity to 
bupivacaine or any other amide-type local anesthetic. 
HIV-MAG pDNA HIV-1 nef/tat/vif, env plasmid  
The HIV-MAG pDNA HIV-1 nef/tat/vif, env is a clear, colorless solution packaged in 2-
mL single-use vials. Each 2-mL vial contains 0.8±0.04 mL of the HIV-1 nef/tat/vif, env 
pDNA at a concentration of 3 mg/mL in 30 mM citrate buffer pH 6.5, containing 150 
mM NaCl, 0.015 EDTA, and 0.25% bupivacaine-HCl.  
The product is contraindicated in participants with known hypersensitivity to 
bupivacaine or any other amide-type local anesthetic. 
IL-12 pDNA adjuvant  
The IL-12 pDNA adjuvant is a clear, colorless solution packaged in 2-mL single-use 
vials. Each 2-mL vial contains 0.9±0.04 mL of IL-12 pDNA at a concentration of 2 
mg/mL in 30 mM citrate buffer pH 6.5, containing 150 mM NaCl, 0.01% EDTA, and 
0.25% bupivacaine-HCl.  
The product is contraindicated in participants with known hypersensitivity to 
bupivacaine or any other amide-type local anesthetic.  
rVSV HIV gag booster vaccine 
The rVSV-HIV gag booster vaccine is a clear, colorless solution packaged in 3-mL 
single-use vials. Each 3-mL single-use vial contains 1.3 mL (5x106 pfu/mL) of the 


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vaccine formulated in an aqueous liquid phosphate buffer containing gelatin as a virus 
stabilizer.  
Control product 
Sodium chloride for injection (USP 0.9%) will be used as a control substance for the  
placebo group. The volume of sodium chloride administered will be the same as that 
for the study vaccine components.   
Dosing and administration 
HIV-MAG pDNA vaccine prime will be administered at a dose of 3000 µg (1500 µg 
of the HIV-1 gag/pol plasmid and 1500 µg of the HIV-1 net/tat/vif, env plasmid) at 
week 0, 4, 12, and 36. Each construct of HIV-MAG pDNA vaccine (1500 µg each) will 
be mixed and combined with 1000 µg of the IL-12 pDNA adjuvant. The resulting 
mixture will be divided into 2 IM injections and administered as 0.75 mL IM injection in 
the left deltoid and 0.75 mL IM injection in the right deltoid with EP using the TDS 
device. 
IL-12 pDNA adjuvant will be mixed with the HIV-MAG pDNA vaccine prime, as noted 
above, and administered at a dose of 1000 µg (500 µg in each IM injection) at week 
0, 4, 12, and 36. 
rVSV HIV gag booster vaccine--The total dose, 1x107 pfu, will be administered as 1 
mL (5x106 pfu) IM injection in the left deltoid and 1 mL (5x106 pfu) IM injection in the 
right deltoid at week 24 and 48. 
Placebo for the IL-12 pDNA adjuvant and HIV-MAG pDNA vaccine (sodium chloride 
for injection, USP 0.9%) will be administered as 0.75 mL IM injection in the left deltoid 
and 0.75 mL IM injection in the right deltoid at weeks 0, 4, 12, and 36 with EP using 
the TDS device. 
Placebo for the rVSV HIV gag (sodium chloride for injection, USP 0.9%) will be 
administered as 1 mL IM injection in the left deltoid and 1 mL IM injection in the right 
deltoid at week 24 and 48. 
 
Dose Adjustments/Modifications/Delays 
Delaying vaccinations for a participant 
Under certain circumstances, a participant’s scheduled vaccination will be delayed. 
The factors to consider when such a decision needs to be made include, but are not 
limited to, the following: 
 
Live attenuated vaccines, other than influenza vaccine, received within 30 days 
prior to the study vaccination(s). 


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 
Influenza vaccine or any vaccines that are not live attenuated (e.g., 
pneumococcal vaccines) received within 14 days prior to the study 
vaccination(s). 
 
Allergy treatment with antigen injections received within 30 days prior to the 
study vaccination(s). 
 
Abnormal vital signs or clinical symptoms prior to the study vaccinations that may 
interfere with assessment of the vaccine reaction. 
In order to avoid vaccination delays and missed vaccinations, participants who plan to 
receive licensed vaccines or allergy treatments will be counseled to schedule receipt 
of these substances outside the intervals indicated above, whenever possible. 
Because the effects of these substances on the safety and immunogenicity 
assessments and their interactions with the study vaccines are unknown, the 
substances should also be avoided in the 2-week interval between a study 
vaccination and completion of the next scheduled post-vaccination follow-up visit.  
 
Participant departure from the vaccination schedule 
Every effort should be made to follow the vaccination schedule according to the 
protocol. With the exception of the first pDNA vaccination, if a participant misses a 
vaccination and the 14-day window period for the vaccination has passed, that 
vaccination cannot be administered. The participant should be asked to continue with 
the remaining study visits. The participant should resume the vaccination schedule for 
the next vaccination unless there are circumstances that require further delay or 
permanent discontinuation of the vaccination.  
 
If a participant receives only 1 of the 2 scheduled injections (i.e. half of the vaccine/ 
placebo dose), the principal investigator will determine whether the vaccination 
schedule can be resumed with the next scheduled injection. 
 
Tracking of dose 
The vials for the HIV-MAG pDNA vaccine prime, IL-12 pDNA adjuvant, and rVSV-HIV 
gag booster vaccine will be labeled as described in Section 6.1.1 with the assigned 
study subject numbers and no other forms of subject identifiers, and they will be kept 
as directed by the sponsor. Tracking will be based on the number of vials used for 
each subject, accounting for any amount left in the last vial for each subject. 
6.4 Concomitant Medications and Procedures  
All concomitant prescription medications taken during study participation will be 
documented in Clinical Research Information Management System of the NIAID 
(CRIMSON). For this protocol, a prescription medication is defined as a medication 
that can be prescribed only by a properly authorized/licensed clinician.  Medications 
to be reported in CRIMSON documents are concomitant prescription medications, 


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over-the-counter medications, and non-prescription medications taken at the time of 
AEs (all grades). 
6.5 Prohibited Prescription Medications and Procedures 
Treatment with immunosuppressive medications received within 6 months before the 
first study vaccination (not including [1] corticosteroid nasal spray for allergic rhinitis; 
[2] topical corticosteroids for mild, uncomplicated dermatitis; or [3] oral/parenteral 
corticosteroids given for non-chronic conditions not expected to recur ̵length of 
therapy ≤10 days) will not be permitted unless discussed with and approved by the  
principal investigator. 
7 Study Schedule 
For all the study visits, unless otherwise specified, subjects will come to the NIH Clinical 
Center to undergo the procedures. Unless otherwise specified, the visit window for the 
post-entry study visits is ± 5 days. 
7.1 Screening 
Screening may occur over the course of several contacts/visits, up to and including, 
before the first vaccination on day 0 (week 0). All inclusion and exclusion criteria must 
be assessed within 8 weeks before enrollment, unless otherwise specified in the 
eligibility criteria.  
After signing informed consent, subjects will undergo the following procedures: 
 Medical history and a targeted physical examination, including weight, vital signs, 
and a symptom-directed evaluation based on symptoms or complaints reported by 
each participant. 
 Assessment of concomitant medications.  
 Deltoid skinfold measurement. 
 Blood collection for:  
o HBsAg. 
o Rapid plasma reagin test. 
o Anti-HIV and anti-HCV antibody tests. 
o Complete blood count (CBC) with differential, PT, activated PTT. 
o Chemistry panel to include: ALT, AST, alkaline phosphatase, creatinine, 
CPK, total and direct bilirubin, and serum albumin levels. 
o Flow cytometry panel (includes CD4+ cell count).  
o Plasma HIV and HCV viral RNA levels. 
o Storage of PBMCs. 
 Urinalysis. 
 Serum or urine pregnancy test (for women of child-bearing potential).   
 Electrocardiogram (ECG). 
7.2 Enrollment/Baseline 


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During enrollment at week 0, eligible subjects will be randomized in a 1:1 ratio to  
receive placebo or the HIV-MAG pDNA vaccine prime plus the IL-12 pDNA adjuvant 
and the rVSV-HIV gag booster vaccine. The first dose of placebo or the vaccine 
regimen will be administered at this visit, and enrollment is defined as the day of 
receipt of the first study vaccine.  
During week 0, subjects will undergo the following procedures (prior to the first study 
vaccination): 
 Medical history and a targeted physical examination, including weight, vital signs, 
and a symptom-directed evaluation based on symptoms or complaints reported by 
each participant. 
 Assessment of concomitant medications.  
 HIV transmission risk behavior assessment and counseling 
 Leukapheresis for research studies (see Section 8.2) 
 Blood collection for: 
o Flow cytometry panel (includes CD4+ cell count). 
o Plasma HIV viral RNA levels. 
o Serum baseline VSV serology. 
o HLA typing. 
o Storage of serum and PBMCs. 
o CBC with differential. 
o Chemistry panels, to include: ALT, AST, alkaline phosphatase, creatinine, 
CPK, total and direct bilirubin, and serum albumin levels. 
 Serum or urine pregnancy test (for women of child-bearing potential).   
 Assessment of reactogenicity parameters (following the first study vaccination) as 
described in Section 8.1. 
 Instructions on the use of a symptom log/diary card. 
7.3 Randomization 
The Pharmaceutical Development Section of the NIH Clinical Center pharmacy will 
generate a 1:1 randomization scheme for the protocol. A table of random numbers will 
be used.  A set of numbers, equivalent to the proposed “N” will be selected. An 
appropriate block will be chosen, based on the “N”.  Within that block, the highest 
numbers will be assigned to one treatment assignment (vaccine), while the lowest 
numbers will be assigned to the alternate treatment (placebo).   
7.4 Vaccination Phase 
Subjects must continue on their current cART regimen during the vaccination phase.  
 
Subjects will be administered either placebo or the HIV-MAG vaccine plus the IL-12 
pDNA adjuvant at week 0, 4, 12, and 36, and the rVSV HIV gag booster vaccine 
(1x107 pfu) at week 24 and 48. 


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During the visits at week 4, 12, 24, 36, 48, and 56, subjects will undergo the following 
procedures: 
 Medical history and a targeted physical examination, including weight, vital signs, 
and a symptom-directed evaluation based on symptoms or complaints reported by 
each participant. 
 Assessment of concomitant medications.  
 Assessment of reactogenicity parameters (at week 4, 12, 24, 36, and 48 only; see 
Section 8.1). 
 Assessment of any new or unresolved AEs/intercurrent illnesses. 
 Blood collection for: 
o CBC with differential. 
o Chemistry panels, to include: ALT, AST, alkaline phosphatase, creatinine, 
CPK, total and direct bilirubin, and serum albumin levels. 
o Flow cytometry panel (includes CD4+ cell count). 
o Plasma HIV viral RNA levels. 
o VSV serology (at week 26 and 50 only). 
 Leukapheresis for research studies including, but not limited to, quantitative co-
cultures of CD4+ cells and related immunologic and virologic studies (at week 36 
and 56 only). 
 Serum or urine pregnancy test (for women of child-bearing potential).   
 Evaluation of symptom log/diary card. 
 HIV transmission risk behavior assessment and counseling (week 56 only) 
 
During the visits at week 14, 26, 38, and 50, blood will be collected for flow cytometry, 
CBC, and storage of plasma and PBMCs for assessment of immunogenicity. For 
select subjects residing outside the local (Bethesda, MD) area, blood samples for 
CD4 counts, and storage, may be collected at their local clinics and sent to the NIH 
Clinical Center for testing and storage.  
 
Any participant who develops oral ulcers within 7 days post-vaccination with the rVSV 
vaccine/placebo will have swabs from the oral lesion(s) collected and sent for VSV 
culture and PCR (see section 8.1). 
7.5 Post-Vaccination ATI Phase 
The ATI phase will begin after the visit at week 56 and will continue until week 72. 
During this phase, CD4 counts and HIV viral RNA levels will be measured every 2 
weeks.  
For select subjects residing outside the local (Bethesda, MD) area, blood samples for 
CD4 counts and HIV viral RNA levels may be collected at their local clinics and sent 
to the NIH Clinical Center via overnight shipment for testing.  


