Efficacy and safety of yimitasvir phospha combined with sofosbuvir in patients with chronic hepatitis C virus infection
Bifen Luo, Jinglan Jin, Huiying Rao, Qin Ning, Jinlin Hou, Lang Bai, Yongfeng Yang, Sujun Zheng, Xiaorong Mao, Jun Quan, Dongliang Yang, Lunli Zhang, Caiyan Zhao, Zhansheng Jia, Fuchun Zhang, Zuojiong Gong, Feng Lin, Guiqiang Wang, Lin Luo, Li Deng, Hongming Xie, Jing Li, Yingjun Zhang, Lai Wei
Abstract
ObjectiveTo assess the efficacy and safety of 100 mg or 200 mg yimitasvir phosphate combined with sofosbuvir in patients with non-cirrhotic chronic hepatitis C virus (HCV) genotype 1 infection who were treatment-naïve or had a virologic failure to prior interferon-based treatment.
MethodsA multicenter, randomized, open-label, phase 2 clinical trial was conducted. The patients were randomly assigned to yimitasvir phosphate 100 mg+ sofosbuvir 400 mg group (Group 100 mg) and yimitasvir phosphate 200 mg+ sofosbuvir 400 mg group (Group 200 mg) in a 1∶1 ratio with the stratified factors of "treatment-naive" or "treatment-experienced" for 12 weeks and followed up for 24 weeks after the end of treatment. During the clinical trial, HCV RNA was tested in all patients. Resistance of virus in patients who didn′t achieved sustained virological response (SVR) was monitored. Safety and tolerability were assessed by monitoring adverse events, physical examination, laboratory examination, electrocardiogram, and vital signs during the study. The primary end point was SVR12 after the end of therapy. Descriptive statistics were used for categorical variables and eight descriptive statistics were used for continuous variables. Descriptive statistics were used and summarized according to HCV genotypes and treatment groups. Safety data were presented using descriptive statistics and summarized according to treatment groups.
ResultsA total of 174 subjects were screened from July 31, 2017 to September 26, 2018. One hundred and twenty-nine patients were successfully enrolled and received treatment, and 127 completed the study. There were 64 patients and 65 patients assigned to Group 100 mg and Group 200 mg, respectively. Among the 129 patients who underwent randomization and were treated, 18.6% were treatment-experienced and: 100% were HCV genotype 1b infection. The total SVR rate was 98.4% (127/129), with 98.4% (63/64, 95% confidence interval [CI]: 91.60%-99.96%) in the Group 100 mg, and 98.50% (64/65, 95%CI: 91.72%-99.96%) in the Group 200 mg. There was no significant difference between the two groups (χ2=0.000 2, P=0.989 2). The SVR rates in treatment-naive group and treatment-experienced group were 98.10% (95%CI: 93.29%-99.77%) and 100.00% (24/24, 95%CI: 85.75%-100.00%), respectively. Virological failure during treatment (including breakthrough, rebound and poor efficacy) and relapse after treatment did not occur during the trial. By Sanger sequencing, 11.6% (15/129) patients had baseline NS5A Y93H/Y or Y93H resistance-associated substitutions (RAS), 1.6% (2/129) patients had baseline NS5A L31M RAS. No mutation was observed in NS5B S282 at baseline. There was no S282 mutation in HCV NS5B. A total of 100 (77.5%) subjects had adverse events. No adverse events ≥Grade 3 or severe adverse events related to the study treatment. No patient prematurely discontinued study treatment owing to an adverse event. No life-threatening adverse event was reported.
ConclusionTwelve weeks of yimitasvir phosphate 100 mg or 200 mg combined with sofosbuvir 400 mg daily is a highly effective and safe regimen for patients without cirrhosis with HCV genotype 1b infection who had not been treated previously or had a virologic failure to prior interferon-based treatment.
Key words:
Hepatitis C, chronic; Yimitasvir; Sofosbuvir; Genotype 1; Viral therapy; Sustained virologic response; Safety
Contributor Information
Bifen Luo
Department of Hepatology, Hepato-Biliary-Pancreatic Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Institute for Precision Medicine, Tsinghua University, Beijing 102218, China
Department of Hepatology, Peking University Hepatology Institute, Peking University People′s Hospital, Beijing 100035, China
Jinglan Jin
Department of Hepato-Biliary-Pancreatic Diseases, The First Hospital of Jilin University, Changchun 130000, China
Huiying Rao
Department of Hepatology, Peking University Hepatology Institute, Peking University People′s Hospital, Beijing 100035, China
Qin Ning
Department of Infectious Diseases, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology, Wuhan 430000, China
Jinlin Hou
Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
Lang Bai
Infectious Diseases Center, West China Hospital, Sichuan University, Chengdu 610000, China
Yongfeng Yang
Department of Hepatology, The Second Hospital of Nanjing, Nanjing 210003, China
Sujun Zheng
Center of Artificial liver, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China
Xiaorong Mao
Department of Infectious Diseases, The First Hospital of Lanzhou University, Lanzhou 730000, China
Jun Quan
Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha 410008, China
Dongliang Yang
Department of Infectious Disease, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China
Lunli Zhang
Department of Infectious Diseases, The First Affiliated Hospital of Nanchang University, Nanchang 330000, China
Caiyan Zhao
Department of Hepatology, The Third Hospital of Hebei Medical University, Shijiazhuang 050051, China
Zhansheng Jia
Department of Infectious Diseases, Tangdu Hospital, the Fourth Military Medical University of the People′s Liberation Army, Xi′an 710038, China
Fuchun Zhang
Department of Hepatology, Guangzhou Eighth People′s Hospital, Guangzhou 510060, China
Zuojiong Gong
Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan 430000, China
Feng Lin
Department of Infectious Diseases, Hainan General Hospital, Haikou 570311, China
Guiqiang Wang
Department of Infectious Diseases, Peking University First Hospital, Beijing 100034, China
Lin Luo
State Key Laboratory of Anti-Infective Drug Development, Sunshine Lake Pharma Co., Ltd, Dongguan 523841, China
Li Deng
State Key Laboratory of Anti-Infective Drug Development, Sunshine Lake Pharma Co., Ltd, Dongguan 523841, China
Hongming Xie
State Key Laboratory of Anti-Infective Drug Development, Sunshine Lake Pharma Co., Ltd, Dongguan 523841, China
Jing Li
State Key Laboratory of Anti-Infective Drug Development, Sunshine Lake Pharma Co., Ltd, Dongguan 523841, China
Yingjun Zhang
State Key Laboratory of Anti-Infective Drug Development, Sunshine Lake Pharma Co., Ltd, Dongguan 523841, China
Lai Wei
Department of Hepatology, Hepato-Biliary-Pancreatic Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Institute for Precision Medicine, Tsinghua University, Beijing 102218, China
Department of Hepatology, Peking University Hepatology Institute, Peking University People′s Hospital, Beijing 100035, China