Efficacy and safety of elbasvir/grazoprevir for 8 or 12 weeks for hepatitis C virus genotype 4 infection: A randomized study

Liver Int. 2020 May;40(5):1042-1051. doi: 10.1111/liv.14313. Epub 2020 Mar 22.

Abstract

Background & aims: Hepatitis C virus (HCV) genotype (GT) 4 infection is prevalent in sub-Saharan Africa and the Middle East, particularly in Egypt. This study evaluated the safety and efficacy of elbasvir/grazoprevir administered for 8 and 12 weeks in participants with HCV GT4 infection.

Methods: In this partially randomized, open-label multicentre study conducted in France (NCT03111108; Protocol MK5172-096), treatment-naive participants with GT4 infection and F0-F2 fibrosis were randomized 2:1 to elbasvir (50 mg)/grazoprevir (100 mg) for 8 or 12 weeks. Treatment-naive participants with F3-F4 fibrosis and all treatment-experienced participants (F0-F4) were assigned to elbasvir/grazoprevir for 12 weeks. The primary endpoint was sustained virologic response (SVR) 12 weeks after the end of therapy.

Results: One hundred and seventeen participants were enrolled. Among treatment-naive participants with F0-F2 fibrosis, SVR was achieved by 94% (50/53) and 96% (26/27) of those receiving elbasvir/grazoprevir for 8 or 12 weeks, respectively, and four participants relapsed. In the 12-week arm, 95% (35/37) achieved SVR and two participants relapsed. NS5A resistance-associated substitutions were present at baseline and virologic failure in five of the participants with relapse. Drug-related adverse events occurred in 42% (n = 22) and 50% (n = 32) of participants receiving 8 and 12 weeks of treatment, respectively. No participant discontinued treatment owing to an adverse event.

Conclusion: These data confirm the efficacy of elbasvir/grazoprevir administered for 12 weeks in treatment-experienced individuals with HCV GT4 infection and those with advanced fibrosis. Treatment-naive individuals with mild fibrosis can be treated effectively with an 8-week regimen.

Keywords: hepatitis C; randomized controlled trial; therapeutics.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / therapeutic use
  • Antiviral Agents / adverse effects
  • Benzofurans
  • Carbamates / therapeutic use
  • Cyclopropanes / therapeutic use
  • Drug Therapy, Combination
  • Egypt
  • France
  • Genotype
  • Hepacivirus* / genetics
  • Hepatitis C, Chronic* / drug therapy
  • Humans
  • Imidazoles
  • Quinoxalines / adverse effects
  • Sulfonamides / therapeutic use

Substances

  • Amides
  • Antiviral Agents
  • Benzofurans
  • Carbamates
  • Cyclopropanes
  • Imidazoles
  • Quinoxalines
  • Sulfonamides
  • grazoprevir
  • elbasvir

Associated data

  • ClinicalTrials.gov/NCT03111108