Protocol 034

OUTLINE OF PROTOCOL 036

A PHASE I, MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL TO EVALUATE THE SAFETY AND IMMUNOGENICITY OF HIV-1 MN RSGP120 AND BIVALENT AIDSVAX™ B/E RGP120 IN COMBINATION WITH QS21 WITH OR WITHOUT ALUM IN HEALTHY HIV-1 UNINFECTED ADULTS

Subjects: Healthy, HIV-1 uninfected adult volunteers with lower-risk behavior for HIV-1 infection, who meet the eligibility criteria. [Total Number of Subjects = 60]

Schema:

Immunizations Scheduled at 0, 1, and 6 Months

Group	Number	Dose of
Group	Number	MN rsgp120/HIV-1	HIV-1 MN rgp120/A244rgp120 (B/E)	MN rgp120/HIV-1*	QS21	Alum
I	13	0.5 µg	-	-	100 µg	-
II	13	3 µg	-	-	100 µg	-
III	13	-	3 µg/3 µg	-	100 µg	12 µg
IV	13	-	-	3 µg	100 µg	6 µg
V	8	-	-	-	100 µg	-
Total	60

* Formulated in alum

ACCRUAL AND IMMUNIZATIONS COMPLETED

Product Description: CHO cell-derived HIV-1 MN rsgp120 [VaxGen] in combination with QS21 [Aquila].

CHO cell-derived AIDSVAX™ B/E (HIV-1 MN gp120/A244 gp120) [VaxGen] in combination with QS21 [Aquila] and alum.

CHO cell-derived HIV-1 MN rgp120 [VaxGen] formulated with alum and combined with QS21 [Aquila].

Time Period: 12 months; first volunteer enrolled on 12/03/98 and the last on 03/30/99.

Clinical Sites: University of Rochester, Johns Hopkins University, Saint Louis University, University of Alabama at Birmingham, University of Washington, Vanderbilt University.

Study Chair: Thomas Evans, University of Rochester.

INCLUSION CRITERIA

Standard inclusion criteria.

EXCLUSION CRITERIA

Standard exclusion criteria, with the addition of:

History of reaction to thimerosal.

STUDY GOALS

The primary objectives of this study are to examine the safety and immune responses elicited by combining MN rgp120 or bivalent AIDSVAX™ B/E rgp120 vaccine (VaxGen) with the adjuvant QS21.
Primary Objective: To assess the safety of the two experimental vaccines when formulated with QS21 or QS21 plus alum. In particular, the study will address whether the new preparation of QS21 in polysorbate 80 is less reactogenic than the QS21 formulation used in AVEG Protocols 016, 016A and 016B.
Secondary Objective: To evaluate the immunogenicity of the monovalent and bivalent HIV-1 candidate vaccines in formulation with QS21 or QS21 plus alum. The following questions will be addressed:
- Is the new QS21 formulation immunologically equivalent to that used in 016B?
- Does QS21, when given with low doses of antigen, induce measurable HIV-1-specific CTL activity?
- Does the QS21 dose-sparing effect extend to an antigen dose of 0.5 µg?
- Does the bivalent vaccine product give responses equivalent to the monovalent product, or is there actually a broadening of the HIV-1-specific binding and neutralizing antibody responses?