HIV-1-Gag Conserved-Element DNA Vaccine (p24CE) as Therapeutic Vaccination in HIV-Infected Persons With Viral Suppression on Antiretroviral Therapy
Phase: PHASE1
Conditions: HIV Infections
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

 
A5369 
 
 
HIV-1-Gag Conserved-Element DNA Vaccine (p24CE) as Therapeutic Vaccination in HIV-
Infected Persons with Viral Suppression on Antiretroviral Therapy 
 
 
A Multicenter Trial of the AIDS Clinical Trials Group (ACTG) 
 
 
Sponsored by: 
 
National Institute of Allergy 
and Infectious Diseases 
 
 
Industry Support Provided by: 
 
Ichor Medical Systems, Inc. 
 
 
IND # 
 
The ACTG HIV Reservoirs and Viral Eradication 
Transformative Science Group: 
Rajesh Gandhi, MD, Chair 
 
Protocol Chair:  
Jeffrey M. Jacobson, MD 
 
 
Protocol Vice Chair:  
Alan Landay, PhD 
 
 
DAIDS Clinical Representative: 
Karin L. Klingman, MD 
 
 
Clinical Trials Specialist: 
Linda Boone, BS 
 
 
 
 
 
 
 
 
 
 
 
Final Version 1.0 
March 9, 2018 
 

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HIV-1-Gag Conserved-Element DNA Vaccine (p24CE) as Therapeutic Vaccination in HIV-
Infected Persons with Viral Suppression on Antiretroviral Therapy 
 
SIGNATURE PAGE 
 
 
I will conduct the study in accordance with the provisions of this protocol and all applicable 
protocol-related documents. I agree to conduct this study in compliance with United States (US) 
Health and Human Services regulations (45 CFR 46); applicable U.S. Food and Drug 
Administration regulations; standards of the International Conference on Harmonisation 
Guideline for Good Clinical Practice (E6); Institutional Review Board/Ethics Committee 
determinations; all applicable in-country, state, and local laws and regulations; and other 
applicable requirements (e.g., US National Institutes of Health, Division of AIDS) and 
institutional policies. 
 
 
 
 
 
Principal Investigator: _______________________________________________ 
 
 
 
Print/Type 
 
 
 
 
 
Signed: ___________________________________ Date: _____________ 
 
 Name/Title 
 
 

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TABLE OF CONTENTS 
Page 
 
SIGNATURE PAGE .................................................................................................................... 2 
SITES PARTICIPATING IN THE STUDY .................................................................................... 5 
PROTOCOL TEAM ROSTER ..................................................................................................... 6 
STUDY MANAGEMENT ............................................................................................................. 9 
GLOSSARY OF PROTOCOL-SPECIFIC TERMS ..................................................................... 11 
SCHEMA .................................................................................................................................. 12 
1.0 
HYPOTHESIS AND STUDY OBJECTIVES ................................................................... 13 
1.1 
Hypothesis ......................................................................................................... 13 
1.2 
Primary Objectives ............................................................................................. 13 
1.3 
Secondary Objectives ........................................................................................ 13 
1.4 
Other Objectives ................................................................................................ 13 
2.0 
INTRODUCTION ........................................................................................................... 14 
2.1 
Background ........................................................................................................ 14 
2.2 
Rationale ........................................................................................................... 15 
3.0 
STUDY DESIGN ........................................................................................................... 23 
4.0 
SELECTION AND ENROLLMENT OF PARTICIPANTS ................................................ 24 
4.1 
Inclusion Criteria ................................................................................................ 24 
4.2 
Exclusion Criteria ............................................................................................... 26 
4.3 
Study Enrollment Procedures............................................................................. 28 
4.4 
Co-enrollment Guidelines ................................................................................... 30 
5.0 
STUDY TREATMENT ................................................................................................... 30 
5.1 
Regimens, Administration, and Duration ............................................................ 30 
5.2 
Study Product Formulation and Preparation ....................................................... 30 
5.3 
Pharmacy: Product Supply, Distribution, and Accountability .............................. 34 
5.4 
Concomitant Medications ................................................................................... 35 
6.0 
CLINICAL AND LABORATORY EVALUATIONS ........................................................... 36 
6.1 
Schedule of Evaluations..................................................................................... 36 
6.2 
Timing of Evaluations ......................................................................................... 40 
6.3 
Instructions for Evaluations ................................................................................ 41 
7.0 
ADVERSE EVENTS AND STUDY MONITORING ......................................................... 50 
7.1 
Definition of Adverse Events .............................................................................. 50 
7.2 
Adverse Event Collection Requirements for this Protocol ................................... 50 
7.3 
Expedited Adverse Event (EAE) Reporting to DAIDS ........................................ 51 
7.4 
Study Monitoring ................................................................................................ 52 
8.0 
CLINICAL MANAGEMENT ISSUES .............................................................................. 52 
8.1 
Toxicity .............................................................................................................. 52 
8.2 
Pregnancy.......................................................................................................... 53 

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CONTENTS (Cont’d) 
Page 
 
9.0 
CRITERIA FOR DISCONTINUATION ........................................................................... 54 
9.1 
Permanent and Premature Treatment Discontinuation ....................................... 54 
9.2 
Premature Study Discontinuation ....................................................................... 54 
10.0 
STATISTICAL CONSIDERATIONS ............................................................................... 54 
10.1 
General Design Issues ....................................................................................... 54 
10.2 
Outcome Measures ............................................................................................ 55 
10.3 
Randomization and Stratification ........................................................................ 57 
10.4 
Sample Size and Accrual ................................................................................... 57 
10.5 
Data and Safety Monitoring ................................................................................ 58 
10.6 
Analyses ............................................................................................................ 59 
11.0 
PHARMACOLOGY PLAN .............................................................................................. 60 
12.0 
DATA COLLECTION AND MONITORING ..................................................................... 60 
12.1 
Records to Be Kept ............................................................................................ 60 
12.2 
Role of Data Management ................................................................................. 60 
12.3 
Clinical Site Monitoring and Record Availability .................................................. 60 
13.0 
PARTICIPANTS ............................................................................................................ 61 
13.1 
Institutional Review Board (IRB) Review and Informed Consent ........................ 61 
13.2 
Participant Confidentiality ................................................................................... 61 
13.3 
Study Discontinuation ........................................................................................ 61 
14.0 
PUBLICATION OF RESEARCH FINDINGS .................................................................. 63 
15.0 
BIOHAZARD CONTAINMENT ...................................................................................... 63 
16.0 
REFERENCES .............................................................................................................. 64 
APPENDIX I SAMPLE INFORMED CONSENT ........................................................................ 68 
 

 
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SITES PARTICIPATING IN THE STUDY 
 
A5369 is a multicenter study open to all U.S ACTG clinical research sites (CRSs). 
 

 
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PROTOCOL TEAM ROSTER 
 
Chair 
Jeffrey M. Jacobson, MD 
Center of Translational AIDS Research, 
Lewis Katz School of Medicine at Temple 
University 
Medical Education and Research Building 
3500 Broad Street 
Suite 746, 7th Floor 
Philadelphia, PA 19140 
Phone: 215-707-6451 
Fax: 215-707-4888 
E-mail: jeffrey.jacobson@temple.edu 
 
Vice Chair 
Alan Landay, PhD 
Immunology/Microbiology 
Rush University Medical Center  
1725 West Harrison Street, Suite 306 POB1 
Chicago, IL 60612 
Phone: 312-942-6554 
E-mail: alanday@rush.edu 
 
DAIDS Clinical Representative 
Karin L. Klingman, MD 
HIV Research Branch 
TRP, DAIDS, NIAID, NIH 
5601 Fishers Lane, Rm 9E40A, MSC 9830  
Rockville, MD 20852 
Phone: 240-627-3067 
E-mail: kklingman@niaid.nih.gov 
 
Clinical Trials Specialist 
Linda Boone, BS 
ACTG Network Coordinating Center 
Social & Scientific Systems, Inc. 
8757 Georgia Avenue, 12th Floor 
Silver Spring, MD 20910-3714 
Phone: 301-628-3363 
Fax: 301-628-3302 
E-mail: lboone@s-3.com 
Statisticians 
Huichao Chen, PhD 
Harvard T.H. Chan School of Public Health 
651 Huntington Avenue 
FXB Building, Room 607 
Boston, MA 02115-6017 
Phone: 617-432-0040 
Fax: 617-432-2843 
E-mail: hchen@sdac.harvard.edu 
 
Carla Roberts-Toler, MS 
Harvard T.H. Chan School of Public 
Health 
651 Huntington Avenue 
FXB Building, Room 643A 
Boston, MA 02115-6017 
Phone: 617-432-2899 
Fax: 617-432-3163 
E-mail: croberts@sdac.harvard.edu 
 
Data Managers 
Dave Rusin, MT 
Frontier Science & Technology Research 
Foundation, Inc. 
4033 Maple Road 
Amherst, NY 14226-1056 
Phone: 716-834-0900 Ext. 7333 
Fax: 716-834-8432 
E-mail: rusin@fstrf.org 
 
Loren Wright 
Frontier Science & Technology Research 
Foundation, Inc. 
4033 Maple Road 
Amherst, NY 14226-1056 
Phone: 716-834-0900 Ext. 7277 
Fax: 716-834-8432 
E-mail: wright.loren@fstrf.org 
 

 
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DAIDS Pharmacist 
Lynette Purdue, PharmD 
Pharmaceutical Affairs Branch 
DAIDS, NIAID, NIH 
Division of AIDS 
5601 Fishers Lane 
Room 9E28 
Rockville, MD 20852 
Phone: 240-627-3061  
Fax: 240-627-3112 
E-mail: lpurdue@niaid.nih.gov 
 
Immunologist  
Nicole Frahm, PhD 
HIV Vaccine Trials Network 
Fred Hutchinson Cancer Research Center 
1100 Fairview Ave N 
LE-200 
Seattle, WA 98109 
Phone: 206-667-6268 
Fax: 206-667-6608 
E-mail: nfrahm@fhcrc.org 
 
Virologist  
Daniel R. Kuritzkes, MD 
Section of Retroviral Therapeutics 
Brigham and Women's Hospital 
Therapeutics (BWHT) CRS 
Harvard Medical School 
65 Landsdowne Street, Room 447 
Cambridge, MA 02139 
Phone: 617-768-8371 
Fax: 617-768-8738 
E-mail: dkuritzkes@partners.org 
 
Investigators 
Barbara K. Felber, PhD 
Human Retrovirus Pathogenesis Section 
National Cancer Institute 
BG 535 RM 209 
1050 Boyles Street 
Frederick, MD 21702 
Phone: 301-846-5159 
Fax: 301-846-7146 
E-mail: barbara.felber@nih.gov 
 
Investigators (Cont’d) 
James I. Mullins, PhD 
University of Washington 
P.O. Box 35870 
Seattle, WA 98195 
Phone: 206-732-6163 
Fax: 206-732-6167 
E-mail: jmullins@uw.edu 
 
George N. Pavlakis, MD, PhD 
Human Retrovirus Section 
National Cancer Institute 
BG 535 RM 210 
1050 Boyles Street 
Frederick, MD 21702 
Phone: 301-846-1474 
Fax: 301-846-6368 
E-mail: george.pavlakis@nih.gov 
 
Brett Williams, MD 
Rush University CRS 
AIDS Clinical Trials Unit  
600 South Paulina Street Suite 140  
Chicago, IL 60612 
Phone: 312-942-2292 
E-mail: brett_williams@rush.edu 
 
Field Representative 
Jenifer Baer, RN 
Infectious Diseases Center 
Cincinnati CRS 
Holmes Division 
231 Albert Sabin Way 
Cincinnati, OH 45267-0405 
Phone: 513-584-8022 
Fax: 513-584-8454 
E-mail: baerjk@uc.edu 
 

 
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Laboratory Technologist 
Gerald L. Tegha, BSc, MSc 
Kamuzu Central Hospital/Tidziwe  
P.O. Box A-104 
100 Mzimba Road 
Kamzu Central Hospital 
Lilongwe  
MALAWI 
Phone: 265-999200668 
Fax: 265-1755954 
E-mail: gtegha@unclilongwe.org 
 
Community Scientific Subcommittee (CSS) 
Representative 
William Royce Hardin, BS 
702 Back Ridge Road 
Penobscot, ME 04476 
Phone: 919-451-0058 
E-mail: wrhardin05@gmail.com 
 
Industry Representative  
Drew Hannaman  
Ichor Medical Systems, Inc. 
6310 Nancy Ridge Dr. #107 
San Diego, CA 92121 
Phone: 858-550-2022 Ext. 103 
Fax: 858-550-2092 
E-mail: dhannaman@ichorms.com 
 
Laboratory Data Manager 
Frederic Bone 
Frontier Science and Technology Research 
Foundation 
4033 Maple Road 
Amherst, NY 14226 
Phone: 716-834-0900 Ext. 7306 
E-mail: bone@fstrf.org 
 

 
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STUDY MANAGEMENT 
 
All general questions concerning this protocol should be sent to actg.coreA5369@fstrf.org via e-
mail. The appropriate team member will respond with a ”cc“ to actg.teamA5369@fstrf.org. 
A response should generally be received within 24 hours (Monday through Friday). 
 
Protocol E-mail Group 
Sites should contact the User Support Group at the Data Management Center (DMC) as soon 
as possible to have the relevant personnel at the site added to the actg.protA5369 e-mail group. 
Include the protocol number in the e-mail subject line.  
• 
Send an e-mail message to actg.user.support@fstrf.org.  
 
Clinical Management:  
For questions concerning entry criteria, toxicity management, concomitant medications, and co-
enrollment, contact the core protocol team.  
• 
Send an e-mail message to actg.coreA5369@fstrf.org. Include the protocol number, patient 
identification number (PID), and a brief relevant history. 
 
Laboratory 
For questions specifically related to immunologic or virologic laboratory tests, contact the 
protocol immunologist or virologist.  
• 
Send an e-mail message to actg.teamA5369@fstrf.org (ATTENTION: Nicole Frahm or Alan 
Landay/Daniel Kuritzkes). 
 
Data Management 
• 
For nonclinical questions about transfers, inclusion/exclusion criteria, electronic case report 
forms (eCRFs), randomization/registration, and other data management issues, contact the 
data manager. Completion guidelines for eCRFs and participant-completed eCRFs can be 
downloaded from the FSTRF website at www.frontierscience.org. 
• 
For transfers, reference the Study Participant Transfer SOP 119, and contact Dave Rusin 
(rusin@fstrf.org) and Loren Wright (wright@fstrf.org) directly.  
• 
For other questions, send an e-mail message to actg.teamA5369@fstrf.org (ATTENTION: 
Dave Rusin and Loren Wright).  
• 
Include the protocol number, PID, and a detailed question. 
 
Randomization/Participant Registration  
For randomization/participant registration questions or problems and study identification number 
SID lists:  
• 
Send an e-mail message to rando.support@fstrf.org or call the DMC Randomization Desk at 
716-834-0900, extension 7301.  
 
DMC Portal and Medidata Rave Problems  
Contact DMC User Support: 
• 
Send an e-mail message to actg.user.support@fstrf.org or call 716-834-0900 x7302. 

 
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Protocol Document Questions 
For questions concerning the protocol document, contact the Clinical Trials Specialist.  
• 
Send an e-mail message to actg.teamA5369@fstrf.org (ATTENTION: Linda Boone). 
 
Copies of the Protocol 
• 
To request a hard copy of the protocol, send an e-mail message to ACTGNCC@s-3.com 
(ATTENTION: Diane Delgado).  
• 
Electronic copies can be downloaded from the ACTG website at 
https://www.actgnetwork.org. 
 
Product Package Inserts and/or Investigator Brochures 
To request copies of product package inserts or investigator brochures, contact the DAIDS 
Regulatory Support Center (RSC) at RIC@tech-res.com or call 301-897-1708. 
 
Protocol Registration 
For protocol registration questions, send an e-mail message to Protocol@tech-res.com or call 
301-897-1707.  
 
Protocol Activation  
For questions related to protocol activation, contact the Clinical Trials Specialist (Linda Boone at 
lboone@s-3.com) or ACTG Site Coordination Group at actgsitecoordination@s-3.com.  
 
Study Product 
For questions or problems regarding study product, dose, supplies, records, and returns, call 
Lynette Purdue, protocol pharmacist, at 240-627-3061.  
 
Study Drug Orders 
Call the Clinical Research Products Management Center (CRPMC) at 301-294-0741. 
 
IND (Investigational New Drug) Number or Questions  
The IND number will be available on the protocol-specific web page (PSWP) within 30 days of 
the submission to the Food and Drug Administration (FDA). For any questions related to the 
IND submission, contact the DAIDS RSC at Regulatory@tech-res.com or call 301-897-1706. 
 
Expedited Adverse Event (EAE) Reporting/Questions  
Contact DAIDS through the RSC Safety Office at DAIDSRSCSafetyOffice@tech-res.com or call 
1-800-537-9979 or 301-897-1709; or fax 1-800-275-7619 or 301-897-1710.  
 
Telephone Calls 
Sites are responsible for documenting telephone calls made to A5369 team members.  
• 
Send an e-mail message to actg.teamA5369@fstrf.org. 
 
Protocol-Specific Web Page 
Additional information about management of the protocol can be found on the protocol-specific 
web page (PSWP). 

 
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GLOSSARY OF PROTOCOL-SPECIFIC TERMS 
 
AA 
 
amino acids 
ART 
 
antiretroviral therapy 
cART  
combination antiretroviral therapy 
CE 
 
conserved elements 
CTL 
 
cytotoxic T lymphocytes 
Gag 
 
group-specific antigen 
HLA 
 
human leukocyte antigen 
HVTN  
HIV Vaccine Trials Network 
IFN-γ  
interferon gamma 
IM/EP  
intramuscular injection (or intramuscularly) followed by in vivo electroporation 
INR 
 
international normalized ratio 
NIH 
 
National Institutes of Health 
pDNA  
plasmid deoxyribonucleic acid 
PT 
 
prothrombin time 
PTT 
 
partial thromboplastin time 
SIV 
 
simian immunodeficiency virus 
TDS-IM 
Intramuscular TriGrid Delivery System (also known as “EP device”) 
TNF-α  
tumor necrosis factor alpha 
VRC 
 
vaccination report card 
 

 
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SCHEMA 
 
A5369 
 
HIV-1-Gag Conserved-Element DNA Vaccine (p24CE) as Therapeutic Vaccination in HIV-
Infected Persons with Viral Suppression on Antiretroviral Therapy 
 
DESIGN 
A5369 is a phase I/IIa, randomized, double-blind, placebo-controlled 
study that will evaluate the safety, immunogenicity, and preliminary 
assessment of efficacy of a novel vaccine encoding “conserved elements” 
(CE) of the HIV-1 Gag core protein, p24Gag, as a therapeutic vaccine in 
HIV-1 infected persons on antiretroviral therapy (ART) with the aim to 
induce potent virus-specific cytotoxic T lymphocytes (CTL) responses. 
 
