Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2019 Jan;54(1):87-95.
doi: 10.1007/s00535-018-1503-x. Epub 2018 Sep 10.

Efficacy and safety of sofosbuvir-velpatasvir with or without ribavirin in HCV-infected Japanese patients with decompensated cirrhosis: an open-label phase 3 trial

Tetsuo Takehara  1 , Naoya Sakamoto  2 , Shuhei Nishiguchi  3 , Fusao Ikeda  4 , Tomohide Tatsumi  5 , Yoshiyuki Ueno  6 , Hiroshi Yatsuhashi  7 , Yasuhiro Takikawa  8 , Tatsuo Kanda  9 , Minoru Sakamoto  10 , Akihiro Tamori  11 , Eiji Mita  12 , Kazuaki Chayama  13 , Gulan Zhang  14 , Shampa De-Oertel  14 , Hadas Dvory-Sobol  14 , Takuma Matsuda  15 , Luisa M Stamm  14 , Diana M Brainard  14 , Yasuhito Tanaka  16 , Masayuki Kurosaki  17
Affiliations
Clinical Trial

Efficacy and safety of sofosbuvir-velpatasvir with or without ribavirin in HCV-infected Japanese patients with decompensated cirrhosis: an open-label phase 3 trial

Tetsuo Takehara et al. J Gastroenterol. 2019 Jan.

Abstract

Background: In Japan, hepatitis C virus (HCV)-infected patients with decompensated cirrhosis currently have no treatment options. In this Phase 3 study, we evaluated sofosbuvir-velpatasvir with or without ribavirin for 12 weeks in patients with any HCV genotype and decompensated cirrhosis [Child-Pugh-Turcotte (CPT) class B or C] in Japan.

Methods: Patients were randomized 1:1 to receive sofosbuvir-velpatasvir with or without ribavirin for 12 weeks. Randomization was stratified by CPT class and genotype. Sustained virologic response 12 weeks following completion of treatment (SVR12) was the primary efficacy endpoint.

Results: Of the 102 patients enrolled, 57% were treatment naive, 78% and 20% had genotype 1 and 2 HCV infection, respectively, and 77% and 20% had CPT class B and C cirrhosis, respectively, at baseline. Overall, 61% of patients were female and the mean age was 66 years (range 41-83). SVR12 rates were 92% (47/51) in each group. Among patients who achieved SVR12, 26% had improved CPT class from baseline to posttreatment week 12. Most adverse events (AEs) were consistent with clinical sequelae of advanced liver disease or known toxicities of ribavirin. Four patients (8%) who received sofosbuvir-velpatasvir and seven (14%) who received sofosbuvir-velpatasvir plus ribavirin experienced a serious AE. The 3 deaths (bacterial sepsis, gastric varices hemorrhage, hepatocellular carcinoma) were attributed to liver disease progression.

Conclusion: Sofosbuvir-velpatasvir for 12 weeks provides a highly effective and well-tolerated therapy for Japanese patients with HCV and decompensated cirrhosis. Ribavirin did not improve efficacy but increased toxicity.

Keywords: Advanced liver disease; Decompensated cirrhosis; Direct-acting antivirals; Sofosbuvir; Velpatasvir.

PubMed Disclaimer

Conflict of interest statement

Tetsuo Takehara has received honoraria and commercial research funding from Gilead. Naoya Sakamoto has received honoraria from Bristol-Myers Squibb, Merck Sharp & Dohme, and Gilead, and has received commercial research funding from Gilead, AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Otsuka, and Shionogi. Shuhei Nishiguchi has received honoraria from Gilead, and has received commercial research funding from Gilead, Toray and Merck Sharp & Dohme. Yoshiyuki Ueno received commercial research funding from Gilead, Bristol-Myers Squibb, AbbVie, and Merck Sharp & Dohme. Hiroshi Yatshuhashi has received commercial research funding from Chugai. Tatsuo Kanda has received commercial research funding from AbbVie, Merck Sharp & Dohme, Chugai, and Sysmex. Minoru Sakamoto has received honoraria from Bristol-Myers Squibb, Merck Sharp & Dohme, and Gilead, and has received commercial research funding from Gilead, AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Otsuka, and Shionogi. Akihiro Tamori has received honoraria from Gilead. Kazuaki Chayama has received honoraria from AbbVie, Merck Sharp & Dohme, Bristol-Myers Squibb, and Gilead. Gulan Zhang, Shampa De-Oertel, Hadas Dvory-Sobol, Takuma Matsuda, Luisa M. Stamm, and Diana M. Brainard are employees of and hold stock in Gilead Sciences. Yasuhito Tanaka has received honoraria from Bristol-Myers Squibb and Gilead Sciences, and has received commercial research funding from Chugai, AbbVie, Bristol-Myers Squibb, Janssen, and Gilead. Masayuki Kurosaki has served in an advisory role to AbbVie, Gilead, GlaxoSmithKline, and Otsuka, and has received honoraria from AbbVie, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Gilead, GlaxoSmithKline, Janssen, Merck Sharp & Dohme, Otsuka, and Toray. Fusao Ikeda, Tomohide Tatsumi, Yasuhiro Takikawa, and Eiji Mita, declare no conflicts of interest.

Comment in

References

    1. American Association for the Study of Liver Diseases and the Infectious Diseases Society of America. HCV guidance: recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org/. Accessed 13 June 2018.
    1. Charlton M, Everson GT, Flamm SL, et al. Ledipasvir and sofosbuvir plus ribavirin for treatment of HCV infection in patients with advanced liver disease. Gastroenterology. 2015;149:649–659. doi: 10.1053/j.gastro.2015.05.010. - DOI - PubMed
    1. Manns M, Samuel D, Gane EJ, et al. Ledipasvir and sofosbuvir plus ribavirin in patients with genotype 1 or 4 hepatitis C virus infection and advanced liver disease: a multicentre, open-label, randomised, phase 2 trial. Lancet Infect Dis. 2016;16:685–697. doi: 10.1016/S1473-3099(16)00052-9. - DOI - PubMed
    1. Curry MP, O’Leary JG, Bzowej N, et al. Sofosbuvir and velpatasvir for HCV in patients with decompensated cirrhosis. N Engl J Med. 2015;373:2618–2628. doi: 10.1056/NEJMoa1512614. - DOI - PubMed
    1. The Japan Society of Hepatology (JSH), Guidelines for the management of hepatitis C virus infection: edition 6.1, full version [Japanese]. 2018. http://www.jsh.or.jp/files/uploads/R1__6.pdf. Accessed 13 June 2018.

MeSH terms

LinkOut - more resources