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Clinical trials in hepatitis D virus: Measuring success
Hepatology ( IF 13.5 ) Pub Date : 2022-08-15 , DOI: 10.1002/hep.32732
Ben L Da 1
Affiliation  

Chronic hepatitis D infection results in the most severe form of chronic viral hepatitis but currently lacks effective treatment options. Therapy with pegylated interferon alpha is recommended for finite treatment duration by major liver societies. Still, it is plagued by low rates of sustained virologic response (SVR) and frequent relapses even if SVR is achieved. Recently, a wave of investigational therapies has come under evaluation, including bulevirtide, lonafarnib, pegylated interferon lambda, and REP-2139 creating excitement with this viral infection. However, there has been significant variability in the endpoints used to evaluate these therapeutics. One of the recently introduced endpoints is characterized by a decline in HDV RNA by 2 logs, with or without achieving an undetectable serum hepatitis D virus (HDV) RNA, as a marker of virologic response. Furthermore, this measure has been combined with alanine aminotransferase normalization, also known as a biochemical response, to formulate the primary endpoint of several late-stage studies. Per recent guidance by the US Food and Drug Administration, these should be surrogate endpoints that will ultimately portend long-term clinical benefits. These clinical benefits may include reducing the risk of progression to cirrhosis, hepatic decompensation, hepatocellular carcinoma, liver transplantation, and mortality. However, the optimal way to measure success in HDV clinical trials remains unknown and will continue to evolve.

中文翻译:

丁型肝炎病毒临床试验:衡量成功

慢性丁型肝炎感染导致最严重的慢性病毒性肝炎,但目前缺乏有效的治疗选择。主要肝病学会推荐使用聚乙二醇干扰素 α 进行有限疗程治疗。尽管如此,它仍受到持续病毒学应答 (SVR) 率低和即使达到 SVR 后仍频繁复发的困扰。最近,一波研究性疗法正在接受评估,包括布维肽、lonafarnib、聚乙二醇化干扰素 λ 和 REP-2139,它们对这种病毒感染产生了兴奋作用。然而,用于评估这些疗法的终点存在显着差异。最近引入的终点之一的特征是 HDV RNA 下降 2 个对数,有或没有达到检测不到血清丁型肝炎病毒 (HDV) RNA,作为病毒学反应的标志。此外,该措施已与谷丙转氨酶标准化(也称为生化反应)相结合,以制定多项后期研究的主要终点。根据美国食品和药物管理局最近的指导,这些应该是最终预示长期临床益处的替代终点。这些临床益处可能包括降低进展为肝硬化、肝功能失代偿、肝细胞癌、肝移植和死亡率的风险。然而,衡量 HDV 临床试验成功的最佳方法仍然未知,并将继续发展。制定几项后期研究的主要终点。根据美国食品和药物管理局最近的指导,这些应该是最终预示长期临床益处的替代终点。这些临床益处可能包括降低进展为肝硬化、肝功能失代偿、肝细胞癌、肝移植和死亡率的风险。然而,衡量 HDV 临床试验成功的最佳方法仍然未知,并将继续发展。制定几项后期研究的主要终点。根据美国食品和药物管理局最近的指导,这些应该是最终预示长期临床益处的替代终点。这些临床益处可能包括降低进展为肝硬化、肝功能失代偿、肝细胞癌、肝移植和死亡率的风险。然而,衡量 HDV 临床试验成功的最佳方法仍然未知,并将继续发展。
更新日期:2022-08-15
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