非酒精性脂肪性肝炎新药临床试验方案的系统评价  

Clinical trial protocols of new drugs for nonalcoholic steatohepatitis:A systematic review

作　　者：黄樱硕[1] 魏巍[2] 佟小非[3,4,5] 孙亚朦 张健雄[1] 董瑞华 贾继东 尤红 HUANG Yingshuo;WEI Wei;TONG Xiaofei;SUN Yameng;ZHANG Jianxiong;DONG Ruihua;JIA Jidong;YOU Hong(Department of Research Ward,Beijing Friendship Hospital,Capital Medical University,Beijing 100050,China;Department of Clinical Epidemiology and EBM,Beijing Friendship Hospital,Capital Medical University,Beijing 100050,China;Liver Research Center,Beijing Friendship Hospital,Capital Medical University,Beijing 100050,China;Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis,Beijing Friendship Hospital,Capital Medical University,Beijing 100050,China;National Clinical Research Center for Digestive Diseases,Beijing Friendship Hospital,Capital Medical University,Beijing 100050,China)

机构地区：[1]首都医科大学附属北京友谊医院研究型病房 [2]首都医科大学附属北京友谊医院临床流行病学与循证医学研究室,北京100050 [3]首都医科大学附属北京友谊医院肝病中心,北京100050 [4]首都医科大学附属北京友谊医院肝硬化转化医学北京市重点实验室,北京100050 [5]首都医科大学附属北京友谊医院国家消化系统疾病临床医学研究中心,北京100050

出　　处：《临床肝胆病杂志》2022年第4期798-804,共7页Journal of Clinical Hepatology

基　　金：国家自然科学基金重点项目(82130018);北京市医院管理局消化内科学科协同发展中心消化专项重点项目(XXZ03);北京市研究型病房示范建设单位项目(BCRW202010)。

摘　　要：目的描述国内外非酒精性脂肪性肝炎(NASH)新药临床试验的注册情况及临床试验特点,为NASH新药临床试验的设计和开展提供参考依据。方法检索美国临床实验数据库、中国临床试验注册中心、国家药品监督管理局药品审评中心,检索日期为建库至2021年8月6日,以“非酒精性脂肪性肝炎”和“NASH”作为关键词,纳入以NASH作为适应证的新药注册试验或干预性研究,并除外肝硬化。由两位研究者独立检索并筛选文献,提取相关信息。结果共纳入196项NASH新药注册试验或干预试验(174项国外注册试验,22项国内注册试验),注册量呈增长趋势,其中Ⅰ期、Ⅰ~Ⅱ期(包括Ⅰb/Ⅱa)、Ⅱ期、Ⅱ~Ⅲ期、Ⅲ期临床试验分别为45项(23.0%)、8项(4.1%)、112项(57.1%)、4项(2.0%)、19项(9.7%)。药物类型以法尼酯X受体类、成纤维细胞生长因子类、过氧化物酶体增殖物激活受体激动剂、胰高血糖素样肽-1类为主,分别为16项(8.16%)、14项(7.14%)、11项(5.61%)、13项(6.63%)。欧美地区申办方发起的NASH创新药试验最多,中国(含台湾地区)近年来的自主创新药临床试验数量逐渐增加,单中心与多中心数量分布近似。其中以NASH患者为受试对象的试验中以病理、影像学、临床诊断作为主要入选标准的试验数量分别为125项、66项和42项。Ⅰ期临床试验主要评价指标为安全性、耐受性和药代动力学指标,Ⅱ、Ⅲ期临床试验主要评价指标为安全性和有效性。中国(含台湾地区)本土NASH创新药物注册试验数量较少但逐渐增长,中药相对化学药物的新药临床试验较少。结论国际NASH创新药临床试验注册量增长较为显著,但多处于早期阶段,入选标准和评价指标差异较大,缺少较统一的衡量指标,新型试验设计较少。国内NASH新药临床试验相对欧美国家数量较少,呈增长趋势。Objective To describe the characteristics and registration status of clinical trials of new drugs for nonalcoholic steatohepatitis(NASH),and to provide a reference for the design and implementation of clinical trials of new drugs for NASH.Methods The U.S.Clinical Trials Database,China Clinical Trial Registry,and Center for Drug Evaluation,National Medical Products Administration,were searched for clinical trials of new drug registration and interventional studies with NASH as the indication published up to August 6,2021,using NASH in English and Chinese characters as the keywords,and liver cirrhosis was excluded.Two researchers independently searched and screened the articles to extract relevant information.Results A total of 196 clinical trials of new drug registration or interventional studies for NASH were included,among which there were 174 trials registered abroad and 22 trials registered in China,and the number of registrations tended to increase year by year.The numbers of phaseⅠ,phaseⅠ/Ⅱ(including Ib/Ⅱa),phaseⅡ,phaseⅡ/Ⅲ,and phaseⅢclinical trials were 45(23.0%),8(4.1%),112(57.1%),4(2.0%),and 19(9.7%),respectively.The main drug types included farnesoid X receptors,fibroblast growth factors,peroxisome proliferator-activated receptor agonists,and glucagon-like peptide-1,with numbers of 16(8.16%),14(7.14%),11(5.61%),and 13(6.63%),respectively.The clinical trials of innovative drugs for NASH initiated by the sponsors in European and American regions accounted for the highest proportion,and there was a gradual increase in the number of clinical trials of innovative drugs in China in recent years,with a similar distribution of single-center and multicenter clinical trials.As for the trials with NASH patients as subjects,the numbers of trials with pathology,imaging,and clinical diagnosis as the main inclusion criteria were 125,66,and 42,respectively.PhaseⅠclinical trials used safety,tolerability,and pharmacokinetic parameters as the main assessment indices,while phaseⅡand phaseⅢclinical trial

关 键 词：非酒精性脂肪性肝炎 临床试验 评价研究 

分 类 号：R969[医药卫生—药理学]