The Safety and Effectiveness of Injections of Human Recombinant Interferon-gamma in Patients With AIDS Who Have Taken Zidovudine

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00001112

Collaborator

(none)

Enrollment

Location

Study Details

Study Description

Brief Summary

To find out which of four doses of (recombinant) human interferon gamma (IFN-G) is most effective in stimulating the white blood cells (monocytes) to fight infection and to see if treatment with IFN-G can strengthen the ability of AIDS patients to control infections. This study will also determine how long after a single injection of IFN-G white blood cells remain stimulated.

AIDS is a disease that progressively destroys that aspect of the body's defense called the immune system. It is particularly harmful to a class of cells called helper T-lymphocytes. The specific opportunistic infections and malignancies associated with AIDS have been treated with therapies that are often poorly tolerated by the patients and are associated with dose-limiting toxicities. The principal focus of AIDS therapy research at present is to control the underlying retroviral infection and to restore immune function with recombinant lymphokines, adoptive immunotherapy, and/or lymphocyte transplants. These treatments include zidovudine (AZT), which has been shown to control the HIV infection, and IFN-G, a lymphokine which activates tumor-destroying and germ-killing functions. Studies are needed to find the dose by which IFN-G works best.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Drug: Zidovudine Drug: Interferon gamma-1b	Phase 1

Detailed Description

Patients, who may participate in all three parts of the study, are maintained on a stable dose of AZT. In part A (optimal dose), five AIDS patients who have had an AIDS related opportunistic infection receive 4 once-weekly increasing doses of IFN-G. Monocyte antimicrobial activity is examined in test tube studies before and after each injection of IFN-G. In part B, five patients receive the optimal dose of IFN-G established in part A. Patients enrolled from part A have completed at least 2 weeks of part A before enrolling in part B. Antimicrobial activity is examined 1, 2, and 3 days after a single injection of the optimal dose of IFN-G (determined in part A). In part C (safety and tolerance of combined treatment of IFN-G and AZT), patients are treated with IFN-G for 4 weeks using the optimal dose and administration schedule derived from parts A and B.

Study Design

Study Type:

Interventional

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Study To Determine the Safety of the Optimal Monocyte Activating Administration Schedule of Subcutaneous Human Recombinant Interferon-gamma in ZDV-Treated Patients With AIDS

Actual Study Completion Date :

Apr 1, 1993

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

Concurrent Medication:

Allowed:

Prophylactic antibiotics.
Tylenol (650 mg orally every 6 hours as needed for temperature > 38.5 degrees C).
Meperidine (25 - 50 mg intravenously, once, for severe rigors if systolic blood pressure is > 90 mmHg).

Patients must meet criteria for AIDS classification (CDC) category IV C-1.

Patients must have had one or more prior opportunistic infections identified in surveillance definition of AIDS. Patients whose AIDS-defining illness is Kaposi's sarcoma are also eligible if they have previously had one of the secondary infectious diseases identified in category C-1.

Prior Medication:

Required:

Patients must have been receiving zidovudine (AZT) on a stable dosage regimen for at least 8 weeks immediately preceding entry into study.

Exclusion Criteria

Co-existing Condition:

Patients with the following are excluded:

Clinically significant cardiac (= or > class II, New York Heart Association) or peripheral vascular disease that requires treatment.
Presence of an active opportunistic infection that requires treatment.
Hemorrhagic diathesis or active bleeding disorder.
Clinically apparent vascular disease.

Concurrent Medication:

Excluded:

Medications required for treatment of active cardiac disease.
Ongoing therapy with anticoagulants or thrombolytic agents.

Patients with the following are excluded:

Clinically significant cardiac (= or > class II, New York Heart Association) or peripheral vascular disease that requires treatment.
Presence of an active opportunistic infection that requires treatment.
Hemorrhagic diathesis or active bleeding disorder.
Clinically apparent vascular disease.