A Phase II Trial of rsCD4 and AZT in Patients With AIDS or Advanced AIDS Related Complex (ARC)

• Status: Terminated
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: All

Summary

Part 1A: To find the dose of zidovudine (AZT) that causes less than a 50 percent drop in HIV-1 p24 antigen levels in patients with AIDS and advanced AIDS related complex (ARC); to determine the pharmacokinetics (blood levels) of rsCD4 administered in combination with AZT. Parts 1B and 2: To test for additive or synergistic activity between rsCD4 and AZT as judged by falls in HIV-1 p24 antigen levels; and to evaluate the safety of rsCD4 and AZT in patients with AIDS and advanced ARC.

AZT has been shown to be effective in the treatment of AIDS and advanced ARC but not without toxicity. The most clinically significant toxicity is dose related inhibition of bone marrow function. Furthermore, HIV-1 isolates from patients treated for more than 6 months with AZT have now been found which appear to have reduced sensitivity to AZT. The incidence of toxicity and occurrence of virus with reduced sensitivity to AZT may result in the inability to administer AZT long-term to patients with AIDS and advanced ARC. Recombinant soluble CD4 (rCD4) has shown antiretroviral effects and has been shown to be safe when given to AIDS and ARC patients either as a single agent or in combination with AZT.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborator: Biogen
• Treatments: Zidovudine

Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

• Nystatin or clotrimazole for suppression of oral thrush.

• Aerosolized pentamidine as chemoprophylaxis for Pneumocystis carinii pneumonia (PCP).

• Trimethoprim / sulfamethoxazole (TMP / SMX) for patients who are clinically and hematologically stable on TMP / SMX PCP prophylaxis.

Patients must have the following:

• Diagnosis of AIDS or advanced AIDS related complex (ARC).

• CD4 cell count < 300 cells/mm3.

• Ability to understand and sign the consent form.

Risk Behavior:

Allowed:

• History of drug abuse with current abstinence or enrollment in a methadone treatment program.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

• Malignancies other than Kaposi's sarcoma.

• AIDS dementia which, in the opinion of the investigator, precludes patients from giving fully informed consent or from complying fully with the requirements of this protocol.

• Active infection with an opportunistic pathogen requiring ongoing therapy.

• Preexisting antibodies to rCD4.

Concurrent Medication:

Excluded:

• Investigational drugs.

• Antiretroviral agents such as dextran sulfate or AL721.

• Cytotoxic chemotherapy.

Concurrent Treatment:

Excluded:

• Radiation therapy.

Patients with the following are excluded:

• Malignancies other than Kaposi's sarcoma.

• AIDS dementia which, in the opinion of the investigator, precludes patients from giving fully informed consent or from complying fully with the requirements of this protocol.

• Active infection with an opportunistic pathogen requiring ongoing therapy.

• Preexisting antibodies to rCD4.

Prior Medication:

Excluded:

• Zidovudine (AZT) for longer than 30 days or prior treatment with AZT for < 30 days if discontinued for toxicity due to AZT.

• Excluded within 30 days of study entry:

• Immunomodulators.

• Previous participation in any group of another part of this study. For example, patients treated in Part 1A of this study may not reenter the study to be treated in Part 2.

• Chemotherapy.

Prior Treatment:

Excluded within 30 days of study entry:

• Radiation therapy.

Active use of illicit drugs or abuse of alcohol at time of protocol entry.