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 Details
Study Description
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).
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
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.
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.]
Study Design
Outcome Measures
Primary Outcome Measures
Eligibility Criteria
Criteria
Inclusion Criteria
You may be eligible for this study if you:
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Are HIV-positive.
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Are 18-60 years old.
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Have a CD4 count less than 50 cells/mm3 or between 300-500 cells/mm3 within 30 days of study entry.
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Are expected to live at least 12 weeks.
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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:
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Have a history of cytomegalovirus (CMV) end-organ disease.
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Have a history of invasive fungal disease, unless the condition has been stable for 2 months.
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Have a history of severe allergic reactions to IL-2 or IL-12.
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Have a history of heart problems, autoimmune or rheumatologic disease, gastrointestinal bleeding, or any condition that would keep you from completing the study.
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Have MAC-related symptoms (fever, weight loss, frequent diarrhea) for at least 2 months prior to study entry.
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Are enrolled in another experimental research treatment study.
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Abuse alcohol or drugs.
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Are pregnant or breast-feeding.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | UCLA CARE Center CRS | Los Angeles | California | United States | 90095 |
2 | USC CRS | Los Angeles | California | United States | |
3 | Stanford CRS | Palo Alto | California | United States | |
4 | Ucsf Aids Crs | San Francisco | California | United States | |
5 | Harbor-UCLA Med. Ctr. CRS | Torrance | California | United States | 90502 |
6 | Northwestern University CRS | Chicago | Illinois | United States | 60611 |
7 | Rush Univ. Med. Ctr. ACTG CRS | Chicago | Illinois | United States | 60612 |
8 | Weiss Memorial Hosp. | Chicago | Illinois | United States | 60640 |
9 | Indiana Univ. School of Medicine, Infectious Disease Research Clinic | Indianapolis | Indiana | United States | |
10 | Massachusetts General Hospital ACTG CRS | Boston | Massachusetts | United States | 02114 |
11 | Beth Israel Deaconess Med. Ctr., ACTG CRS | Boston | Massachusetts | United States | 02215 |
12 | NY Univ. HIV/AIDS CRS | New York | New York | United States | 10016 |
13 | Univ. of Rochester ACTG CRS | Rochester | New York | United States | 14642 |
14 | Unc Aids Crs | Chapel Hill | North Carolina | United States | |
15 | Hosp. of the Univ. of Pennsylvania CRS | Philadelphia | Pennsylvania | United States | 19104 |
16 | University of Washington AIDS CRS | Seattle | Washington | United States | 98104 |
Sponsors and Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
- Study Chair: Mark Jacobson,
- Study Chair: Richard Pollard,
Study Documents (Full-Text)
None provided.More Information
Publications
- ACTG 325
- 11299