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

NCT ID: NCT00865566

Last Updated: 2021-10-15

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

2504 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-05-31

Study Completion Date

2017-10-06

Brief Summary

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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.

Detailed Description

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In 2007, the Joint United Nations Programme on HIV/AIDS estimated that 33.2 million people were living with HIV/AIDS globally. The U.S. HIV prevalence data reported in October 2008 by the Centers for Disease Control and Prevention estimate that 1.1 million adults and adolescents were living with diagnosed or undiagnosed HIV infection in the United States at the end of 2006. Nearly half of all U.S. HIV infections (48.1%) were found in men who have sex with men (MSM). Given the difficulty of maintaining behaviors that prevent HIV transmission over a lifetime and the occurrence of nonconsensual sex, the need for a safe and effective vaccine is clear. The primary purpose of this study is to determine the safety and efficacy of a VRC DNA/rAd5 vaccine regimen in healthy, at-risk, circumcised men and MTF transgender persons who have sex with men.

Participants will be randomly assigned to one of two arms. Participants in Arm 1 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. Participants in Arm 2 will receive placebo injections at study entry and on Days 28, 56, and 168.

Participants who do not become HIV infected will be actively followed for a minimum of 24 months and will continue to be followed by the study for long-term safety surveillance for a total of 5 years following enrollment. Participants will be contacted annually during the period of long-term safety surveillance.

Participants who are found to be HIV infected prior to receiving their first injection or who receive their first injection but were HIV infected prior to study start will be followed on a modified schedule.

Participants who become HIV infected will be followed for 6 months post-diagnosis.

At most study visits, participants will undergo a physical exam and blood draw.

NOTES:

As of April 2013, all vaccinations in this study have been stopped. Participants have been notified of whether they received the study vaccines or placebo. Participants diagnosed with HIV infection will attend study visits for 6 months for health monitoring. Participants who are not diagnosed with HIV infection will attend planned study visits for 24 months and will be followed by the study clinic at least annually for a total of 5 years following study enrollment.

As of June 2017, this study has been closed. Therefore, to avoid further burden on study participants, further participant follow-up for the study is suspended.

Conditions

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HIV Infections

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Caregivers

Study Groups

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1

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.

Group Type EXPERIMENTAL

DNA plasmid vaccine

Intervention Type BIOLOGICAL

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

Recombinant adenoviral serotype 5 (rAD5) vector vaccine

Intervention Type BIOLOGICAL

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

2

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.

Group Type PLACEBO_COMPARATOR

DNA vaccine placebo

Intervention Type BIOLOGICAL

1 mL IM via Biojector® in either deltoid

HIV-1 recombinant adenovirus vaccine placebo

Intervention Type BIOLOGICAL

1 mL administered IM by needle and syringe in either deltoid

Interventions

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DNA plasmid vaccine

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

Intervention Type BIOLOGICAL

Recombinant adenoviral serotype 5 (rAD5) vector vaccine

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

Intervention Type BIOLOGICAL

DNA vaccine placebo

1 mL IM via Biojector® in either deltoid

Intervention Type BIOLOGICAL

HIV-1 recombinant adenovirus vaccine placebo

1 mL administered IM by needle and syringe in either deltoid

Intervention Type BIOLOGICAL

Other Intervention Names

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VRC-HIVDNA016-00-VP VRC-HIVADV014-00-VP VRC-PBSPLA043-00-VP phosphate buffered saline (PBS) VRC-DILUENT013-DIL-VP final formulation buffer (FFB)

Eligibility Criteria

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Inclusion Criteria

* 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:

1. Unprotected anal intercourse with one or more male or MTF transgender partner(s)
2. 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.

Exclusion Criteria

* 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
* Autoimmune disease. People with mild, stable, and uncomplicated autoimmune disease that does not require immunosuppressive medication and that, in the judgment of the site investigator, is likely not subject to exacerbation and likely not to complicate reactogenicity and adverse event assessments are not excluded.
* Immunodeficiency
* Bleeding disorder
* History of malignancy
* Seizure disorder. People with a history of seizures who have had no seizures within the 3 years prior to study entry are not excluded.
* Asthma other than mild, well-controlled asthma
* Hereditary angioedema (HAE), acquired angioedema (AAE), or idiopathic angioedema
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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HIV Vaccine Trials Network

NETWORK

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Scott Hammer

Role: STUDY_CHAIR

Columbia University

Magdalena Sobieszczyk

Role: STUDY_CHAIR

Columbia University

Michael Yin

Role: STUDY_CHAIR

Columbia University

Locations

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Alabama CRS

Birmingham, Alabama, United States

Site Status

The AIDS Research Alliance of America CRS

Los Angeles, California, United States

Site Status

UCLA CARE Center CRS

Los Angeles, California, United States

Site Status

Bridge HIV CRS

San Francisco, California, United States

Site Status

University of Colorado Hospital CRS

Aurora, Colorado, United States

Site Status

Orlando Immunology Center CRS

Orlando, Florida, United States

Site Status

The Hope Clinic of the Emory Vaccine Center CRS

Decatur, Georgia, United States

Site Status

UIC Project WISH CRS

Chicago, Illinois, United States

Site Status

VRC Clinical Trials Core CRS

Bethesda, Maryland, United States

Site Status

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

Boston, Massachusetts, United States

Site Status

Fenway Health (FH) CRS

Boston, Massachusetts, United States

Site Status

NY Univ. HIV/AIDS CRS

New York, New York, United States

Site Status

Columbia P&S CRS

New York, New York, United States

Site Status

New York Blood Center CRS

New York, New York, United States

Site Status

University of Rochester Vaccines to Prevent HIV Infection CRS

Rochester, New York, United States

Site Status

Case Clinical Research Site

Cleveland, Ohio, United States

Site Status

Penn Prevention CRS

Philadelphia, Pennsylvania, United States

Site Status

Vanderbilt Vaccine (VV) CRS

Nashville, Tennessee, United States

Site Status

University of Texas Southwestern CRS

Dallas, Texas, United States

Site Status

Baylor Vaccine Research Center CRS

Houston, Texas, United States

Site Status

Care-Id Crs

Annandale, Virginia, United States

Site Status

Seattle Vaccine and Prevention CRS

Seattle, Washington, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 18443427 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19031031 (View on PubMed)

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.

Reference Type RESULT
PMID: 20636279 (View on PubMed)

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.

Reference Type DERIVED
PMID: 24099601 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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10753

Identifier Type: REGISTRY

Identifier Source: secondary_id

HVTN 505

Identifier Type: -

Identifier Source: org_study_id

NCT00919789

Identifier Type: -

Identifier Source: nct_alias