A Study to Evaluate the Effects of Interleukin-12 (rhIL-12) in HIV-Positive Patients With CD4 Cell Counts Less Than 50 Cells/mm3 or 300-500 Cells/mm3

Study Overview
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Brief Summary
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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
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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. Note: If 3 or more patients in the rhIL-12 arm of a given dose in Part A experience a primary toxicity endpoint, then accrual and further drug administration will be discontinued. [AS PER AMENDMENT 6/16/97: If a cohort has exactly two patients in the rhIL-12 arm that experience a primary toxicity endpoint, then the next cohort receives study drug at the same dose as the current cohort, but administered only once a week. If a cohort receiving study drug administered once a week has at least two subjects experience a primary toxicity endpoint, then further drug administration in Part A is stopped. Any cohort that receives study drug once a week is the last cohort in Part A; no further dose escalation is performed]. Part B (18 subjects with 300-500 CD4+ cells/mm3): Patients are randomized to receive either the maximum tolerated dose (determined in Part A) of rhIL-12 or matching placebo subcutaneously twice a week for 4 weeks. [AS PER AMENDMENT 01/29/99: Because of slow accrual for cohort 3 of Part A, concurrent enrollment will begin for Part B while cohort 3 of Part A is completed. There will be no further dose escalation in Part A. Part A will remain open to accrual until the final enrollee to Part B completes 4 weeks of study treatment. For Part B, 27 patients will be randomized with equal probability to one of two rhIL-12 doses or placebo. Semiweekly injections are given for 4 weeks.]

Official Title
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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

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Interleukin-12


Participation Criteria
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Eligibility Criteria
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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-12. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Interleukin-12|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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T-Lymphocytes, Recombinant Proteins, Dose-Response Relationship, Drug, Mycobacterium avium Complex, CD4 Lymphocyte Count, Interleukin-12, Killer Cells, Natural, Th1 Cells, Interferon Type II