Clinical trial NCT00000833: A Phase I Study of Combination Therapy With Didanosine (ddI) and Ribavirin in HIV-Infected Children.
Official title: A Phase I Study of Combination Therapy With Didanosine (ddI) and Ribavirin in HIV-Infected Children.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: Ribavirin
Didanosine
Drug Therapy, Combination
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Antiviral Agents
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 20
Sex: ALL
Minimum age (years): 3
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief 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.

Detailed 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. \[AS PER AMENDMENT 7/2/96: Note: In each cohort of 10 subjects at least 2 of 5 children from the older half of the cohort will have an ICD p24 antigen at entry.\]

Eligibility 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Washington
country: United States
facility: Children's Hosp of Washington DC
state: District of Columbia
city: Washington
country: United States
facility: Howard Univ Hosp
state: District of Columbia
city: Jacksonville
country: United States
facility: Univ of Florida Health Science Ctr / Pediatrics
state: Florida
city: New Orleans
country: United States
facility: Tulane Univ / Charity Hosp of New Orleans
state: Louisiana
city: Boston
country: United States
facility: Children's Hosp of Boston
state: Massachusetts
city: Newark
country: United States
facility: Univ of Medicine & Dentistry of New Jersey / Univ Hosp
state: New Jersey
city: Newark
country: United States
facility: Children's Hosp of New Jersey / UMDNJ - New Jersey Med Schl
state: New Jersey
city: Bronx
country: United States
facility: Bronx Lebanon Hosp Ctr
state: New York
city: New Hyde Park
country: United States
facility: Schneider Children's Hosp
state: New York
city: New York
country: United States
facility: Columbia Presbyterian Med Ctr
state: New York
city: New York
country: United States
facility: Incarnation Children's Ctr / Columbia Presbyterian Med Ctr
state: New York
city: New York
country: United States
facility: Harlem Hosp Ctr
state: New York
city: Research Triangle Park
country: United States
facility: Glaxo Wellcome Inc
state: North Carolina
city: Houston
country: United States
facility: Texas Children's Hosp / Baylor Univ
state: Texas
city: San Juan
country: Puerto Rico
facility: Univ of Puerto Rico / Univ Children's Hosp AIDS
Study officials:
name: Van Dyke R
role: STUDY_CHAIR
name: McSherry G
role: STUDY_CHAIR
References:
citation: 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