Clinical trial NCT00000857: 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
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: Recombinant Proteins
T-Lymphocytes
Dose-Response Relationship, Drug
Mycobacterium avium Complex
CD4 Lymphocyte Count
Interleukin-12
Killer Cells, Natural
Th1 Cells
Interferon Type II
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

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.

\[AS PER AMENDMENT 01/29/99: Because of slow accrual for cohort 3 of Part A, concurrent enrollment will begin for Part B while cohort 3 of Part A is completed. There will be no further dose escalation in Part A. Part A will remain open to accrual until the final enrollee to Part B completes 4 weeks of study treatment. For Part B, 27 patients will be randomized with equal probability to one of two rhIL-12 doses or placebo. Semiweekly injections are given for 4 weeks.\]

Eligibility criteria: 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA CARE Center CRS
state: California
city: Los Angeles
country: United States
facility: USC CRS
state: California
city: Palo Alto
country: United States
facility: Stanford CRS
state: California
city: San Francisco
country: United States
facility: Ucsf Aids Crs
state: California
city: Torrance
country: United States
facility: Harbor-UCLA Med. Ctr. CRS
state: California
city: Chicago
country: United States
facility: Northwestern University CRS
state: Illinois
city: Chicago
country: United States
facility: Rush Univ. Med. Ctr. ACTG CRS
state: Illinois
city: Chicago
country: United States
facility: Weiss Memorial Hosp.
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Univ. School of Medicine, Infectious Disease Research Clinic
state: Indiana
city: Boston
country: United States
facility: Massachusetts General Hospital ACTG CRS
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Med. Ctr., ACTG CRS
state: Massachusetts
city: New York
country: United States
facility: NY Univ. HIV/AIDS CRS
state: New York
city: Rochester
country: United States
facility: Univ. of Rochester ACTG CRS
state: New York
city: Chapel Hill
country: United States
facility: Unc Aids Crs
state: North Carolina
city: Philadelphia
country: United States
facility: Hosp. of the Univ. of Pennsylvania CRS
state: Pennsylvania
city: Seattle
country: United States
facility: University of Washington AIDS CRS
state: Washington
Study officials:
name: Mark Jacobson
role: STUDY_CHAIR
name: Richard Pollard
role: STUDY_CHAIR
References:
citation: Jacobson MA, Spritzler J, Landay A, Chan E, Katzenstein D, Schock B, Fox L, Roe J, Kundu S, Pollard R; AACTG 325 Protocol Team. A Phase I, placebo-controlled trial of multi-dose recombinant human interleukin-12 in patients with HIV infection. AIDS. 2002 May 24;16(8):1147-54. doi: 10.1097/00002030-200205240-00008.