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.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 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)。α-干扰素(干扰素)单独或与利巴韦林和聚乙二醇化干扰素(聚乙二醇化干扰素)与RV联合使用已被FDA批准用于18岁以上的受试者。Rebtrol(利巴韦林和Intron A)最近被批准用于治疗至少3岁及以上儿童的丙型肝炎。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5-18岁的丙型肝炎病毒RNA+干扰素-NA儿童将参加这项多中心第三阶段临床试验。11个儿科中心将与NIDDK和罗氏实验室公司合作，后者将提供聚乙二醇化干扰素(PegasysT)，剂量为180mcg/1.73m2/周×48周，无治疗随访24周。RV按15 mg/kd/天口服。分裂的b.i.d。(非&gt；1200 mg/天)×48周，免费随访24周。在第24周时，被随机分到PEG+安慰剂组的儿童如果没有出现病毒消失(AmplicorT聚合酶链式反应检测到的病毒拷贝数为100拷贝/毫升)，将被转到PEG+RV(一种富有同情心的联合治疗组)。这些儿童将在24周的联合治疗后接受评估。如果在联合治疗24周后没有出现病毒消失，Peg-2a和RV将被停止，并将被密切跟踪24周。如果在24周的联合治疗后，他们出现病毒消失，他们将再接受24周的治疗，并在24周内停止支付医疗费。在被随机分到聚乙二醇组和RV组的儿童中，如果他们在24周时没有表现出病毒消失，这些药物将被停止使用。初步分析将在意向治疗的基础上进行；主要终点将是在治疗结束后24周(距基线72周)持续的病毒应答。其他终点包括生化和临床安全评估，以及身体成分和生长发育以及与健康有关的生活质量。治疗试验将在第一年到第三年进行，长期随访将在第四年和第五年停止治疗。因此，这项试验将提供急需的数据，以指导CHC的安全和有效治疗，CHC是儿童肝病的主要原因。