 
DURATION 
Participants will be on study for 48 weeks. 
 
 
SAMPLE SIZE 
40 participants randomized 2:1:1 to the p24CE/full-length Gag DNA 
vaccine arm versus full-length Gag DNA vaccine arm versus placebo 
arm. 
 
 
POPULATION 
HIV-infected individuals receiving ART with plasma HIV-1 RNA <50 
copies/mL for at least 2 years (one “blip” allowed), current CD4 T cell 
counts >500 cells/mm3, and nadir CD4 T cell counts >350 cells/mm3 (by 
documentation or candidate recall). 
 
STRATIFICATION  
Randomization will be stratified by indication of willingness to have the  
 
 
 
leukapheresis procedure at study screening. 
 
 
REGIMEN 
Arm 1: p24CE1/2 pDNA vaccine at weeks 0 and 4, followed by p24CE1/2 
pDNA admixed with full-length p55gag pDNA vaccine at weeks 12 and 24. 
 
Arm 2: full-length p55gag pDNA vaccine at weeks 0, 4, 12, and 24. 
 
Arm 3: placebo (Sodium Chloride for Injection, USP 0.9%) at weeks 0, 4, 
12, and 24. 
 
The active vaccines/placebo will be administered by intramuscular 
injection/electroporation.

 
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1.0 
HYPOTHESIS AND STUDY OBJECTIVES 
 
1.1 
Hypothesis 
 
The administration of p24CE Gag DNA vaccine followed by p24CE DNA + full-length 
Gag DNA vaccine boost to HIV-infected persons on antiretroviral therapy (ART) will 
focus newly induced immune responses to immunogenic conserved epitopes of Gag and 
away from decoy variable epitopes, compared to the administration of full-length Gag 
DNA vaccine alone, and compared to placebo. The vaccine regimes will be safe and 
well tolerated. 
 
1.2 
Primary Objectives 
 
1.2.1 To compare the additional number of p24CEs recognized by a CD4 and/or CD8 
T cell response in participants in each study arm at week 26 compared to 
baseline. 
 
1.2.2 To evaluate the safety of the p24CE/full-length Gag DNA vaccine and the full-
length Gag DNA vaccine in HIV-infected persons receiving ART. 
 
1.3 
Secondary Objectives 
 
1.3.1 To compare the percent of individual study participants in each study arm with a 
CD4 and/or CD8 T cell response to an increased number of conserved elements 
(CEs) at week 26 compared to baseline. 
 
1.3.2 To compare the percent of individual study participants in each study arm with a 
CD4 T cell response to an increased number of CEs at week 26 compared to 
baseline. 
 
1.3.3 To compare the percent of individual study participants in each study arm with a 
CD8 T cell response to an increased number of CEs at week 26 compared to 
baseline. 
 
1.3.4 To compare the change in total magnitude of CD4 T cell responses against each 
CE added together across study arms. 
 
1.3.5 To compare the change in total magnitude of CD8 T cell responses against each 
CE added together across study arms. 
 
1.4 
Other Objectives 
 
1.4.1 To further characterize the HIV-specific cellular immune responses induced by 
the p24CE/full Gag DNA vaccine compared to full-length Gag DNA vaccine alone 
and to placebo control using a viral inhibition assay.  
 

 
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1.4.2 To assess the HIV-specific humoral immune response induced by the p24CE/full 
Gag DNA vaccine compared to full-length Gag DNA vaccine alone and to 
placebo control. 
 
1.4.3 To assess cellular and soluble markers of immune activation, exhaustion, and 
checkpoint inhibition in HIV-infected participants receiving the p24CE/full-length 
Gag DNA vaccine compared to participanats receiving the full-length Gag DNA 
vaccine alone or placebo.  
 
1.4.4 To assess the effects of the p24CE DNA/full-length Gag DNA vaccine on 
measures of the latent cell reservoir of HIV-1 compared to full-length Gag 
vaccine alone or placebo. 
 
1.4.5 To evaluate the tolerability of the intramuscular injection/electroporation (IM/EP) 
delivery of the DNA vaccines in HIV-infected individuals. 
 
1.4.6 To evaluate the effect of the gut microbiome on immune responses to the 
vaccine. 
 
2.0 
INTRODUCTION 
 
2.1 
Background 
 
Oral ART has been highly successful in the management of human immunodeficiency 
virus type 1 (HIV-1) infection, achieving dramatic viral suppression in most infected 
persons maintaining access to care. However, ART does not eradicate HIV-1 and 
morbidities still occur. When ART is discontinued, viral rebound occurs, usually within 2-
4 weeks. 
 
Therapeutic vaccination has a potential role either as a component of a strategy to 
eliminate cells latently infected with HIV-1, where cells need to express HIV antigen to 
be targeted by anti-HIV immunotherapy, or as a functional cure in itself to achieve 
indefinite host control of HIV-1 infection to undetectable levels off ART. HIV-1 vaccine 
development for both prevention and therapy has been hindered by the high rate of 
mutation of the virus and the tendency of immune responses to focus on epitopes that 
can readily mutate without negatively impacting virus viability and thus divert the immune 
system from responding against protective epitopes [1].  
 
Thus, the approach taken here was to develop protective immunogens [1-3] that direct 
immune targeting to conserved regions of viral proteins while excluding variable 
immunodominant epitopes, thereby avoiding the potential negative effects of directing T 
cell responses to ‘‘decoy’’ epitopes that do not benefit virologic control [1,4]. The 
immunogen designs were based on selection of epitopes that are conserved among all 
HIV-1 sequences and are associated with virologic control in HIV-1 infected individuals 
[1-3, 5-13]. Cytotoxic T lymphocyte (CTL) activity against conserved viral epitopes have 
been noted in elite controllers and long-term non-progressors [3, 14]. Furthermore, 
mutations affecting the conserved regions of HIV-1 proteins often impair viral fitness [15-

 
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20]. 
There is substantial evidence that Gag-specific CD4 and CD8 T cell responses correlate 
with control of viremia [3,21-24], including reduced viremia after infection in the Step 
preventive vaccine trial [25]. The pDNA vaccine to be studied here encodes seven CEs 
of HIV-1 p24Gag that were selected by database exploration and viral load/CTL 
response data. These protein sequences are typically found in >98% of the HIV-1 Group 
M viruses worldwide and represent 54% of the p24Gag protein [9].  
 
2.2 
Rationale 
 
p24CE pDNA vaccine regimen  
This trial will evaluate the safety, immunogenicity, and provide a preliminary assessment 
of the efficacy of a novel vaccine encoding CEs of the HIV-1 Gag core protein, p24Gag, 
as a therapeutic vaccine in HIV-1 infected persons on ART with the aim to induce potent 
virus-specific CTL responses and reduce virus rebound set point after discontinuation of 
ART. Induction of such CTL responses targeting conserved, subdominant epitopes has 
application in a therapeutic setting against HIV infection, and this vaccine regimen 
induces potent CTL responses targeting the presumed Achilles’ heel of the virus. 
 
The study will use p24CE and p55gag plasmids in a pDNA prime-pDNA boost vaccine 
regimen comprising p24CE prime followed by p24CE+p55gag booster vaccination. This 
vaccine regimen has been selected for the clinical trial HVTN 119 to test safety and 
immunogenicity in HIV-naïve persons. 
 
As noted above, HIV sequence diversity and potential “decoy” epitopes are hurdles in 
the development of an effective AIDS vaccine. To target immune responses towards 
critical viral epitopes, we engineered immunogens encoding CEs of HIV-1 selected on 
the basis of stringent conservation, functional importance, broad HLA-coverage, and 
association with viral control [1, 26, 27]. We engineered a pDNA vaccine targeting seven 
CEs within the HIV-1 p24Gag protein and demonstrated that this vaccine is able to 
induce potent cellular and humoral immune responses in mice and macaques [9, 10, 
28]. CE-specific T cells are polyfunctional and highly cytotoxic. We further developed a 
novel, improved vaccine regimen that includes priming with HIV p24CE pDNA, critical to 
induce immune responses to subdominant epitopes, and p24CE pDNA together with a 
plasmid expressing the full-length immunogen p55Gag as a boost. We found this to be 
the most effective protocol to induce CE-targeted responses with the greatest breadth, 
magnitude, and cytotoxic capability in macaques [29]. Thus, this vaccine regimen alters 
the immunodominance hierarchy and induces robust immune responses to subdominant 
epitopes. In contrast, this result could not be achieved by vaccination with complete 
p55gag pDNA, which induced few and mostly monofunctional responses recognizing CE, 
these responses being found in only 50% of the vaccinated animals and having limited 
breadth [9, 10, 28]. The combination of pDNA vaccines expressing CE and full-length 
immunogen provides a novel strategy to maximize the breadth and magnitude of cellular 
and humoral immunity targeting the subdominant, highly conserved regions of HIV. 
Therapeutic vaccination by this method could induce novel responses unlikely to be 
overcome by viral mutations and has the potential to provide an additional critical step 
towards reduction of the long-term viral reservoir.  

 
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p24CE pDNA vaccine 
The p24CE vaccine is composed of two gene segments (p24CE1 and p24CE2) on one 
plasmid, referred to as p24CE1/2 pDNA, expressing carefully selected portions of the 
HIV-1 capsid protein, p24Gag, the most abundant protein in HIV virions (Figure 2.2-1). 
p24Gag was chosen because of its availability as an immune target during infection, and 
because CTL responses to Gag, and in particular the p24Gag component of Gag, have 
been associated with greater control of HIV viremia in numerous studies [20-23, 30-37]. 
The sequences expressed by p24CE1/2 pDNA correspond to the portions of p24Gag 
found in nearly every HIV-1 (M group) strain observed to date throughout the world; 
while they elicit immune responses in HIV-infected individuals, these responses are 
subdominant to the more variable segments of Gag. Unlike most of the HIV-1 genes and 
their encoded proteins, CEs have rarely, if at all, been observed to mutate (for the most 
part they are composed of amino acids [AA] conserved in 98-100% of all HIV-1 M- group 
infections) and represent components that are enriched with those essential to virus 
infectivity. We hypothesize that by targeting these potentially critical regions of the HIV-1 
p24Gag protein, this vaccine approach may elicit specific immune responses linked to 
protection and viral control, rather than immune responses that may include decoy 
responses with detrimental effects or limited antiviral potential. In a therapeutic vaccine 
application, this vaccine may induce new cellular immune responses not overcome by 
virus mutations and contribute to virus control. Allowing pre-existing anti-HIV immune 
responses to ebb, as occurs during ART, may also contribute to a more robust response 
to the CE. 
 

 
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Figure 2.2-1. Alignment of p24CE1, p24CE2, and p24Gag proteins. The schematic 
representation at the top of the  shows the p55Gag and its proteolytic processing 
products including p24Gag protein. Below is the alignment of the amino acid (AA) 
sequences of the majority consensus p24Gag sequences of different HIV-1 clades 
and of the seven CE encoded by the p24CE1/2 pDNA vaccine. The AA sequences of 
the p24Gag of different HIV-1 clades (A, B, C), group M consensus, COT-M, and of 
the p24CE1 and p24CE2 proteins are shown (Note that consensus agreement, 
indicated by “.”, does not necessarily indicate strong sequence conservation at that 
site). The CE1 to CE7 sequences with the single AA change per CE are indicated. 
 
 
The p24CE1/2 pDNA is a dual promoter plasmid (Figure 2.2-2) generated to express the 
p24CE1 gene from the human cytomegalovirus (CMV) promoter and the p24CE2 gene 
from the simian CMV promoter in the opposite transcriptional orientation. There are 7 CE 
segments of 13, 18, 24, 20, 20, 14, and 18 AA in each of the p24CE constructs [1]. One 
“toggled” amino acid is included in each of the 7 CE segments, resulting in two protein 
coding elements (p24CE1 and p24CE2) differing by a total of 7 codons, each sharing 
127 amino acids with p24Gag. Coding sequences were optimized to enhance 
expression in human cells [38-41]. The p24CE sequences represent 54% of p24Gag, 
including most extended coiled regions of the protein. CE regions are enriched for AA at 
p24Gag hexamer interfaces [42], which provides a structural rationale for their 

 
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conservation. Also, CE are enriched with AA sites that, if mutated to the second-most 
common AA at that site in the HIV database, would result in noninfectious virus [27, 42]. 
The plasmid also contains two polyadenylation signals (bovine growth hormone polyA 
signal for p24CE1 and the simian virus 40 polyA signal for p24CE2). 
 
The CE segments are separated by linkers of 0-3 AA in length composed of Alanine, or 
Alanine and Lysine, or Alanine and Glycine. The total length of the proteins spans 157 
AA, including 17 AA of the GM-CSF signal peptide and 13 AA of linker sequences. The 
linker sequences are designed for efficient proteolytic cleavage [9]. The length and 
sequence of the linker sequences were therefore set based on the existing knowledge of 
cleavage specificities [43], as well as to avoid fortuitous junctional homologies with HIV 
and the human proteome, the latter determined by searching against the HIV and human 
proteome databases [44]. 
 
Figure 2.2-2: Schematic of the p24CE1/2 pDNA (plasmid code 306H): p24CE1/2 
pDNA uses a plasmid backbone derived from pVR1012 [45], which has been used in 
previous DNA vaccine studies. p24CE1/2 pDNA was manufactured and produced at 
a concentration of 4 mg/mL, in 30 mM citrate buffer pH 6.5 containing 150 mM NaCl, 
0.01% EDTA and 0.25% bupivacaine-HCl by Ajinomoto Althea, San Diego, CA. 
p24CE pDNA has been tested in macaques monitored for >2 years without any 
adverse effects. 
 
 
p55gag pDNA 
The p55gag pDNA (plasmid 114H) contains an expression-optimized full-length HIV-1 
p55gag gene from the HIV-1 molecular clone HXB2 (Genbank NP_057850) cloned into 
the pCMVkan plasmid between the human CMV promoter and the bovine growth 
hormone polyA signal (Figure 2.2-3). Related plasmids expressing HIV p55Gag have 
been tested in several clinical trials, including HVTN 060, 063, 070, 080, and 087, and 
no significant adverse effects related to vaccine were reported. 
 

 
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Figure 2.2-3. Schematic of p55gag pDNA. p55gag pDNA was manufactured and 
produced at a concentration of 4 mg/mL, in 30 mM citrate buffer pH 6.5 containing 
150 mM NaCl, 0.01% EDTA and 0.25% bupivacaine-HCl by Ajinomoto Althea, San 
Diego, CA. p55gag pDNA will be admixed with pCE1/2 pDNA to produce a single 
injectable solution for the booster vaccination. 
 
 
 
Preclinical immunogenicity studies of p24CE pDNA in macaques 
A variety of model systems were used to ensure that delivery of p24CE pDNA would 
induce strong immune responses [9, 10, 26, 29]. The p24CE pDNA studies conducted in 
macaques are shown in Figure 2.2-4. Cellular immune responses were measured in 
blood 2 weeks after the last vaccination by stimulation of peripheral blood mononuclear 
cells (PBMC) with peptides spanning the 7 CE [10, 29]. All animals developed CE-
specific cellular responses, as measured by IFN-γ production, with a frequency ranging 
from 0.1% to 0.8% of total T cells in blood. These responses were elicited by both CD4 
and CD8 T cells, of both central (CD28+, CD95+) and effector memory phenotype (CD28-
, CD95+), and included cytotoxic and polyfunctional CE-specific T cells, as defined by 
their granzyme B content, ability to secrete two cytokines (IFN-γ and TNF-α), and ability 
to degranulate (CD107a). In addition to cellular immune responses, vaccination with 
p24CE plasmids induced robust antibody responses to CE, not achieved by vaccination 
with p55gag DNA. These studies demonstrated that vaccination with CE pDNA induces 
potent immune responses to subdominant epitopes, notachieved by vaccination with 
pDNA expressing the full-length Gag (see Figure 2.2-5). 
 

 
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Figure 2.2-4. p24CE pDNA vaccine is immunogenic in macaques. Macaques (N=16) 
were vaccinated twice with a mixture of p24CE1&p24CE2 pDNA (N=6) or the dual-
expression vector p24CE1/2 (N=10). The frequency of CE-specific IFN-γ+ T cells was 
measured 2 weeks after the last priming vaccination using CE-specific peptide pools 
composed of a mixture of 15-mer overlapping by 11 AA and 10-mer peptides 
overlapping by 9 AA covering both p24CE1 and p24CE2 proteins. The CE-specific CD4 
(open bars, labeled CD4) and CD8 (filled bars, labeled CD8) T cells are shown. 
 
 
 
Preclinical macaque studies of p24CE1/2 DNA prime/co-delivery of p24CE1/2 and 
p55gag pDNA boost vaccine regimen 
A novel prime-boost regimen was developed to maximize magnitude, breadth, and the 
generation of cytotoxic T cell responses recognizing the CE [10, 26, 29]. This regimen 
includes p24CE1/2 and p55gag plasmids in a pDNA prime-pDNA boost vaccine regimen 
comprising p24CE pDNA prime followed by p24CE+p55gag pDNA booster vaccination. 
Booster vaccination including p55gag pDNA significantly increased T cell responses and 
also induced highly cytotoxic CE-specific IFN-γ+ T cells with Granzyme B+ co-expression 
of >89%. 
 
The breadth of the response, measured by the number of CE recognized per animal, 
was compared among groups that received different CE-based vaccines (CE pDNA 
only, CE/gag pDNA, and CE/CE+gag pDNA) (Figure 2.2-5). The CE+gag pDNA booster 
vaccination induced responses with significantly increased breadth (2-6 CE per animal), 
compared to CE or CE/gag pDNA vaccines with 1-3 or 1-4 CE per animal, with no 
difference between the latter groups. All CE-based DNA vaccines induced broader 
responses than the HIV p55gag pDNA only vaccine, which induced responses to 0-2 CE 
per animal. 
 

 
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Figure 2.2-5. Increased breadth of the HIV CE-specific responses induced by a 
CE/CE+gag pDNA vaccine regimen (Note: gag = p55gag. The plot shows the number of 
CE recognized by each macaque immunized with different vaccine regimens, counting 
both CD4 and CD8 T cells recognizing CE peptides. Recognition was defined by being 
>2x the no peptide control and greater than 0.01% of the total T cells. The median 
number CE, range of CE responses, and the number of animals analyzed are indicated. 
A comparison of the CE breadth using different vaccine regimens are shown including 
HIV CE pDNA only, HIV CE prime/gag pDNA boost, HIV CE prime/CE+gag pDNA boost, 
or HIV gag pDNA. P values are from ANOVA (Dunnett’s test). 
 
