Protocol 005A

OUTLINE OF PROTOCOL 005A

A PHASE I CLINICAL TRIAL TO EVALUATE THE SAFETY OF THE MF59/MTP-PE ADJUVANT EMULSION

Subjects: Healthy, HIV-1 uninfected adult volunteers.

Schema:

MTP-PE Adjuvant Dose	Treatment	Accrual	Immunization Schedule
MTP-PE Adjuvant Dose	Treatment	Accrual	Day 0	Day 30
10 µg	MF59/MTP-PE MF59 only	3 1	X X	X X
25 µg	MF59/MTP-PE MF59 only	3 1	X X	X X
50 µg	MF59/MTP-PE MF59 only	3 1	X X	X X
100 µg	MF59/MTP-PE MF59 only	3 1	X X	X X
Total		n = 16

Adjuvant dose levels filled sequentially with randomization between adjuvant/emulsion and emulsion only. Initiation of each dose level was separated by at least 72 hours. 50 µg dose was added during the course of the study.

ACCRUAL, IMMUNIZATIONS, AND FOLLOW-UP COMPLETED

Product Description: MF59 adjuvant emulsion ± MTP-PE (muramyl tripeptide-phosphatidylethanolamine) adjuvant [Chiron/BIOCINE]

Time Period: First volunteer entered on 01/2891 and the last was enrolled on 02/14/91; follow-up of 60 days.

Clinical Sites: University of Rochester

Study Chair: Raphael Dolin, University of Rochester

INCLUSION CRITERIA

Age: >18 and <50
Sex: Male or Female [NOTE: For females, negative pregnancy test at time of entry]
Normal history and physical examination
Normal complete blood count and differential defined as:
- Hematocrit >35% for women; >39% for men
- White count >4000 cells/mm³ with normal differential
- Total lymphocyte count >500 cells/mm³
- Platelets (120,000-550,000)
Normal urinalysis
Normal ALT (<1.1 x institutional upper normal limit) and creatinine (0.1-1.6 mg/dl)
Availability for 60 days of follow-up

EXCLUSION CRITERIA

History of immunodeficiency, chronic illness, autoimmune disease, or use of immunosuppressive medications
Evidence of depression or under treatment for psychiatric problems during the past year

STUDY GOALS

To determine the safety of multiple doses of MTP-PE/MF59 adjuvant emulsion in volunteers. The study will evaluate local and systemic reactions.

REFERENCE

Keefer MC, Graham BS, McElrath MJ, Matthews TJ, Stablein DM, Corey L, Wright PF, Lawrence D, Fast PE, Weinhold K, Hsieh RH, Chernoff D, Dekker C, Dolin R, NIAID AIDS Vaccine Evaluation Group. Safety and immunogenicity of env 2-3, a human immunodeficiency virus type 1 candidate vaccine, in combination with a novel adjuvant, MTP-PE/MF59. AIDS Res Hum Retroviruses. 1996;12:683-693.