AIDSVAX® Program: VaxGen Trials: VAX003 and VAX004
Between 1998 and 2003, the world’s first Phase III clinical trials of a HIV/AIDS vaccine – AIDSVAX® - were conducted by VaxGen, Inc., a South San Francisco-based biotechnology company. The first trial (known as VAX004) was conducted in North America and Europe; and the second trial (VAX003) was conducted in Bangkok, Thailand in collaboration with the Thai Ministry of Public Health and the School of Tropical Medicine of Mahidol University.
The founders of GSID - Don Francis, Phil Berman and Carter Lee - were all senior executives with VaxGen. Together, all three left VaxGen in early 2004 to form GSID, where one of their first accomplishments was to negotiate a license and material transfer agreement with VaxGen to obtain rights to all of the clinical data and specimens gathered during the AIDSVAX clinical trials. Under this agreement, GSID established a specimen repository of more than 300,000 tubes of serological material, over 1.2 million electronic pages of clinical information and volumes of other scientific data generated during and after the conduct of the trials.
AIDSVAX Trial Design
Trial Design Summary
Vaccine Summary
Determination of Efficacy
Results and Subgroup Analysis
VaxGen Trial Papers
Additional Resources
AIDSVAX Trial Design
Both Phase III clinical trials were double-blind and placebo-controlled, where the test group of volunteers received AIDSVAX while the placebo group received a comparable-appearing placebo containing alum alone. During the trials, neither volunteers, clinical researchers, nor VaxGen knew which volunteers were given the vaccine or placebo until the trials were completed and un-blinded. Each volunteer was vaccinated seven times over a 30-month period. The purpose of the booster doses, at months 1, 6, 12, 18, 24 and 30 was to stimulate high antibody levels throughout the entire trial period. During each follow-up visit, the volunteers received counseling on how to avoid the risk of HIV infection, were asked a series of clinical questions and had their blood drawn at months 0, 1, 6, 12, 18, 24, 30 and 36 for serological testing.
Trial Design Summary
|
VAX004 Study |
VAX003 Study |
HIV transmission |
Sexual |
Blood borne |
Volunteers |
5,400
5,100 MSM (men who have sex with men) and 300 women |
2,500
2,500 men and women IDUs (IV drug users) |
Location |
North America and the Netherlands |
Thailand |
Expected annual infection rate |
1.5% |
4.0% |
Expected retention rate |
80% |
Duration of follow-up |
36 months |
Follow-up after infection |
24 months |
Clinical trial sites |
61 |
17 |
Start date |
June 1998 |
March 1999 |
Fully enrolled |
October 1999 |
August 2000 |
Analysis completed |
Q1 2003 |
Q4 2003 |
Vaccine Summary
|
VAX004 Study |
VAX003 Study |
Vaccine |
AIDSVAX® B/B′ |
AIDSVAX® B/E |
Vaccine design |
Bivalent rgp120 with alum |
Vaccine antigens |
MNrgp120/HIV-1 plus GNE8 rgp120/HIV-1
(subtype B and B′) |
MNrgp120/HIV-1 plus A244 rgp120/HIV-1
(subtype B and E) |
rgp120 dose |
300 µg (MN)/ 300 µg (GNE8) |
300 µg (MN)/ 300 µg (A244) |
Placebo |
alum |
Randomization:
Vaccine to Placebo |
2:1 |
1 :1 |
Vaccine administration |
Intramuscular (deltoid) |
Determination of efficacy
The degree to which AIDSVAX prevented infection was determined by comparing the number of infections between the vaccine and placebo groups. If AIDSVAX was determined effective, the number of infections in the placebo group would have had to been higher than the number of infections in the vaccine group.
Results and Subgroup Analyses
For both VAX004 and VAX003, no efficacy for prevention of acquisition or for modification of HIV infection was detected. Intriguing findings in subgroup analyses of VAX004 suggested vaccine efficacy for acquisition of HIV infection in Blacks or non-whites, women and high risk volunteers. However vaccine efficacy in the subgroups could not be explained because of the small number of infections in each subgroup.
For more information about the GSID HIV Data Browser, please click here.
VaxGen Trial Papers
Vax003 Trial - Pitisuttithum P, Gilbert P, Gurwith M, Heyward W, Martin M, van Griensven F, Hu D, Tappero JW, Choopanya K; Bangkok Vaccine Evaluation Group. Randomized, double-blind, placebo-controlled efficacy trial of a bivalent recombinant glycoprotein 120 HIV-1 vaccine among injection drug users in Bangkok, Thailand. J Infect Dis. 2006, 194(12):1661-71. (link)
VAX004 Trial - Flynn NM, Forthal DN, Harro CD, Judson FN, Mayer KH, Para MF: Placebo-controlled phase 3 trial of a recombinant glycoprotein 120 vaccine to prevent HIV-1 infection. J Infect Dis 2005, 191(5):654-665. (link)
Additional Resources