 
 
Immunogenicity of the CE pDNA vaccine regimen in SIV-infected ART-treated 
macaques.  
We previously showed that therapeutic SIV pDNA vaccination induces potent immune 
responses able to significantly reduce viremia after ART interruption [46, 47]. 
Importantly, in these studies we reported that despite initial rebounds after ART 
interruption, viral loads then decreased dramatically in many DNA-vaccinated animals, 
resulting in significant long-term decreases in viremia.  
 
We hypothesize that CE pDNA vaccine could contribute to cure by inducing broad, 
effective immunity with less likelihood of immune escape. To test the CE vaccine 
concept as a potential therapeutic approach in the macaque model, we engineered SIV 
p27CE homologs to the HIV p24CE immunogens [29]. Analogous immunogenicity 
studies were conducted with the SIV p27CE in macaques and the results mirrored those 
obtained with the HIV constructs. The immunogenicity of the p27CE pDNA vaccine 
regimen was further tested in SIVmac251-infected macaques treated with cART (Gilead, 
ViiV) for 10 months. Four of the animals received the SIV p27CE DNA vaccine regimen 
(priming with p27CE, two-booster vaccination with p27CE+p57gag pDNA), two macaques 
received sham pDNA (Figure 2.2-6), and all were analyzed for CE-specific T cell 
responses 2 weeks later. The two sham DNA vaccinated macaques showed no T cell 

 
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responses to CE (Figure 2.2-6) or total Gag (not shown), as expected, due to successful 
cART treatment. Robust T cell responses to CE reaching more than 1% of T cells in 
blood (Figure 2.2-6) as well as to complete Gag (not shown) were induced upon 
vaccination. 
 
Figure 2.2-6: Immunogenicity of CE of pDNA vaccine in cART-treated macaques. Six 
macaques were infected with SIVmac251 for 3 months and treated with cART (Gilead, 
ViiV) for 10 months, and were vaccinated 2x with p27CE pDNA vaccine regimen 
(N=4) or sham DNA (N=2) via IM electroporation. Animals were primed with 1 mg of 
p27CE pDNA and boosted with 1 mg p27CE and 1 mg gag pDNA. T cell responses 
were measured 2 weeks after the third vaccination using a CE-specific peptide pool. 
 
 
 
Rationale for Placebo 
Unlike in HIV-negatives, the continued but variable expression of HIV-1 antigens from 
cells otherwise latently infected with HIV-1, and perhaps continued low-level viral 
replication in tissues, probably continue to stimulate immune responses in persons on 
ART, possibly including those we would like to induce with this vaccine regimen. This 
natural fluctuation in HIV-antigen-specific immune responses over time in HIV-infected 
individuals necessitates having a control group receiving placebo to which the immune 
responses induced in the vaccine groups will be compared.  
 
Rationale for Full-length gag DNA vaccine alone arm of the study 
We hypothesize that the initial administration of p24CE gag DNA vaccine to HIV-infected 
persons on ART will focus newly induced immune responses to immunogenic conserved 
epitopes of Gag and away from decoy variable epitopes. The inclusion of the 
comparison arm in which only full-length gagDNA vaccine is given is critical to test this 
hypothesis.  
 
Rationale for the microbiome section of the study 
The gut microbiome appears to play a role in directing T cell responses. Mice in a 
melanoma model with high spontaneous antitumor immunity were noted to have a gut 
microbiota enriched with Bifidobacterium [48]. Oral administration of Bifidobacterium 
improved tumor control similar to administration of a PD-1 blocker, and this effect was 
amplified when mice were treated with both PD-1 blocker and oral Bifidobacterium. 
Tumor control appears to be driven by CD8 T cell infiltration into the tumor. Two species 

 
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of Bacteroides also appear to be associated with response to CTLA-4 blockade [49]. 
Germ-free mice and those treated with antibiotics did not have tumor response to CTLA-
4 blockade. Response to CTLA-4 blockade was restored by immunization and gavage 
with Bacteroides fragilis polysaccharides. It remains unclear whether T cells are primed 
by interaction with microbiota and their products or whether there is cross-reactivity 
between microbial and melanoma antigens.  
 
The influence of gut microbiota on B cell responses is complex and understudied. Cross-
reactivity between bacterial and HIV antigens reduced the efficacy of antibody 
responses to previous HIV vaccine. Analysis of antibody responses to an HIV-1 DNA 
prime vaccine demonstrated that vaccine-induced monoclonal antibodies against gp41 
were non-neutralizing and frequently polyreactive with host and environmental antigens 
[50]. The vaccine induced anti-gp41 antibody reacted with whole cell lysates of several 
anaerobic and aerobic intestinal microbiota. There appears to be a pre-existing pool of B 
cells that are cross reactive between intestinal microbiota and gp41. Studies in mice 
suggest that interaction with commensal microbes may be necessary for the 
development of neutralizing antibody to influenza vaccine [51]. Toll-like receptor (TLR)-
deficient mice had inadequate plasma cell responses to influenza vaccine; this trend was 
also seen in germ-free and antibiotic-treated mice. Flagellated E. coli administered orally 
restored vaccine response but aflagellated E. coli did not, consistent with TLR-based 
sensing of flagellar proteins. 
 
Stool microbiota analysis in elite controllers has suggested that gut microbes may 
contribute to CD8 T cell control of HIV. Nowak et al. found in principal coordinate 
analysis based on beta-diversity results that elite controllers clustered tightly together 
separate from either healthy controls or viremic participants [52]. These elite controllers 
had significantly lower weighted unifrac diversity. Elite controllers also had a significantly 
higher prevalence of the phylum Bacteroidetes and lower prevalence of Proteobacteria 
and Actinobacteria compared to viremic participants.  
 
We hypothesize that participants with a more robust T cell response to p24CE1/2 pDNA 
vaccine will have a higher prevalence of the genus Bifidobacterium and/or the genus 
Bacteroides and lower weighted unifrac diversity of the stool microbiome. 
 
3.0 
STUDY DESIGN 
 
A5369 is a phase I/IIa, randomized, double-blinded, placebo-controlled study in which 40 
study participants will be randomized 2:1:1 to the p24CE/full-length gagDNA vaccine 
arm versus full-length gagDNA vaccine arm versus placebo arm. HIV-specific 
immunologic assays will be done at baseline and after the last dose of vaccine. Cells 
and plasma will also be obtained after the second prime vaccine dose, processed, and 
stored. Immunologic assays may be performed at this timepoint depending on the 
results of the assays done at baseline and after the last dose of vaccine. HIV-1 reservoir 
assays will be done at baseline and after the last dose of vaccine. Enrollment slots for 
participants agreeing to have leukaphereses will be reserved for a minimum of 20 
participants. These participants are required to have leukapheresis at both the pre-entry 
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4.0 
SELECTION AND ENROLLMENT OF PARTICIPANTS 
 
4.1 
Inclusion Criteria 
 
4.1.1 HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or 
chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry 
and confirmed by a licensed Western blot or a second antibody test by a method 
other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 
RNA assay. 
 
NOTE: The term “licensed” refers to a U.S. FDA-approved kit, which is required 
for all IND studies.  
 
WHO (World Health Organization) and CDC (Centers for Disease Control and 
Prevention) guidelines mandate that confirmation of the initial test result must 
use a test that is different from the one used for the initial assessment. A reactive 
initial rapid test should be confirmed by either another type of rapid assay or an 
E/CIA that is based on a different antigen preparation and/or different test 
principle (e.g., indirect versus competitive), or a Western blot or a plasma HIV-1 
RNA viral load. 
 
4.1.2 Receiving a stable ART regimen for a minimum of 2 years prior to study entry 
and with no changes in the components of their antiretroviral therapy for at least 
90 days prior to study entry. One of the agents must include an integrase 
inhibitor, non-nucleoside reverse transcriptase inhibitors (NNRTI), or a boosted-
protease inhibitor (PI).  
 
NOTE: Changes in the ART regimen for reasons other than virologic 
breakthrough during the 2-year period are acceptable. 
 
4.1.3 CD4 cell count >500 cells/mm3 obtained within 60 days prior to study entry at any 
U.S. laboratory that has a CLIA certification or its equivalent. 
 
4.1.4 Nadir CD4 cell count >350 cells/mm3. 
 
NOTE: Candidate recall or documentation is acceptable.  
 
4.1.5 One documented plasma HIV-1 RNA that is below the limit of detection of an 
FDA-approved assay between 24 and 36 months prior to the screening HIV-1 
RNA, one documented plasma HIV-1 RNA that is below the limit of detection of 
an FDA-approved assay between 12 and 24 months prior to the screening HIV-1 
RNA, and one documented HIV-1 RNA that is below the limit of detection of an 
FDA-approved assay collected fewer than 12 months prior to the screening HIV-
1 RNA (see section 4.1.6).  
 

 
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NOTE: A single, unconfirmed plasma HIV-1 RNA above the limit of detection but 
<400 copies/mL is allowed if followed by an HIV-1 RNA below detectable limits, 
but not in the 6 months prior to screening. 
4.1.6 Plasma HIV-1 RNA level that is below the limit of detection of an FDA-approved 
assay within 60 days prior to study entry.  
 
4.1.7 The following laboratory values obtained within 60 days prior to entry by any U.S. 
laboratory that has a CLIA certification or its equivalent: 
• 
Absolute neutrophil count (ANC) ≥750 cells/mm3 
• 
Hemoglobin ≥10.0 g/dL for men and ≥9.0 g/dL for women 
• 
Platelet count ≥100,000/mm3 
• 
Prothrombin time (PT), partial thromboplastin time (PTT), and INR <1.5 x 
upper limit of normal (ULN) 
• 
Creatinine clearance ≥50 mL/min estimated by the Cockcroft-Gault equation  
 
NOTE: A program for calculating creatinine clearance by the Cockcroft-Gault 
method is available on www.fstrf.org. 
 
• 
Alanine aminotransferase (ALT) (SGPT) ≤2.5 x ULN 
• 
Total bilirubin <1.6 x ULN (if on atazanavir ≤5 x ULN) 
 
4.1.8 HCV antibody negative result within 60 days prior to study entry or, if the HCV 
antibody result is positive, a negative HCV RNA result prior to study entry.  
 
4.1.9 Negative HBsAg result obtained within 60 days prior to study entry.  
 
4.1.10 Men and women age 18 to ≤65 years  
 
4.1.11 Documentation of the availability of the stored pre-entry peripheral blood 
mononuclear cell (PBMC) specimens for T cell assays. Sites must receive 
confirmation from the processing lab via phone, e-mail, or fax that specimens 
have been entered into the ACTG Laboratory Data Management System 
(LDMS). 
 
4.1.12 Ability and willingness of participant or legal guardian/representative to provide 
informed consent 
 
4.1.13 Ability and willingness of participant to continue cART throughout the study. 
 
4.1.14 For females of reproductive potential, negative serum or urine pregnancy test 
within 15 days prior to entry by any clinic or laboratory that has a CLIA 
certification or its equivalent, or is using a point of care (POC)/CLIA-waived test. 
 
NOTE: Reproductive potential is defined as girls who have reached menarche 
and women who have not been post-menopausal for at least 12 consecutive 
months with follicle-stimulating hormone (FSH) ≥40 IU/mL or 24 consecutive 

 
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months if an FSH is not available, or have not undergone surgical sterilization 
(e.g., hysterectomy, bilateral oophorectomy, tubal ligation, or salpingectomy). 
 
4.1.15 If participating in sexual activity that could lead to pregnancy, willingness of 
female participants to use two forms of effective contraception while receiving 
study medication and for 3 months after stopping study medication is required. 
 
NOTE A: Effective forms of contraception include:  
• 
Barrier methods (condoms [male or female] with or without a spermicidal 
agent, diaphragm, or cervical cap [with spermicide])  
• 
Hormone-based contraception (oral, patch, parenteral, implants, or vaginal 
ring) 
• 
Intrauterine device (IUD) 
 
NOTE B: If the female participant is not of reproductive potential (women who are 
post-menopausal as defined above, or women who have undergone surgical 
sterilization [e.g., hysterectomy, bilateral oophorectomy, tubal ligation or 
salpingectomy]), she is eligible without requiring the use of a contraceptive 
method. Acceptable documentation of surgical sterilization and menopause is 
participant-reported history. 
 
4.1.16 Indication of willingness to have the leukapheresis procedure. 
 
NOTE: Leukapheresis will be required if the study has reached 50% of the 
accrual target and less than 20 participants have agreed to have the 
leukapheresis procedure. 
 
4.2 
Exclusion Criteria 
 
4.2.1 History of malignancy within the last 5 years prior to study entry or current 
malignancy requiring cytotoxic therapy.  
 
NOTE: A history of non-melanoma skin cancer (e.g., basal cell carcinoma or 
squamous cell skin cancer) is not exclusionary.  
 
4.2.2 History of HIV-related opportunistic infections within the last 5 years prior to study 
entry. 
 
NOTE: The CDC classifications are available on the A5369 protocol-specific 
webpage (PSWP). 
 
4.2.3 History of or active autoimmune disorders including but not limited to 
inflammatory bowel diseases, scleroderma, severe psoriasis, myocarditis, uveitis, 
pneumonitis, systemic lupus erythematosus, rheumatoid arthritis, optic neuritis, 
myasthenia gravis, adrenal insufficiency, autoimmune thyroiditis, or sarcoidosis. 
 

 
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NOTE: For questions related to the definition of autoimmune disorders, sites 
should contact the A5369 core team per the Study Management section. 
 
4.2.4 Bleeding diathesis or condition associated with prolonged bleeding time that 
would contraindicate IM injection. 
 
4.2.5 A skin-fold measurement of the cutaneous and subcutaneous tissue for eligible 
injection sites (on the medial deltoid muscles) that exceeds 40 mm.  
 
NOTE: The skin-fold measurement must be conducted in accordance with the 
procedure described in the TDS-IM Instructions for Use (see A5369 MOPS). 
 
4.2.6 Use of any prior HIV vaccine (prophylactic and/or therapeutic) within 1 year prior 
to study entry. 
 
NOTE: A documented study placebo recipient may participate. 
 
4.2.7 Use of any investigational treatment within 6 months prior to study entry. 
 
4.2.8 Any licensed or experimental non-HIV vaccination (e.g., hepatitis B, influenza, 
pneumococcal polysaccharide) within 4 weeks prior to study entry.  
 
NOTE: Participants with anticipated need to receive non-HIV vaccinations within 
2 weeks prior to the scheduled study vaccination #2 (week 4), or #3 (week 12), or 
#4 (week 24) injection should be excluded. 
 
4.2.9 Use of any infusion blood product or immune globulin within 3 months prior to 
study entry.  
 
4.2.10 Acute or serious illness, in the opinion of the site investigator, requiring systemic 
treatment and/or hospitalization within 30 days prior to entry. 
 
4.2.11 Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), systemic 
cytotoxic chemotherapy, or investigational therapy within 60 days prior to study 
entry.  
 
NOTE: Participants receiving stable physiologic glucocorticoid doses, defined as 
prednisone ≤10 mg/day or the equivalent, will not be excluded. Stable 
physiologic glucocorticoid doses should not be discontinued for the duration of 
the study. In addition, participants receiving inhaled or topical corticosteroids will 
not be excluded. 
 
4.2.12 Intent to use immunomodulators (e.g., IL-2, IL-12, interferons, or TNF modifiers) 
during the course of the study.  
 
4.2.13 Known or suspected hypersensitivity to any vaccine component, including 
hypersensitivity to amide-type local anesthetics, such as lidocaine (Xylocaine), 

 
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mepivacaine (Polocaine/Carbocaine), etidocaine (Duranest), bupivacaine 
(Marcaine), or prilocaine. 
 
4.2.14 Current use of any electronic stimulation device, such as cardiac demand 
pacemakers, automatic implantable cardiac defibrillator, nerve stimulators, or 
deep brain stimulators. 
4.2.15 History of cardiac arrhythmia or palpitations (e.g., supraventricular tachycardia, 
atrial fibrillation, frequent ectopy, or sinus bradycardia [i.e., <50 beats per minute 
on exam]) prior to study entry. 
 
NOTE: Sinus arrhythmia is not excluded. 
 
4.2.16 History of syncope or fainting episode within 1 year of study entry. 
 
4.2.17 Seizure disorder or any history of prior seizure. 
 
4.2.18 Extensive tattoos covering the site of administration (upper left and right medial 
deltoid muscles). 
 
4.2.19 Presence of any surgical or traumatic metal implants at the site of administration 
(medial deltoid muscles). 
 
4.2.20 Immune deficiency other than HIV. 
 
4.2.21 Breastfeeding or pregnancy. 
 
4.2.22 Active drug or alcohol use or dependence that, in the opinion of the site 
investigator, would interfere with adherence to study requirements. 
 
4.2.23 Current HCV antiviral therapy.  
 
4.2.24 Type I or type II diabetes mellitus. 
 
4.2.25 Weight <50 kg or >200 kg. 
 
4.2.26 Known to have been started on antiretroviral therapy within 3 months of the 
presumed or known date of first acquiring HIV-1 infection; i.e., treated during 
acute HIV-1 infection.  
 
4.3 
Study Enrollment Procedures 
 
4.3.1 Prior to implementation of this protocol, and any subsequent full version 
amendments, each site must have the protocol and the protocol consent form(s) 
approved, as appropriate, by their local institutional review board (IRB)/ethics 
committee (EC) and any other applicable regulatory entity (RE). Upon receiving 
final approval, sites will submit all required protocol registration documents to the 
DAIDS Protocol Registration Office (DAIDS PRO) at the Regulatory Support 

 
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Center (RSC). The DAIDS PRO will review the submitted protocol registration 
packet to ensure that all of the required documents have been received.  
 
Site-specific informed consent forms (ICFs) WILL be reviewed and approved by 
the DAIDS PRO, and sites will receive an Initial Registration Notification from the 
DAIDS PRO that indicates successful completion of the protocol registration 
process. A copy of the Initial Registration Notification should be retained in the 
site's regulatory files. 
 
Upon receiving final IRB/EC and any other applicable RE approvals for an 
amendment, sites should implement the amendment immediately. Sites are 
required to submit an amendment registration packet to the DAIDS PRO at the 
RSC. The DAIDS PRO will review the submitted protocol registration packet to 
ensure that all required documents have been received. Site-specific ICF(s) 
WILL NOT be reviewed and approved by the DAIDS PRO, and sites will receive 
an Amendment Registration Notification when the DAIDS PRO receives a 
complete registration packet. A copy of the Amendment Registration Notification 
should be retained in the site's regulatory files. 
For additional information on the protocol registration process and specific 
documents required for initial and amendment registrations, refer to the current 
version of the DAIDS Protocol Registration Manual.  
 
