Sofosbuvir-velpatasvir plus ribavirin in Japanese patients with genotype 1 or 2 hepatitis C who failed direct-acting antivirals

Hepatol Int. 2018 Jul;12(4):356-367. doi: 10.1007/s12072-018-9878-6. Epub 2018 Jul 20.

Abstract

Background/purpose: In Japan, there is a growing population of patients with chronic hepatitis C virus (HCV) infection who failed a direct-acting antiviral (DAA)-based regimen. In this Phase 3 study, we evaluated sofosbuvir-velpatasvir plus ribavirin in Japanese patients with genotype 1 or 2 HCV infection who previously received DAAs.

Methods: Patients were randomized 1:1 to receive sofosbuvir-velpatasvir plus ribavirin for 12 or 24 weeks. Randomization was stratified by HCV genotype and presence of cirrhosis. The primary endpoint was sustained virologic response 12-week post-treatment (SVR12).

Results: Of 117 participants, 81% had HCV genotype 1 infection, 33% had cirrhosis, and 95% had NS5A resistance-associated substitutions (RAS) at baseline. Overall, SVR12 rates were 97% (58/60; 95% CI 88-100%) with 24 weeks of treatment and 82% (47/57; 95% CI 70-91%) with 12 weeks. For HCV genotype 1 and 2 infected patients, the SVR12 rates with 24 weeks of treatment were 98% and 92%, respectively. In both treatment groups, SVR12 rates in HCV genotype 1 patients were statistically superior to a historical control rate of 50% (p < 0.001). For patients with NS5A RASs at baseline, 85% (46/54) in the 12-week group and 96% (54/56) in the 24-week group achieved SVR12. The most common adverse events were upper respiratory tract viral infection, anemia, and headache. Three (2.6%) patients discontinued treatment because of adverse events.

Conclusion: Sofosbuvir-velpatasvir plus ribavirin was highly effective and well tolerated in Japanese patients who previously failed a DAA-based regimen. Baseline NS5A RASs did not affect treatment outcomes.

Keywords: Antiviral resistance; DAA-experienced; NS5A inhibitor; NS5B polymerase inhibitor; Salvage therapy.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / therapeutic use*
  • Carbamates / administration & dosage
  • Carbamates / therapeutic use
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Genotype
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / genetics
  • Heterocyclic Compounds, 4 or More Rings / administration & dosage
  • Heterocyclic Compounds, 4 or More Rings / therapeutic use
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Ribavirin / administration & dosage
  • Ribavirin / therapeutic use
  • Sofosbuvir / administration & dosage
  • Sofosbuvir / therapeutic use
  • Sustained Virologic Response
  • Treatment Failure
  • Young Adult

Substances

  • Antiviral Agents
  • Carbamates
  • Heterocyclic Compounds, 4 or More Rings
  • Ribavirin
  • velpatasvir
  • Sofosbuvir