短文：在SOUND-C3 2b期研究纳入的IL28B非CC型丙型肝炎病毒1a型感染患者中使用法达普韦、地洛布韦和利巴韦林的情况

Short article: Faldaprevir, deleobuvir and ribavirin in IL28B non-CC patients with HCV genotype-1a infection included in the SOUND-C3 phase 2b study.

作者信息

Zeuzem Stefan, Mantry Parvez, Soriano Vicente, Buynak Robert J, Dufour Jean-François, Pockros Paul J, Wright David, Angus Peter, Buti Maria, Stern Jerry O, Kadus Werner, Vinisko Richard, Böcher Wulf, Mensa Federico J

机构信息

aJ.W. Goethe University Hospital, Frankfurt am Main bBoehringer Ingelheim Pharma GmbH & Co. KG, Biberach cBoehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany dThe Liver Institute at Methodist Dallas Medical Center, Dallas eCentral Texas Clinical Research, Austin, Texas fNorthwest Indiana Center for Clinical Research, Valparaiso, Indiana gScripps Clinic, La Jolla, California hBoehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut, USA iHospital Carlos III, Madrid jHospital Universitario Valle de Hebrón and CIBERehd del Instituto Carlos III, Barcelona, Spain kUniversity Clinic for Visceral Surgery and Medicine, University of Bern, Bern, Switzerland lAustin Health, Heidelberg, Victoria, Australia.

出版信息

Eur J Gastroenterol Hepatol. 2016 Aug;28(8):923-6. doi: 10.1097/MEG.0000000000000649.

DOI:10.1097/MEG.0000000000000649

PMID:27140229

Abstract

BACKGROUND

SOUND-C3 was a multicentre, open-label, phase 2b study exploring the safety and efficacy of the interferon-free combination of faldaprevir (an NS3/A4 protease inhibitor), deleobuvir (BI 207127, a non-nucleoside polymerase inhibitor) and ribavirin in treatment-naive patients with chronic hepatitis C virus (HCV) genotype-1 infection. Results in patients with HCV genotype-1b and in IL28B CC genotype patients with HCV genotype-1a have been described previously. This report describes the results in IL28B non-CC genotype patients with HCV genotype-1a.

METHODS

Patients were randomized to receive faldaprevir 120 mg once daily with deleobuvir at either 800 mg twice daily (b.i.d.; N=26) or 600 mg three times daily (t.i.d.; N=25), and weight-based ribavirin for 24 weeks. The primary endpoint was sustained virological response 12 weeks after treatment (SVR12).

RESULTS

In each group, five patients completed 24 weeks of treatment. SVR12 rates were 19% (5/26) and 8% (2/25) in the b.i.d. and t.i.d. groups, respectively. On-treatment breakthrough [50% (13/26) and 68% (17/25) in the b.i.d. and t.i.d. groups, respectively] was the most frequent reason for not achieving SVR12. Adverse events led to premature treatment discontinuation in six (23%) patients in the b.i.d. group and in two patients (8%) in the t.i.d. group. The majority of adverse events were mild or moderate; the most frequently reported were nausea (67%), fatigue (35%) and diarrhoea (35%).

CONCLUSION

In this small study, the interferon-free regimen of faldaprevir, deleobuvir and ribavirin resulted in high rates of virological breakthrough and low rates of SVR12 in IL28B non-CC genotype patients infected with genotype-1a HCV (http://www.clinicaltrials.gov NCT01132313).

摘要

背景

SOUND-C3是一项多中心、开放标签的2b期研究，旨在探索在初治的慢性丙型肝炎病毒（HCV）1型感染患者中，使用法达普韦（一种NS3/A4蛋白酶抑制剂）、地瑞夫韦（BI 207127，一种非核苷聚合酶抑制剂）和利巴韦林的无干扰素联合方案的安全性和疗效。此前已报道了HCV 1b型患者以及IL28B CC基因型的HCV 1a型患者的研究结果。本报告描述了IL28B非CC基因型的HCV 1a型患者的研究结果。

方法

患者被随机分组，分别接受每日一次120毫克法达普韦，同时接受每日两次800毫克（bid；N = 26）或每日三次600毫克（tid；N = 25）的地瑞夫韦，以及基于体重的利巴韦林治疗24周。主要终点是治疗12周后的持续病毒学应答（SVR12）。

结果

每组中均有5名患者完成了24周的治疗。bid组和tid组的SVR12率分别为19%（5/26）和8%（2/25）。治疗期间突破（bid组和tid组分别为50%（13/26）和68%（17/25））是未达到SVR12的最常见原因。不良事件导致bid组6名（23%）患者和tid组2名（8%）患者提前终止治疗。大多数不良事件为轻度或中度；最常报告的是恶心（67%）、疲劳（35%）和腹泻（35%）。