Once a candidate for study entry has been identified, details will be carefully 
discussed with the candidate. The candidate (or, when necessary, the legal 
representative if the candidate is under guardianship) will be asked to read and 
sign the approved protocol consent form.  
 
For participants from whom a signed informed consent has been obtained, an 
ACTG Screening Checklist must be entered through the DMC Participant 
Enrollment System.  
 
4.3.2 Protocol Activation 
 
Prior to enrollment, sites must complete the Protocol Activation Checklist found 
on the ACTG Member website. This checklist must be approved prior to any 
screening of participants for enrollment.  
 
4.3.3 Randomization/Participant Registration 
 
For participants from whom informed consent has been obtained, but who are 
deemed ineligible or who do not enroll into the initial protocol step, an ACTG 
Screening Failure Results form must be completed and keyed into the database.  
Participants who meet the enrollment criteria will be registered to the study 
according to standard ACTG DMC procedures.  
 

 
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4.4 
Co-enrollment Guidelines  
 
• 
US sites are encouraged to co-enroll participants in A5128, “Plan for Obtaining 
Informed Consent to Use Stored Human Biological Materials (HBM) for Currently 
Unspecified Analyses.” Co-enrollment in A5128 does not require permission from the 
A5369 protocol chairs. 
• 
For specific questions and approval for co-enrollment in other studies, sites should 
first check the PSWP or contact the protocol team via e-mail as described in the 
Study Management section. 
 
5.0 
STUDY TREATMENT  
 
CRS pharmacists should consult the Pharmacy Guidelines and Instructions for DAIDS 
Clinical Trials Networks for standard pharmacy operations. 
 
5.1 
Regimens, Administration, and Duration 
 
ARM 1: p24CE1/2 pDNA 4 mg administered by one injection/electroporation at week 0 
and week 4 
 
Then  
p24CE1/2 pDNA 2 mg admixed with full-length p55gag pDNA 2 mg administered by one 
injection/electroporation at week 12, and week 24 
ARM 2: full-length p55gag pDNA 4 mg administered by one injection/electroporation at 
week 0, week 4, week 12, and week 24 
ARM 3: Placebo (Sodium Chloride for Injection, USP 0.9%) 1 mL administered by one 
injection/electroporation at week 0, week 4, week 12, and week 24 
 
5.2 
Study Product Formulation and Preparation 
 
Study Product 
 
p24CE1/2 [labeled as p24CE1/2 pDNA 4 mg/mL] 
p24CE1/2 pDNA is a clear, colorless solution in a 2 mL single-use vial. Each 2 mL vial 
contains 0.7 ± 0.1 mL p24CE1/2 pDNA at a concentration of 4 mg/mL in 30 mM citrate 
buffer pH 6.5 containing 150 mM NaCl, 0.01% EDTA, and 0.25% bupivacaine-HCl.  
 
Store at -20˚C 
 
The product is contraindicated in participants with known hypersensitivity to bupivacaine. 
Provided by DAIDS, NIAID, NIH, DHHS (Bethesda, MD, USA). 
 
Please refer to the Investigator’s Brochure for additional information. 
 

 
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p55gag pDNA [labeled as p55 Gag pDNA 4 mg/mL] 
p55gag pDNA is a clear, colorless solution in a 2 mL single-use vial. Each 2 mL vial 
contains 0.7 ± 0.1 mL p55gag pDNA at a concentration of 4 mg/mL in 30 mM citrate buffer 
pH 6.5 containing 150 mM NaCl, 0.01% EDTA, and 0.25% bupivacaine-HCl.  
 
Store at -20˚C 
 
The product is contraindicated in participants with known hypersensitivity to bupivacaine.  
 
Please refer to the Investigator’s Brochure for additional information. 
 
Provided by DAIDS, NIAID, NIH, DHHS (Bethesda, MD, USA) 
 
Placebo  
Sodium Chloride for Injection, USP 0.9% will not be provided by the study and must be 
obtained by the site. Pharmacists must record the lot numbers of the Sodium Chloride 
for Injection, USP 0.9% used to prepare the placebo injections.  
 
Empty Sterile Mixing Vials will be required for this protocol and will not be provided by 
the study.  
 
Intramuscular TriGrid Delivery System (TDS-IM v2.0) (ICHOR Medical Systems, San 
Diego, California), a device for electroporation mediated intramuscular administration of 
DNA based-biologic candidates. TDS-IM v2.0 Stimulator and Applicator which are 
reusable components, will be provided to the clinic by arrangement with the ACTG 
Leadership and Operations Center. 
 
TDS-IM v2.0 Cartridges are sterile, single-use components specifically designed for use 
with the TDS-IM v2.0 system. Each Cartridge consists of a plastic, injection-molded 
body, which encloses the 4-electrode TriGridTM array and the 22-gauge injection needle. 
Each Cartridge interfaces with a compatible glass 1 mL syringe containing the dose for 
delivery. TDS-IM v2.0 single-use Cartridge and single-pack sterile glass syringes will be 
provided by ICHOR through arrangement by the ACTG Leadership and Operations 
Center. 
 
Refer to the Ichor Intramuscular TriGrid Delivery System Instructions for more 
detailed information.  
 
Preparation of Study Products 
Prior to mixing the study products, the pharmacist will inspect the sterile pouch 
containing the TriGrid™ Application Cartridge for integrity and verify the Cartridge has 
not passed expiration. If any tears or gaps in the sterile pouch are noted or if the 
expiration date has been reached, the Application Cartridge should be placed in 
quarantine and the protocol pharmacist should be informed. Note: In the event that the 
Cartridge Cap has become detached from the Cartridge in the sterile pouch, the 
Cartridge may still be used if the Cartridge Cap can be replaced without contaminating 

 
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the patient contact portion of the Cartridge. 
 
Open the cartridge in the aseptic preparation area with the Tyvek shield down and 
ridged plastic cover up so that the syringe loading port is up. 
See Figure 5.2-1 below. 
 
Figure 5.2-1: Directions for Preparing the Glass Syringe for each Treatment Arm. 
 
 
With the syringe tip up, carefully unscrew the plunger barrel clockwise to detach the 
plunger barrel from the plunger stopper. Note: At first, the barrel feels like it will not 
release but keep turning and it will unscrew.  
 
Load the glass syringe into the cartridge. The flange on the glass syringe has two flat 
sides. Hold the flat sides with your finger tips and line the flange up with the slots in the 
port (away from the orange cartridge cap) and gently drop into place. Gently push down 
on the barrel of the syringe until you feel the syringe click into place. The syringe tip 
does NOT have to be inserted into the slip-tip of the needle but instead it will be lined up 
with the needle. The applicator will push the syringe forward to attach with the needle.  
 
Label the cartridge as ACTG 5369 Study Product 4 mg or Placebo 1 mL and include a 4-
hour expiration date from the time the vial is removed from the refrigerator/freezer. The 
label must also contain the words “Administer as soon as possible.” Attach the label so 
that it can be easily removed for loading into the applicator. It is suggested to use the 
outside of the curved cartridge alignment guide. Attach a duplicate label to a zip-lock 
plastic bag, and place the cartridge in the plastic bag to dispense to the clinician. Any 
unused portion of reconstituted vials or expired prefilled syringes must be disposed of in 
accordance with institutional or pharmacy policy. 
 
ARM 1: Week 0 and Week 4 p24CE1/2. Two vials of p24CE1/2 pDNA (4 mg/mL) will be 
needed to prepare the syringe. 

 
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Remove two vials of p24CE1/2 pDNA from the freezer and allow to thaw at room 
temperature for 15-30 minutes until no crystals are observed. 
 
Gently swirl and invert the vials for at least 10 inversions (do not shake vigorously). 
Inspect the vial prior to use. If the vial contains material different from its description 
above, do not use the vial and contact the protocol pharmacist.  
 
Remove syringe cap from the glass syringe and add a needle. Using aseptic technique, 
withdraw sufficient quantity fluid from each of the two vials of p24CE1/2 pDNA (4mg/mL) 
to load the glass syringe with 1 mL. Holding glass syringe upright, remove the needle. 
Pull the plunger out partway to allow air space to develop at the top. Push the fluid to the 
top of the syringe. 
 
ARM 1 Week 12 and Week 24 p24CE1/2 admixed with p55gag. One vial of p24CE1/2 
pDNA (4 mg/mL), one vial of p55gag pDNA (4 mg/mL), and one empty 5 mL sterile vial 
will be needed to prepare the dose. 
 
Remove one vial of p24CE1/2 pDNA and one vial of p55gag pDNA from the freezer and 
allow to thaw at room temperature for 15 to 30 minutes until no crystals are observed. 
 
Gently swirl and invert the vials for at least 10 inversions (do not shake vigorously). 
Inspect the vials prior to use. If the vial contains material different from its description 
above, do not use the vial and contact the protocol pharmacist. 
 
Using aseptic technique, withdraw 0.6 mL from the vial of p24CE1/2 pDNA (4 mg/mL) 
with a 1 mL low void 25 Ga syringe and inject into an empty mixing sterile vial. Withdraw 
0.6 mL from the vial of p55gag pDNA (4 mg/mL) with a 1 mL low void 25 Ga syringe and 
inject this into the mixing. Gently swirl and invert the vial for 10 inversions to mix. 
 
Remove syringe cap from the glass syringe and add a needle. Withdraw 1 mL of the 
admixture. Holding glass syringe upright, remove the needle. Pull the plunger out part 
way to allow air space to develop at the top. Push the fluid to the top of the glass 
syringe. Load the glass syringe into the cartridge. See directions above. 
 
Label the cartridge as ACTG 5369 Study Product 4 mg or Placebo 1 mL and include a 4-
hour expiration date from the time the vial is removed from the refrigerator/freezer. The 
label must also contain the words “Administer as soon as possible.” Any unused portion 
of reconstituted vials or expired prefilled syringes must be disposed of in accordance 
with institutional or pharmacy policy. 
 
ARM 2: Week 0, Week 4, Week 12, and Week 24 p55gag pDNA. Two vials of p55gag 
pDNA (4 mg/mL) will be needed to prepare the dose. 
 
Remove two vials of p55gag pDNA from the freezer and allow to thaw at room 
temperature for 15 to 30 minutes until no crystals are observed. 
 

 
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Gently swirl and invert the vials for at least 10 inversions (do not shake vigorously). 
Inspect the vials prior to use. If the vial contains material different from its description 
above, do not use the vial and contact the protocol pharmacist. 
 
Remove syringe cap from the glass syringe and add a slip-tip needle. Using aseptic 
technique, withdraw sufficient quantity fluid from each of the two vials of p24CE1/2 
pDNA (4 mg/mL) to load the glass syringe with 1 mL. Holding glass syringe upright, 
remove the needle. Pull the plunger out partway to allow air space to develop at the top. 
Push the fluid to the top of the syringe. 
 
Load the glass syringe into the cartridge. See directions above. 
 
Label the cartridge as ACTG 5369 Study Product 4 mg or Placebo 1 mL and include a 4-
hour expiration date from the time the vial is removed from the refrigerator/freezer. The 
label must also contain the words “Administer as soon as possible.” Any unused portion 
of reconstituted vials or expired prefilled syringes must be disposed of in accordance 
with institutional or pharmacy policy. 
 
ARM 3: Placebo Week 0, Week 4, Week 12, and Week 24. One vial Sodium Chloride for 
Injection, USP 0.9% will be needed to prepare the syringes. 
 
The vial should be visually inspected prior to use. 
 
Remove syringe cap from the glass syringe and add a needle. Using aseptic technique, 
withdraw 1 mL from the vial with the glass syringe to load the glass syringe with 1 mL. 
Holding glass syringe upright, remove the needle. Pull the plunger out partway to allow 
air space to develop at the top. Push the fluid to the top of the syringe 
 
Load the glass syringe into the cartridge. See directions above. 
 
Label the cartridge as ACTG 5369 Study Product 4 mg or Placebo 1 mL and include a 4-
hour expiration date from the time the vial is removed from the refrigerator/freezer. The 
label must also contain the words “Administer as soon as possible.” Any unused portion 
of reconstituted vials or expired prefilled syringes must be disposed of in accordance 
with institutional or pharmacy policy. 
 
5.3 
Pharmacy: Product Supply, Distribution, and Accountability 
 
5.3.1 Study Product Acquisition/Distribution 
 
p24CE1/2 pDNA (4 mg/mL) and p55gag pDNA (4 mg/mL) will be available through 
the NIAID Clinical Research Products Management Center (CRPMC). The site 
pharmacist should obtain the study products for this protocol by following the 
instructions in the manual Pharmacy Guidelines and Instructions for DAIDS 
Clinical Trials Networks.  
 
 

 
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5.3.2 Study Product Accountability 
 
The site pharmacist is required to maintain complete records of all study products 
received from the NIAID CRPMC and subsequently dispensed. All unused study 
products in U.S. CRSs must be returned to the NIAID CRPMC (or as otherwise 
directed by the sponsor) after the study is completed or terminated. The 
procedures to be followed are in the manual Pharmacy Guidelines and 
Instructions for DAIDS Clinical Trials Networks.  
 
5.4 
Concomitant Medications 
 
Whenever a concomitant medication or study agent is initiated or a dose changed, 
investigators must review the concomitant medication’s and study agent’s most recent 
package insert, Investigator’s Brochure, or updated information from DAIDS to obtain the 
most current information on drug interactions, contraindications, and precautions. 
 
Additional drug information may be found on the ACTG Precautionary and Prohibited 
Medications Database located at http://tprc.pharm.buffalo.edu/home/di_search/. 
 
5.4.1 Required Medications 
 
All participants are required to take their current antiretroviral (ARV) regimen until 
study completion. ARV medications will not be provided by the study. 
 
If the participant develops toxicity related to his/her previously-stable ART, then 
the protocol team should be consulted (preferably before appropriate therapy 
modification). 
 
5.4.2 Prohibited Medications 
 
For a list of prohibited medications, refer to the A5369 PSWP. 
 
5.4.3 Precautionary Medications 
 
A list of precautionary medications can be generated using the ACTG 
Precautionary and Prohibited Medications Database located at 
http://tprc.pharm.buffalo.edu/home/di_search/. 

 
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6.0 
CLINICAL AND LABORATORY EVALUATIONS 
 
6.1 
Schedule of Evaluations 
 
Evaluation 
Screening 
Pre-Entry 
Entry 
(Week 0) 
Post-Entry Evaluations 
(Weeks) 
Premature 
Treatment/Study 
Discontinuation 
Evaluations 
Post 
Vaccination #1 
4 
Deferred Week 
4 (See section 
6.3.10) 
Post 
Vaccination #2 
6 
12 
Deferred Week 
12 
(See section 
6.3.10) 
Post 
Vaccination #3 
24 
Deferred Week 
24 
(See section 
6.3.10) 
Post 
Vaccination #4 
26 
48 
Documentation of 
HIV 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medication History 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Clinical 
Assessment 
X 
 
X 
 
X 
X 
 
 
X 
X 
 
X 
X 
 
X 
X 
X 
Skin Pinch 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
EKG 
X 
If Clinically Indicated 
Hematology 
X 
 
X 
 
X 
X 
 
 
X 
X 
 
X 
X 
 
X 
X 
X 
Liver Function 
Tests 
X 
 
X 
 
X 
X 
 
 
X 
X 
 
X 
X 
 
 
X 
X 
Blood Chemistries 
X 
 
X 
 
X 
X 
 
 
X 
X 
 
X 
X 
 
 
X 
X 
Calculated 
Creatinine 
Clearance 
X 
 
X 
 
X 
X 
 
 
X 
X 
 
X 
X 
 
 
X 
X 
Urinalysis 
X 
 
X 
 
X 
X 
 
 
X 
X 
 
X 
X 
 
 
 
X 

 
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Evaluation 
Screening 
Pre-Entry 
Entry 
(Week 0) 
Post-Entry Evaluations 
(Weeks) 
Premature 
Treatment/Study 
Discontinuation 
Evaluations 
Post 
Vaccination #1 
4 
Deferred Week 
4 (See section 
6.3.10) 
Post 
Vaccination #2 
6 
12 
Deferred Week 
12 
(See section 
6.3.10) 
Post 
Vaccination #3 
24 
Deferred Week 
24 
(See section 
6.3.10) 
Post 
Vaccination #4 
26 
48 
PT, PTT, and INR 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy Testing 
X 
X 
X 
 
X 
X 
 
 
X 
X 
 
X 
X 
 
 
 
 
Hepatitis B and C 
Assessment 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CD4+/CD8+ 
X 
X 
X 
 
 
 
 
 
X 
X 
 
X 
X 
 
 
 
X 
Advanced Flow 
Cellular Immune 
Responses 
 
X 
X 
 
 
 
 
X 
 
 
 
 
 
 
X 
X 
X 
Phenotyping of 
Immune Activation 
Markers 
 
X 
X 
 
 
 
 
X 
 
 
 
 
 
 
X 
X 
X 
Humoral Immune 
Responses 
 
X 
X 
 
 
 
 
X 
 
 
 
 
 
 
X 
X 
X 
Soluble Activation 
Markers 
 
X 
X 
 
 
 
 
X 
 
 
 
 
 
 
X 
X 
X 
Viral Inhibition 
Assay 
 
X 
X 
 
 
 
 
X 
 
 
 
 
 
 
X 
X 
X 
HLA-Typing 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Stored Plasma and 
PBMC 
 
X 
X 
 
 
 
 
X 
 
 
 
 
 
 
X 
X 
X 
HIV-1 RNA  
X 
 
X 
 
 
 
 
 
X 
X 
 
X 
X 
 
 
X 
X 

 
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Evaluation 
Screening 
Pre-Entry 
Entry 
(Week 0) 
Post-Entry Evaluations 
(Weeks) 
Premature 
Treatment/Study 
Discontinuation 
Evaluations 
Post 
Vaccination #1 
4 
Deferred Week 
4 (See section 
6.3.10) 
Post 
Vaccination #2 
6 
12 
Deferred Week 
12 
(See section 
6.3.10) 
Post 
Vaccination #3 
24 
Deferred Week 
24 
(See section 
6.3.10) 
Post 
Vaccination #4 
26 
48 
Plasma HIV-1 RNA 
Single Copy Assay 
(SCA) 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
CD4 T Cell 
Associated HIV-1 
RNA/DNA 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Whole Viral 
Genome 
Sequencing 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
CD4 T Cell 
Purification from 
PBMC 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Study Vaccine/ 
Placebo 
Administration and 
Evaluation 
 
 
X 
 
X 
X 
 
 
X 
X 
 
X 
X 
 
 
 
 
Telephone Contact 
 
 
 
X 
 
 
X 
 
 
 
X 
 
 
X 
 
 
 
Vaccination Report 
Card Distribution 
and Collection 
 
 
X 
 
X 
X 
 
 
X 
X 
 
X 
X 
 
 
 
X 
Tolerability 
Assessment 
 
 
X 
 
X 
X 
 
 
X 
X 
 
X 
X 
 
 
 
X 
Leukapheresis 
(Optional) 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 

 
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Evaluation 
Screening 
Pre-Entry 
Entry 
(Week 0) 
Post-Entry Evaluations 
(Weeks) 
Premature 
Treatment/Study 
Discontinuation 
Evaluations 
Post 
Vaccination #1 
4 
Deferred Week 
4 (See section 
6.3.10) 
Post 
Vaccination #2 
6 
12 
Deferred Week 
12 
(See section 
6.3.10) 
Post 
Vaccination #3 
24 
Deferred Week 
24 
(See section 
6.3.10) 
Post 
Vaccination #4 
26 
48 
Stool (Optional) 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
 

 
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6.2 
Timing of Evaluations 
 
6.2.1 Screening and Pre-Entry Evaluations  
 
Screening and pre-entry evaluations must occur at least 24 hours apart and prior 
to the participant starting any study treatments. 
 
