Clinical trial NCT00486408: Expanded Characterization of Immune Response to Merck Adenovirus 5 Gag/Pol/Nef Vaccine Given to HIV Uninfected Adults
Official title: A Phase 1B Open-label Clinical Trial to Expand the Characterization of the Immune Responses to the Merck Adenovirus Serotype 5 HIV-1 Gag/Pol/Nef Vaccine in Healthy, HIV-1-uninfected Adult Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: HIV Seronegativity
HIV Preventive Vaccine
Adenovirus
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: HIV Vaccine Trials Network
First posted: 2007-06-14
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to intensively characterize the immune response, particularly the T-cell response, to a three-dose regimen of an adenovirus-based HIV-1 vaccine in HIV-uninfected adults.

Detailed description: This study will look for relationships among the immune responses induced by MRKAd5 HIV-1 gag/pol/nef vaccine. The study will also determine if the T cells that respond to different vaccine epitopes have correspondingly different functional profiles. The study will evaluate the safety and tolerability of the vaccine regimen as well.

This study will last 60 weeks. All enrolled participants will receive vaccinations at Weeks 0, 4, and 26. There will be between 8 and 20 study visits including the screening visit, depending on the site location. A physical exam, interview, and blood collection will occur at most or all visits. All participants will undergo leukapheresis approximately 4 weeks after their last vaccination and at Week 52. Medical history, an HIV test, a pregnancy test, and HIV and risk reduction counseling will occur at selected visits. Additional blood collection is now occurring in this study to collect more information about the relationship between the immune response and efficacy to the vaccine.

Eligibility criteria: Note: As of 09/19/07, enrollment and vaccinations have been discontinued.

Inclusion Criteria:

* Good general health
* HIV uninfected
* Weight of 110 pounds or greater
* Have access to a participating HIV Vaccine Trials Unit (HVTU) and are willing to be followed during the study
* Willing to receive HIV test results
* Understand the vaccination procedure
* Willing to use acceptable methods of contraception for at least 21 days prior to study entry and until the last study visit

Exclusion Criteria:

* HIV vaccines or placebos in prior HIV trial. Participants who can provide documentation that they received a placebo in a prior HIV trial may be eligible.
* Immunosuppressive medications within 168 days prior to first study vaccination
* Blood products within 90 days prior to first study vaccination or within 14 days after the injection
* Immunoglobulin within 90 days prior to first study vaccination or within 14 days after the injection
* Live attenuated vaccines within 42 days prior to first study vaccination or within 14 days after the injection
* Investigational research agents within 30 days prior to first study vaccination
* Medically indicated subunit or killed vaccines within 5 days prior to first study vaccination or within 14 days after the injection
* Allergy treatment with antigen injections within 30 days prior to first study vaccination
* Clinically significant medical condition, abnormal physical exam findings, abnormal laboratory results, or past medical history that may affect current health
* Any medical, psychiatric, or social condition that, in the opinion of the investigator, would interfere with the study.
* History of anaphylaxis and/or allergy to vaccine components
* Autoimmune disease or immunodeficiency
* Uncontrolled hypertension
* Bleeding disorder
* Cancer. Participants with surgically removed cancer that is unlikely to recur are not excluded.
* Seizure disorder
* Absence of the spleen
* Abnormal laboratory values
* Mental illness that would interfere with the study
* Hysterectomy
* Pregnancy or breastfeeding

Primary outcomes:
measure: Relatedness of different immune response to vaccine
timeFrame: Throughout study
measure: Features and number of HIV-specific CD4 and CD8 T cells produced in response to the vaccine
timeFrame: Throughout study
measure: Characterization of different functions of T cells that have responded to the vaccine
timeFrame: Throughout study
measure: Safety and tolerability of three doses of vaccine
timeFrame: Throughout study
Secondary outcomes:
measure: Changes in physical features of certain immune cells in response to the vaccine
timeFrame: Throughout study
measure: Indications of an immune response to the vaccine
timeFrame: Throughout study
measure: Presence of T cells in the genital tract
timeFrame: Throughout study
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Vaccine CRS
state: Alabama
city: Rochester
country: United States
facility: University of Rochester Vaccines to Prevent HIV Infection CRS
state: New York
city: Nashville
country: United States
facility: Vanderbilt Vaccine (VV) CRS
state: Tennessee
city: Seattle
country: United States
facility: Seattle Vaccine and Prevention CRS
state: Washington
Study officials:
affiliation: HVTN Core Operations Center, Fred Hutchinson Cancer Research Center (FHCRC)
name: Ann Duerr, MD, PhD, MPH
role: STUDY_CHAIR
affiliation: University of Rochester
name: Mike Keefer, MD
role: STUDY_CHAIR
References:
citation: Barouch DH, Nabel GJ. Adenovirus vector-based vaccines for human immunodeficiency virus type 1. Hum Gene Ther. 2005 Feb;16(2):149-56. doi: 10.1089/hum.2005.16.149.
citation: Horton H, Russell N, Moore E, Frank I, Baydo R, Havenar-Daughton C, Lee D, Deers M, Hudgens M, Weinhold K, McElrath MJ. Correlation between interferon- gamma secretion and cytotoxicity, in virus-specific memory T cells. J Infect Dis. 2004 Nov 1;190(9):1692-6. doi: 10.1086/424490. Epub 2004 Sep 30.
citation: Tobery TW, Dubey SA, Anderson K, Freed DC, Cox KS, Lin J, Prokop MT, Sykes KJ, Mogg R, Mehrotra DV, Fu TM, Casimiro DR, Shiver JW. A comparison of standard immunogenicity assays for monitoring HIV type 1 gag-specific T cell responses in Ad5 HIV Type 1 gag vaccinated human subjects. AIDS Res Hum Retroviruses. 2006 Nov;22(11):1081-90. doi: 10.1089/aid.2006.22.1081.