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Trial Design
We are currently conducting two large, placebo-controlled, double-blind, Phase III clinical trials, one principally in North America and the other in Thailand. A placebo-controlled, double-blind trial is one in which one group of volunteers receives a placebo and the other group receives the experimental vaccine, and neither the volunteers nor the clinicians knows whether a volunteer is receiving the placebo or the experimental vaccine. The test group of volunteers receives AIDSVAX while the placebo group receives a comparable-appearing placebo containing alum alone. All vials of vaccine and placebo are coded. During the trials, neither volunteers nor researchers know which volunteers are given the vaccine or placebo until the Phase III clinical trials are completed or stopped by the independent review board. Each volunteer is vaccinated a total of seven times, including six boosters, during a 30-month period. The purpose of the six boosters, one each six months, is to stimulate high antibody levels throughout the entire trial period. During each visit, the volunteers receive counseling on how to avoid the risk of HIV infection. Follow-up with volunteers will continue for at least six months after the last vaccination is administered.
Volunteers in North America consist of HIV-negative men who have sex with men and HIV-negative women who have HIV-infected sexual partners or are part of a population at higher risk of HIV infection. Volunteers in Thailand consist of HIV-negative injection drug users with a high risk for blood-borne transmission of HIV. In both North America and Thailand, the volunteers are recruited, vaccinated and monitored by clinics with HIV expertise and experience with these particular population groups.
The size of each Phase III clinical trial was established by a statistical model that included: (1) the probability of demonstrating 30% efficacy at statistical significance in inhibiting HIV infection; (2) the rate of infection of the volunteer group; and (3) assumptions concerning the rate of retention of the volunteers in the trial for a 36 month clinical observation period.
Within these parameters, the clinical trial in North America is designed for 5,400 volunteers, randomized 2:1 for vaccine:placebo recipients. The trial in Thailand is designed for 2,500 volunteers, randomized 1:1 for vaccine:placebo recipients. The North American Phase III clinical trial is taking place in 54 clinics in the U.S., one clinic each in Puerto Rico and in The Netherlands, and three clinics in Canada. The trial in Thailand is occurring in 17 methadone clinics under direction of the Bangkok Metropolitan Administration.
Each Phase III clinical trial is conducted in two overlapping steps:
- Recruitment of volunteers during an estimated 12 to 14 month period; and
- A 36 month clinical observation period.
For each individual, the 36 month observation period begins on the day of their first vaccination. As a result, the entire clinical trial will be completed upon recruitment of the volunteers and completion of their collective 36 month observation periods.
Enlistment of Clinical Sites and Volunteers
We enlist clinical sites based on their ability to perform clinical trials, and to recruit the appropriate type and number of volunteers for the Phase III clinical trials. Our North American trial called for approximately 1,700 HIV-negative volunteers to be recruited from an already established group of at-risk individuals at 12 clinical centers. These centers, currently sponsored by the National Institutes of Health as part of a vaccine preparedness trial, have over the past four years established a system for the recruitment of at-risk volunteers. The trial design further called for the remaining 3,700 HIV-negative volunteers to be recruited by the 49 additional clinical sites. Based on experience at the 12 clinical centers, we are assuming an incidence of 1.5% HIV infection per year, and a retention rate of at least 80% for volunteers for the entire 36 month observation period.
In Thailand, a group of injection drug users is being recruited through a combined effort of the Bangkok Metropolitan Administration, Mahidol University and the Centers for Disease Control and Prevention. The trial design calls for an estimated 600 HIV-negative volunteers to be recruited from an already established group and for the remaining 1,900 HIV-negative volunteers to be recruited from injection drug users in the Bangkok population. Based on prior experience, we are assuming a 4% incidence of HIV in these groups, with a retention rate of over 75% during the 36 month observation period.
