Clinical trial NCT00865566: 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
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: HIV Infections
Keywords: HIV Seronegativity
HIV Preventive Vaccine
HIV Treatment Vaccine
Adenovirus
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: HIV Vaccine Trials Network
First posted: 2009-03-19
Enrollment: 2504
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

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.

Eligibility 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

Primary outcomes:
measure: Participant Dropout Through Month 48
timeFrame: Enrollment through Month 48 visit
measure: Participant Dropout Prior to Unblinding
timeFrame: Enrollment until the date of dropout, through April 22, 2013 (up to Month 24 visit)
measure: Participant Dropout After Unblinding
timeFrame: April 23, 2013 through trial closure (up to Month 48 visit)
measure: HIV-1 Infections Diagnosed After Day 0 Including All Available Follow-up Through the Maximum Month 48 Visit
timeFrame: Enrollment through Month 48 visit
measure: HIV-1 Infections Diagnosed After Day 0 Through the Month 24 Visit
timeFrame: Enrollment through Month 24 visit
measure: Number of Participants Experiencing Local Reactogenicity: Pain and/or Tenderness
timeFrame: Through 3 days post each study vaccination, and to resolution for events present at the third day post vaccination
measure: Number of Participants Experiencing Local Reactogenicity: Erythema and/or Induration
timeFrame: Through 3 days post each study vaccination, and to resolution for events present at the third day post vaccination
measure: Number of Participants Experiencing Systemic Reactogenicity
timeFrame: Through 3 days post each study vaccination, and to resolution for events present at the third day post vaccination
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama CRS
state: Alabama
city: Los Angeles
country: United States
facility: The AIDS Research Alliance of America CRS
state: California
city: Los Angeles
country: United States
facility: UCLA CARE Center CRS
state: California
city: San Francisco
country: United States
facility: Bridge HIV CRS
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital CRS
state: Colorado
city: Orlando
country: United States
facility: Orlando Immunology Center CRS
state: Florida
city: Decatur
country: United States
facility: The Hope Clinic of the Emory Vaccine Center CRS
state: Georgia
city: Chicago
country: United States
facility: UIC Project WISH CRS
state: Illinois
city: Bethesda
country: United States
facility: VRC Clinical Trials Core CRS
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital Vaccine CRS (BWH VCRS)
state: Massachusetts
city: Boston
country: United States
facility: Fenway Health (FH) CRS
state: Massachusetts
city: New York
country: United States
facility: NY Univ. HIV/AIDS CRS
state: New York
city: New York
country: United States
facility: Columbia P&S CRS
state: New York
city: New York
country: United States
facility: New York Blood Center CRS
state: New York
city: Rochester
country: United States
facility: University of Rochester Vaccines to Prevent HIV Infection CRS
state: New York
city: Cleveland
country: United States
facility: Case Clinical Research Site
state: Ohio
city: Philadelphia
country: United States
facility: Penn Prevention CRS
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt Vaccine (VV) CRS
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern CRS
state: Texas
city: Houston
country: United States
facility: Baylor Vaccine Research Center CRS
state: Texas
city: Annandale
country: United States
facility: Care-Id Crs
state: Virginia
city: Seattle
country: United States
facility: Seattle Vaccine and Prevention CRS
state: Washington
Study officials:
affiliation: Columbia University
name: Scott Hammer
role: STUDY_CHAIR
affiliation: Columbia University
name: Magdalena Sobieszczyk
role: STUDY_CHAIR
affiliation: Columbia University
name: Michael Yin
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.