Screening 
Screening evaluations to determine eligibility must be completed within 60 days 
prior to study entry unless otherwise specified. 
 
In addition to data being collected on participants who enroll into the study, 
demographic, clinical, and laboratory data on screening failures will be captured 
in a Screening Failure Results form and entered into the ACTG database.  
 
Pre-Entry  
Pre-entry evaluations must be completed at least 24 hours after screening 
evaluations have been completed and at least 24 hours prior to entry evaluations 
unless otherwise specified. 
 
6.2.2 Entry Evaluations 
 
Entry evaluations must occur at least 24 hours after pre-entry evaluations unless 
otherwise specified. Participant must begin treatment within 72 hours after study 
enrollment. 
 
6.2.3 Post-Entry Evaluations 
 
Post-entry evaluations occur after the study entry visit and vaccination #1 
administration at week 0. Study visits are scheduled as indicated in the SOE. 
 
The visit window for the post-entry evaluations is ±14 days. 
 
NOTE A: The deferred study vaccinations #2, #3, and #4 should be performed 
within 14 days from the time of the previously scheduled week 4, week 12, and 
week 24 visit, respectively (see section 6.3.10). 
 
NOTE B: After study entry, administration of non-HIV vaccines must occur more 
than 2 weeks prior to the scheduled study vaccination #2 (week 4), #3 (week 12), 
and #4 (week 24) injections. 
 
Study Completion Evaluations  
The week 48 evaluations will be completed as the participant’s final on study 
visit. 
 

 
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6.2.4 Discontinuation Evaluations 
 
Evaluations for Randomized Participants Who Do Not Start Vaccination at Entry 
Participants who are enrolled, but who do not receive vaccination #1 will be taken 
off study. No further evaluations are required. These participants will be replaced. 
 
All eCRFs must be keyed for the period up to and including the entry visit. 
 
Premature Treatment Discontinuation Evaluations  
Participants who prematurely discontinue study treatment prior to receiving 
vaccinations #2 or #3 should remain on study (off study treatment) until the final 
visit. No further vaccinations should be administered. The participant should 
complete the premature treatment/study discontinuation evaluations as specified 
in the SOE. If the premature treatment discontinuation visit coincides with a 
regularly scheduled visit, the evaluations should be combined. Participants 
should complete the safety evaluations (clinical assessments, hematology, 
chemistries, and VRC review) per protocol until study completion. 
 
NOTE: Participants who discontinue study treatment prior to receiving 
vaccination #2 may be replaced. Sites should contact the core team. 
 
Premature Study Discontinuation Evaluations  
Participants who discontinue the study prior to the final visit should complete the 
premature treatment/study discontinuation evaluations as specified in the SOE. 
 
6.3 
Instructions for Evaluations 
 
All clinical and laboratory information required by this protocol is to be present in the 
source documents. Sites must refer to the Source Document Guidelines on the DAIDS 
website for information about what must be included in the source document: 
https://www.niaid.nih.gov/sites/default/files/sourcedocappndx.pdf . 
 
All stated evaluations are to be recorded on the eCRF unless otherwise specified. Refer 
to section 7.0 for information on the DAIDS AE Grading Table and AE reporting of 
adverse events requirements. 
 
6.3.1 Documentation of HIV-1 
 
Section 4.1.1 specifies assay requirements for HIV-1 documentation. HIV-1 
documentation is not recorded on the eCRF. 
 
6.3.2 Medical History 
 
The medical history must include all signs and symptoms regardless of grade 
and all diagnoses identified by the ACTG criteria for clinical events and other  

 
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diagnoses regardless of grade within the past 30 days. In addition, the following 
diagnoses should be recorded regardless of when the diagnosis was made: 
• 
AIDS-defining conditions 
• 
Bone fractures (verbal history accepted) 
• 
Coronary heart disease 
• 
Cancer (exclusive of basal/squamous cell skin cancer) 
• 
Diabetes 
• 
Tuberculosis 
• 
Chronic hepatitis C 
• 
Chronic hepatitis B 
 
Any allergies to any medications and their formulations must also be 
documented.  
 
 
 
Document the nadir CD4 count if available. If nadir documentation is not   
 
 
available, then collect and record participant recall. 
 
6.3.3 Medication History 
 
A medication history must be present, including start and stop dates. The table 
below lists the medications that must be included in the history.  
 
Table 6.3.3-1: Medication History 
 
Medication Category 
Complete History or 
Timeframe 
Antiretroviral therapy 
2 years prior to entry 
Immune-based therapy 
1 year prior to entry 
Blinded study treatment 
1 year prior to entry 
HIV-1-related vaccines 
Complete history 
Prescription drugs for treatment 
of opportunistic infections 
1 year prior to entry 
Prescription drugs for 
prophylaxis of opportunistic 
infections 
1 year prior to entry 
Prescription drugs (other) 
1 year prior to entry 
Nonprescription drugs 
30 days prior to entry 
Alternative therapies 
30 days prior to entry 
Dietary supplements 
30 days prior to entry 
Sex-hormone medications or 
sex-hormone analogues or 
antagonists* 
Last 12 months except as 
noted below 
*Includes: hormone-releasing IUDs (e.g., Mirena inserted in the last 5 years); 
oral, injectable, implanted, or patch contraceptives; vaginal ring, creams, or 
inserts; estrogen, progesterone, or testosterone therapy; leuprolide or other 

 
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synthetic gonadotropin-releasing hormone; tamoxifen, raloxifene, aromatase 
inhibitors or any other androgen, estrogen, or progesterone analogue or 
antagonist therapy.  
 
6.3.4 Clinical Assessments 
 
Complete Physical Examination 
A complete physical examination is done at screening and is to include at a 
minimum an examination of the skin, head, mouth, and neck; auscultation of the 
chest; cardiac examination; abdominal examination; and examination of the 
lower extremities for edema. The complete physical examination will also include 
signs and symptoms, diagnoses, and vital signs (height, weight, temperature, 
pulse, respiration rate, and blood pressure). 
 
Targeted Physical Examination 
A targeted physical examination is done at all visits after screening and is to 
include vital signs (weight, temperature, pulse, respiration rate, and blood 
pressure), and is to be driven by any previously identified or new adverse 
event/targeted condition , that the participant has experienced since the last visit 
or at this visit. 
 
At screening, pre-entry, and entry, refer to section 6.3.2, Medical History, for 
reporting requirements. 
 
Post entry, record the following targeted event: 
• 
Uterine Pregnancy  
 
Post-entry, refer to section 7.2 for AE collection requirements. 
 
Concomitant Medications 
Post-entry, the following new and discontinued concomitant medications must be 
recorded on the eCRFs: 
• 
Sex-hormone medications or sex-hormone analogues or antagonists (see 
section 6.3.3 for examples) 
• 
New and discontinued prescription medications 
 
ARV Medications 
Post-entry record all modifications, including initial doses, participant-initiated 
modifications, inadvertent and deliberate delay, and discontinuation.  
 
6.3.5 Skin Pinch 
 
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 is also used to determine the depth of injection for each 
eligible participant to ensure IM administration of the vaccine/placebo prior to the 

 
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first vaccination. The skin thickness ranges and corresponding depth settings on 
the TDS-IM are described in the TDS-IM Instructions for Use (see A5369 
MOPS). 
 
6.3.6 Electrocardiogram (EKG) 
 
EKG will be performed within 60 days prior to study entry. If clinically indicated, a 
follow-up EKG may be performed. 
 
6.3.7 Laboratory Evaluations 
 
At screening, pre-entry, and entry all laboratory values must be recorded on the 
eCRF. For post-entry assessments, record on the eCRF all laboratory values that 
lead to a change in treatment regardless of grade; record abnormal findings as 
per section 7.2. 
 
Hematology 
Hemoglobin, hematocrit, white blood cell count (WBC), differential WBC, 
absolute neutrophil count (ANC), and platelet count, will be performed in real 
time at the local laboratory. 
 
Liver Function Tests 
Total bilirubin, AST (SGOT), ALT (SGPT), alkaline phosphatase, and indirect 
bilirubin will be performed in real time at the local laboratory. 
 
Blood Chemistries 
Electrolytes (sodium, potassium, chloride, and bicarbonate), glucose, phosphate, 
creatinine, total protein, and albumin will be performed in real time at the local 
laboratory. 
 
Calculated Creatinine Clearance 
Calculated CrCl is required as estimated by the Cockcroft-Gault equation. This 
requires the recording of all serum creatinine values regardless of grade. 
 
NOTE: A program for calculating creatinine clearance by the Cockcroft-Gault 
method is available on www.fstrf.org. 
 
Urinalysis 
Dipstick only. 
 
PT, PTT, and INR 
PT, PTT, and INR must be <1.5 x ULN at screening. 
 

 
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Pregnancy Testing 
For women with reproductive potential: Serum or urine -HCG (urine test must 
have a sensitivity of <25 mIU/mL) must be performed as indicated in the SOE 
and whenever pregnancy is suspected. Record pregnancy and pregnancy 
outcomes per section 8.2. 
 
Hepatitis B and C Assessments 
HBsAg and HCV antibody performed by a CLIA-certified laboratory or its 
equivalent. 
 
6.3.8 Immunologic Studies 
 
CD4/CD8 
Obtain absolute CD4/CD8 T cell count and percentages within 60 days prior to 
entry from a laboratory that possesses a CLIA certification or equivalent. 
 
For entry and post-entry evaluations, all laboratories must possess a CLIA 
certification or equivalent and must be certified for protocol testing by the DAIDS 
Immunology Quality Assurance (IQA) Program. 
 
Advanced Flow Cellular Immune Responses 
Advanced flow analysis requires a CD4/CD8 and WBC with differential from a 
sample obtained at the same time. 
 
PBMCs will be stored according to the laboratory processing chart (LPC) and 
utilized for the following advanced flow assays: 
• 
Vaccine-specific CD4 and CD8 T cell responses following stimulation of 
PBMCs with synthetic HIV peptides that span the proteins encoded by the 
vaccine construct, including pools covering individual CE regions. 
• 
ICS parameters will include cytokines such as IFN-γ, IL-2, and TNF-α, and 
may include other cytokines and phenotypic markers to identify T cells of 
specific functionality (such as Th2 and Tfh).  
• 
Markers of cytotoxic potential (e.g., granzyme B) may also be included. Data 
will be reported as percentages of CD4 or CD8 T cells responding to a 
specific peptide pool.  
• 
Additional cell surface markers, cytokines, or functional markers may also be 
analyzed. 
 
Phenotyping of Immune Activation Markers  
PBMCs will be stored according to the LPC and utilized for the following 
advanced flow assays: 
• 
Activated (HLA-DR+/CD38+) CD4 and CD8 T Lymphocytes 
• 
Memory and Naïve (CCR7, CD45RA) T Lymphocyte subsets 
• 
Exhaustion Markers/Checkpoint Inhibitors (including PD-1, TIM-3, TIGIT, 
LAG-3) 
 

 
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Humoral Immune Responses 
Plasma will be stored according to the LPC and utilized for: 
• 
Detection of Gag-specific binding IgG using ELISA or a Binding Antibody 
Multiplex Assay (BAMA) 
 
Soluble Activation Markers 
Plasma will be stored according to the LPC to test for markers including: 
• 
sCD14, IL-6, hs-CRP, 2D-dimer, sCD163, IP10 
 
Viral Inhibition Assay 
A viral inhibition assay using autologous CD4+ T cell targets that are 
superinfected with a reporter virus or a panel of cross-clade viruses to measure 
the ability of HIV-specific CD8+ T cells to suppress viral replication in vitro both 
pre- and post-vaccination. 
 
Human Leukocyte Antigen (HLA) Typing 
HLA typing will be performed on stored PBMCs or plasma that was collected at 
pre-entry. 
 
Stored Plasma and PBMCs 
PBMCs and plasma will be stored for future analysis. For storage and shipping, 
please see the A5369 LPC. 
 
6.3.9 Virologic Studies 
 
Plasma HIV-1 RNA 
Screening HIV-1 RNA must be performed within 60 days prior to study entry by a 
laboratory that possesses a CLIA certification or equivalent. Eligibility will be 
determined based on the screening value.  
 
On study evaluations will be performed at Quest Diagnostics per the SOE. 
 
Plasma HIV-1 RNA Single Copy Assay (SCA) 
Plasma will be stored for determination of HIV-1 RNA by SCA per the SOE. See 
the LPC for details on processing plasma samples for the SCA test.  
 
CD4 T Cell Associated HIV-1 RNA/DNA  
PBMCs will be stored for determination CD4 T cell-associated HIV-1 RNA/DNA 
per the SOE. See the LPC for details on processing PBMC samples.  
 
Whole Viral Genome Sequencing 
Plasma/PBMC will be stored for whole viral genome sequencing per the SOE. 
See the LPC for details on processing plasma/PBMC samples. 
 
CD4T Cell Purification from PBMC  
PBMCs will be stored for CD4 T Cell purification per the SOE. See the LPC for 
details on processing PBMC samples. 

 
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6.3.10 Study Vaccine/Placebo Administration and Evaluation  
 
Vaccine Administration 
All vaccinations including modifications and permanent discontinuations must be 
documented. The vaccine is to be administered via IM injection in the outer 
aspect of the upper arm (deltoid). Details of all vaccinations, including the time 
the vaccine vial is removed from the freezer, reconstituted, administered, and 
route of administration are to be documented in the source documents. 
 
NOTE A: Analgesic medication can be provided to the participant after 
vaccination, if needed. 
 
NOTE B: Participants must remain at the clinic for observation for 30 minutes 
after each vaccination. 
 
Criteria for Deferment  
The following criteria for deferment must be assessed prior to all vaccinations:  
• 
Recent (<72 hours) history of febrile illness (≥101°F [≥38.3°C] oral or 
equivalent) defer the second or third vaccination until at least 24 hours after 
resolution of febrile illness. 
 
In addition the following criteria for deferment must be assessed prior to the 
second, third, and fourth vaccinations:  
• 
Any medical condition that, in the opinion of the investigator, may interfere 
with the evaluation of the study objectives. 
• 
Medical necessity for administration of vaccines other than study pDNA 
vaccine or placebo. 
• 
Plasma HIV-1 RNA increase to >1000 copies/mL. 
 
Deferment of the second vaccination must be for no longer than 14 days beyond 
the scheduled vaccination #2 (week 4). Deferment of the third vaccination must 
be no longer than 14 days beyond the scheduled vaccination #3 (week 12). 
Deferment of the fourth vaccination must be no longer than 14 days beyond the 
scheduled vaccination #4 (week 24). The reason for deferral must be recorded in 
the eCRF.  
 
Laboratory evaluations and specimen collections should be deferred until the 
deferred vaccination visit. The post-vaccination laboratory evaluations and 
specimen collections scheduled for weeks 6 and 26 should also be deferred until 
two weeks after the deferred vaccination visit. If the week 4, 12 or 24 evaluations 
and collection of specimens were not performed at the time of the previously 
scheduled week 4, 12, or 24 visit, they must be performed immediately prior to 
administration of the deferred vaccination. The pregnancy test will need to be 
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If the vaccination #2, #3, or #4 is deferred, the originally scheduled post-vaccine 
evaluations will be performed at the equivalent time interval following the 
vaccination.  
 
If the vaccination #2, #3, or #4 must be deferred for longer than 14 days, then the 
vaccination will not be administered. The participant will be followed in an off 
study treatment/on study status. The participant should complete the treatment 
discontinuation evaluations as specified in the SOE. 
 
NOTE A: If vaccination #2 was missed (i.e., extends beyond the 14-day visit 
window), then vaccinations #3 and #4 will not be administered. The participant 
will be followed in an off study treatment/on study status. 
 
NOTE B: If the deferred vaccination #3 was missed (i.e., extends beyond the 14-
day visit window), then vaccination #4 will not be administered. The participant 
will be followed in an off study treatment/on study status. 
 
The vaccination report card (VRC, described below) data will continue to be 
collected and reviewed during a deferral period.  
 
The core team (actg.corea5369@fstrf.org) must be notified of deferments within 
72 hours. 
 
6.3.11 Telephone Contact  
 
Participants will be contacted by telephone (2 to 3 days post-vaccination) to 
assess for changes in health status and to answer questions about vaccination-
related signs and/or symptoms. See pre-specified telephone script in the A5369 
MOPS. 
 
NOTE: If participants prefer not to be contacted by telephone, then they may 
return to the clinic and the same procedures should be followed as noted above. 
 
6.3.12 Vaccination Report Card (VRC) Distribution and Collection 
 
All participants will be given a new VRC at the time of each vaccination to record 
daily temperatures (oral or equivalent) for 4 days following each vaccination, 
injection-site reactions for 5 days after each vaccination, and systemic reactions 
during the 26-week follow-up. A VRC will be given at week 0 and a new VRC will 
also be given to the participant at weeks 4, 12, and 24 study visits. The VRC will 
be a source document containing data that will be transferred to the appropriate 
eCRFs. 
 
All non-study vaccines or medications taken during the study must be 
documented on the VRC. 
 

 
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All VRCs should be reviewed at all study visits. The following data should be 
transcribed from the VRC to the eCRF: 
• 
Any oral/equivalent temperature ≥101.0°F (≥38.3°C) 
• 
All injection site reactions such as pain, redness, and swelling 
• 
All systemic reactions 
• 
All rash reactions 
• 
All medications taken 
• 
Any vaccines received 
 
NOTE: Participants should take their daily temperature (oral or equivalent) 
measurements at about the same time each day for consistency. 
 