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All subjects will return to the NIH Clinical Center at week 64 and 72 for the following 
procedures: 
 Medical history and a targeted physical examination, including weight, vital signs, 
and a symptom-directed evaluation based on symptoms or complaints reported by 
each participant. 
 Assessment of any new or unresolved AEs/intercurrent illnesses. 
 Blood collection for: 
o CBC with differential. 
o Chemistry panels to include: ALT, AST, alkaline phosphatase, creatinine, 
total and direct bilirubin, and serum albumin levels. 
o Flow cytometry panel (includes CD4+ cell count). 
o Plasma HIV viral RNA levels. 
o Serum or urine pregnancy test (for women of child-bearing potential).   
o HIV genotype (week 72 only, or prior to restarting cART). 
o Storage of serum and PBMCs. 
If a subject develops one or more criteria for ending ATI (see Section 3.1), he/she will 
be asked to return for an unscheduled visit for assessment and confirmation of the 
laboratory/clinical abnormality. If the criteria for ending ATI are met, the subject will 
restart cART and will continue to be followed for 6 months after restarting cART, and 
he/she will undergo the schedule of procedures listed in Section 7.6 below under 
week 84 and 96.  
7.6 Post-Vaccination, Post-ATI Phase  
After the visit at week 72, subjects will restart their cART regimen and will continue 
treatment through week 96 (end of study).  
At week 76 and 80, blood will be collected for CD4+ cell counts and HIV viral RNA 
levels. For select subjects residing outside the local area, blood samples may be 
collected at local clinics and sent to the NIH Clinical Center via overnight shipment for 
testing.  
 
All subjects will return to the NIH Clinical Center at week 84 and 96 to undergo the 
following procedures: 
 Medical history and a targeted physical examination, including weight, vital signs, 
and a symptom-directed evaluation based on symptoms or complaints reported by 
each participant. 
 Assessment of any new or unresolved AEs/intercurrent illnesses. 
 Blood collection for: 
o CBC with differential. 
o Chemistry panels, to include: ALT, AST, alkaline phosphatase, creatinine, 
total and direct bilirubin, and serum albumin levels. 
o Flow cytometry panel (includes CD4+ cell count). 


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o Plasma HIV viral RNA levels. 
o Storage of serum and PBMCs.  
 
If HIV viral RNA levels are detectable at week 84, the testing will be repeated at week 
88 and week 92 (if detectable at week 88). 
 
For subjects who meet criteria to re-start cART prior to week 72 (described in 
Section 3.1),  HIV RNA levels will be done every 4 weeks until levels fall below the 
limit of detection. 
 
As described in Section 3.1, subjects whose HIV RNA levels are below the limit of 
detection (<40 copies/ml) at week 72 may elect to continue on the ATI phase of the 
study and have their CD4 count and HIV RNA levels monitored every 2 weeks until 
HIV RNA levels become detectable or until the final study visit at week 92.  
 
If a subject with HIV RNA levels above the limit of detection (>40 copies/ml) at week 
72  refuses to restart cART (despite the protocol team’s recommendation to do so), 
the subject may continue to have CD4 count and HIV viral levels monitored every 2 
weeks until cART is restarted. If the subject continues to have measurable virema at 
the week 84 visit and continues to refuses to restart cART, the subject will be 
removed from the study and returned to the care of their private physician.  
 
For purposes of data analysis in the subjects described above, the HIV RNA level 
obtained at week 72 will be used for the secondary endpoint analysis.  
8 Study Procedures/Evaluations 
8.1 Clinical Evaluations 
 Medical history and physical examination 
 Deltoid skinfold measurement: The skin-pinch test measures the thickness of 
the cutaneous and subcutaneous tissue at the injection site of both upper arms 
(medial deltoid muscles). This measurement will be used to determine the depth of 
the injection for each eligible subject to ensure IM administration of the vaccine/ 
placebo prior to the first vaccination. The skin-thickness range and corresponding 
depth settings on the TDS-IM are described in the TDS-IM: Instructions for Use 
Manual.   
 Phlebotomy: Blood will be collected for routine serologic, hematologic, and clinical 
chemistry evaluations as described in Section 7.  
 Oral swabs: Subjects who develop oral lesions up to 7 days post-vaccination with 
rVSV/placebo will have the lesions tested for the presence of VSV shedding via 
RT/PCR analysis and in vitro virus culture via the rVSV viral infectivity assay. Vero 
cell cultures will be incubated with participant samples and examined by 


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microscopy for the presence of VSV-induced cytopathic effects. If cytopathic 
effects are observed, VSV titrations will be performed by a plaque assay to quantify 
the amount of virus being shed in test samples. Nucleotide sequence analysis will 
be performed on amplified virus from test sample(s) to verify the presence of VSV. 
All viral infectivity assays will be performed by Profectus Biosciences. 
 Assessment of reactogenicity: For all participants, reactogenicity assessments 
will be performed at baseline prior to any study vaccinations and subsequently 
after each vaccination. All reactogenicity symptoms will be followed until resolution 
and graded according to the Division of AIDS (DAIDS) Table for Grading the 
Severity of Adult and Pediatric Adverse Events, Version 1.0, December 2004 
(Clarification August 2009). 
The reactogenicity assessment period is 3 full days following each HIV-MAG pDNA 
vaccine/placebo injection and 7 full days following the rVSV- HIV gag vaccine/ 
placebo injection according to the schedule shown in Table 2 below. Participants 
will be instructed to record symptoms using a post-vaccination symptom log/diary 
card (see Appendix D) and to contact the site daily during the assessment period. 
Participants will also be instructed to contact the clinic for events that occur during 
the period between each vaccination and the next scheduled visit. In general, any 
participant who self-reports a post-vaccination reaction greater than moderate will 
be evaluated by a clinician within 48 hours after onset, unless the reaction is 
improving and/or has completely resolved.  
Table 2: Schedule of reactogenicity assessments 
Day 
Time 
Performed by 
0a 
Pain assessment immediate: post-vaccination 
OP8 staff 
 
Pain assessment 25-60 minutes: post-vaccination 
OP8 staff 
1 
Reactogenicity between 12:00 AM and 11:59 PM day 1 
OP8 staff or participant 
2 
Reactogenicity between 12:00 AM and 11:59 PM day 2 
OP8 staff or participant 
3 
Reactogenicity between 12:00 AM and 11:59 PM day 3 
OP8 staff or participant 
4-7 
Reactogenicity between 12:00 am and 11:59 pm days 4-7, for 
VSV HIV gag vaccine/placebo only  
OP8 staff or participant 
VSV=vesicular stomatitis virus. 
aDay of vaccination. 
8.2 Research Evaluations 
Leukapheresis: Will be performed for research studies including, but not limited to, 
measurements of  the frequency of CD4+ T cells carrying replication-competent HIV 
by quantitative coculture assays. These studies will determine the rate of decay of the 
CD4+ T-cell reservoir. If leukapheresis cannot be performed for technical reasons 
(e.g. poor venous access) 80 ml of heparinized blood will be drawn instead. 
Other research evaluations measuring the effect of the vaccinations on the HIV 
pathogenesis may include: 


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 Frequency of CD4+ T cells carrying HIV proviral DNA and cell-associated HIV 
RNA. 
 HIV burst size in CD4+ T cells in the presence of autologous CD8+ T cells. 
 Magnitude and breadth of HIV-specific CD4+ and CD8+ T-cell responses. 
 T-cell activation and soluble markers of inflammation. 
 Residual (1-40 copies/mL) plasma viremia. 
 VSV serology: The VSV neutralizing antibody titer will be evaluated to determine 
the magnitude of the immune response elicited to the vector. 
 HIV viral RNA levels. 
 Flow cytometry with CD4+ cell count. 
9 Potential Risks and Benefits 
9.1 Potential Risks 
General risks associated with vaccination/DNA vaccination 
Possible risks associated with vaccines include fever, chills, rash, arthalgias/myalgias, 
nausea, headache, dizziness, fatigue, and anaphylaxis. The theoretical risks of DNA 
vaccination could include the possible integration of plasmid DNA into the host 
genome, resulting in mutations, problems with DNA replication, triggering of 
autoimmune responses, and activation of cancer-causing genes. To date, there is no 
clear evidence from numerous clinical trials for integration of plasmid DNA into the 
host genome triggering autoimmune disease/neoplastic disease.   
 
HIV-MAG pDNA vaccine   
The HIV-MAG pDNA vaccine has been administered to approximately 150 individuals 
to date, and it appears to be well tolerated.  The vaccine plasmids HIV-1 gag/pol and 
HIV-1 nef/tat/vif, env are formulated in 0.25% bupivacaine, thus, there is a risk of 
allergic reaction from bupivacaine, including nausea, vomiting, chills, rash, urticaria, 
angioedema, bronchospasm, or anaphylaxis. Significant AEs, including cardiac arrest 
and death, have occurred following intravenous delivery of bupivacaine. In most 
cases, the events occurred following use of bupivacaine at a dose of 1.6 mg/kg. In the 
current study, bupivacaine will be administered IM at a dose of 2.5 mg/mL (maximum 
2 mL or 5 mg). A 70-kg person would receive a dose of 0.07 mg/kg per dose. 
Participants with a history of allergic reaction to amide-type local anesthetics 
(bupivacaine, lidocaine, mepivacaine, etidocaine, prilocaine) will be excluded from the 
study. 
                                                                                                                                                                 
IL-12 pDNA adjuvant    


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The IL-12 plasmid adjuvant is also formulated in 0.25% bupivacaine, so the risks 
associated with bupivacaine are also associated with this product (see HIV-MAG 
pDNA above).  
In addition, it is possible that administration of the IL-12 pDNA adjuvant might elicit 
antibodies that could affect the native IL-12 cytokine. In the HVTN-080 study, an 
assay was performed to test for the presence of IL-12 neutralizing antibody following 
administration of the IL-12 pDNA (1,000 µg or placebo). Results showed that 1 
subject tested positive for IL-12 neutralizing antibodies following vaccination (49 
NU/mL), but the subject also had a high levels (39 NU/mL) at baseline. Another 
subject was positive for IL-12 neutralizing antibodies at baseline (31 NU/mL) followed 
by lower post-vaccination levels (9 NU/mL).  
 
Electroporation  
EP has been associated with transient muscle contractions and injection-site 
discomfort, such as pain, soreness, bruising, redness, swelling, itching, and stiffness 
of the upper arm. The procedure also carries the theoretical risks of electrical injury or 
infection at the injection site, disruption of the function of the implanted electronic 
medical devices (e.g., pacemaker, implantable cardiac defibrillator), or the 
exacerbation of cardiac arrhythmias. Participants with a history of clinically significant 
cardiac arrhythmia (excluding sinus arrhythmia), pacemakers, implantable cardiac 
defibrillator, or certain metal implants will be excluded. Electroporation with the TDS 
device has been used in about 280 people to date who participated in clinical trials. 
Adverse responses reported in association with use of the device have been largely 
limited to acute discomfort during the procedure application, and transient injection-
site soreness of mild–to-moderate severity for up to 1 week following administration. 
 
rVSV HIV gag  
Results from a randomized, double-blind, placebo-controlled, dose-escalation study of 
60 healthy volunteers (HVTN 090) showed that local (Figure 9) and systemic (Figure 
10) reactogenicity was self-limited, mild-to-moderate in intensity, and increased with 
dose; headache was the common AE (52%) followed by malaise/fatigue (43%). At the 
highest dose (108 pfu), 92% of the subjects reported having systemic symptoms, 
including flu-like syndrome (41%), fever (41%), and moderate chills (33%). Of the AEs 
considered related to the study product and reported by 30% of participants, the 
following were experienced by >1 participant: lymphadenopathy (3), decreased 
neutrophil count (3), mouth ulceration (3), other oral lesions (3), presyncope (3), and 
upper respiratory tract infection (2). Other AEs considered related to the study product 
and reported by 1 person each were asthenia, axillary pain, injection-site hematoma, 
increased levels of AST, myalgia, dizziness, hypoesthesia (at the injection site), 
oropharyngeal pain, and hot flushes. No severe reactogenicity, encephalitis, or 
product-related SAEs were reported.  
 
