A Randomized Study of Activity, Safety, and Tolerance of Oral Ro 24-7429 (Tat Antagonist) in Patients With HIV Infection

HIV Infections Clinical Trial

Official title:

A Randomized Study of Activity, Safety, and Tolerance of Oral Ro 24-7429 (Tat Antagonist) in Patients With HIV Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000760
• Other study ID #: ACTG 213
• Secondary ID: NV14224A
• Status: Completed
• Phase: Phase 1
• First received: November 2, 1999
• Last updated: July 31, 2008

Study information

• Verified date: November 1998
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

To study the anti-HIV activity of the various doses of Ro 24-7429 monotherapy based on virologic and immunologic endpoints. To study the safety and tolerance of Ro 24-7429. To explore relationships between exposure to Ro 24-7429 and its metabolites and antiviral activity and drug toxicity. To determine a safe, tolerable, and active dose regimen of Ro 24-7429, and to make preliminary observations of Ro 24-7429 in combination with another antiretroviral nucleoside.

The HIV genome contains a number of genes that regulate viral replication. Control of the activity of these genes and their encoded proteins represents a potential target for development of new antiretroviral drugs. The tat (transactivator of transcription of HIV) antagonist Ro 24-7429 is the first compound for clinical testing that utilizes this approach for therapy of HIV infection.

Description:

The HIV genome contains a number of genes that regulate viral replication. Control of the activity of these genes and their encoded proteins represents a potential target for development of new antiretroviral drugs. The tat (transactivator of transcription of HIV) antagonist Ro 24-7429 is the first compound for clinical testing that utilizes this approach for therapy of HIV infection.

Ninety-six patients (four treatment arms of 24 patients each) are randomized to receive oral Ro 24-7429 at 1 of 3 doses or nucleoside control (either zidovudine or didanosine). The study will be blinded only for the arms receiving Ro 24-7429. Treatment continues for 12 weeks. After 12 weeks, patients on the nucleoside control arm receive the highest tolerated dose of Ro 24-7429 in addition to their nucleoside.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 96
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years and older

Eligibility

Inclusion Criteria

Concurrent Medication:

Allowed:

• Chemoprophylaxis for P. carinii pneumonia, TB, and mucocutaneous candidiasis.

• Methadone maintenance.

• Hormonal contraceptives.

Patients must have:

• HIV-1 seropositivity.

• CD4 count 50 - 500 cells/mm3.

• Life expectancy of at least 24 weeks.

• Stable weight (+/- 2 kg) by 28 days prior to study entry (by history).

NOTE:

• At least 50 percent of patients must be p24 antigen positive (>= 50 pg/ml).

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms and conditions are excluded:

• Known or suspected hypersensitivity to benzodiazepines.

• Presence of any malignancy other than basal cell carcinoma or limited cutaneous Kaposi's sarcoma (defined as no more than five lesions with no mucosal involvement).

• Ongoing diarrhea, defined as more than 2 liquid stools per day.

• History, physical exam, or laboratory results consistent with a subclinical AIDS-defining opportunistic infection.

• Grade 2 or greater signs and symptoms of AIDS Dementia Complex.

• Evidence of clinically significant cardiac, respiratory, hepatic, gastrointestinal, endocrine, hematologic, psychiatric, neurologic, dermatologic, or allergic disease.

Concurrent Medication:

Excluded:

• Chronic suppressive therapy for CMV, MAI, toxoplasmosis, cryptococcosis, cryptosporidiosis, coccidioidomycosis, and histoplasmosis.

• ddC, ddI, AZT (except for control groups) or other experimental antiretrovirals or immunomodulating agents.

• Other medications excluded from the study.

Patients with the following prior conditions are excluded:

• History of serious adverse reactions to benzodiazepines.

• History of intolerance to AZT at 600 mg/day or less or ddI at 400 mg/day or less.

• History of unexplained fever, defined as a temperature of 38.5 deg C or greater with or without night sweats for more than 7 of the past 28 days.

Prior Medication:

Excluded:

• Benzodiazepines within 14 days prior to study entry.

Active drug or alcohol abuse that would interfere with study compliance.

Study Design

Endpoint Classification: Safety Study, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Infection

Intervention

Drug:
• Ro 24-7429

• Zidovudine

• Didanosine

Locations

Country	Name	City	State
United States	Johns Hopkins Hosp	Baltimore	Maryland
United States	Harvard (Massachusetts Gen Hosp)	Boston	Massachusetts
United States	Case Western Reserve Univ	Cleveland	Ohio
United States	UCSD	San Diego	California

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Hoffmann-La Roche

Country where clinical trial is conducted

United States, 

References & Publications (3)

Haubrich RH, Flexner C, Lederman MM, Hirsch M, Pettinelli CP, Ginsberg R, Lietman P, Hamzeh FM, Spector SA, Richman DD. A randomized trial of the activity and safety of Ro 24-7429 (Tat antagonist) versus nucleoside for human immunodeficiency virus infection. The AIDS Clinical Trials Group 213 Team. J Infect Dis. 1995 Nov;172(5):1246-52. — View Citation

Haubrich RH. A randomized study of safety, tolerance, pharmacokinetics, and activity of oral Ro 24-7429 (TAT antagonist) in patients with HIV infection. The ACTG 213 Team. Int Conf AIDS. 1993 Jun 6-11;9(1):69 (abstract no WS-B26-5)

Lathey JL, Marschner IC, Kabat B, Spector SA. Deterioration of detectable human immunodeficiency virus serum p24 antigen in samples stored for batch testing. J Clin Microbiol. 1997 Mar;35(3):631-5. — View Citation

External Links

•   Click here for more information about Didanosine
•   Click here for more information about Zidovudine