Safety and Efficacy of a Three-Dose Regimen of an Adenoviral HIV Vaccine (MRKAd5 HIV-1 Gag/Pol/Nef) in HIV Uninfected South African Adults
Biological: MRKAd5 HIV-1 gag/pol/nef
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
|Official Title:||A Multicenter Double-Blind Randomized Placebo-Controlled Phase IIB Test-of-Concept Study to Evaluate the Safety and Efficacy of a Three-Dose Regimen of the Clade B-based Merck Adenovirus Serotype 5 HIV-1 Gag/Pol/Nef Vaccine in HIV-1 Uninfected Adults in South Africa|
- Acquisition of HIV-1 infection [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
- Viral load set point (HIV-1 RNA) in study participants who become HIV infected [ Time Frame: At approximately 3 months postdiagnosis ] [ Designated as safety issue: No ]
- Acquisition of HIV-1 infection among participants with baseline Ad5 neutralizing antibody titers of 200 or less [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
- Viral load setpoint in such study participants [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
- Durability of effect of vaccine on suppression of HIV-1 viral RNA and preservation of CD4 counts [ Time Frame: At 18 months after diagnosis of HIV infection ] [ Designated as safety issue: No ]
- One time questionnaire evaluating impact of discontinuation of vaccination on participants [ Time Frame: After vaccination discontinuation ] [ Designated as safety issue: No ]
|Study Start Date:||January 2007|
|Study Completion Date:||August 2012|
|Primary Completion Date:||August 2012 (Final data collection date for primary outcome measure)|
Three doses of MRKAd5 HIV-1 gag/pol/nef vaccine
Biological: MRKAd5 HIV-1 gag/pol/nef
Experimental Clade-B based Adenovirus serotype 5 HIV-1 gag/pol/nef vaccine
Placebo Comparator: 2
The HIV epidemic is a major global health challenge. The Joint United Nations Program on HIV/AIDS (UNAIDS) reported that in 2004, 3 million people worldwide died of AIDS and an estimated 5 million people acquired HIV. Studies in animal models and observational data from humans suggest that cell-mediated immune responses may be key to controlling HIV infection. MRKAd5 HIV-1 gag/pol/nef, a clade B-based adenovirus serotype 5 HIV-1 vaccine, has been shown to elicit T-cell mediated immune responses. The vaccine appears to be safe and generally well tolerated in previous Phase 1 and 2 studies in HIV-uninfected people. The purpose of this study is to evaluate the safety and efficacy of the MRKAd5 HIV-1 gag/pol/nef vaccine in HIV-uninfected participants from South Africa, where clade C is predominant. The study will address whether a clade B-based vaccine designed to elicit T-cellular immunity will demonstrate efficacy in reducing acquisition of infection, or reducing HIV viral load in persons who become infected in a non-clade B region.
This study will last about 42 months for HIV-uninfected participants; for those who become HIV infected, visits continue for 18 months after diagnosis. Participants will be randomly assigned to receive 3 doses of either vaccine or placebo. All participants will receive their injections at study entry and at Months 1 and 6. Participants will be asked to complete a post-vaccination symptom log for the 3 days following each vaccination to monitor body temperature and symptoms known to be associated with the vaccine. At all study visits, participants will be asked about any adverse events they may have experienced. There will be at least 14 study visits over the first 4 years of the study. A physical exam, medication history, risk reduction counseling, and blood collection will occur at every visit. Participants will be asked to complete a social impact questionnaire at Weeks 12, 78, and 208; an outside testing and belief questionnaire at Weeks 30, 78, 130, 182, and 208; and a circumcision status assessment at Week 208. Participants will undergo HIV testing to check their HIV status approximately every 3 months.
Participants who become HIV infected during the study will have eight study visits at Weeks 4, 8, 12, 16, 20, 26, 52, and 78 post-diagnosis. A physical exam, risk reduction counseling, blood and urine collection, and a pregnancy test will occur at all visits. Genital secretion collection may also occur at some visits. Participants who become HIV infected and need to begin anti-HIV therapy will be discontinued from this study, but encouraged to enroll in the study HVTN 802.
As of September 17, 2007 enrollment and vaccinations for this study were suspended. Participants already enrolled have been asked to continue attending follow-up visits with this study.
Participants who were not diagnosed with HIV infection during their participation in the study will be eligible to enroll in a substudy. The purpose of the substudy is to expand HIV testing and to gather data on behavioral risk factors for HIV infection among participants in the original study. Participants in the substudy will attend a study visit, which will include a physical examination, HIV risk reduction counseling, blood collection, and a behavioral risk questionnaire. Some participants may have an HIV test as part of this visit; these participants will attend a second study visit 2 weeks later to receive their HIV test results. Upon completion of the substudy, researchers will contact participants to provide further information about the substudy results.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00413725
|Soweto HVTN CRS|
|Johannesburg, Gauteng, South Africa, 1862|
|Pretoria, Gauteng, South Africa, 0204|
|Durban, KwaZulu-Natal, South Africa, 4001|
|Cape Town, Western Cape Province, South Africa, 7750|
|CAPRISA Aurum CRS|
|Klerksdorp, South Africa, 2571|
|Study Chair:||Glenda Gray, MD||Chris Hani Baragwanath Hospital|
|Study Chair:||James Kublin, MD, MPH||Fred Hutchinson Cancer Research Center|