Clinic personnel will review the VRC for completeness, accuracy, and clarity at all 
visits. (In case of premature study discontinuation, the VRC will be reviewed for 
completeness, accuracy, and clarity at the time of discontinuation.) If either 
vaccination #2, #3, or #4 is deferred, then the VRC will be completed until the 
vaccination is administered. All comments are to be reviewed by the study 
personnel and, if necessary, discussed with the participant for clarification. 
 
Any information gained by contact with the participant should be clearly 
documented, initialed, and dated at the bottom of the VRC. The VRC is 
considered a source document and no original information recorded by the 
participant should be crossed-out or altered in any manner by study personnel. 
 
Participants will be asked to notify the study personnel immediately if any 
unexpected or severe reaction occurs. The participant will be asked to notify 
immediately the study investigator if he/she experiences a rash. The rash should 
be examined by the site investigator or clinic personnel within 72 hours of rash 
onset.  
 
6.3.13 Tolerability Assessment  
 
The tolerability assessment measures the acceptability of the vaccine 
administration procedure. The tolerability questionnaire consists of questions that 
capture the participant’s level of discomfort experienced at different time points 
during the vaccination process. Participants will mark their responses for each 
designated time point immediately after completion of the vaccine administration 
procedure.  
 
6.3.14 Leukapheresis (Optional) 
 
Leukapheresis will be performed at pre-entry and week 26. Enrollment slots for 
participants agreeing to have leukapheresis will be reserved for a minimum of 20 
participants. Participants agreeing to have leukapheresis performed at pre-entry 
are also required to have leukapheresis performed at week 26. 

 
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6.3.15 Stool Sample (Optional) 
 
Stool samples will be collected and stored per the SOE and MOPS.  
 
7.0 
ADVERSE EVENTS AND STUDY MONITORING 
 
7.1 
Definition of Adverse Events 
 
An adverse event (AE) is any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or diagnosis that occurs in a study participant during the 
conduct of the study REGARDLESS of the attribution (i.e., relationship of event to 
medical treatment/study product/device or procedure/intervention). This includes any 
occurrence that is new in onset or aggravated in severity or frequency from the baseline 
condition.  
 
7.2 
Adverse Event Collection Requirements for this Protocol 
 
All AEs defined below must be recorded on the eCRFs if any of the following criteria 
have been met: 
• 
All grade ≥3 AEs 
• 
All AEs that led to a change in study treatment/intervention regardless of grade 
• 
All AEs meeting SAE definition or EAE reporting requirement 
 
NOTE: All grade ≥ 3 AEs should be recorded on the eCRF within 48 hours of site 
awareness of the event.   
 
NOTE: SAEs or events meeting EAE reporting requirements should also be entered into 
the DAIDS Adverse Experience Reporting System (DAERS), an Internet-based reporting 
system. 
 
All AEs that are reported must have their severity graded. To grade AEs, sites must refer 
to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse 
Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017, which can be 
found on the DAIDS RSC website at http://rsc.tech-res.com/clinical-research-
sites/safety-reporting/daids-grading-tables. 
 
Serious Adverse Events (SAEs) 
 
An SAE is defined as any untoward medical occurrence that: 
• 
Results in death 
• 
Is life-threatening  
• 
Requires inpatient hospitalization or prolongation of existing hospitalization 
• 
Results in persistent or significant disability/incapacity  
• 
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• 
Is an important medical event that may not be immediately life-threatening or result 
in death or hospitalization but may jeopardize the patient or may require intervention 
to prevent one of the other outcomes listed in the definition above.  
 
7.3 
Expedited Adverse Event (EAE) Reporting to DAIDS 
 
7.3.1 Expedited Adverse Event Reporting to DAIDS 
 
Requirements, definitions and methods for expedited reporting of Adverse 
Events (AEs) are outlined in Version 2.0 of the DAIDS EAE Manual, which is 
available on the RSC website at http://rsc.tech-res.com/clinical-research-
sites/safety-reporting/manual. 
 
The DAIDS Adverse Experience Reporting System (DAERS), an internet-based 
reporting system, must be used for EAE reporting to DAIDS. In the event of 
system outages or technical difficulties, EAEs may be submitted using the DAIDS 
EAE Form. This form is available on the DAIDS RSC website at http://rsc.tech-
res.com/clinical-research-sites/safety-reporting/daids/paper-eae-reporting. 
 
For questions about DAERS, please contact NIAID CRMS Support at 
CRMSSupport@niaid.nih.gov. Please note that site queries may also be sent 
from within the DAERS application itself. 
 
For questions about expedited reporting, please contact the DAIDS RSC Safety 
Office at (DAIDSRSCSafetyOffice@tech-res.com). 
 
7.3.2 Reporting Requirements for this Study 
 
• 
The SAE Reporting Category, as defined in Version 2.0 of the DAIDS EAE 
Manual, will be used for this study. 
• 
The study agents for which expedited reporting are required are: p24CE1/2 
pDNA vaccine, full-length p55gag pDNA vaccine, and placebo for p24CE1/2 
pDNA vaccine and full-length p55gag pDNA vaccines. 
• 
In addition to the SAE Reporting Category identified above, other adverse 
events that must be reported in an expedited manner are: Grade 3 or higher 
AEs or SAEs related to the electroporation or leukapheresis procedures. 
 
7.3.3 Reporting of Error Codes for the TDS-IM 
 
Error codes for the EP device must be reported to the A5369 protocol team in 
real time. These error codes should be recorded on the CRF and keyed in the 
database in a timely manner. 
 
 
 
  

 
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7.3.4 Grading Severity of Events 
 
The Division of AIDS Table for Grading the Severity of Adult and Pediatric 
Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017, 
must be used and is available on the DAIDS RSC website at http://rsc.tech-
res.com/clinical-research-sites/safety-reporting/daids-grading-tables. 
 
7.3.5 Expedited AE Reporting Period 
 
• 
The expedited AE reporting period for this study is as per the EAE manual. 
• 
After the protocol-defined AE reporting period, unless otherwise noted, only 
suspected, unexpected serious adverse reactions (SUSARs), as defined in 
Version 2.0 of the EAE Manual, will be reported to DAIDS if the study staff 
become aware of the events on a passive basis (from publicly available 
information). 
 
7.4 
Study Monitoring 
 
SDAC prepared reports, pooled over treatment arms, accrual, baseline characteristics, 
study conduct (including premature treatment and study discontinuations), and AEs will 
be regularly monitored during the trial by the protocol core team. The protocol core team, 
blinded to active treatment versus placebo assignment, will review the individual safety 
data frequently to assess the relation of all reported AEs to study treatment. 
 
The DAIDS clinical representative will review and assess EAE reports for potential 
impact on the study participant safety and protocol conduct as per DAIDS policies, 
guidance documents, and SOPs, as applicable. 
 
The study will undergo interim review at least annually by an independent ACTG-
appointed Study Monitoring Committee (SMC). The SMC will review accrual, baseline 
characteristics, conduct of the study (including premature treatment and study 
discontinuations), data completeness, and AEs by treatment arm. The first interim review 
will occur approximately 6 months after the enrollment of the first study participant, or 
after 20 participants enroll, whichever occurs first.. An interim review may also be 
convened if a concern is identified by the DAIDS clinical representative, the study chairs, 
or study statisticians in consultation with the team. See section 10.0 for statistical 
considerations related to interim monitoring. 
 
Detailed plans for study monitoring will be outlined in a Study Monitoring Plan developed 
by the Statistical and Data Management Center (SDMC) prior to enrollment of the first 
participant. 
 
8.0 
CLINICAL MANAGEMENT ISSUES 
 
8.1 
Toxicity  
 
Only toxicities considered to be related to the study-provided vaccines or EP procedure 

 
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using the TDS-IM will be managed directly by this protocol.  
 
NOTE: In the event that a participant develops toxicity related to his/her previously-
stable ART, consultation with the core team via email (actg.corea5369@fstrf.org), is 
required (preferably before appropriate therapy modification). 
 
8.1.1 Vaccine or EP Toxicity Management 
 
Participants must remain at the clinic for observation for 30 minutes after each 
vaccination. The protocol team should be contacted within 48 hours for any 
Grade 3 or 4 reactions thought definitely, possibly, or probably related to study 
vaccine or TDS-IM. 
 
8.1.1.1 Grade 1 or 2 Local or Systemic Reactions 
 
Local reactions of mild (Grade 1) or moderate (Grade 2) severity will 
usually resolve spontaneously. If needed, they may be managed with 
local application of cold packs, oral acetaminophen, oral nonsteroidal 
anti-inflammatory agents, or a combination of these measures as 
appropriate. 
 
8.1.1.2 Grade 3 or 4 Local Reactions  
 
For severe (Grade 3) or potentially life-threatening (Grade 4) local 
reactions, the protocol team must be notified within 48 hours. For Grade 
4 local reactions, definitive medical and/or surgical intervention should 
be undertaken as appropriate. Further vaccinations should not be 
administered prior to consultation with the core team via email 
(actg.corea5369@fstrf.org, ATTN: Protocol chair and vice chair). 
 
8.1.1.3 Systemic Reactions  
 
The protocol team should be contacted within 48 hours for any nonlocal 
Grade 3 or 4 reaction thought definitely, possibly, or probably related to 
vaccinations. Further vaccines should not be administered prior to 
consultation with the core team via email (actg.corea5369@fstrf.org, 
ATTN: Protocol chair and vice chair). 
 
8.2 
Pregnancy  
 
Pregnancy and pregnancy outcome will be recorded on the eCRFs. Pregnancies that 
occur on study should be reported prospectively to The Antiretroviral Pregnancy 
Registry. More information is available at www.apregistry.com. Telephone: 800-258-
4263; Fax: 800-800-1052.  
 
Pregnant women will discontinue study medication and will be encouraged to continue 
on study/ off study treatment. At the end of the pregnancy, outcome and AEs for 

 
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participant and infant will be recorded on the outcome eCRF. 
 
If a woman has completed the study or chooses to discontinue from the study before the 
end of the pregnancy, then site staff should request permission to contact her regarding 
pregnancy outcomes at the end of pregnancy. If the information is obtained, pregnancy 
outcomes will be submitted on an eCRF at the end of the pregnancy.  
 
9.0 
CRITERIA FOR DISCONTINUATION 
 
9.1 
Permanent and Premature Treatment Discontinuation 
 
• 
Drug-related toxicity (see section 8.1 Toxicity). 
• 
Requirement for prohibited concomitant medications (see section 5.4). 
• 
Pregnancy (participants who choose to remain on study will be followed off 
treatment/on study). 
• 
Breastfeeding. 
• 
Occurrence of a primary safety endpoint (see section 10.2.1.2). 
• 
Request by participant to terminate study treatment. 
• 
Failure by the participant to attend two consecutive clinic visits. The core team 
should be consulted before the participant is discontinued. 
• 
Request of the primary care provider if she or he thinks the study treatment is no 
longer in the best interest of the participant. 
• 
Clinical reasons believed life-threatening by the physician, even if not addressed in 
the toxicity section of the protocol. 
 
9.2 
Premature Study Discontinuation   
 
• 
Failure to receive the first vaccination. 
• 
Poor adherence to anti-HIV medications as judged by the site investigator. 
• 
Participant fails to comply with the protocol. 
• 
Request by the participant to withdraw. 
• 
At the discretion of the IRB/EC, FDA, NIAID, Office for Human Research Protections 
(OHRP), other government agencies as part of their duties, investigator, or industry 
supporter.  
 
10.0 
STATISTICAL CONSIDERATIONS  
 
10.1 
General Design Issues 
 
A5369 is a phase I/IIa, randomized, double-blind, placebo-controlled study to evaluate 
the safety, immunogenicity, and efficacy of p24CE/full-length Gag DNA, as a therapeutic 
vaccine in HIV-1 infected persons. The study targets to enroll 40 participants. All 
participants are well-suppressed on ART, current CD4 T cell counts >500 cells/mm3, and 
nadir CD4 T cell counts >350 cells/mm3. Each participant will receive active 
vaccine/placebo at weeks 0, 4, 12, and 24 delivered by electroporation after 
intramuscular injection. The primary efficacy outcome will be based on HIV-specific 

 
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immunologic assays at baseline and week 26. 
 
10.2 
Outcome Measures 
 
Primary and secondary outcome measures listed below will be addressed in the study’s 
primary Statistical Analysis Plan, which will define the content of the Primary Analysis 
Report. This report will form the basis for the primary study manuscript and results 
reporting to ClinicalTrials.gov. Outcomes of interest for secondary and exploratory 
objectives intended for subsequent publications are to be listed under “Other Outcome 
Measures.” 
 
10.2.1 Primary Outcome Measures  
  
10.2.1.1 
Immunogenicity  
 
The number of CEs with a CD4 and/or CD8 T cell response at week 
26 compared to baseline in an individual study participant. A CE 
response (for a participant at a given timepoint) is defined by a 
criterion that uses Fisher’s exact test to compare the proportion of 
peptide-stimulated CD4 and/or CD8 T cells that are cytokine positive 
to the proportion that are cytokine positive in the unstimulated sample 
(negative control), and applying a stringent p-value of 10e-5 as a 
cutoff.  
 
NOTE: For this primary endpoint, we will sum the CD4 and CD8 
responses. 
 
10.2.1.2 
Safety 
 
Occurrence of at least one ≥ Grade 3 AE except injection site pain or 
tenderness of less than 48 hours duration, that is possibly, probably, 
or definitely related to study treatment (as judged by the core team, 
blinded to treatment arm) any time from the first day of study 
treatment until 28 days after the last study vaccine administration.  
 
 
 
 
      Grade 4 AEs and deaths at any time on study will be considered  
 
 
 
      a primary safety outcome. 
 
10.2.2 Secondary Outcome Measures  
 
10.2.2.1 
The number of CEs with a CD4 T cell response at week 26 compared 
to baseline in an individual study participant. 
 
10.2.2.2 
The number of CEs with a CD8 T cell response at week 26 compared 
to baseline in an individual study participant. 
 

 
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10.2.2.3 
The total magnitude of CD4 T cell responses against each CE added 
together in each study arm at week 26 compared to baseline. 
 
10.2.2.4 
The total magnitude of CD8 T cell responses against each CE added 
together in each study arm at week 26 compared to baseline. 
 
10.2.3 Other Outcome Measures  
 
10.2.3.1 
HIV-specific cellular responses. 
 
10.2.3.2 
HIV-specific humoral immune responses. 
 
10.2.3.3 
Cellular and soluble markers of immune activation, exhaustion, and 
checkpoint inhibition. 
 
10.2.3.4 
Measures of latent cell reservoir of HIV-1. 
 
10.2.3.5 
Tolerability 
 
• 
At any visit answering “no” to the question, “In your opinion, would 
this study’s vaccination procedure be acceptable as part of a 
treatment for HIV, if it proved to be effective?” 
• 
At any visit answering “no” to the question, “In your opinion, would 
this study’s vaccination procedure be acceptable if it could 
contribute to increased scientific knowledge about how best to 
administer vaccines to prevent or treat infections?”. 
• 
For participants administered vaccine/placebo by the EP device: 
a) rated pain when the device was placed on the skin and the 
vaccine/placebo was injected, b) rated pain at the time of the 
electrical stimulation and muscle contraction, and c) rated pain: i) 
10 minutes and ii) 30 minutes after the procedure was completed  
• 
Premature treatment discontinuation for reasons related to study 
treatment or related to any real or perceived effect of study 
vaccination or its administration.  
 
10.2.3.6 
Gut microbiota 
 
• 
Measures of microbial diversity (Shannon index, alpha, beta 
diversity). 
• 
Prevalence of individual bacterial taxa. 
• 
Measures of bacterial metabolic pathways. 
 

 
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10.3 
Randomization and Stratification 
 
Participants will be randomized 2:1:1 to the p24CE/full-length Gag DNA vaccine arm 
versus full-length Gag DNA vaccine arm versus placebo arm, using the permuted block 
method. Randomization will be stratified by indication of willingness to have the 
leukapheresis procedure.  
 
10.4 
Sample Size and Accrual 
 
The primary comparison will be between the p24CE/full-length Gag DNA and placebo 
arms. Statistical power is estimated based on a two-sided, 5% significance level, 
Fisher’s exact test of whether a participant has a larger number of CEs with a CD4 
and/or CD8 T cell response at week 26 compared to baseline (i.e., a yes/no binary 
outcome), considering n=18 versus n=9 evaluable participants in the two arms, 
respectively. This is a conservative calculation because the primary analysis uses the 
more powerful Wilcoxon rank sum test (see section 10.6.1, Primary Immunogenicity).  
 
The table below provides several scenarios to detect a difference (ranging from 0.50 to 
0.75) between the two arms in the probability that a participant has increased CE 
responses. 
 
Table 10.4-1: Power and Effect Size 
 
Power 
P_p24CE 
P_placebo Effect 
Size 
72% 
0.60 
0.10 
0.50 
80% 
0.64 
0.10 
0.54 
82% 
0.65 
0.10 
0.55 
89% 
0.70 
0.10 
0.60 
90% 
0.71 
0.10 
0.61 
94% 
0.75 
0.10 
0.65 
97% 
0.80 
0.10 
0.70 
98% 
0.85 
0.10 
0.75 
 
Power is 80% to detect a difference of 0.64 versus 0.10 in the probability that a 
participant has more recognized CEs at week 26 compared to baseline. The protocol 
team believes that a difference of 0.54 in the probability of increased CE responses 
between the p24CE vaccine arm and the placebo arm for the primary comparison is a 
clinically relevant immunogenicity effect size that would lend support for further 
development of the p24CE vaccine. The targeted anti-HIV immune responses being 
induced in less than 50% of study participants receiving the p24CE vaccine compared to 
placebo would not be seen as being clinically meaningful and would discourage further 
studies of this vaccine regimen. Power to detect a difference of 0.85 versus 0.10 
between the p24CE vaccine arm and the placebo arm is >98%. 
 

 
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Power is also calculated for a secondary analysis to compare the p24CE vaccine arm 
and the full-length Gag vaccine arm. Considering n=9 evaluable participants in the full-
length Gag vaccine arm, the study has approximately 80% power to detect a difference 
of 0.85 versus 0.30 when comparing the p24CE and full-length Gag vaccine arms.  
 
The sample size calculation is based on the assumption that in the absence of 
intervention, while an HIV+ individual remains on stable and suppressive ART (i.e., 
placebo arm), the HIV-specific immune responses to the CE elements would be 
relatively stable over time. Hence the team expects only a small probability that 
longitudinal assays for a placebo participant would identify an increase in the number of 
CEs recognized by CD4 or CD8 T cells.  
 
NOTE: The sample size calculation may change pending the testing of A5321 samples. 
 
