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非酒精性脂肪性肝炎治疗药物临床试验指南解读
DOI: 10.3969/j.issn.1001-5256.2021.06.002
利益冲突声明：所有作者均声明不存在利益冲突。
作者贡献声明：饶慧瑛、魏来负责撰写文章；魏来负责审阅修改，最终定稿。
Interpretation of clinical trial guidelines for nonalcoholic steatohepatitis
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摘要: 2019年12月，我国国家药品监督管理局发布了《非酒精性脂肪性肝炎治疗药物临床试验指导原则(试行)》，该指导原则主要针对非酒精性脂肪性肝炎伴有显著肝纤维化及代偿期肝硬化(F2~4)的成人患者，介绍了临床试验的终点、总体设计、不同具体研发阶段以及安全性等方面的考虑。同时结合美国以及欧盟的相关指导原则，尝试探讨临床试验与实践的关系。Abstract: In December 2019, National Medical Products Administration of China issued Guidelines for Clinical Trials of Drugs for Treatment of Nonalcoholic Steatohepatitis (Interim), which mainly targeted at adult patients with nonalcoholic steatohepatitis with significant liver fibrosis and compensated liver cirrhosis (F2-F4). This article introduces related considerations from the aspects of clinical trial endpoint, overall clinical trial design, specific research and development stages, and safety. With reference to related guidelines of the United States and the European Union, this article attempts to explore the association between clinical trial and clinical practice.
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Key words:
- Non-alcoholic Fatty Liver Disease /
- Drug Discovery /
- Clinical Trial /
- Practice Guideline
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表 1 NASH新药临床试验人群的比较
部分要点 FDA NMPA 入组前组织学诊断 患者应在尽可能接近入组时(入组前6个月内)有NASH肝纤维化的组织学诊断 肝组织活检至入组的时间窗一般不超过6个月，在该时间窗内需注意患者是否接受可能影响肝组织学变化的干预 入组标准 NASH活动评分(NAS)＞或=4分的关键入排标准，其中炎症和气球样变各至少1分，同时NASH CRN纤维化分级应＞1级且低于4级 尽管肝组织学检查存在有创性、取样和评价误差等局限性，但仍然是目前NASH诊断的“金标准”。
入组标准：NAS评分≥4分，其中炎症和气球样变各至少1分；同时，CRN纤维化≥F2合并症 2型糖尿病(T2DM)患者：入组前应至少服用3个月稳定剂量的抗糖尿病药物且有血糖适度控制的记录。如入选糖尿病患者，应按是否合并T2DM进行分层随机 NASH患者常同时合并糖尿病、高血压、高脂血症、痛风等代谢相关疾病，而且，此类患者的心脑血管事件风险增加。在NASH药物早期临床试验中应至少开展与常用抗糖尿病药、抗高血压药、调脂药等的药物相互作用研究 体质量 基础治疗或体质量应该至少稳定3个月，才能入组。体质量稳定的定义：体质量变化不超过5% 应该提供明确证据证明患者在随机入组前6~8周体质量和代谢参数保持稳定。稳定的体质量定义为变化不超过5% 
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