A Randomized Phase II Study of Two Doses of Interferon Alfa-2a (IFN Alfa-2a) in Combination With Zidovudine (AZT) and Dideoxycytidine (ddC) Versus AZT and ddC Only in Patients With HIV Infection and Less Than 400 CD4 Cells/mm3

Sponsor

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

Overall Status

Completed

CT.gov ID

NCT00000754

Collaborator

Hoffmann-La Roche (Industry), Glaxo Wellcome (Industry)

Enrollment

Locations

Patients Per Site

Study Details

Study Description

Brief Summary

To determine the safety and efficacy of two doses of interferon alfa-2a ( IFN alfa-2a ) in combination with zidovudine ( AZT )/zalcitabine ( ddC ) versus AZT/ddC only in patients with HIV infection and CD4 count < 400 cells/mm3.

AZT and ddC inhibit HIV by acting as reverse transcriptase chain terminators, while IFN alfa-2a inhibits translation of viral proteins. Combining agents that act at different sites of viral replication may improve HIV inhibition and produce more effective and sustained anti-HIV effects.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Drug: Interferon alfa-2a Drug: Zidovudine Drug: Zalcitabine	Phase 2

Detailed Description

Patients are randomly assigned to one of three treatment arms to receive AZT/ddC alone or combined with one of two doses of IFN alfa-2a. Treatment continues for up to 12 months after enrollment of the last patient. Patients are followed at 2, 4, and 8 weeks and every 8 weeks thereafter. Mean duration of follow-up is expected to be 13 months.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

A Randomized Phase II Study of Two Doses of Interferon Alfa-2a (IFN Alfa-2a) in Combination With Zidovudine (AZT) and Dideoxycytidine (ddC) Versus AZT and ddC Only in Patients With HIV Infection and Less Than 400 CD4 Cells/mm3

Actual Study Completion Date :

Feb 1, 1995

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

Concurrent Medication:

Allowed:

Isoniazid for < grade 2 peripheral neuropathy (if patient is also taking 50 mg/day pyridoxine).
Phenytoin for < grade 2 peripheral neuropathy.
A 21-day course of adjuvant systemic corticosteroid therapy for moderate to severe Pneumocystis carinii pneumonia (PCP).
Chemoprophylaxis for PCP, candidiasis, herpes simplex infection (up to 1 g acyclovir daily), and Mycobacterium tuberculosis.

Patients must have:

HIV infection.
CD4 count < 400 cells/mm3 within 30 days prior to study entry.

NOTE:

Minimal Kaposi's sarcoma is allowed.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms and conditions are excluded:

Active opportunistic infection requiring acute therapy.
Need for maintenance therapy for cytomegalovirus infection, toxoplasmic encephalitis, or mycobacterial infection.
Malignancy (other than minimal Kaposi's sarcoma) requiring therapy.
Grade 2 or worse peripheral neuropathy.

Concurrent Medication:

Excluded:

Other antiretroviral drugs, biologic response modifiers, cytotoxic chemotherapy, or investigational drugs (unless approved by the protocol chairs).
Recombinant erythropoietin, G-CSF, or GM-CSF.
Drugs that cause peripheral neuropathy, e.g., gold, hydralazine, nitrofurantoin, vincristine, cisplatin, disulfiram, and diethyldithiocarbamate (unless approved by the protocol chairs).

Concurrent Treatment:

Excluded:

Radiation therapy (unless approved by the protocol chairs).

Patients with the following prior conditions are excluded:

History of intolerance to AZT at 600 mg/day or less.
Unexplained temperature of 38.5 degrees C persisting for 14 days or longer.
Unexplained, chronic diarrhea defined as 3 or more stools per day persisting for 14 days or longer.

Prior Medication:

Excluded:

Acute therapy for opportunistic infection within 14 days prior to study entry.
Prior ddC, ddI, or IFN alfa-2a.

Active substance abuse.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alabama Therapeutics CRS	Birmingham	Alabama	United States	35294
2	Ucsd, Avrc Crs	La Jolla	California	United States
3	UCSD Maternal, Child, and Adolescent HIV CRS	San Diego	California	United States
4	Univ. of Miami AIDS CRS	Miami	Florida	United States