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

NCT ID: NCT00000760

Last Updated: 2008-08-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 96 participants
• Study Classification: INTERVENTIONAL

Brief 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.

Detailed 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.

Conditions

HIV Infections

Keywords

Didanosine; Acquired Immunodeficiency Syndrome; AIDS-Related Complex; Antiviral Agents; Zidovudine; Gene Products, tat

Study Design

• Primary Study Purpose: TREATMENT

Interventions

Ro 24-7429

Intervention Type: DRUG

Zidovudine

Intervention Type: DRUG

Didanosine

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Principal Investigators

Richman DD

Role: STUDY_CHAIR

Haubrich R

Role: STUDY_CHAIR

Locations

UCSD

San Diego, California, 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

Countries

United States

References

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. doi: 10.1093/infdis/172.5.1246.

Reference Type: BACKGROUND

PMID: 7594660 (View on PubMed)

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)

Reference Type: BACKGROUND

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. doi: 10.1128/jcm.35.3.631-635.1997.

Reference Type: BACKGROUND

PMID: 9041402 (View on PubMed)

Other Identifiers

NV14224A

Identifier Type: -

Identifier Source: secondary_id

ACTG 213

Identifier Type: -

Identifier Source: org_study_id