Journal of Clinical and Translational Hepatology

Journal of Clinical and Translational Hepatology

Saturday, 11 / 16 / 2019

Articles

Efficacy and Safety of All-oral, 12-week Ravidasvir Plus Ritonavir-boosted Danoprevir and Ribavirin in Treatment-naïve Noncirrhotic HCV Genotype 1 Patients: Results from a Phase 2/3 Clinical Trial in China

ORIGINAL ARTICLE

Efficacy and Safety of All-oral, 12-week Ravidasvir Plus Ritonavir-boosted Danoprevir and Ribavirin in Treatment-naïve Noncirrhotic HCV Genotype 1 Patients: Results from a Phase 2/3 Clinical Trial in China

Xiaoyuan Xu1, Bo Feng2, Yujuan Guan3, Sujun Zheng4, Jifang Sheng5, Xingxiang Yang6, Yuanji Ma7, Yan Huang8, Yi Kang9, Xiaofeng Wen10, Jun Li11, Youwen Tan12, Qing He13, Qing Xie14, Maorong Wang15, Ping An16, Guozhong Gong17, Huimin Liu18, Qin Ning19, Rui Hua20, Bo Ning21, Wen Xie22, Jiming Zhang23, Wenxiang Huang24, Yongfeng Yang25, Minghua Lin26, Yingren Zhao27, Yanhong Yu28, Jidong Jia29, Dongliang Yang30, Liang Chen31, Yinong Ye32, Yuemin Nan33, Zuojiong Gong34, Quan Zhang35, Peng Hu36, Fusheng Wang37, Yongguo Li38, Dongliang Li39, Zhansheng Jia40, Jinlin Hou41, Chengwei Chen42, Jinzi J. Wu43 and Lai Wei*,44

1Peking University First Hospital, Beijing, China
2Peking University People’s Hospital, Beijing, China
3Guangzhou Eighth People’s Hospital, Guangzhou, China
4Beijing YouAn Hospital, Capital Medical University, Beijing, China
5The First Affiliated Hospital of Medical School of Zhejiang University, Hangzhou, China
6Sichuan Provincial People’s Hospital, Chengdu, China
7West China Hospital, Sichuan University, Chengdu, China
8Xiangya Hospital, Central South University, Changsha, China
9Henan Provincial People’s Hospital, Zhengzhou, China
10Liuzhou People’s Hospital, Liuzhou, China
11Jiangsu Province Hospital, Nanjing, China
12Zhenjiang No.3 People’s Hospital, Zhenjiang, China
13The Third People’s Hospital of Shenzhen, Shenzhen, China
14Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
15People’s Liberation Army Bayi Hospital, Nanjing, China
16Shenyang Sixth People’s Hospital, Shenyang, China
17The 2nd Xiangya Hospital of Central South University, Changsha, China
18Xixi Hospital of Hangzhou, Hangzhou, China
19Tongji Medical College of Huazhong University of Science & Technology, Wuhan, China
20The First Hospital of Jilin University, Changchun, China
21Baoji Center Hospital, Baoji, China
22Beijing Ditan Hospital, Beijing, China
23Huashan Hospital Affiliated to Fudan University, Shanghai, China
24Chongqing Medical University No.1 Affiliated Hospital, Chongqing, China
25The Second Hospital of Nanjing, Nanjing, China
26Fujian Fuzhou Municipal Infectious Disease Hospital, Fuzhou, China
27No.1 Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
28The First Affiliated Hospital of Guangxi Medical University, Nanning, China
29Beijing Friendship Hospital, Capital Medical University, Beijing, China
30Wuhan Union Hospital, Wuhan, China
31Shanghai Public Health Clinical Center, Shanghai, China
32Foshan No.1 People’s Hospital, Foshan, China
33The Third Hospital of Hebei Medical University, Shijiazhuang, China
34Wuhan University Renmin Hospital, Wuhan, China
35The Affiliated Hospital of Guizhou Medical University, Guiyang, China
36The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
37PLA 302 Hospital, Beijing, China
38The First Affiliated Hospital of Harbin Medical University, Harbin, China
39Fuzhou General Hospital of Nanjing Military Command, Fuzhou, China
40Tang Du Hospital, Fourth military Medical University, Xi’an, China
41Nanfang Hospital, Nanfang Medical University, Guangzhou, China
42The 85 branch of the Chinese People’s Liberation Army Hospital, Shanghai, China
43Ascletis BioScience Co., Ltd. Hangzhou, China
44Tsinghua Changgeng Hospital, Beijing, China
*Correspondence to: Lai Wei, Tsinghua Changgeng Hospital, No. 168 Li Tang Road, Chang Ping District, Beijing 102218, China. Tel: +86-10-88326666, Fax: +86-10-68318386, 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):213-220 DOI: 10.14218/JCTH.2019.00033
Received: July 30, 2019 Accepted: September 15, 2019 Published online: September 30, 2019

Abstract

Background and Aims: Ravidasvir (RDV) is a new generation pangenotypic hepatitis C virus (HCV) NS5A inhibitor, with high barrier to baseline resistance-associated species. This is the first phase 2/3 study conducted in Mainland China confirming the efficacy and safety of RDV + ritonavir-boosted danoprevir + ribavirin for 12 weeks in treatment-naïve noncirrhotic patients with genotype 1 infection in a large population.

Methods: In this multicenter, randomized, double-blinded, placebo-controlled phase 2/3 trial (NCT03362814), we enrolled 424 treatment-naïve, noncirrhotic adult HCV genotype 1 patients. All patients were randomized at 3:1 ratio to receive a combination of RDV 200mg once daily plus ritonavir-boosted danoprevir 100mg/100mg twice daily and oral ribavirin 1000/1200mg/day (body weight <75/≥75 kg) (n = 318) or placebo (n = 106) for 12 weeks. The primary end-point was the rate of sustained virologic response 12 weeks after the end of treatment, and the safety was evaluated and compared between treatment and placebo groups.

Results: The overall rate of sustained virological response at 12 weeks after treatment is 99% (306/309, 95%, CI: 97%–100%) under per protocol set analysis. All patients harboring baseline NS5A resistance-associated species in the treatment group (76/76, per protocol set) achieved sustained virological response at 12 weeks after treatment. No treatment-related serious adverse events were reported. Laboratory abnormalities showed mild or moderate severity (grade 1 and grade 2) in liver function tests.

Conclusions: In treatment-naïve, noncirrhotic HCV Chinese patients infected with HCV genotype 1, all-oral regimen of RDV + ritonavir-boosted danoprevir + ribavirin for 12 weeks was highly efficacious, safe, and well tolerated.

Keywords

Ravidasvir, Danoprevir, HCV, SVR, Treatment-naïve, Noncirrhotic, GT1

 

Journal of Clinical and Translational Hepatology 2019 vol. 7, 213-220  [ 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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