VSV infection in humans is rare, but it can occur when animal handlers and 
veterinarians come in close contact with infected livestock and through inadvertent 


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exposure of laboratory personnel. The most common portals of infection in humans 
are skin and mucous membranes of the nose, mouth, and eyes, although there is also 
serological evidence that suggests that some vesiculoviruses may be directly 
transmitted to humans through insect bites. Human infection with VSV can either be 
asymptomatic, or it may lead to disease symptoms, which include myalgia, headache, 
fatigue, oral ulcers, and fever that resolve in 3–5 days without complications. Because 
the vaccine candidate is a live, replication competent vector, there is a theoretical risk 
of human disease, including neurologic manifestations. The vaccine vector was 
specifically attenuated to eliminate neurovirulence, which has been tested in sensitive 
animal models (refer to the investigator’s brochure for more information on 
neurovirulence testing). Furthermore, no evidence of encephalitis or other neurologic 
events was observed following administration of the vaccine in subjects participating 
in the HVTN 090 trial. However, as a precaution, subjects may not participate in the 
current study if they have a neurological/neuropsychiatric disorder that could be 
confused with reactions to the VSV HIV gag vaccine, or could interfere with the 
assessment of safety.  
 
There is also a hypothetical risk of eliciting autoimmune responses in vaccine 
recipients. This risk is based on the identification of a peptide octamer and other 
shorter peptides in the Indiana serotype VSV (VSVIN) N protein that are very similar in 
sequence to peptides found in Ro60kD, which bind the anti-Ro/SSA antibodies found 
in sera of subjects with systemic lupus erythematosis (SLE).40 Antibodies that bind the 
Ro protein can also be elicited in rabbits that are hyperimmunized with purified VSVIN 
N protein.41 In addition, antibodies have been detected in SLE subjects that cross 
react with the VSVIN M and, to a lesser extent, N core proteins, but at a much lower 
frequency to the VSVIN G protein.42 However, it is not clear what these observations 
mean since antibodies that react to the peptide octamer in Ro60kD account only for a 
small minority of the anti-Ro60kD auto-antibodies in SLE subjects.43 Also, the 
detection of antibodies in the sera of SLE subjects that react with the VSVIN M and N 
proteins, but not with the G protein, is puzzling, because the VSV G protein has 
strong antigenic properties and typically elicits a very robust and durable humoral 
immune response. Furthermore, the epidemiology of SLE does not support a specific 
role for VSVIN as a causative agent, since VSVIN is found only in the Americas, and 
the frequency of SLE in the United Kingdom and the USA is very similar.44 Based on 
the  literature currently available, there is no convincing evidence that infection with 
VSVIN leads to the development of SLE. 
 
Analytical treatment interruption  
The risks from a 16-week ATI performed under close virological and immunological 
monitoring are minimal in this subject population. There is a theoretical risk that ATI 
could lead to the development of HIV drug resistance. This may be a particular 
concern for individuals taking NNRTIs. However, this potential risk with NNRTIs is 
essentially eliminated by undertaking the procedures described in Section 3.1. Given 
the study population, the short duration of the ATI, the frequency of immunological 


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and virological monitoring, and strict criteria for restarting cART, it is extremely 
unlikely that the ATI will lead to the development of any opportunistic infections or 
AIDS-defining conditions. 
 
Leukapheresis 
The potential risks associated with leukapheresis include lightheadedness, dizziness, 
possible fainting, tingling around the mouth and in the fingers and toes, nausea, chills, 
vomiting, mild muscle cramps,  loss of <1 pint of blood, or pain, bruising, or discomfort 
at the needle insertion sites. More serious, but rare, complications include nerve 
damage at the needle insertion site, seizures and air embolism. Most procedures are 
performed without an incident. Blood components removed during leukapheresis are 
generally replaced by the body within a few hours or a few days. No infections 
associated with this procedure have been reported in thousands of cases performed 
over the last 10 years at the NIH.   
 
Phlebotomy  
This may be associated with discomfort, bruising, local hematoma formation and, on 
rare occasions, infections, lightheadedness, and fainting. The amount of blood drawn 
for research purposes will be within the limits allowed for adult subjects by the NIH 
CC (Medical Administrative Policy 95-9: Guidelines for Limits of Blood Drawn for 
Research Purposes in the Clinical Center: 
http://internal.cc.nih.gov/policies/list_policies.asp?index=med_chrono). 
 
HLA typing 
Some HLA types have been associated with an increased risk of certain diseases  
like arthritis and other rheumatologic disorders, or a faster progression to AIDS. HLA 
typing will be performed on samples collected from all the enrolled subjects. Results 
from the HLA typing will become part of each subject’s medical record at the NIH. 
Medical records containing this information are maintained in a secure place.  
9.2 Potential Benefits 
Improvement of HIV-specific immune control from the vaccine regimen is a potential 
benefit for subjects randomized to the vaccine arm.   
10  Research Use of Stored Human Samples, Specimens or Data 
 
Intended use: Stored blood samples and data collected under this protocol may be 
used to study the effect of the HIV-MAG pDNA vaccine prime in combination with the 
IL-12 pDNA adjuvant and the rVSV HIV gag booster vaccine on the virologic and 
immunologic parameters listed in Section 8.2. Samples may also be used to study 
other aspects of the immunopathogenesis of HIV infection or measure serum levels of 
antiretroviral agents during ATI.  
 
Storage: Access to stored samples will be limited using a locked room or a locked 
freezer. Samples and data will be stored using codes assigned by the investigators. 


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Data will be kept in password-protected computers. Only investigators will have 
access to the samples and data.  
 
Tracking: Samples will be tracked utilizing the repository operated by SAIC 
Frederick, Inc. Data will be stored and maintained in the NIAID CRIMSON database. 
 
Disposition at the completion of the protocol: At the completion of the protocol 
(termination), samples and data will either be destroyed, or after IRB approval, 
transferred to another existing protocol.  
 
Reporting the loss or destruction of samples/specimens/data to the IRB: 
 
Any loss or unanticipated destruction of the samples or data (for example, due to 
freezer malfunction) that meets the NIH Intramural protocol deviation definition or 
results in a deviation that compromises the scientific integrity of the data collected 
for the study will be reported to the NIAID IRB.  
 
Additionally, subjects may decide at any point not to have their samples stored. In 
this case, the principal investigator will destroy all known remaining samples and 
report what was done to the subject and the IRB. This decision will affect the 
subject’s participation in this protocol, but it may not affect participation in other 
protocols at the NIH.  
11 Remuneration Plan for Subjects 
Subjects will receive financial compensation for leukapheresis according to the NIH  
Clinical Center volunteer guidelines: $100 for a 2-pass leukapheresis procedure or $200 
for a 4-pass leukapheresis procedure.  
12 Assessment of Safety 
12.1 Documenting, Recording, and Reporting Adverse Events  
At designated visits with the subject, information regarding AEs will be elicited by 
appropriate questioning and examinations, and it will be:  
 Immediately documented in the electronic database and medical record. 
 Reported as outlined below (e.g., IND sponsor, IRB, Food and Drug 
Administration [FDA]). 
12.2 Definitions  
Adverse event  
An AE is any untoward or unfavorable medical occurrence in a human subject, 
including any abnormal sign (e.g., abnormal physical exam or laboratory finding), 
symptom, or disease temporally associated with the subject’s participation in the 
research, whether or not considered related to the research. 
 
Adverse reaction   
An adverse reaction (AR) is an AE that is caused by an investigational agent (drug 
or biologic). 


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Suspected adverse reaction  
A suspected AR (SAR) is an AE for which there is a reasonable possibility that the 
investigational agent caused the AE. ‘Reasonable possibility’ means that there is 
evidence to suggest a causal relationship between the drug and the AE. A SAR 
implies a lesser degree of certainty about the causality than an AR, which implies a 
high degree of certainty. 
 
Serious adverse event  
An SAE is an AE that results in one or more of the following outcomes: 
 Death. 
 A life-threatening (i.e., an immediate threat to life) event. 
 An inpatient hospitalization or prolongation of an existing hospitalization. 
 A persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions. 
 A congenital anomaly/birth defect. 
 A medically important event.* 
*Medical and scientific judgment should be exercised in deciding whether 
expedited reporting is appropriate in other situations, such as important medical 
events that may not be immediately life threatening or result in death or 
hospitalization, but they may jeopardize the subject or may require intervention to 
prevent one of the other outcomes listed above.  
 
Unexpected adverse event 
An AE is unexpected if it is not listed in the investigator’s brochure or package  
insert (for marketed products), or it is not listed at the specificity or severity that has 
been observed. It is the responsibility of the IND sponsor to make this 
determination. 
 
Serious and unexpected suspected adverse reaction  
A serious and unexpected suspected AR (SUSAR) is a SAR that is both serious 
and unexpected.   
 
Unanticipated problem  
An unanticipated problem (UP) is an event, incident, experience, or outcome that 
is—  
1. Unexpected in terms of nature, severity, or frequency in relation to— 
a. The research risks that are described in the IRB-approved research 
protocol and informed consent document; investigator’s brochure, or other 
study documents; and 
b. The characteristics of the subject population being studied; and 
2. Possibly, probably, or definitely related to participation in the research; and 
3. Places subjects or others at a greater risk of harm (including physical, 
psychological, economic, or social harm) than was previously known or 


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recognized (per the IND sponsor, an AE with a serious outcome will be 
considered increased risk). 
 
Unanticipated problem that is not an adverse event  
An unanticipated problem that is not an AE is incident, experience, or outcome that 
is not associated with an AE, which meets the 3 criteria of a UP. Examples include 
breaches of confidentiality, accidental destruction of study records, and  
unaccounted-for study drug. 
 
Protocol Deviation 
Any change, divergence, or departure from the IRB approved study procedures in 
a research protocol. Protocol deviations are designated as serious or non-serious 
and further characterized as: 
 
1. Those that occur because a member of the research team deviates from the 
protocol. 
2. Those that are identified before they occur, but cannot be prevented. 
3. Those that are discovered after they occur 
 
 
Serious Protocol Deviation: A deviation that meets the definition of a Serious 
Adverse Event or compromises the safety, welfare or rights of subjects or others. 
 
 
Non-compliance: The failure to comply with applicable NIH HRPP policies, IRB 
requirements, or regulatory requirements for the protection of human subjects. 
Non-compliance is further characterized as: 
1. Serious: Non-compliance that 
a. Increases risks, or causes harm, to participants 
b. Decreases potential benefits to participants 
c. Compromises the integrity of the NIH-HRPP 
d. Invalidates the study data 
2. Continuing: Non-compliance that is recurring 
3. Minor: Non-compliance that, is neither serious nor continuing. 
Protocol specified events 
Protocol specified events are AEs specified in the protocol that the principal 
investigator, IND sponsor, or medical monitor would like to review in real time 
rather than weeks or months later, when they would otherwise appear in various 
line listings. These events may or may not also be SAEs.  
12.3 Investigator Assessment of Adverse Events 
If a diagnosis is clinically evident (or subsequently determined), the diagnosis 
rather than the individual signs and symptoms or lab abnormalities will be recorded 
as the AE. 
 


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All AEs occurring from the time when the first vaccine dose is administered through 
the specified study follow-up period, recorded, and reported. The principal 
investigator will evaluate all AEs with respect to Seriousness (criteria listed 
above), Severity (intensity or grade), and Causality (relationship to study agent 
and relationship to research) according to the following guidelines.  
12.3.1 Severity 
The principal investigator will grade the severity of each AE according to the 
Division of Aids Table for Grading the Severity of Adult and Pediatric Adverse 
Events Version 1.0, December, 2004, (Clarification August 20) which can be 
found at:   
http://rsc.techres.com/Document/safetyandpharmacovigilance/Table_for_Gradin
g_Severity_of_Adult_Pediatric_Adverse_Events.pdf  
  
Subjective reactogenicity symptoms (such as malaise, fatigue, injection site 
pain, headache, chills) will not be given a grade 3 score unless they persist for 
>3 days. 
 
Some grade 1 lab parameters on the DAIDS toxicity table (fibrinogen, low 
calcium levels, high fasting glucose, low phosphate levels, low potassium levels, 
low sodium levels, elevated uric acid levels [males only]) fall within the NIH lab 
reference range for normal values. These normal values will not be reported as 
grade 1 AEs. The grade 1 values for these tests will be reported as follows: 
 
Fibrinogen: 100–176 mg/dL. 
 
