A Third-Party Blinded, Placebo Controlled Comparative Study of AS-101 Administered Intravenously in HIV Positive Patients With Advanced Disease

A Third-Party Blinded, Placebo Controlled Comparative Study of AS-101 Administered Intravenously in HIV Positive Patients With Advanced Disease

To compare the effect of AS-101 to that of placebo on clinical efficacy and immunologic function in HIV positive patients with advanced disease. To compare the effect of AS-101 to that of placebo on occurrence of disease progression in HIV positive patients with advanced disease as defined by: (1) development of new diagnostically confirmed major opportunistic infection(s); or (2) development of AIDS-related dementia. To compare the effect of zidovudine (AZT) plus AS-101 versus AZT alone (placebo arm) on clinical efficacy and immunologic function in patients who require anti-viral therapy due to disease progression. Garlic capsules will be given to all study participants to mask the obvious garlic odor of AS-101.

Inclusion Criteria

Concurrent Medication:

Allowed:

• Standard therapy including acyclovir or ganciclovir for infections that develop during the study period. (Prophylactic acyclovir is not permitted.) Standard therapy for persistent infections may continue.
• Immunomodulators or specific therapy for malignancies (including Kaposi's sarcoma) allowed only with permission of Wyeth-Ayerst medical monitor.
• Zidovudine (AZT) may be added only if there is disease progression and after the patient has been in the study for a minimum of eight weeks.
• Garlic capsules will be given to all study participants to mask side effects of AS-101.
• Required:
• Accepted standard prophylaxis for patients with prior Pneumocystis carinii pneumonia (PCP).

Patients must have the following:

• Diagnosis of AIDS or AIDS-related complex (ARC).
• Life expectancy > 6 months.
• Provide written informed consent.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

• Evidence of severe liver dysfunction (serum albumin < 2.5 g/dl, prothrombin time > 15 seconds or SGOT or SGPT > 3 x upper limits of normal), gastrointestinal, renal, respiratory, endocrine, hematologic, cardiovascular system abnormalities or psychiatric disorders which would prevent compliance with the protocol.
• Evidence of AIDS related dementia.
• Presence of disseminated Kaposi's sarcoma defined as any visceral lesions or > 20 cutaneous lesions; or Kaposi's sarcoma without at least one other AIDS defining characteristic.
• Presence of any lymphoma.
• Active opportunistic infection currently requiring treatment unless the infection has stabilized and continuing treatment is only required to prevent relapse (e.g., CNS toxoplasmosis or resolving tuberculosis).

Concurrent Medication:

Excluded:

• Prophylactic acyclovir.
• Immunomodulators or specific therapy for malignancies (including Kaposi's sarcoma) allowed only with permission of Wyeth-Ayerst medical monitor.
• Zidovudine (AZT) may be added only if there is disease progression and after the patient has been in the study for a minimum of eight weeks.

Patients with the following are excluded:

• Evidence of severe organ dysfunction as defined in Exclusion complications or other specified disease conditions.
• Unlikely or unable to comply with the requirements of the protocol.

Prior Medication:

Excluded within 8 weeks of study entry:

• Any immune stimulation agents such as BCG vaccine, interferons, or other immune modulators within 8 weeks.
• Any immunosuppressive agent within 8 weeks.
• Excluded within 12 weeks of study entry:
• Zidovudine (AZT).