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
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
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.
As of 9/19/07, clinical research sites were notified that HVTN 503 has been suspended;
therefore, enrollment is discontinued and all participants will be unblinded and
encouraged to continue follow-up visits.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention
Acquisition of HIV-1 infection
Glenda Gray, MD
Chris Hani Baragwanath Hospital
United States: Food and Drug Administration
HVTN 503 (Phambili)