Phosphate (low): There is no grade 1 reportable value.  
 
Sodium (low): 130–134 mmol/L. 
 
Potassium (low): 3.0–3.2 mmol/L. 
 
Calcium (low): 1.95–2.04 mmol/L. 
 
Glucose (high, fasting): 116–125 mg/dL. 
 
Uric Acid (males): 8.7–10.0 mg/dL.  
12.3.2 Causality    
Causality (likelihood that the event is related to the study agent) will be  
assessed considering the factors listed under the following categories:  
 
Definitely related 
   
 
Reasonable temporal relationship. 
 
Follows a known response pattern. 
 
Clear evidence to suggest a causal relationship. 
 
There is no alternative etiology. 
 
Probably related 
 
 
Reasonable temporal relationship. 


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 
Follows a suspected response pattern (based on similar agents). 
 
No evidence of a more likely alternative etiology. 
 
Possibly related 
 
Reasonable temporal relationship. 
 
Little evidence for a more likely alternative etiology. 
 
Unlikely related  
 
Does not have a reasonable temporal relationship.  
OR 
 
Good evidence for a more likely alternative etiology. 
 
Not related 
 
 
Does not have a temporal relationship.          
OR 
 
Definitely due to an alternative etiology. 
 
Note:    
Other factors (e.g., dechallenge, rechallenge) should also be considered for 
each causality category when appropriate. Causality assessment is based on 
available information at the time of the assessment of the AE. The investigator 
may revise the causality assessment as additional information becomes 
available. 
12.4 Investigator Reporting Responsibilities to the Sponsor  
12.4.1 Adverse Events 
Line listings, frequency tables, and other summary AE data will be submitted to 
the IND sponsor per the Safety Review and Communications Plan (SRCP – see 
below), or as needed for periodic safety assessments, review of IND annual 
reports, review of IND safety reports, and preparation of final study reports. 
12.4.2 Serious Adverse Events 
SAEs (whether or not they are also UPs) must be reported on the SAE/UP report  
form and sent  to the sponsor Clinical Safety Office (CSO) by fax or e-mail 
attachment. Deaths and immediately life-threatening SAEs must be reported 
within 1 business day after the site becomes aware of the event. All other SAEs 
must be reported within 3 business days of site awareness.  
 
Sponsor clinical safety office contact information:  
OCRPRO Clinical Safety Office 
5705 Industry Lane 
Frederick, MD 21704 


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Phone 301-846-5301 
Fax 301-846-6224 
E-mail: rchspsafety@mail.nih.gov  
12.4.3 Unanticipated Problems 
Non-serious AEs that are UPs must also be reported on the SAE/UP report form 
and sent to the CSO by fax or e-mail attachment no later than 7 calendar days 
of site  awareness of the event. UPs that are not AEs are not reported to the 
sponsor CSO.  
12.4.4 Protocol Specified Events  
Autoimmune disorders are AEs of special interest. A sample list of autoimmune 
disorders is provided in Appendix C. These protocol specified events must be 
reported to the CSO on a SAE/UP report form within 3 business days of site the 
awareness.   
12.4.5 Pregnancy 
Pregnancy itself is not an AE. However, complications of pregnancies are AEs 
and may be SAEs. Pertinent obstetrical information for all pregnancies, including 
pregnancies disclosed by the subject as occurring in a partner of a male subject, 
will be reported to the CSO via fax or e-mail within 3 business days from the site 
awareness of the pregnancy.   
 
Pregnancy outcome data (e.g., delivery outcome, spontaneous or elective 
termination of the pregnancy) will be reported to the CSO within 3 business days 
of the site awareness on a protocol-specified form. In the event of pregnancy, 
the following steps will be taken: 
 Discontinuation of the study agents. 
 Unblind per the unblinding section of the protocol. 
 Withdraw from the study but continue following for safety. 
 Report to safety oversight committee (Data and Safety Monitoring Board 
[DSMB]) and the IRB. 
 Advise research subject to notify the obstetrician of study agent exposure. 
12.5 Investigator Reporting Responsibilities to the NIAID IRB   
12.5.1 Expedited Reporting to the NIAID IRB 
 
Serious and non-serious Unanticipated Problems, deaths, serious deviations, 
and serious or continuing non-compliance will be reported within 7 calendar 
days of investigator awareness. SAEs that are possibly, probably, or definitely 
related to the research will be reported to the NIAID IRB within 7 calendar 
days of investigator awareness, regardless of expectedness. 


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12.5.1.1.  Waiver of Reporting Anticipated Protocol Deviations, Expected 
UP nonAEs and Deaths to the NIAID IRB 
 
Anticipated deviations in the conduct of the protocol will not be reported 
to the IRB unless they occur at a rate greater than anticipated by the 
study team. Expected adverse events will not be reported to the IRB 
unless they occur at a rate greater than that known to occur in HIV(+) 
population. If the rate of these events exceeds the rate expected by the 
study team, the events will be classified and reported as though they are 
unanticipated problems. Deaths related to the natural history of HIV (+) 
population will be reported at the time of continuing review. 
12.5.2 Annual Reporting to the NIAID IRB  
The following items will be reported to the NIAID IRB in summary at the time of 
continuing review: 
 
Serious and non-serious unanticipated problems  
 
Expected serious adverse events that are possibly, probably, or 
definitely related to the research 
 
Serious adverse events that are not related to the research 
 
All adverse events, except expected AEs and deaths granted a waiver 
of reporting.  
 
Serious and Non-Serious Protocol deviations  
 
Serious, continuing, and minor non-compliance 
 
Any trends or events which in the opinion of the investigator should be 
reported 
12.6 Follow-up of Adverse Events and Serious Adverse Events 
AEs that occur following enrollment of subjects (i.e., after the first vaccination) are 
followed until the final outcome is known or until the end of the study follow-up 
period.  
 
SAEs that have not resolved by the end of the follow-up period are followed until the 
final outcome is known. If it is not possible to obtain a final outcome for an SAE 
(e.g., the subject is lost to follow up), the reason a final outcome could not be 
obtained will be recorded by the investigator on the  SAE/UP report form.  
 
SAEs that occur after study completion (month 24) that are reported to and are 
assessed by the investigator to be possibly, probably, or definitely related must be 
reported to the CSO, as described above. 
12.7 Sponsor’s Reporting Responsibilities 
SUSARs as defined in 21 Code of Federal Regulations (CFR) 312.32 and 
determined by the IND sponsor will be reported to the FDA and all participating 
investigators as IND safety reports.  


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The IND sponsor will also submit an IND annual report of the progress of the 
investigation to the FDA as defined in 21 CFR 312.33.  
12.8 Halting Criteria for the Protocol  
Halting the study requires immediate discontinuation of the study agents  
administered for all subjects and suspension of enrollment until a decision is made 
about whether or not to continue study agent administration.   
 
 
The halting criteria (as determined by the study principal investigator and IND 
sponsor secondary to aggregate data review) for this study include: 
 
Any SAE or grade 4 AE that is possibly, probably, definitely related to the study 
agent; OR 
 
Any death; OR 
 
Any safety issue that the study principal investigator or IND sponsor 
determines should halt the study.  
 
Any related AE that is ≥ grade 3 (not including transient, subjective reactogenicity 
symptoms such as malaise, fatigue, injection site pain, headache, chills) will be 
reviewed within 48 hours of site awareness, by the principal investigator and IND 
sponsor medical monitor, to consider the need for halting the protocol. 
 
The IRB, the IND sponsor, DSMB, or the FDA may halt the study at any time due 
to safety concerns.  
 
Halting is carried out by or through the principal investigator (or designee if 
unavailable) within 24 hours of the decision to halt the trial, regardless of the party 
initiating the halt, whether the halt is due to the criteria defined above or another 
issue. 
12.8.1 Reporting of Study Halting 
If the study is halted, a description of the event(s) or safety issue must be 
reported by the principal investigator within 1 business day to the sponsor CSO 
and the NIAID IRB by fax or e-mail.  
12.8.2 Resumption of a Halted Study 
The IND sponsor, in collaboration with the principal investigator and the DSMB, 
will determine if it is safe to resume the study. The IND sponsor will notify the 
principal investigator of this decision. The conditions for resumption of the 
study will be defined in this notification. The principal investigator will notify the 
IRB of the decision to resume the study. 
12.9 Pausing Criteria for a Subject or Group  


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The decision to suspend administration of the study agent(s) for a single subject,  
or for all the subjects in the study, requires discontinuation of the study agent 
administrated for the study subject(s) until a decision is made whether or not to 
continue study agent administration.   
 
The pausing criteria for a single subject or for all the subjects in this study include:  
 
 A subject or 3 subjects experience an SAE or grade 3 or greater AE (not 
including transient, subjective reactogenicity symptoms such as malaise, 
fatigue, injection site pain, headache, chills, or total bilirubin in subjects taking 
atazanavir)  that is unexpected (as determined by the IND sponsor) and is 
possibly, probably, or definitely  related to the study agent;  
OR 
 2 subjects experience grade 4 local or systemic reactogenicity symptom(s) or 
AE that is considered to be related to the study vaccination. 
            OR 
 Any safety issue that the site investigator determines should pause 
administration of the study agent to a single subject or to all the subjects in the 
study. 
 The IND sponsor, in collaboration with the principal investigator , may also 
pause for an individual subject or the entire group if a safety concern is identified 
during routine aggregate data analysis. 
12.9.1 Reporting of Pausing for a Subject or Group 
If a pausing requirement is met, a description of the AE(s) or safety issue must 
be reported by the principal investigator by fax or e-mail within 1 business day 
to the sponsor CSO, principal investigator, IRB, and the DSMB.    
12.9.2 Resumption of Pausing for a Subject or Group 
The IND sponsor in collaboration with the principal investigator and/or the 
relevant DSMB will determine if it is safe to resume administration of the study 
agents to the subject/group. The IND sponsor will notify the principal 
investigator of this decision. The principal investigator will notify the IRB of the 
decision to resume administration of the study agent prior to resumption. 
12.10 Withdrawal Criteria for an Individual Subject 
An individual subject will be withdrawn for any of the following:  
 An individual subject’s decision.  
(The investigator will attempt to determine the reason for the subject’s decision,  
and will strongly suggest a follow-up plan to help ensure the subject safely 
returns to baseline or better, if possible). 
 Co-enrollment in a study with an investigational research agent (rare exception 
allowing the continuation of the study vaccinations granted by the principal 
investigator).  


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 2 consecutive viral loads >400 copies/mL while on cART during the vaccination 
phase of the study. 
 Development of an AIDS defining opportunistic infection (OI). Any subject who 
develops an AIDS OI will have repeat assessments of of CD4 counts weekly 
until counts rise to >200 cells/mm3 on at least 2 successive assessments”. 
 2 consecutive CD4 counts showing a >30% decline from pre-vaccination 
baseline or an absolute CD4 cell count <350 cells/mm3 while on cART during 
the vaccination phase of the study. 
 Any SAE or grade 4 local or systemic reactogenicity symptom, lab abnormality, 
or AE that is subsequently considered to be related to the study vaccination(s). 
 Clinically significant type 1 hypersensitivity reaction associated with the study 
vaccination(s). In the event of a type 1 hypersensitivity reaction that is NOT 
considered to be clinically significant, (e.g., brief, mild, and self limited skin 
reaction without other symptoms), the principal investigator, in consultation with 
the sponsor medical monitor, may consider possible additional vaccinations 
with appropriate precautions. 
 Any clinical AE, laboratory abnormality, or other medical condition or situation 
such that continued participation in the study would not be in the best interest 
of the subject. Subjects will be followed for the duration of the study for 
indicated safety assessments. 
 Non-compliance with study procedures to the extent that it is potentially harmful 
to the subject or to the integrity of the study data. 
 Pregnancy. 
 Participant misses more than 1 study vaccinations. 
 
