A Phase I Study of Combination Therapy With Didanosine (ddI) and Ribavirin in HIV-Infected Children.

HIV Infections Clinical Trial

Official title:

A Phase I Study of Combination Therapy With Didanosine (ddI) and Ribavirin in HIV-Infected Children.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000833
• Other study ID #: ACTG 274
• Secondary ID: 11250
• Status: Completed
• Phase: Phase 1
• Est. completion date: July 1998

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To compare the safety, toxicity, and tolerance of two doses of ribavirin in combination with didanosine (ddI) to HIV-infected children. To determine the toxicity of ddI/ribavirin and compare it to the expected toxicity of ddI monotherapy. To determine the effect of concurrent ribavirin on the pharmacokinetics of ddI. To determine a dosage of ribavirin that would be suitable for a Phase II/III evaluation of ddI/ribavirin.

Ribavirin, a broad spectrum antiviral agent, may enhance the antiretroviral activity of didanosine ( ddI ) without a concomitant increase in toxicity. Ribavirin alters the intracellular metabolism of ddI, enhancing the antiretroviral activity of the active form of ddI.

Description:

Ribavirin, a broad spectrum antiviral agent, may enhance the antiretroviral activity of didanosine ( ddI ) without a concomitant increase in toxicity. Ribavirin alters the intracellular metabolism of ddI, enhancing the antiretroviral activity of the active form of ddI.

Patients are divided into two cohorts. Subjects will be stratified by age 3 months to < 24 months and >= 24 months to 12 years. Fifty % of patients from each age group will be assigned to each cohort. Cohort 1 receives ddI monotherapy for 4 weeks, followed by combination ddl/ribavirin therapy for an additional 20 weeks. Cohort 2 receives combination ddI/ribavirin for 24 weeks. In both cohorts, after study medications are stopped, patients are treated with prescription antiretrovirals for 4 more weeks. [AS PER AMENDMENT 7/2/96: Note: In each cohort of 10 subjects at least 2 of 5 children from the older half of the cohort will have an ICD p24 antigen at entry.]

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: July 1998
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Months to 12 Years

Eligibility

Inclusion Criteria

Concurrent Medication:

Recommended:

• PCP prophylaxis.

Allowed:

• Acetaminophen for no more than 72 hours.

• Immunoglobulin.

• Corticosteroids.

• Erythropoietin.

• G-CSF and GM-CSF.

• Ethionamide or isoniazid for TB if no alternative available.

• Immunizations according to current recommendations.

Patients must have:

• HIV infection.

• Immunologic abnormality or clinical symptoms as detailed in the Disease Status field.

• No active AIDS-defining opportunistic infection or malignancy, no progressive encephalopathy attributable to HIV and no chronic persistent diarrhea.

• Consent of parent or guardian.

PER AMENDMENT 7/2/96:

• At least 2 of the 5 children in the older half of each cohort must have an ICD p24 antigen concentration >= 70 pg/ml at screening.

Prior Medication:

Allowed:

• Up to 6 weeks of prior immunomodulator therapy.

• Maternal immunomodulator or antiretroviral therapy, including during pregnancy.

• Prior corticosteroids or intravenous immunoglobulin.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Current grade 3 or worse neuropathy/lower motor neuropathy.

• Clinical or laboratory grade 3 or worse toxicities.

• Active serious bacterial infection.

Concurrent Medication:

Excluded:

• Chemotherapy for active malignancy.

• Antiretrovirals other than study drugs.

• Immunomodulators unless specifically allowed.

Patients with the following prior condition are excluded:

• History of grade 3 or worse neuropathy/lower motor neuropathy.

Prior Medication:

Excluded:

• Prior ddI or oral ribavirin.

• Aerosolized ribavirin within 6 weeks prior to study entry.

• Antiretroviral or immunomodulator therapy (other than corticosteroids or IVIG) within 1 week prior to blood draws for study entry.

Ongoing drug or alcohol abuse.

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Ribavirin

• Didanosine

Locations

Country	Name	City	State
Puerto Rico	Univ of Puerto Rico / Univ Children's Hosp AIDS	San Juan
United States	Children's Hosp of Boston	Boston	Massachusetts
United States	Bronx Lebanon Hosp Ctr	Bronx	New York
United States	Texas Children's Hosp / Baylor Univ	Houston	Texas
United States	Univ of Florida Health Science Ctr / Pediatrics	Jacksonville	Florida
United States	Schneider Children's Hosp	New Hyde Park	New York
United States	Tulane Univ / Charity Hosp of New Orleans	New Orleans	Louisiana
United States	Columbia Presbyterian Med Ctr	New York	New York
United States	Harlem Hosp Ctr	New York	New York
United States	Incarnation Children's Ctr / Columbia Presbyterian Med Ctr	New York	New York
United States	Children's Hosp of New Jersey / UMDNJ - New Jersey Med Schl	Newark	New Jersey
United States	Univ of Medicine & Dentistry of New Jersey / Univ Hosp	Newark	New Jersey
United States	Glaxo Wellcome Inc	Research Triangle Park	North Carolina
United States	Children's Hosp of Washington DC	Washington	District of Columbia
United States	Howard Univ Hosp	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (1)

McKinney RE Jr. Ongoing and future trials of antiretroviral therapy in the pediatric AIDS clinical trials group (PACTG). Conf Retroviruses Opportunistic Infect. 1996 Jan 28-Feb 1;3rd:173