A Phase I Dose Escalation Study of Synthetic Hypericin in HIV-Infected Patients With Less Than 300 CD4 Lymphocytes

National Institute of Allergy and Infectious Diseases (NIAID)

Status and phase: Completed; Phase 1

Conditions: HIV Infections

Treatments: Drug: Hypericin

Study type: Interventional

Funder types: Industry; NIH

Identifiers

NCT00000645

11125 (Registry Identifier)

ACTG 150

Details and patient eligibility

About

To determine the maximum tolerated dose (MTD) of hypericin, to define the types of toxicities that may be observed, and to determine what doses of the drug are associated with improvements in virological and immunological surrogate markers of HIV infection. To determine the bioavailability of synthetic hypericin given in 2 percent benzyl alcohol solution.

Hypericin is unlike other drugs presently being used to treat AIDS patients. Hypericin shows anti-HIV activity in test tube experiments.

Full description

Hypericin is unlike other drugs presently being used to treat AIDS patients. Hypericin shows anti-HIV activity in test tube experiments.

Each group of eight patients receives a given dose of hypericin by intravenous infusion. Doses are given three times per week for 8 weeks. When all eight patients at a dose level have been entered and four of the eight patients have completed 3 weeks of therapy without evidence of dose-limiting toxicity, additional patients may begin to receive drug at the next dose level. Concurrently, six patients wll participate in an oral-dosing bioavailability study. NOTE: The initial study was stopped secondary to an MTD being reached.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

• Prophylaxis for Pneumocystis carinii pneumonia (required for patients with CD4+ < 200).
• Symptomatic treatment with analgesics, antihistamines, antiemetics, antidiarrheal agents, or other supportive therapy.
• Short courses (< 10 days) with ketoconazole or fluconazole for oral candidiasis or acyclovir for herpes lesions.
• Topical medications such as clotrimazole troches or nystatin suspensions.

Concurrent Treatment:

Allowed:

• Blood transfusions.

Patients must have HIV infection with CD+4 lymphocyte count of < 300 cells/mm3.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded.

• Kaposi's sarcoma requiring systemic therapy.

Concurrent Medication:

Excluded:

• Continued use of opiates or drugs known to induce photosensitivity.

Patients with the following are excluded:

• Active or chronic opportunistic infection at time of study entry that required curative or suppressive therapy.
• Significant liver disease, orthostatic hypotension, cardiac disease, seizure disorder, lymphoma, hypotension.

Prior Medication:

Excluded:

• Zidovudine (AZT), dideoxyinosine (ddI), dideoxycytidine (ddC), interferon, other antiretroviral agents or immunomodulating drugs within 1 month prior to study entry. Ribavirin within 3 months of study entry.
• Ganciclovir (DHPG), antimycobacterial drugs, MAO inhibitors, hypertension-inducing, nephrotoxic, or hepatotoxic drugs within 14 days of entry.
• Cytotoxic chemotherapy within 1 month prior to study entry.

Active substance abuse.