Safety and Effectiveness of HIV-1 DNA Plasmid Vaccine and HIV-1 Recombinant Adenoviral Vector Vaccine in HIV-Uninfected, Circumcised Men and Male-to-Female (MTF) Transgender Persons Who Have Sex With Men

NCT00865566 | Terminated Phase 2 Results DMC

• 2 other identifiers: HVTN 50510753
• Study Type: interventional
• Target: 2,504
• Locations: 1 country
• Sites: 22

Brief Summary

The purpose of this study is to determine the safety and efficacy of a VRC DNA/rAd5 vaccine regimen in healthy, circumcised men and male-to-female (MTF) transgender persons who have sex with men. NOTES: As of April 2013, all vaccinations in this study have been stopped. As of June 2017, this study has been closed.

Conditions

HIV Infections

Keywords

HIV Seronegativity; HIV Preventive Vaccine; HIV Treatment Vaccine; Adenovirus

Outcome Measures

Primary Outcomes (8)

• Participant Dropout Through Month 48

  For participants remaining uninfected, dropout is assessed only for primary follow-up, i.e. clinic visits. Protocol versions 4 and earlier included 24 months of primary follow-up, and versions 5 and later included 48 months. Participants may terminate early after completing primary follow-up, and participants who were found to be HIV-1 infected are analyzed as non-dropouts, so the number of dropouts and number of early terminations need not match.

  Enrollment through Month 48 visit

• Participant Dropout Prior to Unblinding

  The trial was unblinded on April 23, 2013, and the protocol was in version 4 at the time. For participants remaining uninfected, dropout is assessed only for primary follow-up, i.e. clinic visits. Protocol versions 4 and earlier included 24 months of primary follow-up, and versions 5 and later included 48 months. Participants may terminate early after completing primary follow-up, and participants who were found to be HIV-1 infected are analyzed as non-dropouts, so the number of dropouts and number of early terminations need not match.

  Enrollment until the date of dropout, through April 22, 2013 (up to Month 24 visit)

• Participant Dropout After Unblinding

  The trial was unblinded on April 23, 2013, and the protocol was in version 4 at the time. For participants remaining uninfected, dropout is assessed only for primary follow-up, i.e. clinic visits. Protocol versions 4 and earlier included 24 months of primary follow-up, and versions 5 and later included 48 months. Participants may terminate early after completing primary follow-up, and participants who were found to be HIV-1 infected are analyzed as non-dropouts, so the number of dropouts and number of early terminations need not match.

  April 23, 2013 through trial closure (up to Month 48 visit)

• HIV-1 Infections Diagnosed After Day 0 Including All Available Follow-up Through the Maximum Month 48 Visit

  For time-to-event analysis, an event is defined as HIV-1 infection and participants are censored if they dropped out early or completed the trial. HIV-1 diagnosis date is defined as the date of the earliest specimen collection yielding a positive HIV test. Participants remaining uninfected were censored at the latest specimen collection with a negative HIV-1 test.

  Enrollment through Month 48 visit

• HIV-1 Infections Diagnosed After Day 0 Through the Month 24 Visit

  For time-to-event analysis, an event is defined as HIV-1 infection and participants remaining uninfected through the month 24 visit were censored. HIV-1 diagnosis date is defined as the date of the earliest specimen collection at or prior to month 24 which yielded a positive HIV test. Participants remaining uninfected through the month 24 visit were censored at the latest specimen collection with a negative HIV-1 test at or prior to the month 24 visit.

  Enrollment through Month 24 visit

• Number of Participants Experiencing Local Reactogenicity: Pain and/or Tenderness

  For each sign or symptom, we define the maximum observed grade for each participant over all vaccinations and post-vaccination assessments. Local and systemic signs and symptoms are assessed and graded based on The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December, 2004 (Clarification dated August 2009). Local reactogenicity parameters are pain, tenderness, erythema, and induration. We present the maximum grade for pain and/or tenderness, and erythema and/or induration.

  Through 3 days post each study vaccination, and to resolution for events present at the third day post vaccination

• Number of Participants Experiencing Local Reactogenicity: Erythema and/or Induration

  For each sign or symptom, we define the maximum observed grade for each participant over all vaccinations and post-vaccination assessments. Local and systemic signs and symptoms are assessed and graded based on The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December, 2004 (Clarification dated August 2009). Local reactogenicity parameters are pain, tenderness, erythema, and induration. We present the maximum grade for pain and/or tenderness, and erythema and/or induration.

