Coblopasvir and sofosbuvir for treatment of chronic hepatitis C virus infection in China: A single-arm, open-label, phase 3 trial

  • Liver Int. 2020 Nov;40(11):2685-2693. doi: 10.1111/liv.14633.
Yanhang Gao  1 ,  Fei Kong  1 ,  Guangming Li  2 ,  Cheng Li  2 ,  Sujun Zheng  3 ,  Jianmei Lin  4 ,  Xiaofeng Wen  5 ,  Jinghua Hu  6 ,  Xiaozhong Wang  7 ,  Xiaofeng Wu  8 ,  Huichun Xing  9 ,  Jidong Jia  10 ,  Zhansheng Jia  11 ,  Yujuan Guan  12 ,  Chenghao Li  13 ,  Guicheng Wu  14 ,  Zhiliang Gao  15 ,  Zhuangbo Mou  16 ,  Qin Ning  17 ,  Qing Mao  18 ,  Yongfeng Yang  19 ,  Jing Ning  20 ,  Li Li  20 ,  Hai Pan  20 ,  Desheng Zhou  20 ,  Yanhua Ding  21 ,  Hong Qin  20 ,  Junqi Niu  1
Affiliations
  • 1. Department of Hepatology, the First Hospital of Jilin University, Changchun, China.
  • 2. Cirrhosis Department, Zhengzhou Sixth Municipal People's Hospital, Zhengzhou, Henan, China.
  • 3. Difficult & Complicated Liver Diseases and Artificial Liver Center, Beijing You An Hospital, Capital Medical University, Beijing, China.
  • 4. Department of Infectious Diseases, Sichuan Provincial People's Hospital, Chengdu, Sichuan, China.
  • 5. Department of Hepatology, Liuzhou People's Hospital, Liuzhou, China.
  • 6. Liver Failure Treatment and Research Center, the Fifth Medical Center of PLA General Hospital, Beijing, China.
  • 7. Department of Hepatology, Xinjiang Uygur Autonomous Region Traditional Chinese Medicine Hospital, Urumqi, Xinjiang, China.
  • 8. Department of Hepatology, Shenyang Sixth People's Hospital, Shenyang, Liaoning, China.
  • 9. Department of Hepatology Division 3, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
  • 10. Liver Research Center, Beijing Youyi Hospital Affiliated to Capital Medical University, Beijing, China.
  • 11. Department of Infectious Diseases, the Second Affiliated Hospital of People's Liberation Army Air Force Medical University, Xi'an, Shaanxi, China.
  • 12. Department of Hepatology, Guangzhou Eighth People's Hospital, Guangzhou, China.
  • 13. Department of Gastroenterology, Yanbian University Affiliated Hospital, Yanji, Jilin, China.
  • 14. Department of Hepatology, Chongqing University Three Gorges Hospital, Chongqing Three Gorges Central Hospital, Wanzhou, Chongqing, China.
  • 15. Department of Infectious Diseases, the Third Affiliated Hospital of Dr Sun Yat-Sen University, Guangzhou, Guangdong, China.
  • 16. Department of Hepatology, Ji'nan Municipal Hospital of Infectious Diseases, Ji'nan, Shandong, China.
  • 17. Department of Infectious Diseases, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
  • 18. Institute of Infectious Diseases, the First Affiliated Hospital of People's Liberation Army Medical University, Chongqing, China.
  • 19. Department of Hepatology, Nanjing Second Municipal Hospital, Nanjing, China.
  • 20. Research and Development Center, Beijing Kawin Technology Share-Holding Co., Ltd, Beijing, China.
  • 21. The Department of Phase I Clinical Trial, the First Hospital of Jilin University, Changchun, Jilin, China.
PMID: 33047868 DOI: 10.1111/liv.14633
Abstract

Background & aim: An affordable, pangenotypic regimen remains as an unmet medical need for chronic hepatitis C patients in China. This single-arm, open-label, multicenter, phase 3 trial evaluated the efficacy and safety of coblopasvir, a pangenotypic non-structural protein 5A (NS5A) inhibitor, combined with sofosbuvir for treating Chinese patients with chronic hepatitis C virus (HCV) Infection.

Methods: Treatment-naïve and interferon-experienced adult patients, including those with advanced fibrosis (F3) or compensated cirrhosis (F4), were treated with a universal, combinational regimen of coblopasvir 60 mg and sofosbuvir 400 mg, once daily, for 12 weeks. The primary efficacy endpoint was sustained virological response at post-treatment week 12 (SVR12).

Results: Overall, 371 patients (men, 51%; age, 47 ± 11 years; genotype 1a < 1%, 1b 48%, 2a 26%, 3a 6%, 3b 7% and 6 12%) were enrolled from 19 sites. Fifty-one patients (14%) had F3, 39 patients (11%) had F4 and 39 patients (11%) were interferon experienced. The overall SVR12 was 97% (95% CI, [94%, 98%]) for the full analysis set and was equal to or above 90% for all predefined subsets. Ten patients (3%) experienced virological relapse and two patients did not complete follow-up. No adverse events (AEs) occurred at a frequency ≥5%, and the most often reported AEs (≥1%) were neutropenia and fatigue. The majority of AEs were mild to moderate and transient without specific medical intervention.

Conclusions: The universal, pangenotypic combo of coblopasvir plus sofosbuvir is an efficacious and safe treatment for Chinese patients monoinfected with HCV of genotype 1, 2, 3 and 6, including those with compensated cirrhosis.

Lay summary: The regimen of coblopasvir and sofosbuvir is a safe and effective treatment for Chinese patients with genotype 1, 2, 3 and 6 HCV Infection, including those with compensated cirrhosis. Therefore, this regimen would be a novel choice of treatment for this patient population.

Keywords
coblopasvir; pangenotypic regimen; safety; sofosbuvir; sustained virological response.
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