Lai WeiSeng Gee LimQing XieKính Nguyen VănTeerha PiratvisuthYan HuangShanming WuMing XuHong TangJun ChengHung Le ManhYanhang GaoZhuangbo MouAbhasnee SobhonslidsukXiaguang DouSatawat ThongsawatYuemin NanChee Kiat TanQin NingHoi Poh TeeYimin MaoLuisa M. StammSophia LuHadas Dvory-SobolHongmei MoDiana M. BrainardYong Feng YangLong DaoGui Qiang WangTawesak TanwandeePeng HuPisit TangkijvanichLunli ZhangZhi Liang GaoFeng LinThi Tuyet Phuong LeJia ShangGuozhong GongJun LiMinghua SuZhongping DuanRosmawati MohamedJin Lin HouJidong JiaJinan Infectious Disease HospitalThe First Bethune Hospital of Jilin UniversityPeking University People's HospitalPeking University First HospitalThe First Affiliated Hospital of Guangxi Medical UniversityBeijing YouAn Hospital, Capital Medical UniversityThe Second Hospital of NanjingHainan Provincial People's HospitalSecond Xiangya Hospital of Central-South UniversityXiangya Hospital of Central-South UniversityShanghai Jiao Tong University School of MedicineGuangzhou Eighth People's HospitalHenan Provincial People's HospitalWest China School of Medicine/West China Hospital of Sichuan UniversityBeijing Friendship Hospital, Capital Medical UniversityBeijing Ditan Hospital Capital Medical UniversityBach Mai HospitalNational University Hospital, SingaporeSongklanagarind HospitalKing Chulalongkorn Memorial Hospital, Faculty of Medicine Chulalongkorn UniversityUCLSun Yat-Sen UniversityChongqing Medical UniversitySingapore General HospitalFaculty of Medicine, Ramathibodi Hospital, Mahidol UniversityMaharaj Nakorn Chiang Mai HospitalUniversity of Malaya Medical CentreFaculty of Medicine, Siriraj Hospital, Mahidol UniversityHebei Medical UniversityChina Medical University ShenyangNanchang UniversityGilead Sciences IncorporatedSouthern Medical UniversityTongji Medical CollegeShanghai Public Health Clinical CentreNational Hospital for Tropical DiseasesJiangsu Province People's HospitalPeople's Hospital 115Hospital Tengku Ampuan Afzan2020-01-272020-01-272019-02-01The Lancet Gastroenterology and Hepatology. Vol.4, No.2 (2019), 127-134246812532-s2.0-85059554222https://repository.li.mahidol.ac.th/handle/20.500.14594/51945© 2019 Elsevier Ltd Background: Treatment with combined sofosbuvir and velpatasvir has resulted in high sustained virological response rates in patients chronically infected with hepatitis C virus (HCV) with genotypes 1–6 in clinical trials and real-world settings, but its efficacy and safety has not been assessed in Asia, a region with diverse HCV genotypes. Methods: In this single-arm, open-label, phase 3 trial, we recruited patients from 38 sites across China, Thailand, Vietnam, Singapore, and Malaysia, who were chronically infected with HCV genotypes 1–6, and were HCV treatment-naive or treatment-experienced, either without cirrhosis or with compensated cirrhosis. Patients self-administered a combined sofosbuvir (400 mg) and velpatasvir (100 mg) tablet once daily for 12 weeks. The primary efficacy endpoint was sustained virological response, defined as HCV RNA less than 15 IU/mL at 12 weeks after completion of treatment (SVR12), assessed in all patients who received at least one dose of study drug. The primary safety endpoint was the proportion of adverse events leading to premature discontinuation of study drug. This trial is registered with ClinicalTrials.gov, number NCT02671500, and is completed. Findings: Between April 14, 2016, and June 30, 2017, 375 patients were enrolled in the study, of whom 374 completed the full treatment course and one discontinued treatment. Overall, 362 (97% [95% CI 94–98]) of 375 patients achieved SVR12. Among 42 patients with HCV genotype 3b, all of whom had baseline resistance-associated substitutions in NS5A, 25 (89% [95% CI 72–98]) of 28 patients without cirrhosis and seven (50% [23–77]) of 14 patients with cirrhosis achieved SVR12. The most common adverse events were upper respiratory tract infection (36 [10%] patients) and headache (18 [5%] patients). There were no discontinuations due to adverse events. Serious adverse events were reported in three (1%) patients, none of which was judged to be related to sofosbuvir–velpatasvir treatment. Interpretation: Consistent with data from other phase 3 studies, single-tablet sofosbuvir–velpatasvir for 12 weeks is an efficacious and safe treatment for Asian patients with chronic HCV infection, but might have lower efficacy in those infected with HCV genotype 3b and with cirrhosis. Funding: Gilead Sciences.Mahidol UniversityMedicineArticleSCOPUS10.1016/S2468-1253(18)30343-1