Efficacy and safety of elbasvir/grazoprevir in treatment-naive Chinese adults with hepatitis C virus infection: A randomized trial

Lai Wei, Ji Dong Jia, Zhong Ping Duan, Fu Sheng Wang, Jun Qi Niu, Wen Xie, Wen Xiang Huang, Ming Xiang Zhang, Yan Huang, Mao Rong Wang, Shan Ming Wu, Ying Ren Zhao, Zhan Sheng Jia, Xu Min Zhao, Sheng Mei Mu, Li Wen Liang, Zaiqi Wang, Amy Puenpatom, Peggy Hwang, Michael N Robertson, Paul Ingravallo, Ernest Asante-Appiah, Bo Wei, Barbara Evans, George J Hanna, Rohit Talwani, Lai Wei, Ji Dong Jia, Zhong Ping Duan, Fu Sheng Wang, Jun Qi Niu, Wen Xie, Wen Xiang Huang, Ming Xiang Zhang, Yan Huang, Mao Rong Wang, Shan Ming Wu, Ying Ren Zhao, Zhan Sheng Jia, Xu Min Zhao, Sheng Mei Mu, Li Wen Liang, Zaiqi Wang, Amy Puenpatom, Peggy Hwang, Michael N Robertson, Paul Ingravallo, Ernest Asante-Appiah, Bo Wei, Barbara Evans, George J Hanna, Rohit Talwani

Abstract

Background and aim: In China, clinical experience with direct-acting antiviral treatments for hepatitis C virus (HCV) infection is still emerging. C-CORAL is a phase 3, multinational, placebo-controlled, double-blind trial of elbasvir/grazoprevir (EBR/GZR) in participants with HCV infection from the Asia-Pacific region and Russia. Here, we report the data from participants enrolled in China.

Methods: Treatment-naive participants with chronic HCV genotype (GT) 1, GT4, or GT6 infection were randomly assigned to receive 50 mg EBR/100 mg GZR for 12 weeks (immediate-treatment group, ITG) or placebo followed by deferred treatment with EBR/GZR (deferred-treatment group, DTG). The primary efficacy end-point was sustained virologic response at 12 weeks after completing treatment (SVR12), and the primary safety end-point was a comparison of safety between participants receiving EBR/GZR and placebo (NCT02251990; Protocol PN-5172-067).

Results: A total of 152 participants in China were randomly assigned (ITG, n = 115; DTG, n = 37). SVR12 was achieved in 96.7% (146/151) participants overall and in 97.3% (142/146) of those with GT1b infection. Four participants relapsed (GT1b, n = 3; GT6a, n = 1). Drug-related AEs were reported in 25 (21.7%) and 9 (24.3%) participants receiving EBR/GZR and placebo, respectively; no drug-related serious adverse events (AEs) occurred. Two (1.7%) participants receiving EBR/GZR had late hepatic transaminase elevations. Patient-reported outcomes indicate improved quality of life at follow-up week 4 in participants receiving EBR/GZR compared to placebo.

Conclusion: EBR/GZR administered for 12 weeks represents a highly effective and safe treatment option for Chinese individuals with HCV GT1 infection.

Keywords: hepatitis C clinical; hepatitis C virus clinical trials; viral hepatitis; virology, hepatitis C virus treatment.

© 2020 The Authors. JGH Open: An open access journal of gastroenterology and hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Figures

Figure 1
Figure 1
Participant disposition. AE, adverse event; EBR, elbasvir; GZR, grazoprevir.
Figure 2
Figure 2
Sustained virologic response at 12 weeks after completion of treatment. EBR, elbasvir; GZR, grazoprevir; SVR12, sustained virologic response at 12 weeks after completion of treatment. †One participant in the deferred‐treatment group discontinued from the study owing to an adverse event during the initial placebo treatment phase and did not enter the deferred EBR/GZR active treatment phase. ‡One participant in the deferred‐treatment group completed treatment during the active treatment phase and was lost to follow‐up.
Figure 3
Figure 3
SVR12 subgroup analyses. CI, confidence interval; GT, genotype; HCV, hepatitis C virus; IU, international unit; SVR12, sustained virologic response at 12 weeks after completion of treatment. †Asymptotic CI for proportion.
Figure 4
Figure 4
Differences in health‐related quality of life between immediate (EBR/GZR) and deferred (placebo) treatment groups at treatment week 4, treatment week 12, and follow‐up week 4 (prior to unblinding). Data represent treatment difference (immediate − deferred) mean change from baseline ± 95% CI in the (a) SF‐36v2 and (b) EQ‐VAS and FACIT‐fatigue scale scores. CI, confidence interval; EBR, elbasvir; EQ‐VAS, EuroQol‐Visual Analog Scales; FACIT‐Fatigue Scale, Functional Assessment of Chronic Illness Therapy‐Fatigue Scale; GZR, grazoprevir; SF‐36v2, short‐form 36 survey version 2; TW4, treatment week 4; TW12, treatment week 12; FW4, follow‐up week 4.

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