PEGYLATED INTERFERON +/- RIBAVIRIN FOR CHILDREN WITH HCV (PEDS-C)

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. There are approximately 150,000 infants, children, and adolescents in the United States with chronic hepatitis C virus (CHC) infection. Alpha-interferon(IFN) alone or in combination with ribavirin and pegylated interferon (PEG) in combination with RV have been approved by the FDA for use in subjects over 18 years of age. Rebtrol (ribavirn and Intron A) has recently been approved for use in treating hepatitis C in children at least 3 years of age and older. Published reports of IFN monotherapy in children with CHC have suggested that response rates are higher than in adults. PEG + RV is the most effective therapy for adults with CHC. Given that RV is a teratogen, and that subjects <18years of age may have high response rates to PEG alone, the purpose of this proposal is to perform a randomized controlled trial to compare the safety and efficacy of PEG + placebo vs. PEG +RV (1:1 randomization). 112 HCV RNA+ IFN-na¿¿ve children 5-18 years of age will be enrolled in this multi-center Phase III clinical trial. 11 pediatric centers will work in collaboration with the NIDDK and Roche Laboratories Inc, which will supply the pegylated interferon (Pegasys¿¿¿), to be given at a dose of 180mcg/1.73m2 sq week x 48 weeks, with a treatment-free follow-up of 24 weeks. RV will be given at 15 mg/kd/day p.o. divided b.i.d. (not >1200mg/day) X 48 weeks with a treatment free follow-up of 24 weeks. Children randomized to PEG+ placebo who fail to exhibit viral disappearance (HCV RNA <100copies/ml by Amplicor¿¿¿ polymerase chain reaction assay) at week 24 will be crossed over to PEG+RV (a compassionate combination therapy arm). These children will be assessed after 24 weeks of combination therapy. If they do not exhibit viral disappearance after 24 weeks of combination therapy, Peg-2a and RV will be stopped and they will be followed closely for 24 weeks. If after 24 weeks of combination therapy they exhibit viral disappearance, they will be treated for an additional 24 weeks and followed for 24 weeks off therpay. In children who were randomized to PEG+RV who fail to exhibit viral disappearance at week 24 the drugs will be discontinued. The primary analysis will be on an intent to treat basis; the primary endpoint will be sustained viral response 24 weeks off therapy (72 weeks from baseline). Other endpoints include biochemical and clinical safety assessments as well as body composition and growth and health related quality of life. The treatment trial will take place over years 1 through 3 with the longterm follow-up off treatment in years 4 and 5.This trial would thus provide critically needed data to guide safe and effective treatment of CHC, a major cause of liver disease in children.