美国食品药品监督管理局《慢性乙型肝炎病毒感染: 治疗药物的开发行业指南》的更新要点解读(临床部分)

沙迪; 吴艺迪; 牛俊奇; 王美霞

doi:10.3969/j.issn.1001-5256.2022.08.008

美国食品药品监督管理局《慢性乙型肝炎病毒感染: 治疗药物的开发行业指南》的更新要点解读(临床部分)

DOI: 10.3969/j.issn.1001-5256.2022.08.008

沙迪¹,
吴艺迪¹,
牛俊奇²,
王美霞^3, , ,

1.
齐鲁制药有限公司临床研究中心, 济南 250100
2.
吉林大学第一医院感染病与病原生物学中心肝胆胰内科, 长春 130021
3.
北京积水潭医院临床试验机构管理办公室暨Ⅰ期临床试验研究室, 北京 100031

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作者贡献声明：牛俊奇负责文章设计与指导；沙迪、吴艺迪负责收集数据、起草文章初稿；王美霞参与了文章全文校对和文章关键内容修改。

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通信作者:
王美霞, wangmeixiad@163.com

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出版历程
- 收稿日期: 2022-05-17
- 录用日期: 2022-07-08
- 出版日期: 2022-08-20

Updated key points of chronic hepatitis B virus infection: developing drugs for treatment issued by the U.S. food and drug administration(clinical part)

Di SHA¹,
Yidi WU¹,
Junqi NIU²,
Meixia WANG^{3
, ,
,}

1.
Clinical Research Center, Qilu Pharmaceutical Co., Ltd., Jinan 250100, China
2.
Department of Hepatology, Center for Infectious Diseases and Pathogen Biology, The First Hospital of Jilin University, Changchun 130021, China
3.
Clinical Trial Institution Management Office & Phase Ⅰ Clinical Trial Study Office, Beijing Jishuitan Hospital, Beijing 100031, China

More Information

Corresponding author: WANG Meixia, wangmeixiad@163.com(ORCID: 0000-0003-1877-6301)

摘要

摘要: 2018年11月美国食品药品监督管理局(FDA)发布了关于《慢性乙型肝炎病毒感染药物研发的指导意见(征求意见稿)》(以下简称：征求意见稿), 2022年4月, FDA发布了《慢性乙型肝炎病毒感染: 治疗药物的开发行业指南》, 本指南在征求意见稿的基础上, 对一些细节进行了更新。本指南进一步强调了HBsAg清除在临床试验中的重要性, 将持续抑制治疗分为两类, 即对照核苷(酸)类似物的非劣效性(NI)或优效试验和对照核苷(酸)类似物的Add-on优效试验, 后者已经不推荐将HBV DNA作为试验的主要治疗终点, 对以HBV DNA为靶点的创新药研发提出了巨大的挑战。新的有限持续时间治疗, 应该以HBsAg清除、停止治疗期间降低病毒学复发和肝脏疾病进展风险作为主要目的和诉求。不推荐HBsAg较基线值的下降作为Ⅲ期临床试验的主要治疗终点, 因为下降值与临床应答的相关性尚不明确。此外, 本指南对停止治疗、治疗巩固期的持续时间, 以及核苷(酸)类似物停药标准进行了规定。
- 乙型肝炎, 慢性 /
- 抗病毒药 /
- 诊疗准则 /
- 美国食品和药品监督管理局
Abstract: In November 2018, the U.S. food and drug administration (FDA) issued guidance for the development of drugs for chronic hepatitis B virus infection (draft for comments) (hereinafter referred to as draft for comments), and in April 2022, the FDA issued Chronic Hepatitis B Virus Infection: Developing Drugs for Treatment, which has been updated with some details based on the Draft for Comments. This guidance further emphasizes the importance of HBsAg clearance in clinical trials, and classifies chronic suppressive therapy into two categories, namely noninferiority (NI) (or superiority) test with nucleos(t)ide analogues as control and add-on superiority trial with nucleos(t)ide analogues as control, and as for the latter, HBV DNA is no longer recommended as a primary endpoint of the trial, which poses a huge challenge to the development of innovative drugs targeting HBV DNA. The new finite duration therapy should aim to eliminate HBsAg and reduce virologic relapse and the risk of liver disease progression during treatment cessation. Reduction in HBsAg from baseline is not recommended as a primary endpoint for phase Ⅲ clinical trials, since the correlation between such reduction and clinical response remains unclear. In addition, this guidance also specifies the duration of treatment cessation and treatment consolidation period and the criteria for withdrawal of nucleos(t)ide analogues.
- Hepatitis B, Chronic /
- Antiviral Agents /
- Practice Guideline /
- United States Food and Drug Administration

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参考文献(19)

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