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Sponsored by: |
National Institute of Allergy and Infectious Diseases (NIAID) |
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Information provided by: | National Institute of Allergy and Infectious Diseases (NIAID) |
ClinicalTrials.gov Identifier: | NCT00000881 |
Part A: To determine the safety and pharmacokinetics of sequential single doses of cidofovir in HIV-infected children with end-organ cytomegalovirus (CMV) disease. Part B: To determine the safety (including time to progression of CMV retinitis by retinal exam), pharmacokinetics, and long-term (6 months) tolerance of multiple-dose cidofovir in HIV-infected children with CMV retinitis. Part B: To determine the effect of multiple-dose cidofovir on the virologic parameters of CMV retinitis (viral load, shedding, and resistance to antiviral agents).
[AS PER AMENDMENT 1/7/98: To determine the safety, tolerance and pharmacokinetics of sequential single doses of cidofovir in HIV-infected children with CMV retinitis. To determine the safety (including time to progression of CMV retinitis by retinal exam), pharmacokinetics, and long-term (6-month) tolerance of multiple doses of cidofovir in HIV-infected children with CMV retinitis.] While the intravenous formulation of cidofovir has been approved for the treatment of CMV retinitis in HIV-infected individuals, information is limited regarding its safety and tolerance in HIV-infected children. Intravenous cidofovir requires less frequent administration for both induction and maintenance therapy of CMV retinitis than other currently available therapies. If found to be safe and well tolerated in HIV-infected children with CMV retinitis, intravenous cidofovir would add significantly to agents available to treat this debilitating opportunistic infection.
Condition | Intervention | Phase |
---|---|---|
Cytomegalovirus Infections Cytomegalovirus Retinitis HIV Infections |
Drug: Cidofovir Drug: Probenecid |
Phase I |
Study Type: | Interventional |
Study Design: | Treatment, Pharmacokinetics Study |
Official Title: | A Phase I/II Study of Cidofovir for HIV-Infected Children With Invasive CMV (Cytomegalovirus) Disease |
Estimated Enrollment: | 14 |
While the intravenous formulation of cidofovir has been approved for the treatment of CMV retinitis in HIV-infected individuals, information is limited regarding its safety and tolerance in HIV-infected children. Intravenous cidofovir requires less frequent administration for both induction and maintenance therapy of CMV retinitis than other currently available therapies. If found to be safe and well tolerated in HIV-infected children with CMV retinitis, intravenous cidofovir would add significantly to agents available to treat this debilitating opportunistic infection.
In this two-part study, patients are stratified by age (3 months to < 2 years versus 2 years to < 13 years). In Part A, 8 patients (4 per cohort) receive a single intravenous dose of cidofovir with concurrent probenecid. If 1 patient in a cohort experiences life-threatening grade 3/4 toxicity, accrual for that cohort is stopped. If 1 patient in a cohort experiences non-life-threatening grade 3/4 toxicity, 2 additional patients are entered in that cohort. A second dose of cidofovir may be studied in Part A based on the pharmacokinetic and safety data obtained with the initial dose. Patients who complete Part A of the study without serious toxicity may be treated in Part B.
In Part B, 12 patients (8 in the older cohort and 4 in the younger cohort) receive maintenance therapy with cidofovir at the dose established in Part A. Patients who complete 6 months of treatment in Part B may continue therapy until all patients have completed the study. NOTE: For patients who require induction or reinduction, cidofovir is given weekly for 2 weeks before initiating the Part B regimen.
[AS PER AMENDMENT 1/7/98: Each subject receives sequential single doses of intravenous cidofovir, with a 2-week interval between doses and with concurrent probenecid. If the single doses prove safe and well tolerated and individual pharmacokinetic profiles are acceptable, subjects proceed to multi-dosing cidofovir given every 2 weeks for 6 months beginning 14-21 days after the second single dose. Subjects remain on intravenous or oral ganciclovir for treatment of CMV retinitis until they enter the multi-dosing phase of the study. Subjects who require reinduction during the multi-dosing phase receive intravenous cidofovir once weekly for 2 weeks before resuming the every-2-weeks regimen. Patients are stratified by age (3 months to < 2 years vs. 2 years to < 13 years), with 4 patients entered in the younger cohort and 8 in the older. In the younger age cohort, if 1 patient experiences life- or vision-threatening grade 3/4 toxicity or 2 experience non-life-threatening grade 3/4 toxicity, the age cohort will stop. If 1 patient experiences non-life-threatening grade 3/4 toxicity, 2 additional patients will be enrolled in this age cohort. In the older age cohort, if 1 patient experiences severe life- or vision-threatening toxicity or 2 experience serious, non-life-threatening toxicities, enrollment for both cohorts will be suspended while safety data are reviewed. If 2 of the 8 patients experience severe, non-life-threatening toxicity, enrollment may continue.]
Ages Eligible for Study: | 3 Months to 13 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria
Concurrent Medication:
Allowed:
Ganciclovir required during sequential single-dose phase.]
Patients must have:
< 18 months of age:
>= 18 months of age:
Part A:
Part B:
[AS PER AMENDMENT 1/7/98:
Prior Medication:
Required:
Allowed:
[AS PER AMENDMENT 1/7/98:
Exclusion Criteria
Co-existing Condition:
Patients with the following conditions are excluded:
Concurrent Medication:
Excluded:
Excluded within 7 days prior to enrollment:
Patients with the following prior conditions are excluded:
[AS PER AMENDMENT 1/7/98:
United States, Massachusetts | |
Children's Hosp of Boston | |
Boston, Massachusetts, United States, 021155724 | |
Puerto Rico | |
Univ of Puerto Rico / Univ Children's Hosp AIDS | |
San Juan, Puerto Rico, 009365067 |
Study Chair: | Dankner W | |
Study Chair: | Spector S |
Study ID Numbers: | ACTG 352 |
Study First Received: | November 2, 1999 |
Last Updated: | June 23, 2005 |
ClinicalTrials.gov Identifier: | NCT00000881 |
Health Authority: | United States: Federal Government |
AIDS-Related Opportunistic Infections Cytomegalovirus Infections Antiviral Agents cidofovir |
Cidofovir Opportunistic Infections Sexually Transmitted Diseases, Viral Eye Diseases Eye Infections Acquired Immunodeficiency Syndrome Cytomegalovirus Retinitis Retinitis Cytomegalovirus Immunologic Deficiency Syndromes Herpesviridae Infections |
Cytomegalovirus retinitis Virus Diseases HIV Infections AIDS-Related Opportunistic Infections Sexually Transmitted Diseases Probenecid Cytomegalovirus Infections DNA Virus Infections Cytomegalic inclusion disease Retroviridae Infections Retinal Diseases |
Anti-Infective Agents Communicable Diseases RNA Virus Infections Anti-HIV Agents Slow Virus Diseases Immune System Diseases Eye Infections, Viral Antineoplastic Agents Physiological Effects of Drugs Infection |
Renal Agents Antiviral Agents Gout Suppressants Pharmacologic Actions Anti-Retroviral Agents Radiation-Sensitizing Agents Uricosuric Agents Therapeutic Uses Lentivirus Infections Antirheumatic Agents |