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
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).
|Study Design:||Endpoint Classification: Safety Study
Primary Purpose: Treatment
|Official Title:||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|
|Study Completion Date:||June 2001|
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.]
Please refer to this study by its ClinicalTrials.gov identifier: NCT00000857
|United States, California|
|UCLA CARE Center CRS|
|Los Angeles, California, United States, 90095|
|Los Angeles, California, United States|
|Palo Alto, California, United States|
|Ucsf Aids Crs|
|San Francisco, California, United States|
|Harbor-UCLA Med. Ctr. CRS|
|Torrance, California, United States, 90502|
|United States, Illinois|
|Rush Univ. Med. Ctr. ACTG CRS|
|Chicago, Illinois, United States, 60612|
|Weiss Memorial Hosp.|
|Chicago, Illinois, United States, 60640|
|Northwestern University CRS|
|Chicago, Illinois, United States, 60611|
|United States, Indiana|
|Indiana Univ. School of Medicine, Infectious Disease Research Clinic|
|Indianapolis, Indiana, United States|
|United States, Massachusetts|
|Massachusetts General Hospital ACTG CRS|
|Boston, Massachusetts, United States, 02114|
|Beth Israel Deaconess Med. Ctr., ACTG CRS|
|Boston, Massachusetts, United States, 02215|
|United States, New York|
|NY Univ. HIV/AIDS CRS|
|New York, New York, United States, 10016|
|Univ. of Rochester ACTG CRS|
|Rochester, New York, United States, 14642|
|United States, North Carolina|
|Unc Aids Crs|
|Chapel Hill, North Carolina, United States|
|United States, Pennsylvania|
|Hosp. of the Univ. of Pennsylvania CRS|
|Philadelphia, Pennsylvania, United States, 19104|
|United States, Washington|
|University of Washington AIDS CRS|
|Seattle, Washington, United States, 98104|
|Study Chair:||Mark Jacobson|
|Study Chair:||Richard Pollard|