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

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.

• Authors: Lai Wei, Jia Shang, Yuanji Ma, Xiaoyuan Xu, Yan Huang, Yujuan Guan, Zhongping Duan, Wenhong Zhang, Zhiliang Gao, Mingxiang Zhang, Jun Li, Jidong Jia, Yongfeng Yang, Xiaofeng Wen, Maorong Wang, Zhansheng Jia, Bo Ning, Yongping Chen, Yue Qi, Jie Du, Jianning Jiang, Lixin Tong, Yao Xie, Jinzi J Wu
• Journal: Journal of clinical and translational hepatology (J Clin Transl Hepatol) Vol. 7 Issue 3 Pg. 221-225 (Sep 28 2019) ISSN: 2225-0719 [Print] United States
• PMID: 31608213 (Publication Type: Journal Article)
• Copyright: © 2019 Authors.