A phase II, single-arm, open-label, multicenter clinical study to evaluate the efficacy and safety of sofosbuvir combined with ribavirin in patients with genotype 2 chronic hepatitis C virus infection

Yinghui Gao; Guangming LI; Qinglong Jin; Yingren Zhao; Zhansheng Jia; Xiaorong Mao; Yongfeng Yang; Jia Shang; Gongchen Wang; Wen Xie; Shanming WU; Mingxiang Zhang; Jinlin Hou; Dongliang LI; Yuemin Nan; Yujuan Guan; Chunxia Zhu; Yangzhou Yuan; Lai Wei

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A phase II, single-arm, open-label, multicenter clinical study to evaluate the efficacy and safety of sofosbuvir combined with ribavirin in patients with genotype 2 chronic hepatitis C virus infection

VernacularTitle: 一项评估索磷布韦联合利巴韦林治疗基因2型慢性丙型肝炎病毒感染受试者的有效性和安全性的单臂、开放、多中心Ⅱ期临床研究
Author: Yinghui GAO ¹ ; Guangming LI ² ; Qinglong JIN ³ ; Yingren ZHAO ⁴ ; Zhansheng JIA ⁵ ; Xiaorong MAO ⁶ ; Yongfeng YANG ⁷ ; Jia SHANG ⁸ ; Gongchen WANG ⁹ ; Wen XIE ¹⁰ ; Shanming WU ¹¹ ; Mingxiang ZHANG ¹² ; Jinlin HOU ¹³ ; Dongliang LI ¹⁴ ; Yuemin NAN ¹⁵ ; Yujuan GUAN ¹⁶ ; Chunxia ZHU ¹⁷ ; Yangzhou YUAN ¹⁷ ; Lai WEI ¹⁸
Author Information

1. Department of Hepatology, Peking University People's Hospital, Beijing 100044, China (now in Peking University International Hospital)
2. Department of Hepatology, Zhengzhou Sixth People's Hospital, Zhengzhou 450061, China
3. Department of Hepatobiliary and Pancreatic, Jilin University First Hospital, Changchun 130021, China
4. Department of Infectious Disease, Xi'an Jiaotong University School of Medicine First Affiliated Hospital, Xi’an 710065, China
5. Center of Infectious Diseases and Liver Diseases, Fourth Military Medical University Tangdu Hospital, Xi’an 710038, China
6. Department of Infectious Disease, Lanzhou University First Hospital, Lanzhou 730000, China
7. Department of Hepatology, Nanjing Second Hospital, Nanjing 210028, China
8. Department of Infectious Disease, Henan Provincial People's Hospital, Zhengzhou 450003, China
9. Department of Hepatology, Dalian Sixth People's Hospital, Dalian 116001, China
10. Center of Liver Disease Study, Beijing Ditan Hospital, Beijing 100015, China
11. Department of Hepatology, Shanghai Public Health Clinical Center, Shanghai 201508, China
12. Department of Traditional and Western Medical Hepatology, Shenyang Sixth People's Hospital, Shenyang 110006, China
13. Department of Infectious Disease, Southern Medical University Southern Hospital, Guangzhou 510515, China
14. Department of Hepatobiliary, Nanjing Military Region Fuzhou General Hospital, Fuzhou 350025, China
15. Department of Traditional and Western Medical hepatology, Hebei Medical University Third Hospital, Shijiazhuang 050000, China
16. Department of Hepatology, Guangzhou Eighth People's Hospital, Guangzhou 510060, China
17. Nanjing Chia Tai Tianqing Co., Ltd, Nanjing 210000, China
18. Department of Hepatology, Peking University People's Hospital, Beijing 100044, China (now in Beijing Tsinghua Changgung Hospital)
Publication Type:Journal Article
Keywords: Hepatitis C; Genotype 2; Direct-acting antiviral agents; Sofosbuvir; Ribavirin; Sustained virological response
From: Chinese Journal of Hepatology 2019;27(5):352-357
CountryChina
Language:Chinese
Abstract: Objective:To evaluate the efficacy and safety of sofosbuvir (Nanjing Zhengda Tianqing Pharmaceutical Co., Ltd.) combined with ribavirin in patients with genotype 2 chronic hepatitis C virus infection.
Methods:Treatment-naïve or treatment experienced genotype 2 chronic hepatitis C patients from sixteen research centers of China were screened. All subjects received once-daily dose of sofosbuvir (400 mg) combined with ribavirin (body weight < 75 kg, 1 000 mg/day, 400 mg in the morning and 600 mg in the evening; body weight > 75 kg, 1 200 mg/d, 600 mg in the morning and 600 mg in the evening) for 12 weeks. Patients were followed-up for a period of 12 weeks after discontinuation of treatment. Continuous variables were expressed as mean ± standard deviation. The proportion of subjects with virologic response at different follow-up time points and 95% confidence intervals were estimated by maximum likelihood ratio and Clopper-Pearson interval.
Results:132 cases with genotype 2 chronic hepatitis C virus infection from sixteen research centers of China were included, 12 cases of whom were associated with cirrhosis, and the remaining 120 cases were not associated with cirrhosis. One hundred and thirty-one cases completed the study, and one patient lost to follow-up at week 4 after the end of treatment. The sustained virological response rate was 96.2% (95% confidence interval: 92.37% - 99.16%) after 12 weeks of drug withdrawal. Virological relapse occurred in four cases. Of the 132 subjects enrolled in the study, 119 (90.2%) reported 617 adverse events during treatment, of which 359 (76.5%) were TEAE related to sofosbuvir and/or ribavirin. There were nine TEAEs of grade 3 and above, and six cases (4.5%) of them had six severe adverse events. Only one serious adverse event was associated with sofosbuvir and ribavirin (unstable angina pectoris). There were no adverse events leading to drug discontinuation or death.
Conclusion:Sofosbuvir combined with ribavirin has a high SVR rate in the treatment of genotype 2 chronic hepatitis C virus infection, and most of the adverse events occurred were mild with acceptable safety profile.