Efficacy of elbasvir and grazoprevir in participants with hepatitis C virus genotype 4 infection: A pooled analysis

Liver Int. 2018 Sep;38(9):1583-1591. doi: 10.1111/liv.13727. Epub 2018 Mar 31.

Abstract

Background & aims: The aim of this integrated analysis was to assess the efficacy of the once-daily combination of elbasvir 50 mg and grazoprevir 100 mg, with and without ribavirin in HCV genotype 4 (GT4)-infected participants enrolled in the Phase 2/3 clinical programme with elbasvir/grazoprevir.

Methods: Treatment-naïve and treatment-experienced participants 18 years of age or older with chronic HCV GT4 infection and baseline HCV RNA ≥10 000 IU/mL were included in the analysis. The analysis population was the full analysis set (FAS; all participants who received at least 1 dose of study medication) and a total of 155 HCV GT4 participants were evaluated. The primary endpoint was sustained virologic response at week 12 (SVR12; HCV RNA less than the lower limit of quantitation at 12 weeks after the completion of study therapy).

Results: Overall, among GT4-infected participants treated with 12 or 16 weeks of elbasvir/grazoprevir ± ribavirin, the SVR12 efficacy rates were 96.4% (107/111) in treatment-naïve participants and 88.6% (39/44) in treatment-experienced participants. The SVR12 rates were 96.0% (97/101) in treatment-naïve participants treated with 12 weeks of elbasvir/grazoprevir and 100% (8/8) in treatment-experienced participants treated with 16 weeks of elbasvir/grazoprevir plus ribavirin. Efficacy was not impacted by GT4 subtype.

Conclusions: The regimens of 12 weeks of elbasvir/grazoprevir without ribavirin, and 16 weeks of elbasvir/grazoprevir plus ribavirin, were efficacious in HCV GT4-infected treatment-naïve and treatment-experienced participants respectively. Baseline NS5A resistance-associated substitutions did not impact the efficacy of elbasvir/grazoprevir in GT4-infected participants.

Trial registration: ClinicalTrials.gov NCT01932762 NCT02105467 NCT02105662 NCT02105688 NCT02252016 NCT02251990 NCT02105701 NCT02358044.

Keywords: elbasvir; genotype 4; grazoprevir; hepatitis C; ribavirin.

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amides
  • Antiviral Agents / administration & dosage*
  • Benzofurans / administration & dosage*
  • Carbamates
  • Cyclopropanes
  • Drug Resistance, Viral
  • Drug Therapy, Combination
  • Female
  • Genotype
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Imidazoles / administration & dosage*
  • Internationality
  • Liver Cirrhosis / virology
  • Male
  • Middle Aged
  • Quinoxalines / administration & dosage*
  • Ribavirin / therapeutic use
  • Sulfonamides
  • Sustained Virologic Response
  • Young Adult

Substances

  • 2-(pyrrolidin-2-yl)-5-(2-(4-(5-(pyrrolidin-2-yl)-1H-imidazol-2-yl)phenyl)benzofuran-5-yl)-1H-imidazole
  • Amides
  • Antiviral Agents
  • Benzofurans
  • Carbamates
  • Cyclopropanes
  • Imidazoles
  • Quinoxalines
  • Sulfonamides
  • Ribavirin
  • grazoprevir

Associated data

  • ClinicalTrials.gov/NCT01932762
  • ClinicalTrials.gov/NCT02105467
  • ClinicalTrials.gov/NCT02105662
  • ClinicalTrials.gov/NCT02105688
  • ClinicalTrials.gov/NCT02252016
  • ClinicalTrials.gov/NCT02251990
  • ClinicalTrials.gov/NCT02105701
  • ClinicalTrials.gov/NCT02358044