If possible, all subjects who discontinue the study treatment prematurely will be 
followed through week 56 for all the study evaluations. 
12.11 Replacement for Withdrawn Subjects 
Any subject who withdraws from the study, or who discontinues the study 
vaccinations, prematurely before the 28th day of the last study vaccination, and 
whose reasons for withdrawing from the study or discontinuing study vaccination 
administration are unrelated to any real or perceived effect of the study 
vaccinations or their administration, will be replaced.  
12.12 Safety Oversight 
12.12.1 Safety Review and Communications Plan  
An SRCP has been developed for the protocol. The SRCP is an internal 
communications document between the principal investigator and the IND 
sponsor CSO, which delineates the safety oversight responsibilities of the 
principal investigator, the CSO, and other stakeholders. The SRCP also 


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includes the overall plan for conducting periodic safety surveillance 
assessments.  
12.12.2 Sponsor Medical Monitor  
A medical monitor, representing the IND sponsor (OCRPRO), has been 
appointed for the safety oversight in this clinical study. The sponsor medical 
monitor will be responsible for performing safety assessments as outlined in the 
SRCP.  
12.12.3 Data and Safety Monitoring Board  
The NIAID intramural DSMB will review the study prior to initiation and twice a 
year thereafter. The Board may convene additional reviews as necessary. The 
Board will review the study data to evaluate the safety, efficacy, study progress, 
and conduct of the study. All SAEs, all UPs, and all IND safety reports will be 
reported by the principal investigator to the DSMB at the same time they are 
submitted to the IRB or IND sponsor. The principal investigator will notify the 
DSMB of any cases of intentional or unintentional unblinding as soon as 
possible. The principal investigator will notify the Board at the time when 
pausing or halting criteria are met and obtain a recommendation concerning 
continuation, modification, or termination of the study. The principal investigator 
will submit the written DSMB summary reports with recommendations to the 
IRB.  
13 Clinical Monitoring Structure 
13.1 Site Monitoring Plan  
As per International Conference on Harmonization (ICH) Good Clinical Practice 
(GCP) 5.18 FDA 21 CFR 312.50, if under IND, clinical protocols are required to be 
adequately monitored by the study sponsor. This study monitoring will be 
conducted according to the NIAID Intramural Clinical Monitoring Guidelines. 
Monitors under contract to the NIAID/OCRPRO will visit the clinical research site to 
monitor aspects of the study in accordance with the appropriate regulations and 
the approved protocol. The objectives of a monitoring visit will be: 1) to verify the 
existence of signed informed consent documents and documentation of the 
informed consent form process for each monitored subject; 2) to verify the prompt 
and accurate recording of all monitored data points, and prompt reporting of all 
SAEs; 3) to compare abstracted information CRIMSON data abstracts with 
individual subjects’ records and source documents (subjects’ charts, laboratory 
analyses and test results, physicians’ progress notes, nurses’ notes, and any other 
relevant original subject information); and 4) to help ensure that investigators are in 
compliance with the protocol. The monitors also will inspect the clinical site 
regulatory files to ensure that regulatory requirements (Office for Human Research 
Protections [OHRP]), FDA, and applicable guidelines (ICH-GCP) are being 


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followed. During the monitoring visits, the investigator (and/or designee) and other 
study personnel will be available to discuss the study progress and monitoring visit. 
 
The investigator (and/or designee) will make the study documents (e.g., consent 
forms, CRIMSON data abstracts, and pertinent hospital or clinical records readily 
available for inspection by the local IRB, the FDA, the site monitors, and the NIAID 
staff for confirmation of the study data.  
 
A specific protocol monitoring plan will be discussed with the principal investigator 
and study staff prior to enrollment. The plan will outline the frequency of the 
monitoring visits based on factors such as the study enrollment, data collection 
status, and regulatory obligations.  
13.1.1 Study Blinding and Unblinding 
Study participants and site staff (except for the NIH pharmacists) will be blinded 
to the participant treatment arm assignments (e.g., active vaccine or control). 
Any discussion about the study product assignment between the pharmacy staff 
and any other protocol staff is prohibited. The DSMB members also are 
unblinded to the treatment assignment for the review of trial safety.  
When a participant leaves the trial prior to study completion, the participant will 
be told he or she must wait until the all the participants are unblinded to learn 
about his or her treatment assignment.  
Emergency unblinding decisions will be made by the principal investigator. if 
time permits, the sponsor medical monitor will be consulted before emergency 
unblinding occurs. 
14 Compliance With NIH Guidelines for Research Involving Products Containing 
Recombinant DNA 
Because this study is evaluating products containing recombinant DNA, it must comply 
with regulations set forth in the NIH’s Guidelines for Research Involving Recombinant 
DNA Molecules. Information about the study must be submitted to site Institutional 
Biosafety Committees and must be approved before participants are enrolled in the 
study. IBC review and approval must be documented by the investigator and submitted 
as part of protocol registration for this trial. 
The NIH guidelines also require that human gene transfer trials conducted at or 
sponsored by institutions that receive NIH funds must be submitted to the NIH Office of 
Biotechnology Activities for review by the Recombinant DNA Advisory Committee.  
The study team and DAIDS will ensure that reporting requirements to the Recombinant 
DNA Advisory Committee, as outlined in Appendix M-I-C-1.Initiation of the Clinical 
Investigation, Appendix M-I-C-3.Annual Reports, and Appendix M-I-C-4.Safety Reporting 
are satisfied per the NIH guidelines. 


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15 Statistical Considerations 
15.1 Study Hypotheses 
The study will test the hypothesis that therapeutic vaccination with the HIV-MAG 
pDNA vaccine prime in combination with the IL-12 pDNA adjuvant and the rVSV 
HIV gag booster will have acceptable safety and tolerability in a population of 
virally suppressed HIV-infected subjects who began cART during acute or early 
infection. The study will also test the hypothesis that HIV-specific immune 
responses induced by this vaccination strategy will have clinically significant 
antiviral activity in the absence of cART. 
15.2 Sample Size Justification  
The primary outcome for this study is the occurrence of SAEs or grade 3 or higher 
AEs. The probability of at least 1 such event among 15 vaccine recipients is 1-(1-
P),15 where P is the probability that a given person has the event. Table 3 shows, 
for different values of P, the probability of observing at least 1 vaccine participant 
with an AE of probability P. For instance, P=.05 corresponds to an AE that occurs 
in about 5% of participants; the probability of this AE being observed for at least 1 
of the 15 vaccine recipients is approximately 54%. This means that we cannot be 
confident of observing relatively rare events with a probability of 5% or less. On the 
other hand, the probability of observing at least 1 vaccine participant with an AE of 
probability 15% is approximately 91%. This means that if we do not observe 
anyone with a given type of AE, we can be relatively confident that it occurs in 
fewer than 15% of the population. 
 
Table 3: Probability of observing at least 1 vaccine recipient out of 15 with an 
AE that has probability P of occurring in a given participant 
P =.05 
P =.10 
P =.15 
P =.20 
P=.25 
54% 
79% 
91% 
96% 
99% 
 
The power for a comparison of the 2 arms with respect to a given AE is low unless 
the event probability is high in the vaccine arm and very low in the placebo arm. For 
example, if the AE probabilities in the 2 arms are .55 and .05, then power using 
Fisher’s exact test is approximately 82%. 
 
To compute the power for the secondary outcome of difference in plasma viremia at 
the end of the ATI phase of the study, we needed to estimate the standard deviation 
of rebound plasma viremia in log10 units. We used data from Rosenberg et al38 and 
Grijsen et al.45 The Rosenberg study had a similar design to the one being 
contemplated here, namely randomization to vaccine or placebo among acutely 
infected participants followed by ART interruption and determination of viral levels 
17-23 weeks following interruption. Rosenberg et al do not give the  standard 
deviation, but back calculation of this quantity from the confidence interval given 


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suggests a standard deviation between 0.64 and 0.90. The Grijsen study had an 
estimated standard deviation of close to 1 in the ART treatment arms, though their 
measure of rebound plasma viremia was determined following a longer period of 
time (36 weeks) from the treatment interruption. To be conservative, we decided to 
adopt the larger standard deviation of 1. Although the Wilcoxon rank sum test will 
be used to compare the 2 groups with respect to viremia, power for the Wilcoxon 
test is very close to that of the t-test (the asymptotic relative efficiency is 
approximately 95%). Therefore, we approximated power for the Wilcoxon test by 
that of the t-test. The power based on a 2-sample t-test with a 2-tailed alpha of .05 
and a total sample size of 30 is approximately 91% to detect a 1.25 log10 reduction 
in the rebound plasma viremia.   
16 Ethics/Protection of Human Subjects 
16.1 Informed Consent Process 
Informed consent is a process where information is presented to enable persons to 
decide voluntarily whether or not to participate as a research subject. It is an on-
going conversation between the human research subject and the researchers, 
which begins before consent is given and continues until the end of the subject's 
involvement in the research. Discussions about the research will provide essential 
information about the study and include: purpose, duration, experimental 
procedures, alternatives, risks, and benefits. Subjects will be given the opportunity 
to ask questions and have the questions answered.  
 
The subjects will sign the informed consent document prior to undergoing any 
research procedures. The subjects may withdraw consent at any time throughout 
the course of the trial. A copy of the informed consent document will be given to 
the subjects for their records. The researcher will document the process of signing 
the consent form in the subject’s medical record. The rights and welfare of the 
subjects will be protected by emphasizing to them that the quality of their medical 
care will not be adversely affected if they decline to participate in this study.  
16.2 Subject Confidentiality 
All records will be kept confidential to the extent provided by federal, state, and 
local law. The study monitors and other authorized representatives of the sponsor 
may inspect all documents and records required to be maintained by the 
investigator, including, but not limited to, medical records. Records will be kept 
locked and all computer entry and networking programs will be done with coded 
numbers only. Clinical information will not be released without written permission of 
the subject, except as necessary for monitoring by the IRB, FDA, NIAID, OHRP, 
pharmaceutical supporter(s), or the sponsor’s designee. 
17 Data Handling and Record Keeping 


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17.1 Data Management Responsibilities 
The investigator is responsible for assuring that the data collected are complete, 
accurate, and recorded in a timely manner. Source documentation (the point of 
initial recording of information) should support the data collected in the electronic 
data system and must be signed and dated by the person recording and/or 
reviewing the data.  
17.2 Data Capture Methods 
Study data will be collected at the study site and maintained on an electronic data 
system (CRIMSON). These forms or systems are to be completed on an ongoing 
basis during the study. Data entered into electronic data systems shall be 
performed by authorized individuals. Corrections to electronic data systems shall 
be tracked electronically (password protected or through an audit trail) with the 
time, date, individual making the correction, and what was changed.  
17.3 Types of Data 
Source documents include, but are not limited to, subjects’ medical records, 
laboratory reports, ECG tracings, x-rays, radiologist’s reports, biopsy reports, 
ultrasound photographs, progress notes, pharmacy records, and any other similar 
reports or records of procedures performed during the subjects’ participation in the 
study. 
17.4  Source Documents and Access to Source Data/Documents 
Source documents include all recordings of observations or notations of clinical 
activities, and all reports and records necessary for the evaluation and 
reconstruction of the clinical trial. Data from the CRIMSON Data System will be 
collected directly from subjects during study visits and telephone calls, or will be 
abstracted from subjects’ diaries/memory cards and medical records. Each 
subject’s medical record must record his/her participation in the clinical trial and, 
after unblinding, study treatment/vaccination (with doses and frequency) or other 
medical interventions or treatments administered, as well as any AEs experienced 
during the trial.  
17.5 Record Retention 
The investigator is responsible for retaining all the essential documents listed in the 
ICH GCP guidelines. All essential documentation for all the study subjects are to 
be maintained by the investigators in a secure storage facility for a minimum of 3 
years per NIAID policies. The FDA requires study records to be retained for up to 2 
years after marketing approval or disapproval (21 CFR 312.62), or until at least 2 
years have elapsed since the formal discontinuation of clinical development of the 
investigational agents for a specific indication. These records are also to be 
maintained in compliance with IRB, state, and federal medical records-retention 


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requirements, whichever is longest. All stored records are to be kept confidential to 
the extent required by federal, state, and local law.  
 
