Clinical Trial Details
— Status: Withdrawn
Administrative data
NCT number |
NCT00000881 |
Other study ID # |
ACTG 352 |
Secondary ID |
11321 |
Status |
Withdrawn |
Phase |
Phase 1
|
First received |
|
Last updated |
|
Study information
Verified date |
October 2021 |
Source |
National Institute of Allergy and Infectious Diseases (NIAID) |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
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.
Description:
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.]