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
|ClinicalTrials.gov Identifier: NCT00000857|
Recruitment Status : Completed
First Posted : August 31, 2001
Last Update Posted : June 3, 2015
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|
|HIV Infections||Drug: Interleukin-12||Phase 1|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||65 participants|
|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|
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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|
|Northwestern University CRS|
|Chicago, Illinois, United States, 60611|
|Rush Univ. Med. Ctr. ACTG CRS|
|Chicago, Illinois, United States, 60612|
|Weiss Memorial Hosp.|
|Chicago, Illinois, United States, 60640|
|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|