  Through 3 days post each study vaccination, and to resolution for events present at the third day post vaccination

• Number of Participants Experiencing Systemic Reactogenicity

  For each sign or symptom, we define the maximum observed grade for each participant over all vaccinations and post-vaccination assessments. Local and systemic signs and symptoms are assessed and graded based on The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December, 2004 (Clarification dated August 2009). Systemic reactogenicity parameters are malaise/fatigue, myalgia, headache, nausea, vomiting, chills, and arthralgia. We present the maximum grade calculated over these parameters.

  Through 3 days post each study vaccination, and to resolution for events present at the third day post vaccination

Study Arms (2)

1

EXPERIMENTAL

Participants will receive a recombinant DNA plasmid vaccine injection at study entry and on Days 28 and 56, followed by a recombinant adenoviral serotype vector vaccine injection on Day 168. As of April 2013, all vaccinations in this study have been stopped.

Biological: DNA plasmid vaccine; Biological: Recombinant adenoviral serotype 5 (rAD5) vector vaccine

2

PLACEBO COMPARATOR

Participants will receive a recombinant DNA plasmid vaccine placebo injection at study entry and on Days 28 and 56, followed by a recombinant adenoviral serotype vector vaccine placebo injection on Day 168. As of April 2013, all vaccinations in this study have been stopped.

Biological: DNA vaccine placebo; Biological: HIV-1 recombinant adenovirus vaccine placebo

Interventions

DNA plasmid vaccine BIOLOGICAL

4-mg injection administered as 1 mL intramuscularly (IM) via Biojector® in either deltoid

Also known as: VRC-HIVDNA016-00-VP

1

Recombinant adenoviral serotype 5 (rAD5) vector vaccine BIOLOGICAL

1 x 10\^10 particle units (PU) administered as 1mL IM by needle and syringe in either deltoid

Also known as: VRC-HIVADV014-00-VP

1

DNA vaccine placebo BIOLOGICAL

1 mL IM via Biojector® in either deltoid

Also known as: VRC-PBSPLA043-00-VP, phosphate buffered saline (PBS)

2

HIV-1 recombinant adenovirus vaccine placebo BIOLOGICAL

1 mL administered IM by needle and syringe in either deltoid

Also known as: VRC-DILUENT013-DIL-VP, final formulation buffer (FFB)

2

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• HIV-1 and -2 negative
• Good general health
• Fully circumcised
• Experienced one or both of the following HIV risk criteria in the 6 months before study entry:
• Unprotected anal intercourse with one or more male or MTF transgender partner(s)
• Anal intercourse with two or more male or MTF transgender partners
• Alanine aminotransferase (ALT) 2.5 or less times the upper limit of normal (ULN)
• Ad5 neutralizing antibody (nAb) titer less than 1:18
• Have access to a participating study site and are willing to be followed during the study
• Demonstrate understanding of the study
• Willing to receive HIV test results
• Willing to discuss HIV infection risks and amenable to risk-reduction counseling
• Agrees not to enroll in another study of an investigational research agent before unblinding of this study
• NOTE: MTF transgender volunteers who have undergone gender reassignment surgery (GRS) are eligible to participate if they provide documentation from a health care provider confirming that they were fully circumcised prior to GRS. MTF transgender volunteers who have not undergone GRS are eligible to participate if they meet all enrollment criteria. Receipt of hormonal therapy does not make a transgender volunteer ineligible.

You may not qualify if:

• HIV vaccines in prior HIV vaccine trial. Participants who can provide documentation that they received a placebo in a prior HIV trial may be eligible.
• Used antiretroviral (ARV) drugs for the purpose of HIV-1 prophylaxis for greater than or equal to 50% of days during the 3 months prior to first vaccination or for 30 consecutive days within the 60 days prior to first vaccination
• Circumcised within 90 days prior to first vaccination or displays evidence that surgical site is not fully healed
• Immunosuppressive medications within 168 days prior to first study vaccination. Participants who have used corticosteroid nasal sprays for allergic rhinitis; topical corticosteroids for mild, uncomplicated dermatitis; or oral/parenteral corticosteroids for nonchronic conditions are not excluded.
• Blood products within 90 days prior to first study vaccination
• Immunoglobulin within 90 days prior to first study vaccination
• Live attenuated vaccines other than influenza vaccine within 30 days prior to first study vaccination
• Investigational research agents within 90 days prior to first study vaccination
• Influenza vaccine or any vaccines that are not live attenuated within 14 days prior to first study vaccination
• Allergy treatment with antigen injections within 30 days prior to first study vaccination or that are scheduled within 14 days after first vaccination
• Clinically significant medical condition, physical examination findings, abnormal laboratory results, or past medical history that, in the judgment of the investigator, has significant implications for current health
• Any medical, psychiatric, or job-related responsibility that would interfere with the study. More information about this criterion can be found in the protocol.
• Any concern that, in the opinion of the investigator, may interfere with a participant's completion of the post-vaccination symptom log
• History of serious adverse reactions to vaccinations, including anaphylaxis or allergy to any of the vaccine's components
• Current anti-tuberculosis prophylaxis or therapy

