GS-9857 in patients with chronic hepatitis C virus genotype 1–4 infection: a randomized, double-blind, dose-ranging phase 1 study

M. Rodriguez-Torres, S. Glass, J. Hill, B. Freilich, D. Hassman, A. M. Di Bisceglie, J. G. Taylor, B. J. Kirby, H. Dvory-Sobol, J. C. Yang, D. An, L. M. Stamm, D. M. Brainard, S. Kim, D. Krefetz, W. Smith, T. Marbury, E. Lawitz

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

GS-9857, an inhibitor of the hepatitis C virus (HCV) nonstructural protein (NS) 3/4A, demonstrates potent activity against HCV genotypes 1–6 and improved coverage against commonly encountered NS3 resistance-associated variants (RAVs). In this study, the safety, tolerability, antiviral activity and pharmacokinetics (PK) of GS-9857 were evaluated in patients with chronic HCV genotype 1–4 infection. Patients with genotype 1–4 infection received placebo or once-daily GS-9857 at doses ranging from 50 to 300 mg for 3 days under fasting conditions. GS-9857 was well tolerated; all reported adverse events (AEs) were mild or moderate in severity. Diarrhoea and headache were the most commonly reported AEs. Grade 3 or 4 laboratory abnormalities were observed in 17% of patients receiving GS-9857; there were no Grade 3 or 4 abnormalities in alanine aminotransferase, aspartate aminotransferase or alkaline phosphatase levels. GS-9857 demonstrated potent antiviral activity in patients with chronic HCV infection, achieving mean and median maximum reductions in HCV RNA of ≥3 log10 IU/mL following administration of a 100-mg dose in patients with HCV genotype 1a, 1b, 2, 3 or 4 infection. The antiviral activity of GS-9857 was unaffected by the presence of pretreatment NS3 RAVs. In patients with genotype 1–4 infection, GS-9857 exhibited linear PK and was associated with a median half-life of 29–42 h, supporting once-daily dosing. Thus, the tolerability, efficacy and pharmacokinetic profile of GS-9857 support its further evaluation for treatment of patients with chronic HCV infection.

Original languageEnglish (US)
Pages (from-to)614-622
Number of pages9
JournalJournal of Viral Hepatitis
Volume23
Issue number8
DOIs
StatePublished - Aug 1 2016

Keywords

  • GS-9857
  • NS3/4A protease inhibitor
  • hepatitis C virus

ASJC Scopus subject areas

  • Hepatology
  • Infectious Diseases
  • Virology

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