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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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
HIV Vaccine Trials Network
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00865566
First received: March 17, 2009
Last updated: November 4, 2014
Last verified: November 2014
  Purpose

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.

NOTE:

As of April 2013, all vaccinations in this study have been stopped.


Condition Intervention Phase
HIV Infections
Biological: DNA plasmid vaccine
Biological: Recombinant adenoviral serotype 5 (rAD5) vector vaccine
Biological: DNA vaccine placebo
Biological: HIV-1 recombinant adenovirus vaccine placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Prevention
Official Title: Phase 2b, Randomized, Placebo-Controlled Test-of-Concept Trial to Evaluate the Safety and Efficacy of a Multiclade HIV-1 DNA Plasmid Vaccine Followed by a Multiclade HIV-1 Recombinant Adenoviral Vector Vaccine in HIV-Uninfected, Adenovirus Type 5 Neutralizing Antibody Negative, Circumcised Men and Male-to-Female (MTF) Transgender Persons, Who Have Sex With Men

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • HIV-1 infection diagnosed after Day 0 through the Month 48 visit [ Time Frame: Measured through the Month 48 visit ] [ Designated as safety issue: Yes ]
  • HIV-1 infection diagnosed after Day 0 including all available follow-up through the maximum Month 48 visit [ Time Frame: Measured through the Month 48 visit ] [ Designated as safety issue: Yes ]
  • Rate of study dropout through the Month 48 visit [ Time Frame: Measured through the Month 48 visit ] [ Designated as safety issue: No ]
  • Rate of study arm drop-out [ Time Frame: Measured through the Month 48 visit ] [ Designated as safety issue: No ]

Enrollment: 2504
Study Start Date: May 2009
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Biological: DNA plasmid vaccine
4-mg injection administered as 1 mL intramuscularly (IM) via Biojector® in either deltoid
Other Name: VRC-HIVDNA016-00-VP
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
Other Name: VRC-HIVADV014-00-VP
Placebo Comparator: 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.
Biological: DNA vaccine placebo
1 mL IM via Biojector® in either deltoid
Other Names:
  • VRC-PBSPLA043-00-VP
  • phosphate buffered saline (PBS)
Biological: HIV-1 recombinant adenovirus vaccine placebo
1 mL administered IM by needle and syringe in either deltoid
Other Names:
  • VRC-DILUENT013-DIL-VP
  • final formulation buffer (FFB)

Detailed Description:

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.

NOTE:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00865566

  Show 21 Study Locations
Sponsors and Collaborators
HIV Vaccine Trials Network
Investigators
Study Chair: Scott Hammer Columbia University
Study Chair: Magdalena Sobieszczyk Columbia University
Study Chair: Michael Yin Columbia University
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00865566     History of Changes
Obsolete Identifiers: NCT00919789
Other Study ID Numbers: HVTN 505, 10753
Study First Received: March 17, 2009
Last Updated: November 4, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
HIV Seronegativity
HIV Preventive Vaccine
HIV Treatment Vaccine
Adenovirus

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases

ClinicalTrials.gov processed this record on November 24, 2014