Regarding the assessment of safety (see section 10.2.1.2), the sample size of 20 
participants receiving the p24CE/Gag DNA vaccine will provide >90% probability of 
observing a p24CE/Gag DNA-related AE that would occur in 11% or more of treated 
participants. The sample size of 10 participants receiving the full-length gag DNA 
vaccine will provide >90% probability of observing a full-length gag DNA-related AE that 
would occur in 21% or more of treated participants. 
 
It is anticipated that the study will take 6-9 months to reach accrual targets. 
 
10.5 
Study Suspension Rule 
 
 
If at any time during the study: 
• 
Two or more participants experience a primary safety outcome that is possibly or 
probably related to study treatment (as judged by the core team, blinded to treatment 
arm), or  
 
• 
One or more participants experience a primary safety outcome that is definitely 
related to study treatment  or that is Grade 4 or death and possibly or probably 
related to study treatment (as judged by the Core Team, blinded to treatment arm),  
then enrollment into the study will be temporarily suspended and the Study Monitoring 
Committee (SMC, unblinded to treatment assignment) will be asked to review all safety 
data; review the relation to study treatment of the event(s) thought by the blinded Core 
Team to be a primary safety outcome; and recommend how the study should proceed 
with respect to resuming enrollment and continuing study treatment.  
 
Pending full SMC review, the protocol team will decide, in consultation with the SMC 
chair or designee, whether to continue study treatment for subjects already enrolled. 
 
10.6 
Data and Safety Monitoring  
 
At SMC reviews, data will be considered as detailed in section 7.4.  
 

 
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10.7 
Analyses 
 
10.7.1 Primary Immunogenicity 
 
The planned analysis will compare Y=sum of CEs recognized by CD4 and CD8 T 
cells at week 26 minus the number at baseline between the p24CE/full-length 
Gag DNA and placebo arms, using a two-sided 5% level Wilcoxon rank-sum test, 
which is anticipated to have greater statistical power than analyzing the binary 
version of whether Y>0, for which statistical power was based. An exact 95% 
confidence interval (CI) for the the median of all paired differences between 
observations in the two arms (i.e., Hodges-Lehmann estimate) will be calculated 
to provide additional insight on the effect of p24CE/full-length Gag DNA vaccine.  
 
The primary immunogenicity analysis for this pilot study will be per protocol, 
limited to participants who received all four study vaccination/placebo 
administrations and who did not take any medication prohibited by the study 
protocol on or prior to their week 26 visit. 
 
10.7.2 Primary Safety 
 
All participants who have been exposed to the study treatment will be included in 
this analysis. AEs attributed to study treatment based on the protocol core team 
review will be summarized separately by treatment arm, including the number 
and percentage of participants experiencing an AE with an exact binomial 95% 
CI. 
 
10.7.3 Secondary Analyses  
 
Secondary analyses will compare Arm 2, the gag-DNA alone vaccine arm, to 
each of the other arms. These analyses will be performed in the same manner as 
the primary analysis. 
 
The percentage of participants in each study arm with a CD4 and/or CD8 cell 
response to an increased number of CEs at week 26 compared to baseline will 
be presented along with an exact binomial 95% CI. Pairwise comparisons among 
study arms will be conducted using Fisher’s exact test. Similar analyses will be 
performed for CD4 and CD8 cell responses separately. 
 
The change in total magnitude of CD4 T cell responses against each CE added 
together among study arms will be compared using the two-sided Wilcoxon rank-
sum test. The analysis for CD8 T cell responses will be conducted in a similar 
manner. All statistical tests will be two-sided at the 5% nominal level of 
significance without adjustment for multiple testing. 
 
For each tolerability endpoint, all occurrences of the endpoint will be summarized 
descriptively (e.g., for each participant with the endpoint, the answers to all of the 
questions in that participant’s tolerability questionnaire will be reported), with an 

 
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exact binomial 95% CI on the probability of the tolerability endpoint for each 
treatment arm. Also, the participant ratings of pain will be described a) when the 
device was placed on the participant’s skin and the vaccine/placebo was 
injected, b) at the time of the electrical stimulation and muscle contraction, c) 10 
minutes and 30 minutes after the procedure was completed, by treatment arm, 
and the left and right deltoid separately. 
 
11.0 
PHARMACOLOGY PLAN 
 
Not applicable.  
 
12.0 
DATA COLLECTION AND MONITORING  
 
12.1 
Records to Be Kept 
 
Electronic case report form (eCRF) screens will be made available to sites for data entry. 
Participants must not be identified by name on any data submitted to the DMC.  
Participants will be identified by the patient identification number (PID) and study 
identification number (SID) provided by the ACTG DMC upon registration. 
 
12.2 
Role of Data Management 
 
12.2.1 Instructions concerning entering study data on eCRFs will be provided by the 
ACTG DMC. Each CRS is responsible for keying the data in a timely fashion. 
 
12.2.2 It is the responsibility of the ACTG DMC to ensure the quality of computerized 
data for each ACTG study. This role extends from protocol development to 
generation of the final study databases. 
 
12.3 
Clinical Site Monitoring and Record Availability 
 
12.3.1 Site monitors under contract to the NIAID will visit participating clinical research 
sites to review the individual participant records, including consent forms, eCRFs, 
supporting data, laboratory specimen records, and medical records (physicians’ 
progress notes, nurses’ notes, individuals’ hospital charts), to ensure protection 
of study participants, compliance with the protocol, and accuracy and 
completeness of records. The monitors also will inspect sites’ regulatory files to 
ensure that regulatory requirements are being followed and sites’ pharmacies to 
review product storage and management. 
 
12.3.2 The site investigator will make study documents (e.g., consent forms, drug 
distribution forms, eCRFs) and pertinent hospital or clinic records readily 
available for inspection by the local IRB, the site monitors, the FDA, the NIAID, 
the OHRP, the industry supporter or designee, and other local, U.S., and 
international regulatory entities for confirmation of the study data. 
 

 
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13.0 
PARTICIPANTS 
 
13.1 
Institutional Review Board (IRB) Review and Informed Consent 
 
This protocol and the informed consent document (Appendix I) and any subsequent 
modifications will be reviewed and approved by the IRB or EC responsible for oversight 
of the study. A signed consent form will be obtained from the participant (or legal 
guardian or person with power of attorney for participants who cannot consent for 
themselves). The consent form will describe the purpose of the study, the procedures to 
be followed, and the risks and benefits of participation. A copy of the consent form will 
be given to the participant, or legal guardian and this fact will be documented in the 
participant’s record. 
 
13.2 
Participant Confidentiality 
 
All laboratory specimens, evaluation forms, reports, and other records that leave the site 
will be identified by coded number only to maintain participant confidentiality. All records 
will be kept locked. All computer entry and networking programs will be done with coded 
numbers only. Clinical information will not be released without written permission of the 
participant, except as necessary for monitoring by the ACTG, IRB/EC, FDA, NIAID, 
OHRP, other local, US, and international regulatory entities as part of their duties, or the 
industry supporters or designees.  
 
13.3 
Study Discontinuation 
 
The study may be discontinued at any time by the ACTG, IRB/EC, FDA, NIAID, OHRP, 
other government agencies as part of their duties to ensure that research participants 
are protected, or the industry supporter. 
 
13.4 
Compliance with NIH Guidelines for Research Involving Products Containing 
 
Recombinant DNA 
 
This protocol was submitted to the Office of Biotechnology Activities (OBA) in 
accordance with Appendix M of the National Institutes of Health (NIH) Guidelines for 
Research Involving Recombinant DNA Molecules (NIH Guidelines 2009) 
http://oba.od.nih.gov/rdna/nih_guidelines_oba.html. The protocol (#1004-1038) was 
reviewed by the NIH Recombinant DNA Advisory Committee (RAC) as notified by the 
OBA on May 4, 2010. 
 
The Principal Investigators and the institution are responsible for ensuring that no 
research subjects are enrolled in the protocol until Institutional Biosafety Committee 
(IBC) approval, IRB approval and all applicable regulatory authorizations have been 
obtained. 
 
The current reporting requirements set forth in Appendix M-I-C-1 of the NIH Guidelines 
require the Principal Investigator to submit additional documentation as specified to the 

 
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OBA. 
 
Within 20 working days of enrolling the first subject in the trial, the investigator at the first 
site must provide OBA with the documents and information listed below (per Appendix 
M-I-C-1 of the NIH Guidelines). 
 
• 
A copy of the protocol approved by the IBC and IRB 
• 
A copy of the informed consent approved by the IRB 
• 
A copy of the IBC approval of the clinical site 
• 
A document outlining the responses to the RAC’s recommendations (if any) and 
any modification to the protocol required by the FDA 
• 
The IND number 
• 
The NIH grant number 
• 
The date of the initiation of the trial 
 
The guidelines allow for formal delegation of all or part of the investigator reporting 
requirements (Appendix M-I-C-4 of the NIH Guidelines). 
 
When adding new sites to the clinical trial, no research subject should be enrolled at the 
site until the following documentation has been submitted to the OBA: 
 
• 
IBC approval from the clinical site 
• 
IRB approval 
• 
IRB-approved informed consent document 
• 
Curriculum vitae of the Principal Investigator(s) – no more than two pages in 
biographical sketch format 
• 
NIH grant number(s) if applicable 
 
During the conduct of the study, the principal investigator is responsible for providing 
OBA with safety reports and annual report. In such cases, OBA requires that these 
documents follow the timelines for submission and format of the homologous FDA 
mandatory reports. 
 
All information communicated to the OBA is publically available unless it is clearly 
labeled as confidential. Since annual reports to the FDA may contain proprietary 
information, the product manufacturer will edit the annual report to remove any 
proprietary information prior to submission to OBA. The DAIDS medical officer will sign 
off on the redacted annual report before submission to OBA. 
 
The safety reports can be sent simultaneously to the FDA and OBA by the RSC SAE 
Office. 
 

 
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14.0 
PUBLICATION OF RESEARCH FINDINGS 
 
Publication of the results of this trial will be governed by ACTG policies. Any 
presentation, abstract, or manuscript will be made available for review by the industry 
supporter prior to submission.  
 
15.0 
BIOHAZARD CONTAINMENT 
 
As the transmission of HIV and other blood-borne pathogens can occur through contact 
with contaminated needles, blood, and blood products, appropriate blood and secretion 
precautions will be employed by all personnel in the drawing of blood and shipping and 
handling of all specimens for this study, as currently recommended by the CDC and the 
National Institutes of Health. 
 
All dangerous goods and materials, including diagnostic specimens and infectious 
substances, must be transported using packaging mandated by CFR 42 Part 72. Please 
refer to instructions detailed in the International Air Transport Association (IATA) 
Dangerous Goods Regulations.  

 
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16.0 
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APPENDIX I SAMPLE INFORMED CONSENT 
 
Division of AIDS 
AIDS CLINICAL TRIAL GROUP (ACTG) 
For protocol A5369 
 
HIV-1-Gag Conserved-Element DNA Vaccine (p24CE) as Therapeutic Vaccination in HIV-
Infected Persons with Viral Suppression on Antiretroviral Therapy 
FINAL Version 1.0, 03/09/18 
 
SHORT TITLE FOR THE STUDY: HIV-1-Gag Conserved-Element DNA Vaccine (p24CE) as 
Therapeutic Vaccination  
 
 
INTRODUCTION 
 
You are being asked to take part in this research study because you are infected with the 
human immunodeficiency virus (HIV) and are currently taking anti-HIV medications. This study 
is sponsored by the National Institutes of Health (NIH). The doctor in charge of this study at this 
site is: (insert name of Principal Investigator). Before you decide if you want to be a part of this 
study, we want you to know about the study.  
 
This is a consent form. It gives you information about this study. The study staff will talk with you 
about this information. You are free to ask questions about this study at any time. If you agree to 
take part in this study, you will be asked to sign this consent form. You will get a copy to keep. 
 
 
WHY IS THIS STUDY BEING DONE? 
 
The study will look to see if two HIV vaccines are safe in people infected with HIV. Additionally, 
the study will look at whether or not the HIV vaccines improve the immune system’s ability to 
fight HIV. This study will also look at whether the intramuscular injection of the study vaccines 
given along with electroporation will be well tolerated. 
 
The HIV vaccine used in this study is experimental. This means that this vaccine has not been 
approved by the Food and Drug Administration (FDA).  
 
 
WHAT DO I HAVE TO DO IF I AM IN THIS STUDY? 
 
To be in this study, you must continue taking your current anti-HIV drugs. Your anti-HIV drugs 
will not be provided to you by the study.  
 

 
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Screening 
If you decide to take part in this research study, you will be asked to sign this consent form. You 
will come to the clinic to have a screening visit. Tests will be done at the screening visit to see if 
it is safe for you to join the study. The screening visit will take about 1 hour, but it may be 
shorter or longer.  
 
At the screening visit: 
 
• 
Your HIV-1 infection will be confirmed. If there is no record available, you will have another 
HIV-1 test. You may have to sign a separate consent form before having this test. 
• 
You will have a complete physical exam and will be asked questions about how you are 
feeling.  
• 
You will also be asked to answer questions about your medical history and medications you 
are taking now and have taken in the past. 
• 
You will have a skin pinch test to measure the thickness of the skin on your upper arm 
muscles. This test will also measure the right depth when giving the injections in the upper 
arm muscles. 
• 
You will have a pregnancy test done, if you are a woman able to become pregnant. You 
cannot take part in this study if you are pregnant or breastfeeding. 
• 
You will have a urinalysis performed to evaluate the health of your kidneys. 
• 
You will have an electrocardiogram (EKG) test done to measure the electrical activity 
of your heart. You will be asked to lie down very still and breathe normally during the 
test.  
 
You will have about 2 tablespoons of blood drawn from a vein in your arm: 
• 
To measure HIV viral load (a viral load test measures how much HIV is in your blood).  
• 
To measure CD4/CD8 T cell counts (the number of white blood cells that fight infection). 
• 
To test for hepatitis B and hepatitis C (viruses that can infect your liver). 
• 
To conduct routine safety tests.  
 
You will be told the results of the tests done at the screening visit. 
 
If you do not enroll into the study 
If you decide not to take part in this study or if you do not meet the eligibility requirements, we 
will still use some of your information. As part of this screening visit, some demographic (for 
example, age, gender, race), clinical (for example, disease condition, diagnosis), and laboratory 
(for example, CD4 cell count, viral load) information is being collected from you so that ACTG 
researchers may help determine whether there are patterns or common reasons why people do 
not join a study. 
 
Pre-Entry 
If you qualify for the study, you will return to the clinic about 2 weeks after your screening visit. 
The visit is expected to last between 3 to 4 hours. 
 

 
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At the pre-entry visit: 
• 
You will have a total of about 3 tablespoons of blood drawn from a vein in your arm. 
• 
You will have blood collected and stored for future immunologic testing (to measure the 
body’s ability to fight infection).  
• 
You will have a pregnancy test done, if you are a woman able to become pregnant. 
• 
You will have blood collected to measure CD4/CD8 T cell counts (the number of white blood 
cells that fight infection). 
• 
You will have blood collected for human leukocyte antigen (HLA) typing and testing. 
• 
You will have blood stored for future tests.  
• 
If you agree, you will have leukapheresis performed. You will also be required to have a 
leukapheresis performed at the week 26 visit. By collecting blood using this procedure, 
researchers are able to get many more white blood cells than is usually possible. 
• 
If you agree, you will have stool samples collected to study the different kind of bacteria in 
your stool. These samples will be stored and will be tested after the study is over. You will 
not be given the results. (This test is optional) 
 
Leukapheresis Procedure 
The leukapheresis procedure may be performed at [insert site-specific details]. The procedure 
will take about [insert site-specific details] and the full visit will last about [insert site-specific 
details]. You will have to remain in a semi-reclining or reclining position for most of this time. 
 
Leukapheresis is a medical procedure that involves removing whole blood from an 
individual/donor and separating the blood into individual components so that leukocytes (white 
blood cells) can be removed. The remaining blood components are then put back into the 
bloodstream of the individual/donor. This will be done by inserting a needle attached to sterile 
tubing in one arm, and first sending your blood through a machine. This machine spins your 
blood to separate the red blood cells (cells that carry oxygen), the white blood cells (cells that 
fight infection) and the platelets (cells that help form clots). The white blood cells will be kept for 
testing. The rest of your blood will be returned to your body through another needle and tube in 
your other arm. Not all of your white blood cells are removed, and your body will make more 
white cells within a few days. Losing the number of white blood cells that are collected does not 
pose a danger to your health. 
 
Entry 
You will return to the clinic at least 24 hours after your pre-entry visit. The entry visit (week 0) 
will last about 1-2 hours, but may be shorter or longer.  
 
At the entry visit: 
• 
You will have a brief physical exam. 
• 
You will be asked about how you are feeling and any medications you have taken since the 
last visit. 
• 
You will have a pregnancy test done, if you are a woman able to become pregnant.  
• 
You will have a total of about 4 tablespoons of blood drawn from a vein in your arm. 
• 
You will have blood drawn for routine safety tests.  
• 
You will have a urinalysis performed to evaluate the health of your kidneys. 

 
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• 
You will have blood drawn for CD4/CD8 T cell counts, HIV viral load, and future 
immunologic testing.  
You will be told the results of the safety tests, HIV viral load, and CD4/CD8 T cell counts done 
during the study. 
 
Study Injections 
When you enter the study, you will be placed into one of the three groups. You will be 
randomized 2:1:1 (by chance) to receive either the p24CE1/2 pDNA vaccine (an HIV vaccine) 
followed by p24CE1/2 + full-length Gag pDNA vaccine (a different HIV vaccine), OR the full-
length Gag pDNA vaccine alone, OR placebo (the placebo is a salt solution that does not 
contain any vaccine, medicine, or drugs).  
 
Neither you nor the study staff will know whether you will receive the vaccine or placebo. You 
will receive the injections at the clinic at weeks 0 (entry), 4, 12, and 24.  
 
Electroporation (EP) Procedure 
To improve the effectiveness of the vaccine, instead of a regular needle and syringe, a small, 
hand-held device will be used to inject the vaccine or placebo into your upper arm muscle. To 
give the vaccine or placebo, the study staff will press the device against your skin and press a 
button. Although you will not be able to see them, the device will put an injection needle and 
four thin wires into your muscle. The vaccine or placebo will be given through the injection 
needle into your muscle. After the injection, the device will give a very short electrical signal to 
your muscle at the spot of the injection. The electrical signal will last for about one half second. 
You will feel twitching in your muscle, which is often painful. Previous participants have 
described the feeling as a short “cramp” or “punch” in their muscle. Right after the electrical 
signals are finished, the device will be removed from your muscle. Your muscle may be sore to 
the touch after the vaccination. If this occurs, it usually does not last for more than 30-60 
minutes. 
 
