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, Naoya Sakamoto, Shuhei Nishiguchi, Fusao Ikeda, Tomohide Tatsumi, Yoshiyuki Ueno, Hiroshi Yatsuhashi, Yasuhiro Takikawa, Tatsuo Kanda, Minoru Sakamoto, Akihiro Tamori, Eiji Mita, Kazuaki Chayama, Gulan Zhang, Shampa De-Oertel, Hadas Dvory-Sobol, Takuma Matsuda, Luisa M. Stamm, Diana M. Brainard, Yasuhito Tanaka & 1 others Masayuki Kurosaki

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
JournalJournal of Gastroenterology
DOIs
Publication statusAccepted/In press - Jan 1 2018

Fingerprint

Ribavirin
Hepacivirus
Fibrosis
Safety
Genotype
Liver Diseases
Japan
Esophageal and Gastric Varices
Virus Diseases
Therapeutics
Random Allocation
Disease Progression
Hepatocellular Carcinoma
Sepsis
Hemorrhage

Keywords

  • Advanced liver disease
  • Decompensated cirrhosis
  • Direct-acting antivirals
  • Sofosbuvir
  • Velpatasvir

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Efficacy and safety of sofosbuvir–velpatasvir with or without ribavirin in HCV-infected Japanese patients with decompensated cirrhosis : an open-label phase 3 trial. / Takehara, Tetsuo; Sakamoto, Naoya; Nishiguchi, Shuhei; Ikeda, Fusao; Tatsumi, Tomohide; Ueno, Yoshiyuki; Yatsuhashi, Hiroshi; Takikawa, Yasuhiro; Kanda, Tatsuo; Sakamoto, Minoru; Tamori, Akihiro; Mita, Eiji; Chayama, Kazuaki; Zhang, Gulan; De-Oertel, Shampa; Dvory-Sobol, Hadas; Matsuda, Takuma; Stamm, Luisa M.; Brainard, Diana M.; Tanaka, Yasuhito; Kurosaki, Masayuki.

In: Journal of Gastroenterology, 01.01.2018.

Research output: Contribution to journalArticle

Takehara, T, Sakamoto, N, Nishiguchi, S, Ikeda, F, Tatsumi, T, Ueno, Y, Yatsuhashi, H, Takikawa, Y, Kanda, T, Sakamoto, M, Tamori, A, Mita, E, Chayama, K, Zhang, G, De-Oertel, S, Dvory-Sobol, H, Matsuda, T, Stamm, LM, Brainard, DM, Tanaka, Y & Kurosaki, M 2018, 'Efficacy and safety of sofosbuvir–velpatasvir with or without ribavirin in HCV-infected Japanese patients with decompensated cirrhosis: an open-label phase 3 trial', Journal of Gastroenterology. https://doi.org/10.1007/s00535-018-1503-x
Takehara, Tetsuo ; Sakamoto, Naoya ; Nishiguchi, Shuhei ; Ikeda, Fusao ; Tatsumi, Tomohide ; Ueno, Yoshiyuki ; Yatsuhashi, Hiroshi ; Takikawa, Yasuhiro ; Kanda, Tatsuo ; Sakamoto, Minoru ; Tamori, Akihiro ; Mita, Eiji ; Chayama, Kazuaki ; Zhang, Gulan ; De-Oertel, Shampa ; Dvory-Sobol, Hadas ; Matsuda, Takuma ; Stamm, Luisa M. ; Brainard, Diana M. ; Tanaka, Yasuhito ; Kurosaki, Masayuki. / Efficacy and safety of sofosbuvir–velpatasvir with or without ribavirin in HCV-infected Japanese patients with decompensated cirrhosis : an open-label phase 3 trial. In: Journal of Gastroenterology. 2018.
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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.",
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TY - JOUR

T1 - Efficacy and safety of sofosbuvir–velpatasvir with or without ribavirin in HCV-infected Japanese patients with decompensated cirrhosis

T2 - an open-label phase 3 trial

AU - Takehara, Tetsuo

AU - Sakamoto, Naoya

AU - Nishiguchi, Shuhei

AU - Ikeda, Fusao

AU - Tatsumi, Tomohide

AU - Ueno, Yoshiyuki

AU - Yatsuhashi, Hiroshi

AU - Takikawa, Yasuhiro

AU - Kanda, Tatsuo

AU - Sakamoto, Minoru

AU - Tamori, Akihiro

AU - Mita, Eiji

AU - Chayama, Kazuaki

AU - Zhang, Gulan

AU - De-Oertel, Shampa

AU - Dvory-Sobol, Hadas

AU - Matsuda, Takuma

AU - Stamm, Luisa M.

AU - Brainard, Diana M.

AU - Tanaka, Yasuhito

AU - Kurosaki, Masayuki

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - Advanced liver disease

KW - Decompensated cirrhosis

KW - Direct-acting antivirals

KW - Sofosbuvir

KW - Velpatasvir

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DO - 10.1007/s00535-018-1503-x

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JO - Journal of Gastroenterology

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