Designing Clinical Trials in Pediatric Nonalcoholic Steatohepatitis: Tips for Patient Selection and Appropriate Endpoints
Designing Clinical Trials in Pediatric Nonalcoholic Steatohepatitis: Tips for Patient Selection and Appropriate Endpoints
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DOI：
10.1002/hep4.1449
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发表时间：
2019-11-08
影响因子：
5.1
通讯作者：
Feldstein, Ariel E.
中科院分区：
文献类型：
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作者：
Alkhouri, Naim;Kohli, Rohit;Feldstein, Ariel E.
非酒精性脂肪性肝病(NAFLD)在儿童中很常见，在儿童或成年早期可能发展为非酒精性脂肪性肝炎(NASH)、晚期纤维化，甚至是肝硬变，这表明在这个年龄段需要药物治疗。多项试验正在评估成人NASH伴肝纤维化的不同治疗目标，美国食品和药物管理局最近为制药业开发治疗非肝硬化性NASH伴肝纤维化的药物提供了明确的指导。儿童NAFLD有几个独特的方面，在组织学、我们对自然病史的理解以及非侵入性测试的实用性方面，它与成人疾病不同。这些差异有可能影响在儿科人群中测试不同药物的临床试验设计。本文的目的是提供对儿童NAFLD的常见误解以及与成人NAFLD的主要区别。我们根据从以前的临床试验中吸取的经验教训，就早期概念验证试验和晚期2期试验的设计提出了我们的建议。我们认为，针对患有NAFLD的儿童的临床药物开发应该与正在进行的成人试验同步进行。
Nonalcoholic fatty liver disease (NAFLD) is common in children and may progress to nonalcoholic steatohepatitis (NASH), advanced fibrosis, and even cirrhosis in childhood or early adulthood, indicating the need for pharmacologic treatment in this age group. Multiple trials are evaluating different therapeutic targets for NASH with fibrosis in adults, and the U.S. Food and Drug Administration has recently provided clear guidance to the pharmaceutical industry on developing drugs for the treatment of noncirrhotic NASH with liver fibrosis. Pediatric NAFLD has several unique aspects that distinguish it from the adult disease in terms of histology, our understanding of the natural history, and the utility of noninvasive tests. These differences have the potential to impact the design of clinical trials to test different drugs in the pediatric population. The aim of this article is to provide a review of common misconceptions regarding pediatric NAFLD and key differences from adult NAFLD. We have provided our recommendations on the design of early proof-of-concept and late phase 2 trials based on lessons learned from previous clinical trials. We believe that clinical drug development for children with NAFLD should happen in parallel with ongoing adult trials.