Before Injection 
Due to the risk of dizziness/lightheadedness or in rare cases, fainting, the injection will be given 
to you while you are in a secure, seated position.  
 
After Injection 
You will be observed by the study staff when coming to a standing position following the 
injection. You may ask for pain-relieving medication after each injection if you need it.  
 
After each injection, you will be asked to stay at the clinic for 30 minutes to be observed and to 
complete a brief survey (Procedure Tolerability Questionnaire). This survey will ask you 
questions on the level of discomfort you may have experienced during the vaccination, including 
the overall acceptability of the procedure. 
 
You will be called 2 to 3 days after each injection to see how you are doing. The telephone call 
will take about 5-10 minutes. If you prefer not to be contacted by telephone, then you will be 
asked to return to the clinic within 2 to 3 days after each vaccination. The study staff may ask 
you to come to the clinic if you are having any side effects from the vaccination.  

 
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Study Diary 
You will be given a diary to record: 
• 
Your temperature for 4 days after each injection. 
• 
Any side effects for 5 days after each injection.  
• 
Any rash or skin irritation around and/or in the middle of the injection site. 
• 
Any medications taken. 
• 
Any non-study vaccines received.  
 
The diary will be given to you at the entry visit. It will take you about 10-15 minutes to complete 
the diary each day. You will bring the diary back to the clinic at your next visit and at every visit 
afterwards until the 26-week follow-up visit. The diary will be collected by the study staff at the 
final visit (week 48); if you stop the study early, the diary will be collected your last study visit. 
 
During the Study 
After your entry visit, the next study visits will take place over a 12-month period (weeks 4, 6, 
12, 24, 26, and 48). Each study visit will last about 1-2 hours, but may be shorter or longer.  
 
At most visits, you will be asked about how you are feeling, what medications you are taking, 
and have a brief physical exam. At the injection visits (weeks 4, 12, and 24), you will have a 
pregnancy test done, if you are a woman able to become pregnant, before you have the 
injection. At weeks 4, 12, and 24, you will also have a urinalysis performed. 
 
At most visits, you will have blood drawn from a vein for routine safety tests. At some visits, you 
will have blood drawn for CD4/CD8 T cell counts, HIV viral load, and future immunologic testing. 
You will have between 2 and 4 tablespoons of blood drawn at each visit. 
 
If you agree, you will have stool sample collectesd at week 26 to study the different kind of 
bacteria in your stool.These samples will be stored and will be tested after the study is over. 
You will not be given the results. (This test is optional.) 
 
If you agreed to have leukapheresis performed at the pre-entry visit you will be required to also 
have leukapheresis performed at the week 26 visit. 
 
NOTE: Your blood that is drawn for future immunologic testing, which is required for this study, 
will be stored with usual protectors of your identity. Your blood samples will be processed in the 
laboratory to produce a certain type of white blood cells, called PBMC (peripheral blood 
mononuclear cells), and plasma. 
 
Other 
If you agree, some of your blood that is left over after all required study testing is done may be 
stored (with usual protectors of your identity) and used for future ACTG-approved HIV-related 
research.  
 
You may refuse or withdraw your permission for storage of leftover samples without any impact 
on you taking part in the study or any penalty or loss of benefits to which you are entitled. You 

 
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can withdraw your permission at any time. If you do not agree to have the leftover samples 
stored or withdraw your permission, the leftover samples will be destroyed. These leftover 
samples may be stored for an indefinite period of time. You might not receive the results of 
testing performed on these leftover samples.  
 
Please initial one of the following lines to indicate whether or not you wish to have your 
specimens stored for research in the future.  
 
________ YES                     ________ NO 
 
 
HOW MANY PEOPLE WILL TAKE PART IN THIS STUDY? 
 
About 40 people will take part in this study 
 
 
HOW LONG WILL I BE IN THIS STUDY? 
 
You will be in this study for about 12 months (48 weeks). 
 
 
WHY WOULD THE DOCTOR TAKE ME OFF THIS STUDY EARLY? 
 
The study doctor may need to take you off the study early without your permission if: 
• 
The study is stopped or cancelled. 
• 
You do not take your anti-HIV medications as prescribed. 
• 
You do not comply with the protocol. 
• 
You choose to stop your participation in the study. 
• 
Your primary care doctor feels the treatment is no longer in your best interest. 
• 
Failure to receive the first vaccination. 
 
The study doctor may also need to take you off the study drug(s) without your permission if: 
• 
You miss two consecutive clinic visits. 
• 
Continuing to receive the study vaccine may be harmful to you. 
• 
You need a drug or treatment that you may not take while on the study. 
• 
You are not able to receive the study vaccine as required by the study. 
• 
You have a bad reaction to the study vaccine and need treatment. 
• 
You become pregnant or start breast-feeding. 
 
If you must stop receiving the study-provided vaccine before the study is over, the study doctor 
may ask you to continue to be part of the study and return for some study visits and procedures. 
 

 
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If I have to permanently stop receiving the study-provided vaccine, or once I leave the study, 
how would vaccine be provided? 
 
During the study: 
 
If you must permanently stop receiving the study-provided vaccine before your study 
participation is over, the study staff will discuss other options that may be of benefit to you. 
 
After the study: 
 
After you have completed your study participation, the study will not be able to continue to 
provide you with the vaccine you received on the study.  
 
 
WHAT ARE THE RISKS OF THE STUDY? 
 
The vaccine or placebo used in this study may have side effects, some of which are listed 
below. Please note that these lists do not include all the side effects seen with the study 
vaccine. These lists include the more serious or common side effects with a known or possible 
relationship. There may be more serious or common side effects that we do not know about yet. 
Therefore, it is important that you report any side effects to the study staff. If you have questions 
concerning additional study vaccine side effects, please ask the medical staff at your site. 
 
There is a risk of serious and/or life-threatening side effects when non-study medications are 
taken with the study vaccine. For your safety, you must tell the study doctor or nurse about all 
medications you are taking before you start the study and also before starting any new 
medications while on the study. Also, you must tell the study doctor or nurse before enrolling in 
any other clinical trials while on this study. 
 
The following side effects can occur from either the vaccine or the placebo in this study. If you 
do have a reaction, it does not mean that you received the study vaccine. 
 
General Vaccination Risks 
The possible risks for vaccines in general 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 whether you receive the vaccine or the placebo in this study. The side effects 
do not 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 30 minutes after 
each injection. There may be other side effects, even serious ones that we do not know about 
yet. Therefore, it is important that you report any side effects to the study staff as soon as they 
occur. 
 

 
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For people infected with HIV, vaccinations can cause a temporary increase in the HIV viral load, 
but this has not been seen when people are also taking medications that lower the amount of 
HIV in the blood. The long-term effects of temporary increases in HIV viral load levels are 
unknown. 
 
Risks of Injections 
• 
Arm discomfort 
• 
Bleeding or bruising at the spot where the needle enters your body 
• 
Small risk of fainting or infection 
• 
Stinging, pain, soreness, redness, itching, swelling, burning, warmth at injection site 
• 
Induration (hardness under the skin) at the site where the vaccine/placebo is given 
 
Risks of Drawing Blood 
Blood tests for screening and study visits will be done by inserting a needle into one of your 
veins and this can cause temporary mild pain or discomfort at the needle site (common), local 
bruising at needle site (rare), infection, and fainting (very rare). 
 
Risks of HIV DNA Vaccines, including pDNA Study Vaccine  
HIV-1 DNA vaccines have been studied in humans and appear to be well tolerated, but we do 
not have long-term follow-up on people taking part in these studies.  
 
Possible risks related to DNA vaccines include muscle damage, or the production of antibodies 
(proteins made by the body’s immune system in response to a foreign substance) to DNA. 
Other potential risks include insertion of the vaccine DNA into the body's DNA (leading to 
cancer) or into the DNA of a bacteria or virus in your body. None of these possible risks of DNA 
vaccines have been seen in laboratory tests or in animals or humans so far, but you need to be 
aware of these possible risks. During the study, regular blood tests and check-ups will be done 
to monitor these possible side effects. 
 
The pDNA vaccine consists of artificial DNA. Since the vaccine in this study has not been given 
to humans for treating HIV infection, all the possible risks or side effects are not known.  
 
The pDNA vaccine was tested in animals at doses similar to or larger than those planned to be 
given in this study without serious side effects. However, people may respond differently to the 
vaccine than animals.  
 
Information about local injection site reactions in humans after injection of the pDNA vaccine is 
not available at this time. However, the local reactions related to intramuscular (IM) injections 
such as pain, hardness under the skin, redness, and swelling may occur and are expected to be 
mostly mild to moderate in severity based on results from earlier HIV clinical trials with related 
products. Information about systemic events (which affect your whole body, such as fever or not 
feeling well) with the pDNA vaccine are not available at this time. Based on results from clinical 
trials with related products in healthy adults and in HIV-infected persons, systemic events are 
expected to be mild to moderate in severity. 
 

 
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It is unknown whether receiving this HIV vaccine will change your response to any future HIV 
therapies or vaccines that you might receive. This might prevent you from taking part in other 
experimental vaccine or immune studies. 
 
Risks of EP Procedure 
This section describes the risks and restrictions we know about. There may also be unknown 
risks, even serious ones. If we learn about new risks during this study, we will tell you. 
• 
Brief twitching/contraction of the upper arm muscle where the vaccination is given will occur 
during the the EP procedure. This may result in a painful sensation, which should last only a 
few seconds. 
• 
It is possible that the EP procedure could cause you to become dizzy or lightheaded. If severe 
enough, this could lead you to faint. Should this happen, you may require additional tests 
and/or hospitalization. 
• 
After the EP device is removed, slight bleeding may occur in the skin at the vaccination site. 
This bleeding, if any, should only last for a few minutes. 
• 
Delivery of the vaccine with the EP device is likely to result in muscle soreness or pain of mild 
to moderate severity at the vaccination site. Redness, swelling, and/or bruising in the area of 
the vaccination could also occur. It is possible that these reactions could persist for several 
days or more after administration.  
 
Other Expected Risks 
Common: 
• 
Muscle pain with severe muscle contractions during vaccination administration 
• 
Mild to moderate injection site pain, tenderness, redness, bruising, or edema (swelling under 
the skin)  
• 
Muscle aches or headache in the first few days following vaccination 
 
Less common: 
• 
Severe vaccination site pain or tenderness 
• 
Joint pain 
• 
Vaccination site bruising (a mass of blood in the tissue caused by injury), laceration (cut or 
slash), or bleeding related to the vaccination procedure 
• 
Dizziness/lightheadedness 
 
Uncommon or rare: 
• 
Fainting 
• 
Severe reaction of the vaccination site including sterile abscess (lumps caused by nonliving 
irritants such as drugs) or secondary bacterial infection 
• 
Allergic reaction, including rash, urticaria (hives), angioedema (swelling of the skin), 
bronchospasm (narrowing of the muscles that help you breathe), or anaphylaxis (life-
threatening allergic reaction) 
 

 
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Unknown frequency or theoretical risks:  
• 
Muscle damage at the vaccination site  
• 
Insertional mutagenesis (a mutation caused by new genetic material put into a normal gene) 
• 
Autoimmune reaction (a process in which your immune system attacks your body) 
 
Risks of Bupivacaine 
The HIV pDNA vaccine contains bupivacaine. Bupivacaine helps the DNA get into the muscle 
cells. It is an anesthetic, similar to the numbing medicine used by dentists. Bupivacaine, like all 
medicines, can have side effects. Bupivacaine can cause problems with the nervous system 
and heart. The nervous system side effects include confusion, dizziness, blurred vision, 
shaking, or seizures. The heart side effects can include decreased heart pumping, fast heart 
rate, low blood pressure, abnormal heartbeats, or even death. Other possible side effects 
include nausea, vomiting, or chills. All of these side effects are very rare, but may happen as a 
result of accidental injection into the bloodstream.  
 
Risks of Leukapheresis 
Leukapheresis has been shown to be safe in HIV-infected donors and does not affect CD4+ T-
cell count or immune status of short-term donors. The needle used is larger than normal blood 
draw and may be uncomfortable. Rarely, a participant may feel faint during or after 
leukapheresis. This sort of reaction can be handled by changing the participant’s position or 
administering intravenous fluids. You may experience chills, nausea, and heartburn caused by 
the citrate anticoagulant that is used during the procedure to keep the collected cells from 
clumping together in the bag. This chemical may use up some of the calcium in your blood 
stream, and tingling in the face, lips, or hands may be noted. If this happens, study staff may 
slow the rate of infusion of this chemical and may offer you one or two calcium carbonate tablets 
to correct the calcium loss. Participants will be observed closely by an experienced blood bank 
technician during the procedure. 
 
 
ARE THERE RISKS RELATED TO PREGNANCY? 
 
The vaccine in this study may be unsafe for unborn babies. If you are having sex that could lead 
to pregnancy, you must agree not to become pregnant or make a woman pregnant for at least 
three months after the final study vaccination. Because of the risk involved, you and your 
partner must agree to use two methods of birth control that you discuss with the study staff. You 
may choose two of the birth control methods listed below: 
• 
Condoms (male or female) with or without a spermicidal agent 
• 
Diaphragm or cervical cap with spermicide 
• 
Intra-uterine device (IUD) 
• 
Hormone-based contraceptive 
 
If you can become pregnant, you must have a pregnancy test before you enter this study. The 
test must show that you are not pregnant. If you think you may be pregnant at any time during 
the study, tell your study staff right away. The study staff will talk to you about your choices. If 
you become pregnant while on the study, you will be asked if you wish to continue in the study 

 
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and come for study visits for routine safety evaluations. You will not receive any further 
injections that are scheduled.  
 
Safety information regarding the performance of this pDNA vaccine in pregnant women is not 
available at this time. Therefore, this vaccine is not to be given to pregnant women or nursing 
mothers. 
 
If you become pregnant while on study, the study staff would like to obtain information from you 
about the outcome of the pregnancy (even if it is after your participation in the study ends). If 
you become pregnant during the study and do not give birth by the time of the final study visit, 
and if you agree, you will be contacted at the end of the pregnancy regarding pregnancy 
outcomes. 
 
If you are taking anti-HIV drugs when you become pregnant, your pregnancy will be reported to 
an international database that collects information about pregnancies in women taking anti-HIV 
drugs. This report will not use your name or other information that could be used to identify you. 
 
 
ARE THERE BENEFITS TO TAKING PART IN THIS STUDY? 
 
If you take part in this study, you should expect no direct benefit. Information learned from this 
study may help others who have HIV. 
 
 
WHAT OTHER CHOICES DO I HAVE BESIDES THIS STUDY? 
 
Instead of being in this study you have the choice of: 
• 
treatment with prescription drugs available to you 
• 
treatment with experimental drugs, if you qualify  
• 
no treatment 
 
Please talk to your doctor about these and other choices available to you. Your doctor will 
explain the risks and benefits of these choices. 
 
 
WHAT ABOUT CONFIDENTIALITY? 
 
We will do everything we can to protect your privacy. In addition to the efforts of the study staff 
to help keep your personal information private, we have gotten a Certificate of Confidentiality 
from the U.S. Federal Government. This certificate means that researchers cannot be forced to 
tell people who are not connected with this study, such as the court system, about your 
participation. Also, any publication of this study will not use your name or identify you 
personally.  
 

 
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Your records may be reviewed by the U.S. Food and Drug Administration (FDA), the ACTG, the 
U.S. Office for Human Research Protections (OHRP), or other local, U.S., and international 
regulatory entities as part of their duties, (insert name of site) institutional review board (IRB) (a 
committee that protects the rights and safety of participants in research), National Institutes of 
Health (NIH), study staff, study monitors, the drug company supporting this study, and their 
designees. Having a Certificate of Confidentiality does not prevent you from releasing 
information about yourself and your participation in the study. 
 
Even with the Certificate of Confidentiality, if the study staff learns of possible child abuse and/or 
neglect or a risk of harm to yourself or others, we are required to tell the proper authorities. 
 
A description of this clinical trial will be available on www.ClinicalTrials.gov, as required by U.S. 
law. This website will not include information that can identify you. At most, the website will 
include a summary of the results. You can search this website at any time.  
 
 
WHAT ARE THE COSTS TO ME? 
 
Taking part in this study may lead to added costs to you and your insurance company. In some 
cases it is possible that your insurance company will not pay for these costs because you are 
taking part in a research study.  
 
The HIV pDNA vaccine or placebo that you may receive will be supplied by the study. Your anti-
HIV drugs will not be provided by the study, so you must get these drugs through your primary 
care provider; you must also pay for them through some other manner, such as your insurance 
or local AIDS Drug Assistance Program (ADAP). 
 
 
WILL I RECEIVE ANY PAYMENT? 
 
[Sites: Please indicate whether you will provide payment to participants. If so, please describe 
the amount to be paid or reimbursed, the payment schedule, and any prorated schedule should 
the participant decide to withdraw or is withdrawn early by the investigator.]  
 
 
WHAT HAPPENS IF I AM INJURED? 
 
If you are injured as a result of being in this study, you will be given immediate treatment for 
your injuries. The cost for this treatment will be charged to you or your insurance company.  
 
There is no program for compensation either through this institution or the National Institutes of 
Health. You will not be giving up any of your legal rights by signing this consent form. 
 
 

 
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WHAT ARE MY RIGHTS AS A RESEARCH PARTICIPANT? 
 
Taking part in this study is completely voluntary. You may choose not to take part in this study 
or leave this study at any time. Your decision will not have any impact on your participation in 
other studies conducted by NIH and will not result in any penalty or loss of benefits to which you 
are otherwise entitled.  
 
We will tell you about new information from this or other studies that may affect your health, 
welfare, or willingness to stay in this study. If you want the results of the study, let the study staff 
know. 
 
 
WHAT DO I DO IF I HAVE QUESTIONS OR PROBLEMS? 
 
For questions about this study or a research-related injury, contact: 
• 
name of the investigator or other study staff 
• 
telephone number of above  
 
For questions about your rights as a research participant, contact: 
• 
name or title of person on the Institutional Review Board (IRB) or other organization 
appropriate for the site 
• 
telephone number of above 
 

 
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SIGNATURE PAGE 
 
If you have read this consent form (or had it explained to you), all your questions have been 
answered and you agree to take part in this study, please sign your name below. 
 
 
 
____________________________ 
__________________________________ 
Participant’s Name (print) 
Participant’s Signature and Date 
 
 
____________________________ 
__________________________________ 
Participant’s Legally Authorized 
Legally Authorized Representative 
Representative (print) 
Signature and Date 
(As appropriate) 
 
 
____________________________ 
__________________________________ 
Study Staff Conducting 
Study Staff’s Signature and Date 
Consent Discussion (print)  
 
 
____________________________ 
__________________________________ 
Witness’s Name (print) 
Witness’s Signature and Date 
(As appropriate)