Protocol 103 PILOT

OUTLINE OF PROTOCOL 103 PILOT

A PLACEBO-CONTROLLED, PHASE I PILOT CLINICAL TRIAL TO EVALUATE THE SAFETY AND IMMUNOGENICITY OF ENV 2-3, A YEAST DERIVED RECOMBINANT ENVELOPE PROTEIN OF HUMAN IMMUNODEFICIENCY VIRUS-1, IN COMBINATION WITH MF59/MTP-PE

Subjects: Adult volunteers with HIV infection who meet the criteria for either Protocols 103A or 103B.

Schema:

MTP-PE Adjuvant Dose	ENV 2-3 Antigen Dose	Accrual	Immunization Schedule in Days
MTP-PE Adjuvant Dose	ENV 2-3 Antigen Dose	Accrual	0	28	112	*252	*336
0 µg (in MF59)	30 µg	2	X	X	X	X	X
10 µg	30 µg	2	X	X	X	X	X
50 µg	30 µg	2	X	X	X	X	X
100 µg	30 µg	2	X	X	X	X	X
Total n = 8			* Study extension

ACCRUAL, IMMUNIZATIONS, AND FOLLOW-UP COMPLETED

Product Description: Yeast-derived HIV-1 SF-2 rgp120 (ENV 2-3) in combination with MF59 adjuvant emulsion ± MTP-PE (muramyl tripeptide-phosphatidylethanolamine) adjuvant [Chiron/BIOCINE]

Time Period: First volunteer entered on 01/07/92 and last enrolled on 01/21/92; follow-up extended to 1 month past the final injection.

Clinical Sites: University of Rochester and University of Washington

Study Chair: Lawrence Corey, University of Washington

INCLUSION CRITERIA

Age: 18-50
Sex: Male or Female
NOTE: For females, negative pregnancy test at time of entry and assurance that adequate birth control measures are employed for the duration of the study.
Normal physical examination (generalized lymphadenopathy, seborrheic dermatitis are acceptable)
Normal complete blood count and lymphocytes defined as:
- Hematocrit >32% for women; >34% for men
- White count >2500 cells/mm³ with normal differential
- Total lymphocyte count >800 cells/mm³
- Average CD4 cell count >400/mm³ on two or more occasions in the month prior to enrollment, with no single count <375/mm³
- Platelets >75,000/mm³
Normal urinalysis
ALT <3 x institutional upper normal limit
Positive ELISA and Western Blot test for HIV
On or off AZT; if on AZT, tolerating it at a dose of 500 or 600 mg/day for at least 4 months
Availability for 6 months of follow-up post vaccination
Negative HIV plasma culture in the 4 months prior to enrollment

EXCLUSION CRITERIA

Use of any other investigational agent within 30 days.
Use of illicit drugs or significant amounts of alcohol that in the opinion of the Principal Investigator, would interfere with compliance with the study.
Use of any potential immunomodulating agents (e.g., isoprinosine, imunothiol, lithium) within 90 days of screening.
Use of immunoglobulins within 60 days.
Use of immunosuppressive medications during the past 3 months
Evidence of psychological disorder during the past year that would impair adherence to the protocol.
Evidence or history of an AIDS defining opportunistic infection.

STUDY GOALS

To assess the side effects of ENV 2-3 in combination with MTP-PE/MF59 in adult volunteers with HIV infection.
Study extension: To evaluate the safety of and immune responses to two additional doses of 30 µg ENV2-3 in MTP-PE/MF59.