A Phase I, Double-Blind, Randomized, Placebo-Controlled Trial of Recombinant Human Interleukin-12 (rhIL-12) in HIV-Infected Subjects With Less Than 50 CD4+ T Cells and Subjects With 300-500 CD4+ T Cells
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 65
- Locations
- 16
Study Overview
Brief Summary
The purpose of this study is to determine the tolerance and effectiveness of rhIL-12 in HIV-positive patients with CD4 cell counts less than 50 cells/mm3 versus 300-500 cells/mm3. This study will look at the ability of rhIL-12 to boost the immune system against HIV and HIV-associated bacterial infections in these patients.
IL-12 is found naturally in the body and rhIL-12 is the commercially produced version. IL-12 may enhance anti-HIV immune system activity by increasing the number of cells that fight infection. IL-12 may also increase the body's ability to fight bacterial infections such as Mycobacterium avium complex (MAC).
Detailed Description
IL-12 has a number of effects in vitro that could be relevant to HIV disease including promotion of TH1 cell development, enhancement of HIV-specific T cell responses in cells from subjects with AIDS, and, of particular relevance to MAC disease, increasing secretion of cytotoxic cytokines such as IFN-gamma from both T lymphocytes and NK cells.
Part A (36 patients with less than 50 CD4+ cells/mm3):
Patients are randomized within one of three sequential dose cohorts and receive either rhIL-12 or matching placebo by subcutaneous injection twice weekly for four weeks. Eligible patients will participate in only 1 of the 3 dosing cohorts. Dose escalation to a new cohort of patients in Part A will occur only if all 3 of the following occur:
(1) At least 9 patients in the rhIL-12 arm have been enrolled in the current dose group and have either been on study drug for at least 4 weeks (temporary discontinuation is allowed) or have permanently discontinued study drug due to a primary toxicity endpoint.
[(2) AS PER AMENDMENT 6/16/97: Fewer than 2 of the 12 patients receiving rhIL-12 at 30 or 100 ng/kg have had a primary toxicity endpoint.] (3) Adequate data from a Genetics Institute/Wyeth Ayerst-sponsored dose escalation trial have been obtained and analyzed to demonstrate the safety of the dose to be administered to the next cohort.
Study Design
- Study Type
- Interventional
- Primary Purpose
- Treatment
- Masking
- Double
Eligibility Criteria
- Ages
- 18 Years to 60 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •You may be eligible for this study if you:
- •Are HIV-positive.
- •Are 18-60 years old.
- •Have a CD4 count less than 50 cells/mm3 or between 300-500 cells/mm3 within 30 days of study entry.
- •Are expected to live at least 12 weeks.
- •Agree to practice abstinence or use effective methods of birth control during the study.
Exclusion Criteria
- •You will not be eligible for this study if you:
- •Have a history of cytomegalovirus (CMV) end-organ disease.
- •Have a history of invasive fungal disease, unless the condition has been stable for 2 months.
- •Have a history of severe allergic reactions to IL-2 or IL-
- •Have a history of heart problems, autoimmune or rheumatologic disease, gastrointestinal bleeding, or any condition that would keep you from completing the study.
- •Have MAC-related symptoms (fever, weight loss, frequent diarrhea) for at least 2 months prior to study entry.
- •Are enrolled in another experimental research treatment study.
- •Abuse alcohol or drugs.
- •Are pregnant or breast-feeding.