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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


Phase 2
18 Years
35 Years
Not Enrolling
Both
HIV Infections

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Trial Information

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
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.


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.

Inclusion Criteria:



- HIV-1 and -2 negative

- Good general health

- ALT less than 2.6 times the upper limit of normal (ULN)

- Sexually active within the 6 months prior to study entry

- Have access to a participating HIV Vaccine Trials Unit (HVTU) and are willing to be
followed during the study

- Demonstrate understanding of the study

- Willing to receive HIV test results

- Female participants must be willing to use acceptable forms of contraception, or not
be of reproductive potential. More information about this criterion can be found in
the protocol.

Exclusion Criteria:

- Adenovirus 5 titer greater than 200, once enrollment of participants in this stratum
has been completed

- HIV vaccines 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.
Participants who have used corticosteroid nasal sprays for allergic rhinitis or
topical corticosteroids for mild, uncomplicated dermatitis 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 within 30 days prior to first study vaccination

- 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 scheduled to receive such vaccines within 14 days after first study
vaccination

- 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. More
information about this criterion can be found in the protocol.

- 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 anaphylaxis or allergy to any of the vaccine's components

- Autoimmune disease

- Immunodeficiency

- Bleeding disorder

- Cancer

- Seizure disorder

- Pregnancy or breastfeeding

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Outcome Measure:

Acquisition of HIV-1 infection

Outcome Time Frame:

Throughout study

Safety Issue:

Yes

Principal Investigator

Glenda Gray, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Chris Hani Baragwanath Hospital

Authority:

United States: Food and Drug Administration

Study ID:

HVTN 503 (Phambili)

NCT ID:

NCT00413725

Start Date:

January 2007

Completion Date:

Related Keywords:

  • HIV Infections
  • HIV Seronegativity
  • HIV Preventive Vaccine
  • Adenovirus
  • HIV Infections
  • Acquired Immunodeficiency Syndrome

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