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

• Published in: Journal of clinical and translational hepatology Vol. 7; no. 3; pp. 1 - 8
• Main Authors: Xu, Xiaoyuan, Feng, Bo, Guan, Yujuan, Zheng, Sujun, Sheng, Jifang, Yang, Xingxiang, Ma, Yuanji, Huang, Yan, Kang, Yi, Wen, Xiaofeng, Li, Jun, Tan, Youwen, He, Qing, Xie, Qing, Wang, Maorong, An, Ping, Gong, Guozhong, Liu, Huimin, Ning, Qin, Hua, Rui, Ning, Bo, Xie, Wen, Zhang, Jiming, Huang, Wenxiang, Yang, Yongfeng, Lin, Minghua, Zhao, Yingren, Yu, Yanhong, Jia, Jidong, Yang, Dongliang, Chen, Liang, Ye, Yinong, Nan, Yuemin, Gong, Zuojiong, Zhang, Quan, Hu, Peng, Wang, Fusheng, Li, Yongguo, Li, Dongliang, Jia, Zhansheng, Hou, Jinlin, Chen, Chengwei, Wu, Jinzi J., Wei, Lai
• Format: Journal Article
• Language: English
• Published: XIA & HE Publishing Inc 28-09-2019
• Subjects: Original
• ISSN: 2225-0719; 2310-8819
• DOI: 10.14218/JCTH.2019.00033

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.