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

• Status: Completed
• Trial end date: 1998-07-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Didanosine; Ribavirin

Criteria

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.