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

聚乙二醇化干扰素/利巴韦林治疗儿童丙肝病毒 (PEDS-C)

• 批准号: 7604636
• 负责人: KATHLEEN SCHWARZ
• 金额: $ 0.5万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7604636
• 关键词: Adolescent; Adult; Age; Age-Years; Alfatronol; Biochemical; Biological Assay; Body Composition; Child; Childhood; Chronic; Clinical; Collaborations; Combined Modality Therapy; Computer Retrieval of Information on Scientific Projects Database; Data; Dose; End Point; Enrollment; Exhibits; Funding; Genetic Crossing Over; Grant; Growth; Hepatitis C; Hepatitis C virus; Infant; Institution; Interferon-alpha; Interferons; Laboratories; Liver diseases; Longterm Follow-up; National Institute of Diabetes and Digestive and Kidney Diseases; Pharmaceutical Preparations; Phase III Clinical Trials; Placebos; Polymerase Chain Reaction; Publishing; Purpose; RNA; Randomized; Randomized Controlled Trials; Rate; Reporting; Research; Research Personnel; Resources; Ribavirin; Safety; Source; Teratogens; United States; United States Food and Drug Administration; United States National Institutes of Health; Upper arm; Viral; Week; Work; base; day; follow-up; health related quality of life; response; treatment trial

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 (PegasysT), 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 AmplicorT 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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以出现在其他 CRISP 条目中 列出的机构是。 对于中心来说，它不一定是研究者的机构。 美国约有 150,000 名患有慢性丙型肝炎病毒 (CHC) 感染的婴儿、儿童和青少年已批准单独使用α-干扰素 (IFN) 或与利巴韦林和聚乙二醇干扰素 (PEG) 联合使用 RV。 FDA 最近批准用于 18 岁以上受试者的 Rebtrol（利巴韦恩和 Intron A）用于治疗至少 3 岁儿童的丙型肝炎。已发表的 IFN 单药治疗 CHC 儿童的反应率高于成人，因为 RV 是一种致畸剂，且受试者< 18岁可能对单独的PEG有较高的反应率，本提案的目的是进行一项随机对照试验来比较PEG+安慰剂与PEG+RV的安全性和有效性（1:1随机化）112。 HCV RNA+ IFN-na¿ 5 名 5-18 岁儿童将参加这项多中心 III 期临床试验，11 个儿科中心将与 NIDDK 和罗氏实验室公司合作，提供聚乙二醇干扰素 (PegasysT)，该试验将于剂量为 180 微克/1.73 平方米每周 x 48 周，并进行 24 周的无治疗随访。 15 mg/kd/day p.i.d（每日两次）× 48 周，随访 24 周，未表现出病毒消失（HCV RNA <100copies/ml）第 24 周的聚合酶链反应检测）将交叉到 PEG+RV（富有同情心的联合治疗组）。这些儿童将在 24 周后接受评估。如果联合治疗 24 周后未表现出病毒消失，则将停止 Peg-2a 和 RV，并对其进行密切随访 24 周；如果联合治疗 24 周后表现出病毒消失，则将停止使用 Peg-2a 和 RV。对于随机接受 PEG+RV 治疗的儿童，如果在第 24 周未能表现出病毒消失，则将停止用药。主要分析将针对治疗意图。基础；主要终点是治疗结束后 24 周（距基线 72 周）的持续病毒反应，其他终点包括生化和临床安全性评估以及身体成分和生长以及与健康相关的生活质量。第 1 年至第 3 年进行治疗，第 4 年和第 5 年进行长期随访。因此，该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。