Sofosbuvir-velpatasvir for treatment of chronic hepatitis C virus infection in Asia: a single-arm, open-label, phase 3 trial

Wei L 1 , Lim SG 2 , Xie Q 3 , Văn KN 4 , Piratvisuth T 5 , Huang Y 6 Show all authors , Wu S 7 , Xu M 8 , Tang H 9 , Cheng J 10 , Le Manh H 11 , Gao Y 12 , Mou Z 13 , Sobhonslidsuk A 14 , Dou X 15 , Thongsawat S 16 , Nan Y 17 , Tan CK 18 , Ning Q 19 , Tee HP 20 , Mao Y 3 , Stamm LM 21 , Lu S 21 , Dvory-Sobol H 21 , Mo H 21 , Brainard DM 21 , Yang YF 22 , Dao L 23 , Wang GQ 24 , Tanwandee T 25 , Hu P 26 , Tangkijvanich P 27 , Zhang L 28 , Gao ZL 29 , Lin F 30 , Le TTP 31 , Shang J 32 , Gong G 33 , Li J 34 , Su M 35 , Duan Z 36 , Mohamed R 37 , Hou JL 38 , Jia J 39

Affiliations 

  • 1 Peking University People's Hospital, Beijing, China
  • 2 National University Hospital, Singapore. Electronic address: mdclimsg@nus.edu.sg
  • 3 Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • 4 National Hospital for Tropical Diseases, Hanoi, Vietnam
  • 5 Songklanagarind Hospital, Songkla, Thailand
  • 6 Xiangya Hospital, Central South University, Changsha, Hunan, China
  • 7 Shanghai Public Health Clinical Centre, Shanghai, China
  • 8 Guangzhou No 8 People's Hospital, Guangzhou, Guangdong, China
  • 9 West China Hospital, Sichuan University, Chengdu, Sichuan, China
  • 10 Beijing Ditan Hospital, Beijing, China
  • 11 Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
  • 12 The First Hospital of Jilin University, Changchun, Jilin, China
  • 13 Jinan Infectious Disease Hospital, Jinan, Shandong, China
  • 14 Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
  • 15 Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
  • 16 Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand
  • 17 The 3rd Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
  • 18 Singapore General Hospital, Singapore
  • 19 Tongji Hospital Affiliated to Tongji Medicine College, Huazhong University of Science and Technology, Wuhan, Hubei, China
  • 20 Hospital Tengku Ampuan Afzan, Kuantan, Pahang, Malaysia
  • 21 Gilead Sciences, Foster City, CA, USA
  • 22 The Second Hospital of Nanjing, Affiliated to South East University, Nanjing, Jiangsu, China
  • 23 Bach Mai Hospital, Hanoi, Vietnam
  • 24 Peking University First Hospital, Beijing, China
  • 25 Siriraj Hospital, Mahidol University, Bangkok, Thailand
  • 26 The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
  • 27 King Chulalongkorn Memorial Hospital, Bangkok, Thailand
  • 28 The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
  • 29 The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
  • 30 The People's Hospital of Hainan Province, Haikou, Hainan, China
  • 31 People's Hospital 115, Ho Chi Minh City, Vietnam
  • 32 Henan Province People's Hospital, Zhengzhou, Henan, China
  • 33 The Second Xiangya Hospital of Central South University, Changsha, China
  • 34 Jiangsu Province People's Hospital, Nanjing, Jiangsu, China
  • 35 The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
  • 36 Beijing You-An Hospital, Capital Medical University, Beijing, China
  • 37 University Malaya Medical Centre, Kuala Lumpur, Malaysia
  • 38 Nanfang Hospital of Southern Medical University, Guangzhou, Guangdong, China
  • 39 Beijing Friendship Hospital Affiliate of Capital, Beijing, China
Lancet Gastroenterol Hepatol, 2019 02;4(2):127-134.
PMID: 30555048 DOI: 10.1016/S2468-1253(18)30343-1

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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