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
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 1

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.]
    

Intervention name(s): Interleukin-12
Intervention type(s): Drug
Intervention MeSH terms: Interleukin-12
Masking: Double
Primary purpose: Treatment
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