 


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37. 
Jacobson JM, Pat Bucy R, Spritzler J, et al. Evidence that intermittent structured 
treatment interruption, but not immunization with ALVAC-HIV vCP1452, promotes host 
control of HIV replication: the results of AIDS Clinical Trials Group 5068. The Journal of 
infectious diseases 2006;194:623-32. 
38. 
Rosenberg ES, Graham BS, Chan ES, et al. Safety and immunogenicity of therapeutic 
DNA vaccination in individuals treated with antiretroviral therapy during acute/early HIV-
1 infection. PLoS One 2010;5:e10555. 
39. 
Routy JP, Boulassel MR, Nicolette CA, Jacobson JM. Assessing risk of a short-term 
antiretroviral therapy discontinuation as a read-out of viral control in immune-based 
therapy. J Med Virol 2012;84:885-9. 


                                                                                           HIV-MAG pDNA vaccine version 6.0 
           August 14, 2015 
 
Page 69 of 72 
40. 
Scofield RH, Harley JB. Autoantigenicity of Ro/SSA antigen is related to a nucleocapsid 
protein of vesicular stomatitis virus. Proc Natl Acad Sci U S A 1991;88:3343-7. 
41. 
Huang SC, Pan Z, Kurien BT, James JA, Harley JB, Scofield RH. Immunization with 
vesicular stomatitis virus nucleocapsid protein induces autoantibodies to the 60 kD Ro 
ribonucleoprotein particle. Journal of investigative medicine : the official publication of 
the American Federation for Clinical Research 1995;43:151-8. 
42. 
Hardgrave KL, Neas BR, Scofield RH, Harley JB. Antibodies to vesicular stomatitis virus 
proteins in patients with systemic lupus erythematosus and in normal subjects. Arthritis 
and rheumatism 1993;36:962-70. 
43. 
Routsias JG, Sakarellos-Daitsiotis M, Detsikas E, Tzioufas AG, Sakarellos C, 
Moutsopoulos HM. Antibodies to EYRKK vesicular stomatitis virus-related peptide 
account only for a minority of anti-Ro60kD antibodies. Clinical and experimental 
immunology 1994;98:414-8. 
44. 
Symmons DP. Review of UK data on the rheumatic diseases--8. SLE. British journal of 
rheumatology 1991;30:288-90. 
45. 
Grijsen ML, Steingrover R, Wit FW, et al. No treatment versus 24 or 60 weeks of 
antiretroviral treatment during primary HIV infection: the randomized Primo-SHM trial. 
PLoS Med 2012;9:e1001196. 
 
 
 


                                                                                        HIV-MAG pDNA vaccine version 6.0  
August 14, 2015 
 
Page 70 of 72 
Appendix B: Schedule of Evaluations 
 
See attached document.  
 


HIV-MAG pDNA vaccine version 6.0 
August 14, 2015 
 
Appendix C: AEs of Special Interest 
 
AEs of special interest for this protocol include, but are not limited to, autoimmune disorders; 
representative examples of AES of special interest are listed below.  
Neuroinflammatory disorders 
 
Optic neuritis 
Myasthenia gravis 
Multiple sclerosis  
Encephalitis 
Demyelinating disease 
Neuritis 
Transverse myelitis 
Bell’s palsy 
Guillain-Barré syndrome 
 
 
Musculoskeletal disorders 
 
Systemic lupus erythematosus 
Juvenile rheumatoid arthritis 
Cutaneous lupus 
Polymyalgia rheumatic 
Sjogren’s syndrome 
Reactive arthritis 
Scleroderma, dermatomyositis 
Psoriatic arthropathy 
Polymyositis 
Ankylosing spondylitis 
Rheumatoid arthritis 
Spondyloarthropathy 
 
Gastrointestinal disorders 
 
Crohn’s disease 
Celiac disease 
Ulcerative colitis 
 
 
Metabolic diseases 
 
Autoimmune thyroiditis 
Insulin-dependent diabetes mellitus  
Grave’s or Basedow’s disease 
Addison’s disease 
Hashimoto thyroiditis 
Insulin-dependent diabetes mellitus  
 
Skin disorders 
 
Psoriasis 
Erythema nodosum 
Vitiligo 
Autoimmune bullous skin diseases 
Raynaud’s phenomenon 
 
Others 
 
Autoimmune hemolytic anemia 
Primary sclerosing cholangitis 
Idiopathic thrombocytopenic purpura 
Autoimmune glomerulonephritis 
Antiphospholipid syndrome 
Autoimmune uveitis 
Temporal arteritis 
Autoimmune cardiomyopathy 
Behcet’s syndrome 
Sarcoidosis 
Pernicious anemia 
Stevens-Johnson syndrome 
Autoimmune hepatitis 
Vasculitides 
Primary biliary cirrhosis 
 
 
 
 


                                                                                        HIV-MAG pDNA vaccine version 6.0  
August 14, 2015 
 
Page 72 of 72 
Appendix D: Vaccine Diary Card 
 
See attached document.  

ICF_001.pdf: 
 
 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
   MEDICAL RECORD 
               •  Adult Patient or     •  Parent, for Minor Patient 
 
 
INSTITUTE: 
National Institute of Allergy and Infectious Diseases 
 
 
STUDY NUMBER: 
13-I-0141 
PRINCIPAL INVESTIGATOR: Michael C. Sneller, MD  
 
 
STUDY TITLE: 
A Phase I Randomized, Double-Blind, Placebo-Controlled Study of a Multi-Antigen DNA Vaccine 
Prime Delivered by In Vivo Electroporation, rVSV Booster Vaccine in HIV-Infected Patients Who 
Began Antiretroviral Therapy During Acute/Early Infection 
 
 
Continuing Review Approved by the IRB on 03/09/15 
 
 
 
 
 
Amendment Approved by the IRB on 08/19/15 (F) 
 
 
Date Posted to Web:  08/29/15 
Standard 
 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL 
 
RESEARCH STUDY 
 
•   Adult Patient or    •   Parent, for Minor Patient 
 
NIH-2514-1 (07-09) 
 
P.A.: 09-25-0099 
 
File in Section 4:  Protocol Consent (1) 
 
 
INTRODUCTION 
 
We invite you to take part in a research study at the National Institutes of Health (NIH). 
 
First, we want you to know that: 
 
 
Taking part in NIH research is entirely voluntary. 
 
 
You may choose not to take part, or you may withdraw from the study at any time.  In either case, you will not 
lose any benefits to which you are otherwise entitled.  However, to receive care at the NIH, you must be taking 
part in at least one study or be under evaluation for study participation. 
 
 
You may receive no benefit from taking part.  The research may give us knowledge that may help people in the 
future. 
 
Second, some people have personal, religious or ethical beliefs that may limit the kinds of medical or research treatments 
they would want to receive (such as blood transfusions).  If you have such beliefs, please discuss them with your NIH 
doctors or research team before you agree to the study. 
 
Now we will describe this research study.  Before you decide to take part, please take as much time as you need to ask 
any questions and discuss this study with anyone at NIH, or with family, friends or your personal physician or other 
health professional. 
 
PURPOSE OF THE STUDY 
 
You are invited to participate in this study because you: 
• 
Are infected with the human immunodeficiency virus (HIV), and 
• 
Began your HIV treatment shortly after becoming infected, and 
• 
Are currently on an HIV-treatment regimen and are willing to interrupt your HIV treatment for 16 weeks  


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
13-I-0141 
CONTINUATION:  page  2  of  12  pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
In most people infected with HIV, their immune system (the body’s normal ability to fight off disease) can’t control or 
cure the infection. Combination antiretroviral therapy (‘cART’ – a combination of anti-HIV drugs taken daily) can keep the 
amount of HIV virus very low for a long time. However, if treatment is stopped, the immune system isn’t able to control 
the infection, and HIV levels go up again. Also, cART doesn’t completely remove HIV from your body. 
 
The purpose of this study is to see how well people with HIV tolerate “therapeutic vaccination.” Therapeutic vaccination 
means giving a vaccine to TREAT an infection that someone already has (HIV in this case). Normally, we give vaccines to 
PREVENT a person from getting infections (for example, there are vaccines to prevent the flu and the measles).  
 
We also want to see how levels of HIV, CD4 cells (the ‘good’ immune cells that are damaged by HIV), and other 
measures of HIV infection change after a person receives this vaccination. We plan to show this by stopping cART after 
some people have been given therapeutic vaccination and others have been given a placebo (a salt water-like solution 
that should have no effect), for comparison.  
 
Therapeutic vaccination in this study is produced by Profectus BioSciences and includes 2 different investigational 
vaccines against HIV (HIV-MAG pDNA and VSV HIV gag). The HIV-MAG pDNA vaccine will be combined with an 
investigational ‘adjuvant’ (a substance that should make vaccines more potent) called IL-12 pDNA. The HIV-MAG pDNA 
and adjuvant will be given by an investigational device to inject the vaccines into the muscle in your arm. This injection 
method is called electroporation (EP) and is designed to improve how well your body absorbs some vaccines. 
 
The study vaccines, adjuvant, and EP injection device have not been approved by the Food and Drug Administration 
(FDA); they will be used in the current study with permission from the FDA for experimental use. That means we don’t 
know whether they are safe to use in people, or whether they will work to treat your HIV infection.  
 
STUDY VACCINES 
 
HIV-MAG pDNA (HIV-MAG)/IL-12 pDNA adjuvant (adjuvant): The HIV-MAG vaccine contains some DNA 
(genetic material required for cells to function) made in the laboratory. The particular DNA in the study vaccine tells the 
body to make proteins that are normally found in HIV. It is hoped that making these non-infectious proteins will trigger 
your body to better fight the ‘real’ HIV that you have.  
 
The HIV-MAG vaccine is being given with an adjuvant also made of DNA, which we hope will stimulate your body to 
make IL-12 proteins, which also help fight infection.  
 
VSV HIV gag (VSV): This vaccine will be given to you at 2 time points during the trial, after the HIV-MAG, to try to 
further strengthen your immune response against HIV. VSV carries some DNA that tells your body to make another 
protein that is found in HIV, which may give your body another ‘target’ to attack on ‘real’ HIV in your system.  
 
The VSV vaccine is made from a virus normally spread to animals by insect bites. Infected animals may get a rash or 
sores at the location of the bite, around the mouth, or on their hooves, which go away within 10-12 days. Human 
infection with natural VSV is very rare and can produce a mild self-limited disease similar to that seen in animals.  


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
13-I-0141 
CONTINUATION:  page  3  of  12  pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
The VSV in the current study vaccine has been weakened so that it can’t cause the health problems seen in animals. It 
is very unlikely that someone who receives the study vaccine will develop any symptoms of VSV infection or pass VSV 
to someone else. 
 
WHO WILL BE IN THE STUDY 
 
A total of 30 people, 18 to 65 years of age, with HIV are expected to be enrolled in this study. To be in the study, you 
must be willing to stop your HIV treatment for about 16 weeks during the study period and, if you are sexually active, 
you and your partner must agree to take steps to help reduce the chance of passing on the HIV infection, or of 
pregnancy.  
 
STUDY SCHEDULE 
 
Your study participation time is expected to be about 26 months. Some visits need to be at the NIH Clinical Center in 
Bethesda, Maryland, and some may possibly be done closer to your home. The study staff will let you know what to 
expect in your case.  
 
Screening visit: About 1 to 2 months before the first (baseline) study visit, you will be asked to sign this informed 
consent document, and then you will have the following procedures done over 1 or 2 days: 
• 
Physical exam, medical history, medication list, electrocardiogram (EKG or ECG). 
• 
Test for body fat content, done by a ‘skin-pinch’ test. 
• 
Blood and urine collection, including a pregnancy test and other testing related to HIV and your general health. 
 
During the screening visit and throughout the study until the visit at week 56, you will continue to take HIV medications 
(cART). 
 
Baseline visit: If you are eligible to participate, you will return for a baseline study visit. You will be randomly assigned 
(by chance, like flipping a coin) to receive EITHER the vaccines we are trying to study (HIV-MAG, adjuvant, and VSV) or a 
placebo (‘pretend’ vaccine that is made of salt water, so it should not have any medical effect). Neither the study staff nor 
you will know your group assignment until after the study is completed.    
 
