Grazoprevir and elbasvir plus ribavirin for chronic HCV genotype-1 infection after failure of combination therapy containing a direct-acting antiviral agent

J Hepatol. 2015 Sep;63(3):564-72. doi: 10.1016/j.jhep.2015.04.009. Epub 2015 Apr 18.

Abstract

Background & aims: The Phase-2 C-SALVAGE study evaluated an investigational interferon-free combination of grazoprevir (a NS3/4A protease inhibitor) and elbasvir (a NS5A inhibitor) with ribavirin for patients with chronic HCV genotype-1 infection who had failed licensed DAA-containing therapy.

Methods: C-SALVAGE was an open-label study of grazoprevir 100 mg and elbasvir 50 mg QD with weight-based ribavirin BID for 12 weeks in cirrhotic and non-cirrhotic patients with chronic HCV genotype-1 infection who had not attained SVR after ⩾4 weeks of peginterferon and ribavirin plus either boceprevir, telaprevir, or simeprevir. Exclusion criteria included decompensated liver disease, hepatocellular carcinoma, and HIV or HBV co-infection. The primary efficacy outcome was SVR12 defined as a HCV RNA level below the assay limit of quantification 12 weeks after the end of treatment.

Results: Of the 79 patients treated with ⩾1 dose of study drug, 66 (84%) patients had a history of virologic failure on a regimen containing a NS3/4A protease inhibitor; 12 of the other 13 patients discontinued prior treatment because of adverse experiences. At entry, 34 (43.6%) of 78 evaluable patients harbored NS3 RAVs. SVR12 rates were 76/79 (96.2%) overall, including 28/30 (93.3%) patients with genotype 1a infection, 63/66 (95.5%) patients with prior virologic failure, 43/43 (100%) patients without baseline RAVs, 31/34 (91.2%) patients with baseline NS3 RAVs, 6/8 (75.0%) patients with baseline NS5A RAVs, 4/6 (66.7%) patients with both baseline NS3 and RAVs, and 32/34 (94.1%) cirrhotic patients. None of the five reported serious adverse events were considered drug-related.

Conclusions: Grazoprevir and elbasvir plus ribavirin for 12 weeks provides a promising new treatment option for patients after failure of triple therapy containing an earlier-generation protease inhibitor.

Trial registration: ClinicalTrials.gov NCT02105454.

Keywords: C-SALVAGE; Direct-acting antiviral agents; Elbasvir; Grazoprevir; HCV genotype-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amides
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / adverse effects
  • Benzofurans / administration & dosage
  • Carbamates
  • Cyclopropanes
  • Drug Therapy, Combination
  • Female
  • Genotype
  • Hepacivirus / classification
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology
  • Humans
  • Imidazoles / administration & dosage
  • Male
  • Middle Aged
  • Quinoxalines / administration & dosage
  • Ribavirin / administration & dosage
  • Sulfonamides
  • Treatment Failure

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/NCT02105454