Efficacy and safety of alfosbuvir plus daclatasvir in Chinese patients with hepatitis C virus genotypes 1, 2, 3, and 6 infection: An open-label, phase 2 study
单位：[1]The First Hospital of Jilin University, Changchun.[2]Liuzhou People's Hospital, Liuzhou.[3]The Second Hospital of Nanjing, Nanjing.[4]The 940th Hospital of Joint Logistics Support Force of PLA, Lanzhou.[5]The Sixth People's Hospital of Shenyang, Shenyang.[6]Beijing Friendship Hospital Affiliated with Capital Medical University, Beijing.首都医科大学附属北京友谊医院[7]The Third People's Hospital of Zhenjiang, Zhenjiang.[8]Xiangya Hospital, Central South University, Changsha.[9]The Second Xiangya Hospital of Central South University, Changsha.[10]Guangzhou Eighth People's Hospital, Guangzhou.[11]The First Hospital of Lanzhou University, Lanzhou.[12]Shanghai Public Health Clinical Center, Shanghai.[13]Qingdao Municipal Hospital, Qingdao.[14]Shulan (Hangzhou) Hospital, Hangzhou.[15]Beijing You'an Hospital Affiliated with Capital Medical University, Beijing.[16]Zhengzhou Sixth People's Hospital, Zhengzhou.[17]Nanjing Sanhome Pharmaceutical Co., Ltd, Nanjing.[18]The First Hospital Affiliated to Xinjiang Medical University, Urumchi.
Alfosbuvir is a novel potent HCV NS5B polymerase inhibitor in development for the treatment of chronic HCV infection. Our previous studies indicated that alfosbuvir monotherapy was well-tolerated and druggable in healthy subjects and HCV-infected patients. Here, we evaluate the efficacy and safety of alfosbuvir in combination with daclatasvir in Chinese patients with HCV genotype 1, 2, 3 or 6. In this open-label study, patients with chronic HCV infection were randomly assigned with a 1:1:1 ratio to receive 12 weeks of daclatasvir 60 mg plus alfosbuvir at a dose of 400, 600 or 800 mg (Cohort A, B or C) daily. Randomization was stratified by HCV genotype and the presence or absence of cirrhosis at screening. The primary endpoint was a sustained virologic response 12 weeks after the end of treatment (SVR12). A total of 124 patients were enrolled in the study, all of whom were available for post-treatment week 12 assessments. SVR12 was achieved in 92.7% (38/41), 95.2% (40/42) and 100% (41/41) of patients in Cohort A, B and C respectively. The most common adverse events were hepatic steatosis, upper respiratory tract infection, hypercholesterolaemia, hypertriglyceridaemia, blood bilirubin increased, and total bile acids increased. There were no discontinuations due to adverse events, and no treatment-related serious adverse events were reported. Once-daily oral administration of alfosbuvir plus daclatasvir were highly effective and safe in Chinese patients infected with HCV genotype 1, 2, 3 or 6, suggesting this regimen could be a promising drug candidate for HCV treatment irrespective of genotype. (ClinicalTrials.gov number, NCT04070235).
基金：
Nanjing Sanhome Pharmaceutical Co., Ltd.; National Science and Technology Major Project of China for Significant New Drugs Creation [2019ZX09302053, 2020ZX09101027]
第一作者单位：[1]The First Hospital of Jilin University, Changchun.
通讯作者：
推荐引用方式(GB/T 7714)：
Hua Rui,Kong Fei,Wen Xiaofeng,et al.Efficacy and safety of alfosbuvir plus daclatasvir in Chinese patients with hepatitis C virus genotypes 1, 2, 3, and 6 infection: An open-label, phase 2 study[J].JOURNAL of VIRAL HEPATITIS.2022,doi:10.1111/jvh.13650.
APA：
Hua Rui,Kong Fei,Wen Xiaofeng,Xiong Qingfang,Chen Jiayu...&Niu Junqi.(2022).Efficacy and safety of alfosbuvir plus daclatasvir in Chinese patients with hepatitis C virus genotypes 1, 2, 3, and 6 infection: An open-label, phase 2 study.JOURNAL of VIRAL HEPATITIS,,
MLA：
Hua Rui,et al."Efficacy and safety of alfosbuvir plus daclatasvir in Chinese patients with hepatitis C virus genotypes 1, 2, 3, and 6 infection: An open-label, phase 2 study".JOURNAL of VIRAL HEPATITIS .(2022)
