Efficacy and safety of a two-drug direct-acting antiviral agent regimen ruzasvir 180 mg and uprifosbuvir 450 mg for 12 weeks in adults with chronic hepatitis C virus genotype 1, 2, 3, 4, 5 or 6

J Viral Hepat. 2019 Sep;26(9):1127-1138. doi: 10.1111/jvh.13132. Epub 2019 Jul 11.

Abstract

Ruzasvir (MK-8408, an NS5A inhibitor) and uprifosbuvir (MK-3682, a nonstructural protein 5B nucleotide inhibitor) are highly potent direct-acting antiviral agents for the treatment of hepatitis C virus (HCV) infection. A phase III clinical trial evaluating the two-drug combination of ruzasvir 60 mg plus uprifosbuvir 450 mg suggested suboptimal efficacy in certain HCV genotypes (C-BREEZE 1; NCT02759315). The aim of the present study was to evaluate the efficacy and safety of ruzasvir in combination with uprifosbuvir administered at a higher dose than that assessed in the earlier study (C-BREEZE 2: NCT02956629/Merck protocol PN041). Treatment-naïve or interferon (with or without ribavirin)-experienced participants with or without compensated cirrhosis were enrolled. All participants received ruzasvir 180 mg plus uprifosbuvir 450 mg once daily for 12 weeks. The primary objectives were the proportion of participants with HCV RNA <15 lU/mL at 12 weeks after the end of study therapy (SVR12), and safety and tolerability of the study drug. Overall, 282 participants were enrolled. SVR12 (n/N) was 91.3% (42/46) in participants infected with HCV genotype (GT) 1a; GT1b, 96.7% (29/30); GT2, 91.5% (43/47); GT3, 73.8% (45/61); GT4, 98.2% (55/56); GT5, 100.0% (18/18); and GT6, 90.9% (20/22). Adverse events (AEs) were reported by 61.3% of participants; drug-related AEs were reported by 33.3%. The most frequent (≥5% of participants) drug-related AEs in all participants were fatigue (7.8%) and headache (7.4%). In conclusion, the two-drug combination of ruzasvir 180 mg plus uprifosbuvir 450 mg for 12 weeks was highly effective and well tolerated in participants infected with HCV GT1, GT2, GT4, GT5 and GT6, with a lower efficacy in GT3-infected persons.

Keywords: clinical trial; efficacy; genotype; hepatitis C virus; safety.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / therapeutic use
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Genotype
  • Hepacivirus / drug effects*
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / drug therapy*
  • Heterocyclic Compounds, 4 or More Rings / administration & dosage*
  • Heterocyclic Compounds, 4 or More Rings / therapeutic use
  • Humans
  • Interferons / therapeutic use
  • Male
  • Middle Aged
  • Pyrrolidines / administration & dosage*
  • Pyrrolidines / therapeutic use
  • RNA, Viral / blood
  • Ribavirin / therapeutic use
  • Sustained Virologic Response*
  • Thiazoles / administration & dosage*
  • Thiazoles / therapeutic use
  • Uridine / administration & dosage
  • Uridine / analogs & derivatives*
  • Uridine / therapeutic use
  • Young Adult

Substances

  • Antiviral Agents
  • Heterocyclic Compounds, 4 or More Rings
  • Pyrrolidines
  • RNA, Viral
  • Thiazoles
  • Ribavirin
  • Interferons
  • uprifosbuvir
  • ruzasvir
  • Uridine

Associated data

  • ClinicalTrials.gov/NCT02759315
  • ClinicalTrials.gov/NCT02956629