Protocol 004A

OUTLINE OF PROTOCOL 004A

A PHASE I MULTICENTER CLINICAL TRIAL TO EVALUATE THE SAFETY AND IMMUNOGENICITY OF VACCINIA DERIVED HIV-1 RECOMBINANT ENVELOPE GLYCOPROTEIN (GP160) OF HUMAN IMMUNODEFICIENCY VIRUS

EVALUATION OF 200 µg DOSE

Subjects: Healthy, HIV-1 uninfected adult volunteers without identifiable high-risk behavior for HIV-1 infection.

Schema:

Treatment	Accrual*	Immunization Schedule
Treatment	Accrual*	Day 0	Day 30	Day 180	Day 365
IMMUNO-AG rgp160 200 µg	20	V	V	V	V
Alum Placebo	5	P	P	P	P
Total	n = 25

V: IMMUNO-AG rgp160 200 µg P: Placebo
* Volunteers are randomized into immunization schedule

ACCRUAL, IMMUNIZATIONS, AND FOLLOW-UP COMPLETED

Product Description: Vaccinia/Vero cell-expressed HIV-1 IIIB rgp160 in alum and deoxycholate [IMMUNO-AG]

Time Period: The first volunteer entered on 08/04/92 and the last entered on 10/29/92; follow-up of 24 months.

Clinical Sites: Johns Hopkins University, Saint Louis University, University of Rochester, University of Washington, Vanderbilt University

Study Chair: Robert Belshe, Saint Louis University

INCLUSION CRITERIA

Age: >18 and <60
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 history and physical examination
Normal complete blood count and differential defined as:
- Hematocrit >34% for women; >38% for men
- White count >3500 cells/mm³ with normal differential
- Total lymphocyte count >800 cells/mm³
- T4 cells >400 cells/mm³
- Platelets (120,000-550,000)
Normal urinalysis
Normal ALT (<1.5 x institutional upper normal limit) and creatinine (<1.6 mg/dl)
Negative ELISA for HIV
Normal cell mediated immune responses using Merieux skin test
NOTE: If skin test for TB on the Merieux panel has any reactivity, a PPD skin test will be performed. Volunteers with a positive PPD and a normal chest X-ray showing no evidence of active TB and not requiring INH therapy are eligible for enrollment.
Availability for two years of follow-up

EXCLUSION CRITERIA

Subjects with identifiable high risk behavior for HIV infection as determined by screening questions designed to identify risk factors for HIV infection; specific exclusions include:
- Any history of IV (intravenous) drug use
- Syphilis, gonorrhea, or any other sexually transmitted diseases (including chlamydia or pelvic inflammatory disease) in the last 6 months
- More than two sexual partners, or sexual contact with a high risk partner, in the preceding 6 months
Previous receipt of blood transfusions or cryoprecipitates within the past 6 months
History of immunodeficiency, chronic illness, or use of immunosuppressive medications
Evidence of psychological or psychiatric problems that may lead to non-compliance with study requirements
History of positive PPD and abnormal chest x-ray
Positive syphilis serology (e.g., RPR)
Positive for circulating Hepatitis B surface antigen

STUDY GOALS

The purpose of this amendment is to evaluate the safety and immune response to 200 µg of the rgp160 candidate vaccine using a similar schedule to that in the original protocol. The duration of antibody response and its relationship to the dose and frequency of inoculation will also be evaluated.