The visit will occur over 1 to 3 days for about 2 to 5 hours each day. Before receiving the vaccination, you will have 
medical procedures that are similar to those done at the screening visit (above) as well as: 
• 
Leukapheresis (collection of your white blood cells for the study). 
• 
Instructions on the use of a diary card.  
 
After the study procedures, you will receive the first dose of the study vaccine (HIV-MAG and adjuvant) or the placebo 
vaccine; these will be delivered with the EP device, which is described in the risk section of this document. The study 
doctor will then evaluate you for symptoms related to the vaccine. 
 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
13-I-0141 
CONTINUATION:  page  4  of  12  pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
Vaccination-phase visits: During week 4 through week 56, you will come in for 10 study visits. Each visit will take 
about 2 to 3 hours to complete, except for the visits at week 36 and 56, which will take about 2 to 5 hours to complete.  
Depending on your group assignment, you will be administered again either the HIV-MAG pDNA vaccine and IL-12 pDNA 
adjuvant or the placebo vaccine during the visits at week 4, 12, and 36. In addition, you will receive the other study 
vaccine (VSV HIV gag) or the placebo vaccine during the visits at week 24 and 48.  
 
During the visits at week 4, 12, 24, 36, 48, and 56, you will have the routine medical procedures and other procedures 
done, including: 
• 
Physical exam, medical history, medication list.  
• 
Vital signs. 
• 
Blood draw. 
• 
Blood or urine pregnancy test. 
• 
Leukapheresis (at week 36 and 56 only). 
• 
Evaluation of vaccine-related symptoms (at week 4, 12, 24, 36, and 48 only). 
• 
Evaluation of any new symptoms. 
• 
Evaluation of your diary card.  
• 
Oral swabs—only in individuals who develop mouth sores. 
  
In addition, you will have your blood drawn again during the visits at week 14, 26, 38, and 50. 
 
Treatment-interruption phase visits: During week 58 through week 72, you will come in every 2 weeks for 7 study 
visits; each visit will take about 1 hour to complete.  
 
After the study visit at week 56, you will stop your HIV treatment until the visit at week 72. If you are taking any non-
nucleoside reverse transcriptase inhibitors (NNRTIs; for example, Rescriptor, Sustiva, or Viramune), the NNRTI will be 
switched to another HIV drug that is either a protease inhibitor (for example, Reyataz or Prezista) or an integrase 
inhibitor (for example, Isentress) for about 2 weeks before stopping your HIV treatment. This is to prevent the 
development of resistance to the NNRTI drugs that can potentially occur because these drugs tend to stay in your body 
longer than the other HIV drugs. 
  
Your blood will be drawn every 2 weeks during each study visit. If you live outside the local Bethesda, Maryland area, you 
may be asked to go to your local physician for the blood draws; the study doctor will discuss this possibility with you.  
 
During the visits at week 64 and 72, in addition to the blood draw, you will also have the following procedures done: 
• 
Physical exam with review of medical history. 
• 
Vital signs. 
• 
Evaluation of any new symptoms. 
 
If you develop HIV-related symptoms, your viral levels go up to high levels for more than 4 weeks, or your CD4 cell 
counts (a type of white blood cells) decrease to low levels, you will return to the NIH Clinical Center for an additional visit 
to be evaluated. If the study doctor determines that you can’t continue without your HIV treatment, you will be restarted 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
13-I-0141 
CONTINUATION:  page  5  of  12  pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
on your HIV treatment and will be followed for 6 months. Also, you will undergo the procedures listed under the study 
visits at week 84 and 96 below.  
 
If you and your private physician decide to restart your HIV treatment, you can choose any combination of drugs for the 
HIV treatment. You should call the study team for an appointment BEFORE you restart any HIV treatment. We would like 
to collect additional blood from you before you restart the HIV treatment.  
 
Follow-up phase: During week 76 through week 96, you will come in every month for 4 study visits; each visit will take 
about 1 to 2 hours to complete.  
 
After the visit at week 72, you will restart your HIV treatment and will continue on it through week 96 (end of study). 
Following the week 96 visit you will have completed the study and return to the care of your home physicians.  
 
During the follow-up phase, your blood will be drawn every month until the level of HIV in your blood is suppressed. If 
you live outside the local Bethesda, Maryland area, you may be asked to go to your local physician for the blood draws; 
the study doctor will discuss this possibility with you.  
 
During the visits at week 84 and 96, in addition to the blood draw, you will also have the following procedures done: 
• 
Physical exam with review of medical history. 
• 
Vital signs. 
• 
Evaluation of any new symptoms. 
STUDY PROCEDURES 
 
Physical exam with medical and medication history: You will be evaluated by the study staff and will undergo a 
physical exam. You will be asked about how you are feeling, if you’ve had any illness recently, and about the medications 
you are taking now and have taken in the past, including non-prescription drugs. A weight measurement will also be done 
at some of the visits. 
 
Vital signs: Your blood pressure, heart rate, respiratory rate, and temperature will be recorded.  
 
Skin-pinch test: This test will be done to measure the thickness of the skin on your upper arm muscles for the 
administration of the study vaccines.  
 
Vaccine injection with the EP device: The HIV-MAG pDNA/IL-12 pDNA adjuvant and the placebo vaccine will be 
injected with an investigational EP device, which is a small, hand-held tool. The device will be pressed against your 
upper arm firmly, and the injection needle will then be inserted into your arm, and the contents of the study vaccine/ 
placebo vaccine will be delivered through the needle 3 to 4 seconds later. After the injection, a very small amount of 
electricity will be sent through your arm muscle. You may feel some mild pain or discomfort, which goes away quickly 
for most people. This procedure will be done once in each upper arm for each of the HIV-MAG pDNA/IL-12 pDNA 
vaccinations.  
Blood draw: Blood will be drawn from a vein in your arm to measure your blood cell counts, to see if your organs are 
working well, including your liver and kidneys, and to measure your HIV levels; your blood will also be used to test for 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
13-I-0141 
CONTINUATION:  page  6  of  12  pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
hepatitis B and C, which cause liver disease, and for syphilis, which is a sexually transmitted disease. The total volume of 
blood collected during the study will not exceed the guidelines for blood collected for research in adult subjects at the NIH 
Clinical Center. While in the study, let the study team know if you are participating in other studies or have blood drawn 
for any other reason. 
 
Urine collection: A sample will be collected for routine laboratory tests. 
 
Blood or urine pregnancy test: For women of childbearing potential, a pregnancy test will be done using a blood or 
urine sample. You will not be allowed to participate in the study if you are pregnant. 
 
EKG: This test records the normal electrical activity of your heart. Electrodes, which are soft, sticky patches attached to 
wires, will be placed on the skin of your chest, arms, and legs. The procedure does not cause any pain or harm. 
 
Leukapheresis: For this procedure, some blood will be removed through a needle in your arm, your white blood cells 
will be separated from the blood, and the rest of the blood will be returned to your body through another needle. Citrate, 
a generally harmless chemical to prevent blood from clotting in the machine, will still be in the blood that returns to you.  
This procedure will be done in the Department of Transfusion Medicine at the NIH Clinical Center. You will be asked to 
sign a separate consent form that will describe in more detail how the procedure will be done and the risks associated 
with it. 
 
Leukapheresis provides us with many more white blood cells than we could get from a routine blood draw, but this will 
still be a small fraction of the total number in your body. The body quickly replaces the cells that were removed. The 
procedure will take approximately 1 to 3 hours to complete. A doctor will be available in or near the leukapheresis clinic at 
all times. 
 
Evaluation of vaccine-related symptoms/diary cards: After each vaccination, you will have to wait at the clinic for 
about an hour to see if you experience any symptoms related to the vaccine. You will be asked to write down how you 
feel and your symptoms in a diary card, which will be given to you during the baseline visit. After you receive the study 
vaccine at week 0, 4, 12, and 36, you will be asked to record your symptoms during the first night and the following 3 
days; after you receive the VSV study vaccine at week 24 and 48, you will be asked to record your symptoms during the 
first night and the following 7 days. During these times, you will also be asked to contact the study team at the NIH 
Clinical Center daily. 
 
The diary card will take you about 10 minutes to complete each day. You will be asked to bring the diary card back to the 
clinic during your next visit, and it will be collected by the study staff. If you stop the study early, the diary card will be 
collected during your last visit.  
 
You must contact the study staff if you have any issues or concerns after receiving the vaccinations. If you have a 
problem, we will continue to evaluate you until it goes away. 
 
Oral swabs: Individuals who develop mouth sores up to 7 days after injection with the VSV HIV gag vaccine will have 
samples collected from their sores to test for VSV infection.   
 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
13-I-0141 
CONTINUATION:  page  7  of  12  pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
RISKS ASSOCIATED WITH THE STUDY 
 
General risks associated with vaccines: Possible risks associated with vaccines include fever, chills, rash, aches and 
pains, nausea, headache, dizziness, and fatigue. We know these side effects can occur with other vaccines. They can 
occur if you receive the study vaccines or the placebo vaccine in this study. The side effects don’t usually last long.  
 
As with all vaccines or drugs, you could have an immediate allergic reaction, including itchy rash, hives, low blood 
pressure, sudden body swelling, or even difficulty breathing. Allergic reactions can be life threatening; therefore, the 
study staff will watch you for 1 hour after each vaccination. There may be other side effects, even serious ones that we 
don’t yet know about. Therefore, it is important that you report all the side effects to the study staff as soon as they 
occur. 
  
Very rarely, vaccines may cause your immune system to attack your own body and blood cells. We don’t know the risk for 
having this kind of “auto-immune” problem due to the study vaccines.  
 
Risks associated with the HIV-MAG pDNA vaccine/IL-12 pDNA adjuvant: We don’t know all the risks associated 
with the HIV-MAG pDNA study vaccine because it has only been given to about 150 people. Possible risks related to 
similar DNA vaccines include muscle damage at the site of the injection, “auto-immune” problems (see the paragraph, 
above), or vaccine DNA mixing with your own DNA. This could lead to cancer or unknown side effects. We think the risk 
of these things happening is very low. In other studies, more than 1,000 people have been given DNA vaccines being 
tested against HIV and none of these things has happened so far. We expect the risks of the HIV-MAG pDNA vaccine in 
this study to be similar to those of other HIV DNA vaccines. However, there may be new side effects that we don’t yet 
know about. 
 
In earlier studies of the IL-12 pDNA adjuvant, there have been no severe side effects related to the adjuvant. We don’t 
know if participants in this study will have similar side effects to those seen in earlier studies. 
 
Risks associated with bupivacaine: The HIV-MAG pDNA vaccine and IL-12 adjuvant contain bupivacaine. It is a 
numbing medicine similar to that used by dentists. At much higher doses, bupivacaine and other medications in the same 
group of local anesthetics can cause serious problems with the nervous system (brain, spinal cord, nerve cells) and the 
heart. Other possible side effects include nausea, vomiting, chills, rash, hives, difficulty breathing, and severe allergic 
reactions. However, in this study, we will be using doses about 10 times lower than the dose that has been known to 
cause these side effects. 
 
Risks associated with the EP device: An injection with the EP device will cause brief muscle contractions during the 
procedure. In previous studies using EP, people often felt an initial pain that ranged from mild to moderate. For most 
people, the pain eased quickly (within an hour). EP can also cause soreness, bruising, redness, swelling, itching, or 
hardness/stiffness in the upper arm where you got the injection. A standard vaccine injection (such as tetanus or flu 
vaccine) with an ordinary needle and syringe can also have these same side effects.  
Other unlikely but possible side effects include: 
• 
Infection at the injection site. 
• 
Abnormal heart rhythm. 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
13-I-0141 
CONTINUATION:  page  8  of  12  pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
• 
Damage or malfunction of pacemakers, and other metal medical materials in the body. You cannot be in the 
study if you have heart problems, or have metal medical devices in the upper body or arms.  
 
The EP device has been used in about 280 people so far, and no serious side effects have been observed.  
 
Also, we don’t know if the EP device will increase the risks associated with any of the study products. 
 
