Safety and Immune Response Study of the Vaccine ALVAC vCP1452 Alone or in Combination With AIDSVAX B/B

A Phase II Clinical Trial to Evaluate the Immunogenicity and Safety of a Combined Regimen Using ALVAC vCP1452 and AIDSVAX B/B

The purpose of this study is to see if the vaccines tested are safe when given alone and when given together, and how the immune system responds to the vaccines.

Vaccines are given to people to try to prevent an infection or disease. Early testing in a few people has shown that the HIV vaccines ALVAC vCP1452 and AIDSVAX B/B seem to be safe to use.

There is no cure for HIV infection or AIDS, and drug therapy is too expensive for most affected populations. For this reason, the development of safe, effective vaccines to prevent HIV infections worldwide is needed. ALVAC vCP1452 and MN rgp120/HIV-1 have been shown to be well tolerated in Phase I and II studies. ALVAC vCP1452 given alone or in combination with subunit antigens [AS PER AMENDMENT 10/12/00: antigen] is a candidate vaccine to be evaluated for the ability to produce and express vaccine antigen in greater quantity for a longer time and with improved immunogenicity.

Volunteers are randomized to 1 of 7 [AS PER AMENDMENT 10/12/00: 1 of 4] groups and stratified by risk status. Prior to immunization, evaluations and blood draws are done to monitor hematological, chemical, and immunologic parameters. Volunteers receive 2 injections of the following vaccines at Months 0, 1, 3, and 6:

Group A: ALVAC vCP1452 and alum placebo [AS PER AMENDMENT 10/12/00: AIDSVAX placebo (aluminum hydroxide adjuvant)] at Months 0, 1, 3, and 6.

Group B: ALVAC vCP1452 and alum placebo [AS PER AMENDMENT 10/12/00: AIDSVAX placebo] at Months 0 and 1 and ALVAC vCP1452 and AIDSVAX B/B at Months 3 and 6.

Group C: ALVAC placebo and alum placebo. [AS PER AMENDMENT 10/12/00: ALVAC vCP1452 and AIDSVAX B/B at Months 0, 1, and 6 and ALVAC vCP1452 and AIDSVAX placebo at Month 3.] Group D: ALVAC vCP1452 and alum placebo at Months 0 and 1 and ALVAC vCP1452 and MN rgp120 at Months 3 and 6. [AS PER AMENDMENT 10/12/00: ALVAC placebo and AIDSVAX placebo at Months 0, 1, 3, and 6.] Group E: ALVAC vCP1452 and AIDSVAX B/B at Months 0, 1, and 6; ALVAC vCP1452 and alum placebo at Month 3. [AS PER AMENDMENT 10/12/00: Group E has been discontinued.] Group F: ALVAC vCP1452 and AIDSVAX B/B. [AS PER AMENDMENT 10/12/00: Group F has been discontinued.] Group G: ALVAC vCP1452 and alum placebo at Months 0 and 1; ALVAC vCP1452 and AIDSVAX B/E at Months 3 and 6. [AS PER AMENDMENT 10/12/00: Group G has been discontinued.] Following each pair of injections, volunteers are observed in the clinic for 30 minutes. Volunteers keep a record of body temperature and any other symptoms and report results to their AIDS Vaccine Evaluation Unit. Evaluations are performed by telephone or clinic visit on Days 1 and 2 after each vaccination. [AS PER AMENDMENT 10/12/00: Volunteers record all relevant signs and symptoms occurring 48 hours after each vaccination and provide that information at each clinic visit.] HIV testing is conducted every 3 to 6 months and volunteers are asked to complete social harms questionnaires once at Day 168 and once at the end of the study. Volunteers are followed on the study for a minimum of 18 months after the first immunization. Safety is evaluated by closely monitoring for local and systemic adverse reactions during the course of the trial.

Inclusion Criteria

Volunteers may be eligible for this study if they:

• Are HIV-negative.
• Are 18 to 60 years old.
• Have a CD4 cell count of 400 cells/mm3 or more.
• Agree to use adequate birth control for 1 month before study entry and during the study (female participants).
• Have a normal history and physical examination.
• Are available for 12 months of follow-up for the planned duration of the study.
• Have a negative pregnancy test within 3 days prior to injections.

Exclusion Criteria

Volunteers will not be eligible for this study if they:

• Are pregnant or breast-feeding.
• Have chronic hepatitis B.
• Are taking medications that affect the immune system.
• Have an immune system problem, any long-term illness, or any autoimmune disease.
• Have cancer, except if it has been removed with surgery and cure is likely.
• Have a physical condition, mental condition, or job or work that may interfere with the study.
• Have been suicidal, or have ever needed medicines for a serious mental condition.
• Have received certain vaccines within 60 days of study entry.
• Have used experimental drugs within 30 days prior to study entry.
• Have received any blood products, such as immunoglobulin, in the last 6 months.
• Have active syphilis.
• Have active tuberculosis.
• Have history of severe allergy or any serious reactions to vaccines.
• Have had HIV-1 vaccines in a clinical study.