Capravirine to Treat Children With HIV Infection
This study will test the safety, side effects and anti-HIV activity of different doses of capravirine in children and adolescents with HIV infection. Capravirine belongs to a class of drugs called non-nucleoside reverse transcriptase inhibitors (NNRTIs), which prevent the virus from replicating (making more copies of itself). Other NNRTIs are nevirapine, delavirdine and efavirenz.
HIV-infected children between the ages of 4 months and 21 years may be eligible for this study if they: 1) have received less than 6 weeks of treatment with antiretroviral drugs; 2) have not benefited from antiretroviral therapy after 12 weeks of treatment; 3) cannot continue antiretroviral treatment because of harmful side effects.
For the first week of the study, participants will have a 1-week "washout period" in which they will receive no anti-HIV therapy. During this time, they will have physical, eye and neuropsychologic examinations, blood and urine tests, echocardiogram, electrocardiogram (EKG), chest X-ray, head CT scan and skin tests. These physical exams and tests will be repeated throughout the study to determine changes in health.
After the washout period, patients will take capravirine once a day in the morning for 6 days. After each dose, a small amount of blood will be drawn at 8 different times over 12 hours to measure the activity of the drug and HIV blood levels. A heparin lock will be placed in the vein to avoid multiple needlesticks. After the 6 days of capravirine there will be another washout period, this time for 21 days. During this time, doctors will determine the optimum combination therapy for the individual patient.
After the second washout, patients will begin combination therapy with capravirine plus at least two other anti-HIV medicines. (These may include a reverse transcriptase inhibitor such as zidovudine, didanosine, lamuvidine, zalcitabine, or stavudine, and maybe one or more protease inhibitors such as ritonavir, nelfinavir, saquinavir, indinavir or amprenavir.) For the first week, patients will have a daily blood test to determine HIV blood levels. Afterwards, treatment will continue on an outpatient basis with clinic visits every 4 to 8 weeks for physical exams, lab tests and other procedures as required. The study will last approximately 48 weeks. Patients who benefit from capravirine therapy may be able to continue to receive the drug from the drug company sponsor or as part of another study, or the protocol for this study may be amended to lengthen the treatment period.
|Study Design:||Endpoint Classification: Safety Study
Primary Purpose: Treatment
|Official Title:||A Phase I Study of Capravirine (AG 1549), a Novel Non-Nucleoside Reverse Transcriptase Inhibitor in Children With HIV Infection|
|Study Start Date:||November 2000|
|Estimated Study Completion Date:||October 2004|
This is a pediatric phase I dose escalation study to determine a biologically active dose and to obtain information concerning the safety, tolerability, and pharmacokinetics of capravirine (AG 1549)(5-[(3,5-dichlorophenyl)thio]-4-(1-methylethyl)-1-(4-pyridinylmethyl)-1H-imidazol-2-methanol carbamate), a potent non-nucleoside HIV-1 reverse transcriptase (RT) inhibitor, that induces a novel pattern of resistance mutations. In addition to obtaining needed biological activity, pediatric safety, tolerability, and pharmacokinetic data, the study will utilize capravirine's potent antiretroviral activity and novel resistance mutation pattern, together with serial measurements of plasma HIV viral load, flow cytometry, and genotypic and phenotypic viral resistance analysis to conduct pilot studies in pediatric HIV pathogenesis, the response to antiretroviral therapy, and to develop strategies to optimize the management of pediatric antiretroviral therapy. We will also use initial viral decay dynamics and other patient characteristics to model predictions for the long-term response to antiretroviral therapy. We will enroll children who have become refractory to or have experienced toxicity on prior therapy. The study will include resistance testing on the failing regimen, a one week period off antiretrovirals (washout period), an initial 6 days of capravirine monotherapy followed by capravirine in combination with the optimal antiretroviral therapy as determined by their baseline viral resistance mutation pattern and history. The patients will be followed for at least 48 weeks to assess long-term tolerability and toxicity, and to assess the clinical, virological, and immunological response to capravirine.
|United States, Maryland|
|National Cancer Institute (NCI)|
|Bethesda, Maryland, United States, 20892|