Pegylated Interferon +/- Ribavirin for Children with HCV

描述(由申请人提供)： 在美国，大约有15万名婴儿、儿童和青少年感染了慢性丙型肝炎病毒(CHC)。虽然单独使用干扰素或与拉巴韦林和聚乙二醇化干扰素联合使用RV已被FDA批准用于18岁以上的受试者，但尚未有治疗方法被批准用于儿科受试者。已发表的干扰素单一疗法治疗儿童慢性丙型肝炎的报告表明，应答率高于成人。PEG+RV是成人慢性丙型肝炎最有效的治疗方法。鉴于轮状病毒是一种致畸因素，而且18岁的受试者可能对单独使用聚乙二醇有很高的应答率，这项建议的目的是进行一项随机对照试验，以比较聚乙二醇+安慰剂与聚乙二醇+轮状病毒(1：1随机)的安全性和有效性。112名2-16岁的丙型肝炎病毒RNA+干扰素-NA儿童将参加这项多中心II期临床试验。11个儿科中心将与罗氏实验室公司合作，罗氏实验室公司将提供聚乙二醇化干扰素(PEGASYS(Tm))，剂量为180微克/1.73m2/周×48周，并有24周的无治疗随访。房车15 mg/kd/d，p.o.b.i.d。(非&gt；每天1200毫克)200毫克片剂。所有被随机分配到PEG+RV组的儿童都将接受药代动力学/药效学测试。在第12周时，被随机分到聚乙二醇组和安慰剂组的儿童，如果病毒消失(Amplicor(Tm)聚合酶链式反应分析中的丙型肝炎病毒核糖核酸低于100拷贝/毫升)，将被转到聚乙二醇组和RV组(一种富有同情心的单一疗法/组合“疗法”)。被随机分配到聚乙二醇组和RV组的儿童在12周时没有出现病毒消失，将继续接受聚乙二醇组和RV组的治疗。(一个富有同情心的“组合/组合”治疗臂)，因为缺乏合适的治疗替代方案。初步分析将在意向治疗的基础上进行；主要终点将是在结束治疗24周后持续的病毒应答。其他终点包括生化和临床安全评估。因此，这项试验将提供急需的数据，以指导CHC的安全有效治疗，CHC是儿童肝病的主要原因

DESCRIPTION (provided by applicant): There are approximately 150,000 infants, children, and adolescents in the United States with chronic hepatitis C virus (CHC) infection. While alpha-interferon (IFN) alone or in combination with rabavirin and pegylated interferon (PEG) in combination with RV have been approved by the FDA for use in subjects over 18 years of age, no therapies have been approved for use in pediatric subjects. 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 < 18 years of age may have high response rates to PEG alone, the purpose of this proposal is to perform a randomized controlled trial to comparing the safety and efficacy of PEG + placebo vs. PEG + RV (1:1 randomization). 112 HCV RNA+ IFN-na¿ve children 2-16 years of age will be enrolled in this multi-center Phase II clinical trial. 11 pediatric centers will work in collaboration with Roche Laboratories Inc., which will supply the pegylated interferon (Pegasys(tm)), to be given at a dose of 180 mcg/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.b.i.d. (not > 1200 mg/day) in 200 mg tablets. All children randomized to the PEG+RV arm will undergo pharmacokinetic/pharmacodynamic testing. Children randomized to PEG+ placebo who fail to exhibit viral disappearance (HCV RNA less than 100 copies/ml by Amplicor(tm) polymerase chain reaction assay) at week 12 will be crossed over to PEG and RV (a compassionate monotherapy/combination" therapy arm). Children who were randomized to PEG and RV who fail to exhibit viral disappearance at week 12 will be maintained on PEG + RV. (a compassionate "combination/combination" therapy arm) given the lack of suitable therapeutic alternatives. The primary analysis will be on an intent to treat basis; the primary endpoint will be sustained viral response 24 weeks off therapy. Other endpoints include biochemical and clinical safety assessments. This trial would thus provide critically needed data to guide safe and effective treatment of CHC, a major cause of liver disease in children