Risks associated with the VSV HIV gag vaccine: VSV in the study vaccine has been weakened so that it doesn’t 
cause the illness seen in animals. However, it is still possible, although very unlikely, that the study vaccine could cause 
symptoms that people get from VSV infection, including fever, muscle aches, headaches, fatigue, encephalitis, or mouth 
sores. Encephalitis is a brain disease that can cause confusion, drowsiness, seizures, and loss of consciousness. Only 1 
person (a young child) is reported to have developed possible encephalitis that was possibly caused by natural VSV 
infection. The weakened virus used to make the VSV vaccine for the current study is not expected to cause encephalitis. 
In trials of healthy adults, immunization with the VSV vaccine has been found to be associated with self-limited sores in 
the mouth and a transient (less than 2 days) decreases in lymphocyte counts in some individuals. If you notice sores in 
your mouth, please notify the study team immediately so they can arrange for a mouth swab to look for the VSV virus.  
 
Because the VSV vaccine has only been given to about 60 people so far, there might be other risks associated with this 
vaccine that we don’t yet know about.  
 
Risks associated with treatment interruption: People who started HIV treatment early in their infection may have 
stronger immune responses to the virus. These immune responses cannot control the infection in the vast majority of 
people and treatment with anti-HIV drugs is needed.  The long-term effects, if any, of temporarily stopping your HIV 
treatment are not yet known. It is possible that your CD4 cell counts may decrease, your HIV disease may get worse, or 
the number of cells in which the virus remains latent (hidden or resting) may increase. Studies of temporarily (for 4-6 
months) stopping HIV treatment in individuals treated during early infection have not found decreases in immune 
function or long-term problems. However, there might be risks of temporarily stopping your HIV medications that we 
don’t yet know about. We will monitor your CD4 cell counts and viral levels closely during the 16-week period when you 
will be off treatment. 
 
Another possible risk associated with stopping your treatment includes drug resistance. “Drug resistance” means that a 
drug given to treat HIV no longer works against it. This is a special concern if you are currently taking NNRTIs because 
these drugs tend to remain in the body longer than other drugs do, which could increase the risk of making the virus 
resistant to that drug or other NNRTI drugs. If you are taking any NNRTI drugs, you will be switched to a protease 
inhibitor or an integrase inhibitor about 2 weeks before stopping your HIV treatment to minimize this risk. 
 
There may be an increased risk of transmitting HIV (for example, to a sexual partner who does not have HIV) during the 
treatment interruption if your viral levels increase during this time. However, it is important to realize that even while 
taking HIV treatment you can still pass the HIV virus to others by sexual contact. So, “safe-sex practices” should always 
be used. A member of the study team will review safe-sex practices with you prior to study enrollment and again prior to 
the treatment interruption. 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
13-I-0141 
CONTINUATION:  page  9  of  12  pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
 
Risks associated with the study vaccines during pregnancy: It is not known how the study vaccines will affect a 
developing baby. Therefore, if you are a woman of childbearing potential, you must agree to use 2 acceptable methods of 
contraception (birth control pills, male/female condoms, diaphragm or cervical cap, or intrauterine device) beginning at 
least 3 weeks before the first dose of the study vaccine/placebo vaccine and continuing until your last study visit.  
 
Risks associated with leukapheresis: Donations for this procedure are generally safe and side effects are rare. Pain,  
bruising, or discomfort at the needle injection site may occur. Sometimes leukapheresis can cause a tingling sensation 
around the mouth or in the finger, chills, nausea, heartburn, or mild muscle cramps. These side effects can usually be 
relieved by slowing or temporarily stopping the leukapheresis or taking a calcium-containing antacid, such as Tums. Other 
possible side effects are anxiety, vomiting, and lightheadedness. Temporary lowering of your blood pressure may also 
develop. On rare occasions, fainting or seizure may occur. Very rarely, a nerve problem at the needle injection site may 
occur, or malfunction of the machine used for the procedure may occur, resulting in a loss of about one pint of your 
blood.  
 
There are possible risks from re-infusion of the blood after being processed by the machine, such as infection or a side 
effect from the blood components. However, this has not been seen in many thousands of volunteers who have 
undergone this or similar procedures to date.  
 
Risks associated with HLA testing: Some of the blood drawn from you as part of this study will be used for a test for 
HLA type, which is a genetic test for markers of the immune system. It is usually used to match bone marrow or organ 
transplants. For research, HLA testing might be used to try to identify factors associated with the progression of disease 
or related conditions. In addition, determining the HLA type is necessary to perform certain research studies. Results from 
the HLA testing will become a part of your medical record at the NIH. Medical records containing this information are 
maintained in a secured manner. Although we are committed to confidentiality, a court could still subpoena your medical 
records. All of these issues should be carefully considered before joining the study.  
 
Risks associated with the blood draw: The risks associated with drawing blood from a vein in your arm include pain, 
bruising, and, rarely, infection at the site, hematoma or black and blue mark with a lump caused by blood release into the 
tissues, lightheadedness, and fainting. 
 
BENEFITS ASSOCIATED WITH THE STUDY 
 
It is possible that you may get a treatment that will improve your immune response against your HIV infection, which 
may help to control it better. It is also possible that you may receive no benefit from participating in this study.  
Information learned from the study may help others infected with HIV. 
 
ALTERNATIVES TO PARTICIPATING IN THIS STUDY 
 
You may choose not to participate in this study and continue to receive care from your current physician(s) or enroll in 
other clinical studies.  


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
13-I-0141 
CONTINUATION:  page  10  of  12  pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
WITHDRAWAL FROM THE STUDY 
 
You can stop participating in this study at any time. Tell a member of the study team if you no longer want to participate.  
Samples and data collected prior to this request will be stored for the duration of the protocol unless you specifically 
request the removal of all your samples from the study.  
 
If you decide to leave, we may ask you to return for a final visit to perform some tests and exams to ensure safety. 
However, you will not be required to return for this visit. If you stop taking the study vaccine before the visit at week 24, 
you will continue to be followed for safety purposes; but, you will not be required to stop your HIV treatment after the 
visit at week 56. 
 
If you choose to withdraw your participation in the study, this will not affect your participation in other clinical trials at the 
NIH.   
EARLY REMOVAL FROM THE STUDY 
 
You may be removed from this study early without your consent for the following reasons: 
• You enroll in another clinical study of an experimental treatment. 
• You develop a health problem, an abnormal lab test, or any medical disease that, in the opinion of the study doctor, 
puts you at increased risk of harm or it’s not in your best interest. 
• You become pregnant. 
• You miss more than 1 vaccination. 
• You repeatedly miss the study visits or refuse to comply with the study guidelines or procedures.  
• You exhibit inappropriate or threatening behavior towards NIH staff or other subjects.  
• If the study is stopped or cancelled.  
•  
COMPENSATION 
 
You will receive financial compensation for the leukapheresis procedure according to the NIH Clinical Center volunteer 
guidelines: $100.00 for a 2-pass leukapheresis procedure or $200.00 for a 4-pass leukapheresis procedure. The study 
doctor will let you know which procedure you’re having done.    
 
COSTS ASSOCIATED WITH THE STUDY 
 
There will be no charge to you or your health insurance company for any of the tests, procedures, or medications that are 
directly related to this study. The costs for any other medical care provided outside the NIH during this period will not be 
covered. 
NEW FINDINGS 
 
Any new findings discovered during this study that are considered relevant to your health or to your decision to continue 
in the study will be fully discussed with you. 
 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
13-I-0141 
CONTINUATION:  page  11  of  12  pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
STORED SAMPLES/DATA AND FUTURE RESEARCH 
 
If you agree to participate in this study, you also agree to let us store your blood samples and data for future research. 
The stored samples/data may help us learn more about the effect of the HIV-MAG pDNA/IL-12 pDNA adjuvant and the 
VSV HIV gag vaccine on HIV infection. The samples/data will be labeled with a code that only the study team can link to 
you. Any information that can be traced back to you will be kept as private as possible. If you change your mind and 
decide you do not want us to store your samples, please contact us. We will do our best to comply with your request but 
cannot guarantee that we will always be able to destroy all your samples.  
Your coded samples/data might be sent to other study doctors for their research. Other information, such as your sex, 
age, health history, or ethnicity might also be shared. Your samples will not be sold, and you will not be paid for any 
products that result from this research. Future studies may require health information about you, such as smoking history 
or present health status, which we don’t already have. If so, our study team may contact you. Future research that uses 
your samples/data will not help you, but it may help us learn more about HIV infection and other health problems. In 
general, the research tests performed in this study are not like routine medical tests, and they may not relate directly to 
your medical care.  
 
CONFLICT OF INTEREST 
  
The NIH reviews its staff researchers at least yearly for conflicts of interest. You may ask your study team for additional 
information or a copy of the Protocol Review Guide. This protocol has investigators who are not NIH employees. Non-NIH 
investigators are expected to adhere to the principles detailed in the Protocol Review Guide, but they are not required to 
report their personal financial holdings to the NIH.  Profectus Biosciences is providing the vaccines for this study to NIH 
without charge. No NIH employee involved in this study receives any payment or other benefits from Profectus 
Biosciences. 
 


 
  
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
   MEDICAL RECORD 
•  Adult Patient or    •  Parent, for Minor Patient 
 
STUDY NUMBER: 
13-I-0141 
CONTINUATION:  page  12  of  12  pages 
 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL 
 
RESEARCH STUDY (Continuation Sheet) 
 
•  Adult Patient or   •  Parent, for Minor Patient 
 
NIH-2514-1 (07-09) 
 
P.A.: 09-25-0099 
 
File in Section 4:  Protocol Consent 
 
OTHER PERTINENT INFORMATION 
 
1. Confidentiality. When results of an NIH research study are reported in medical journals or at scientific meetings, 
the people who take part are not named and identified. In most cases, the NIH will not release any information about 
your research involvement without your written permission. However, if you sign a release of information form, for 
example, for an insurance company, the NIH will give the insurance company information from your medical record. This 
information might affect (either favorably or unfavorably) the willingness of the insurance company to sell you insurance. 
 
The Federal Privacy Act protects the confidentiality of your NIH medical records. However, you should know that the Act 
allows release of some information from your medical record without your permission, for example, if it is required by the 
Food and Drug Administration (FDA), members of Congress, law enforcement officials, or authorized hospital 
accreditation organizations. 
 
2. Policy Regarding Research-Related Injuries. The Clinical Center will provide short-term medical care for any 
injury resulting from your participation in research here. In general, no long-term medical care or financial compensation 
for research-related injuries will be provided by the National Institutes of Health, the Clinical Center, or the Federal 
Government.  However, you have the right to pursue legal remedy if you believe that your injury justifies such action. 
 
3. Payments. The amount of payment to research volunteers is guided by the National Institutes of Health policies. In 
general, patients are not paid for taking part in research studies at the National Institutes of Health. Reimbursement of 
travel and subsistence will be offered consistent with NIH guidelines. 
 
4. Problems or Questions. If you have any problems or questions about this study, or about your rights as a research 
participant, or about any research-related injury, contact the Principal Investigator, Dr. Michael Sneller, Building 10, Room 
9N208, Telephone (301) 496-0491. You may also call the Clinical Center Patient Representative at (301) 496-2626. 
 
5. Consent Document.  Please keep a copy of this document in case you want to read it again. 
COMPLETE APPROPRIATE ITEM(S) BELOW: 
 
A. Adult Patient’s Consent 
B. Parent’s Permission for Minor Patient. 
I have read the explanation about this study and have been 
given the opportunity to discuss it and to ask questions.  I 
hereby consent to take part in this study. 
I have read the explanation about this study and have been 
given the opportunity to discuss it and to ask questions.  I 
hereby give permission for my child to take part in this 
study.   
(Attach NIH 2514-2, Minor’s Assent, if applicable.) 
 
  
  
  
Signature of Adult Patient/Legal Representative 
Date 
 
 
 
Print Name 
Signature of Parent(s)/Guardian 
Date 
 
 
 
Print Name 
C. Child’s Verbal Assent (If Applicable) 
The information in the above consent was described to my child and my child agrees to participate in the study. 
 
 
 
  
 
 
 
 
Signature of Parent(s)/Guardian 
Date 
 
Print Name 
THIS CONSENT DOCUMENT HAS BEEN APPROVED FOR USE  
FROM MARCH 9, 2015 THROUGH MARCH 8, 2016.  
 
 
 
 
 
  
 
 
Signature of Investigator 
Date 
 
 
 
Print Name 
Signature of Witness 
Date 
 
 
 
Print Name