Journal of Clinical and Translational Hepatology

Journal of Clinical and Translational Hepatology

Saturday, 11 / 16 / 2019

Articles

Efficacy and Safety of 12-week Interferon-based Danoprevir Regimen in Patients with Genotype 1 Chronic Hepatitis C

ORIGINAL ARTICLE

Efficacy and Safety of 12-week Interferon-based Danoprevir Regimen in Patients with Genotype 1 Chronic Hepatitis C

Lai Wei*,1, Jia Shang2, Yuanji Ma3, Xiaoyuan Xu4, Yan Huang5, Yujuan Guan6, Zhongping Duan7, Wenhong Zhang8, Zhiliang Gao9, Mingxiang Zhang10, Jun Li11, Jidong Jia12, Yongfeng Yang13, Xiaofeng Wen14, Maorong Wang15, Zhansheng Jia16, Bo Ning17, Yongping Chen18, Yue Qi19, Jie Du20, Jianning Jiang21, Lixin Tong22, Yao Xie23 and Jinzi J. Wu24

1Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, China
2People’s Hospital of Henan Province, Henan, China
3West China Hospital, Sichuan University, Chengdu, Sichuan, China
4Peking University People’s Hospital, Beijing, China
5Xiangya Hospital of Central South University, Changsha, Hunan, China
6Guangzhou Eighth People’s Hospital, Guangzhou, Guangdong, China
7Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China
8Huashan Hospital, Fudan University, Shanghai, China
9The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
10The Sixth People’s Hospital of Shenyang, Shenyang, Liaoning, China
11People’s Hospital of Jiangsu Province, Nanjing, Jiangsu, China
12Beijing Friendship Hospital, Capital Medical University, Beijing, China
13Nanjing Medical University Affiliated Second Hospital, Nanjing, Jiangsu, China
14Liuzhou People’s Hospital, Liuzhou, China
15Liver Disease Center of PLA, The 81st Hospital of PLA, Nanjing, Jiangsu, China
16Tangdu Hospital, Air Force Medical University, Xi’an, Shaanxi, China
17Baoji Central Hospital, Baoji, Shaanxi, China
18The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
19The First Hospital Affiliated to Jilin University, Changchun, Jilin, China
20The First Hospital of Changsha, Changsha, Hunan, China
21The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
22The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
23Beijing Ditan Hospital, Capital Medical University, Beijing, China
24Ascletis BioScience Co., Ltd., Hangzhou, Zhejiang, China
*Correspondence to: Lai Wei, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing 100191, China. Tel: +86-1-88326666, Fax: +86-1-68318386, E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

Journal of Clinical and Translational Hepatology 2019;7(3):221-225 DOI: 10.14218/JCTH.2019.00018
Received: May 13, 2019 Accepted: June 30, 2019 Published online: July 22, 2019

Abstract

Background and Aims: Genotype (GT) 1 remains the predominant hepatitis c virus (HCV) GT in Chinese patients. Over 80% of those Chinese patients harbor the interferon-sensitive CC allele of IFNL4rs12979860, which is favorable for interferon-based treatment regimens. This phase III clinical trial aimed to evaluate the efficacy and safety of the ritonavir-boosted danoprevir plus pegylated-interferon α-2a and ribavirin regimen for 12 weeks in treatment-naïve mainland Chinese patients infected with HCV GT1 without cirrhosis.

Methods: One hundred and forty-one treatment-naïve, non-cirrhotic HCV GT1 Chinese patients (age ≥18 years) were enrolled for this single-arm, multicenter, phase III MANASA study (NCT03020082). Patients received a combination of ritonavir-boosted danoprevir (100 mg/100 mg) twice a day plus subcutaneous injection of weekly pegylated-interferon α-2a (180 μg) and oral ribavirin (1000/1200 mg/day body weight <75/≥75 kg) for 12 weeks. The primary end-point was sustained virologic response rate at 12 weeks after the end of treatment. The secondary end-points were safety outcomes, tolerability, virologic response over time and relapse rate.

Results: All enrolled patients were HCV GT1-infected, and most among them (97.9%, 123/141) had the HCV GT1b subtype. Single-nucleotide polymorphism test showed that the majority of patients were of the IFNL4 rs12979860 CC genotype (87.2%, 123/141). Overall, 140 patients completed the 12-week treatment, and 97.1% (136/140) patients achieved sustained virologic response at 12 weeks (per protocol population group, 95% confidence interval: 92.9–99.2%). Only drug-related serious adverse event occurred. Most of the adverse events were grade 1 and grade 2 alanine aminotransferase elevation or liver dysfunction. One patient discontinued treatment because of severe head injury in a car accident.

Conclusions: The triple regimen of ritonavir-boosted danoprevir plus pegylated-interferon α-2a and ribavirin produced a sustained virologic response rate of 97.1% after 12 weeks treatment in noncirrhotic HCV GT1-infected Chinese patients, and was safe and well tolerated.

Trial Registration Clinical-Trials.gov Identifier: NCT03020082

Keywords

Danoprevir, Hepatitis C virus (HCV), Sustained virological response (SVR), Treatment-naïve

 

Journal of Clinical and Translational Hepatology 2019 vol. 7, 221-225  [ Html ] [ PDF Full-text ]

© The Authors 2019. This article is published under the terms of the Creative Commons Attribution-Noncommercial License (CC BY-NC 4.0), which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license.

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