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Guidance for design and endpoints of clinical trials in chronic hepatitis B - Report from the 2019 EASL-AASLD HBV Treatment Endpoints Conference
Journal of Hepatology ( IF 25.7 ) Pub Date : 2020-03-01 , DOI: 10.1016/j.jhep.2019.11.003
Markus Cornberg 1 , Anna Suk-Fong Lok 2 , Norah A Terrault 3 , Fabien Zoulim 4 ,
Affiliation  

Representatives from academia, industry, regulatory agencies, and patient groups convened in March 2019 with the primary goal of developing agreement on chronic hepatitis B virus (HBV) treatment endpoints to guide clinical trials aiming to 'cure' HBV. Agreement among the conference participants was reached on some key points. 'Functional' but not sterilizing cure is achievable and should be defined as sustained HBsAg loss in addition to undetectable HBV DNA 6 months post-treatment. The primary endpoint of phase 3 trials should be functional cure; HBsAg loss in ≥30% of patients was suggested as an acceptable rate of response in these trials. Sustained virologic suppression (undetectable serum HBV DNA) without HBsAg loss, 6 months after discontinuation of treatment would be an intermediate goal. Demonstrated validity in predicting sustained HBsAg loss was considered the most appropriate criterion for the approval of new HBV assays to determine efficacy endpoints. Clinical trials aimed at HBV functional cure should initially focus on patients with HBeAg-positive and HBeAg-negative chronic hepatitis, treatment-naïve or virally suppressed on nucleos(t)ide analogues. A hepatitis flare associated with increase in bilirubin or INR should prompt temporary or permanent cessation of investigational treatment. New treatments must be as safe as existing nucleos(t)ide analogues. The primary endpoint for phase 3 trials for hepatitis D virus (HDV) co-infection should be undetectable serum HDV RNA 6 months after stopping treatment. On treatment HDV RNA suppression associated with normalization of ALT is considered an intermediate goal. Conclusion: For HBV 'functional cure', sustained HBsAg loss with undetectable HBV DNA after completion of treatment is the primary goal and sustained undetectable HBV DNA without HBsAg loss after stopping treatment an intermediate goal.

中文翻译:

慢性乙型肝炎临床试验设计和终点指南 - 2019 EASL-AASLD HBV 治疗终点会议报告

来自学术界、工业界、监管机构和患者团体的代表于 2019 年 3 月召开会议,主要目标是就慢性乙型肝炎病毒 (HBV) 治疗终点达成一致,以指导旨在“治愈”HBV 的临床试验。与会代表就一些关键点达成了一致。可以实现“功能性”而非绝育治愈,应定义为治疗后 6 个月,除检测不到 HBV DNA 外,HBsAg 持续消失。3 期试验的主要终点应该是功能性治愈;在这些试验中,≥30% 的患者 HBsAg 消失被认为是可接受的缓解率。在停止治疗 6 个月后,持续病毒学抑制(血清 HBV DNA 检测不到)且 HBsAg 消失将是一个中间目标。证明在预测持续 HBsAg 消失方面的有效性被认为是批准新的 HBV 检测以确定疗效终点的最合适的标准。旨在 HBV 功能性治愈的临床试验最初应关注 HBeAg 阳性和 HBeAg 阴性慢性肝炎、未接受过治疗或使用核苷(酸)类似物进行病毒抑制的患者。与胆红素或 INR 增加相关的肝炎发作应促使暂时或永久停止研究治疗。新的治疗方法必须与现有的核苷(酸)类似物一样安全。丁型肝炎病毒 (HDV) 合并感染的 3 期试验的主要终点应该是停止治疗 6 个月后检测不到血清 HDV RNA。在治疗中,与 ALT 正常化相关的 HDV RNA 抑制被认为是一个中间目标。结论:
更新日期:2020-03-01
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