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

Condition(s) targeted: HIV Infections

Intervention: Hypericin (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: VIMRx Pharmaceuticals

Official(s) and/or principal investigator(s):
Valentine FT, Study Chair

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.

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

Study design: Treatment, Open Label

Detailed 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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.

Beth Israel Deaconess Med Ctr, Boston, Massachusetts 02215, United States

Bellevue Hosp / New York Univ Med Ctr, New York, New York 10016, United States

Related publications:

Gulick R, Lui H, Anderson R, Kollias N, Hussey S, Crumpacker C. Human hypericism: a photosensitivity reaction to hypericin (St. John's Wort). Int Conf AIDS. 1992 Jul 19-24;8(2):B90 (abstract no PoB 3018)

Mcauliffe V, et al. A phase I dose escalation study of synthetic hypericin in HIV infected patients (ACTG 150). Natl Conf Hum Retroviruses Relat Infect (1st). 1993 Dec 12-16:159

Gulick RM, McAuliffe V, Holden-Wiltse J, Crumpacker C, Liebes L, Stein DS, Meehan P, Hussey S, Forcht J, Valentine FT. Phase I studies of hypericin, the active compound in St. John's Wort, as an antiretroviral agent in HIV-infected adults. AIDS Clinical Trials Group Protocols 150 and 258. Ann Intern Med. 1999 Mar 16;130(6):510-4.

Last updated: June 23, 2005