Pegylated Interferon +/- Ribavirin for Children with HCV

描述（由申请人提供）： 美国约有15万名婴儿、儿童和青少年患有慢性丙型肝炎病毒（CHC）感染。虽然α-干扰素（IFN）单独或与雷巴韦林和聚乙二醇化干扰素（PEG）联合RV已被FDA批准用于18岁以上的受试者，但尚未批准任何疗法用于儿科受试者。 已发表的报告表明，IFN单药治疗儿童CHC的反应率高于成人。PEG + RV是成人CHC最有效的治疗方法。 鉴于RV是一种致畸剂，并且< 18岁的受试者可能对PEG单独治疗有较高的应答率，本提案的目的是进行一项随机对照试验，以比较PEG +安慰剂与PEG + RV（1：1随机化）的安全性和疗效。112名2-16岁的HCV RNA+ IFN初治儿童将入组本多中心II期临床试验。 11个儿科中心将与罗氏实验室公司合作，其将提供聚乙二醇化干扰素（Pegasys（TM）），以180 mcg/1.73m2平方米每周× 48周的剂量给予，并进行24周的无治疗随访。RV将以15 mg/kd/天p.o.b.i.d.给药。(not> 1200 mg/天）。所有随机分配至PEG+RV组的儿童将接受药代动力学/药效学检测。随机分配至PEG+安慰剂组且在第12周时未显示病毒消失（通过Amplicor（tm）聚合酶链反应测定，HCV RNA低于100拷贝/ml）的儿童将交叉至PEG和RV组（同情性单药治疗/联合”治疗组）。随机分配至PEG和RV组的儿童，如果在第12周时未显示病毒消失，则将继续接受PEG + RV治疗。（同情的“组合/组合”治疗组），因为缺乏合适的治疗替代方案。主要分析将基于意向治疗;主要终点将是停止治疗24周后的持续病毒应答。其他终点包括生化和临床安全性评估。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