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• HIV Vaccine Trials Network: collaborator

Study Sites (22)

Alabama CRS

Birmingham, Alabama, 35294, United States

Location

The AIDS Research Alliance of America CRS

Los Angeles, California, 90015, United States

Location

UCLA CARE Center CRS

Los Angeles, California, 90035, United States

Location

Bridge HIV CRS

San Francisco, California, 94143, United States

Location

University of Colorado Hospital CRS

Aurora, Colorado, 80045, United States

Location

Orlando Immunology Center CRS

Orlando, Florida, 32803, United States

Location

The Hope Clinic of the Emory Vaccine Center CRS

Decatur, Georgia, 30030, United States

Location

UIC Project WISH CRS

Chicago, Illinois, 60612, United States

Location

VRC Clinical Trials Core CRS

Bethesda, Maryland, 20816, United States

Location

Brigham and Women's Hospital Vaccine CRS (BWH VCRS)

Boston, Massachusetts, 02115-6110, United States

Location

Fenway Health (FH) CRS

Boston, Massachusetts, 02215-4302, United States

Location

NY Univ. HIV/AIDS CRS

New York, New York, 10016, United States

Location

Columbia P&S CRS

New York, New York, 10032-3732, United States

Location

New York Blood Center CRS

New York, New York, 10065, United States

Location

University of Rochester Vaccines to Prevent HIV Infection CRS

Rochester, New York, 14642, United States

Location

Case Clinical Research Site

Cleveland, Ohio, 44106, United States

Location

Penn Prevention CRS

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt Vaccine (VV) CRS

Nashville, Tennessee, 37232-2582, United States

Location

University of Texas Southwestern CRS

Dallas, Texas, 75235, United States

Location

Baylor Vaccine Research Center CRS

Houston, Texas, 77030, United States

Location

Care-Id Crs

Annandale, Virginia, 22003, United States

Location

Seattle Vaccine and Prevention CRS

Seattle, Washington, 98109-1024, United States

Location

Related Publications (4)

• Lu S. Immunogenicity of DNA vaccines in humans: it takes two to tango. Hum Vaccin. 2008 Nov-Dec;4(6):449-52. doi: 10.4161/hv.4.6.6179. Epub 2008 Nov 28.

  PMID: 18443427 BACKGROUND

• Patterson S, Papagatsias T, Benlahrech A. Use of adenovirus in vaccines for HIV. Handb Exp Pharmacol. 2009;(188):275-93. doi: 10.1007/978-3-540-71029-5_13.

  PMID: 19031031 BACKGROUND

• Benmira S, Bhattacharya V, Schmid ML. An effective HIV vaccine: A combination of humoral and cellular immunity? Curr HIV Res. 2010 Sep;8(6):441-9. doi: 10.2174/157016210793499286.

  PMID: 20636279 RESULT

• Hammer SM, Sobieszczyk ME, Janes H, Karuna ST, Mulligan MJ, Grove D, Koblin BA, Buchbinder SP, Keefer MC, Tomaras GD, Frahm N, Hural J, Anude C, Graham BS, Enama ME, Adams E, DeJesus E, Novak RM, Frank I, Bentley C, Ramirez S, Fu R, Koup RA, Mascola JR, Nabel GJ, Montefiori DC, Kublin J, McElrath MJ, Corey L, Gilbert PB; HVTN 505 Study Team. Efficacy trial of a DNA/rAd5 HIV-1 preventive vaccine. N Engl J Med. 2013 Nov 28;369(22):2083-92. doi: 10.1056/NEJMoa1310566. Epub 2013 Oct 7.

  PMID: 24099601 DERIVED

MeSH Terms

Conditions

HIV Infections; Adenoviridae Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; DNA Virus Infections

Results Point of Contact

• Title: Jessica Andriesen, PhD, Associate Director of HVTN SDMC Operations
• Organization: Fred Hutchinson Cancer Research Center

jandries@fredhutch.org

206-667-5812

Study Officials

• Scott Hammer

  Columbia University

  STUDY CHAIR

• Magdalena Sobieszczyk

  Columbia University

  STUDY CHAIR

• Michael Yin

  Columbia University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2009
• First Posted: March 19, 2009
• Study Start: May 1, 2009
• Primary Completion: October 6, 2017
• Study Completion: October 6, 2017
• Last Updated: October 15, 2021
• Results First Posted: February 27, 2019

Record last verified: 2021-10

Locations

US (22)