Sofosbuvir-velpatasvir for treatment of chronic hepatitis C virus infection in Asia: a single-arm, open-label, phase 3 trial.
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| Abstract | 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.
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| Authors | Lai Wei, Seng Gee Lim, Qing Xie, Kính Nguyen Văn, Teerha Piratvisuth, Yan Huang, Shanming Wu, Ming Xu, Hong Tang, Jun Cheng, Hung Le Manh, Yanhang Gao, Zhuangbo Mou, Abhasnee Sobhonslidsuk, Xiaguang Dou, Satawat Thongsawat, Yuemin Nan, Chee Kiat Tan, Qin Ning, Hoi Poh Tee, Yimin Mao, Luisa M Stamm, Sophia Lu, Hadas Dvory-Sobol, Hongmei Mo, Diana M Brainard, Yong-Feng Yang, Long Dao, Gui-Qiang Wang, Tawesak Tanwandee, Peng Hu, Pisit Tangkijvanich, Lunli Zhang, Zhi Liang Gao, Feng Lin, Thi Tuyet Phuong Le, Jia Shang, Guozhong Gong, Jun Li, Minghua Su, Zhongping Duan, Rosmawati Mohamed, Jin Lin Hou, Jidong Jia |
| Journal | The lancet. Gastroenterology & hepatology (Lancet Gastroenterol Hepatol) Vol. 4 Issue 2 Pg. 127-134 (02 2019) ISSN: 2468-1253 [Electronic] Netherlands |
| PMID | 30555048 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study) |
| Copyright | Copyright © 2019 Elsevier Ltd. All rights reserved. |
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