Sofosbuvir (GS-7977) plus peginterferon/ribavirin in treatment-naïve patients with HCV genotype 1: A randomized, 28-day, dose-ranging trial

Maribel Rodriguez-Torres, Eric Lawitz, Kris V. Kowdley, David R. Nelson, Edwin Dejesus, John G. McHutchison, Melanie T. Cornpropst, Michael Mader, Efsevia Albanis, Deyuan Jiang, Christy M. Hebner, William T. Symonds, Michelle M. Berrey, Jay Lalezari

Research output: Contribution to journalArticle

82 Scopus citations

Abstract

Background & Aims Sofosbuvir (formerly GS-7977) is a pyrimidine nucleotide analog inhibitor of the hepatitis C virus (HCV) NS5B polymerase. We assessed the safety, tolerability, antiviral activity, and pharmacokinetics of sofosbuvir plus pegylated-interferon (PegIFN)/ribavirin (RBV) in a 28-day, dose-ranging trial in treatment-naïve patients infected with genotype 1 HCV. Methods In this double-blind study, 64 patients were randomized (1:1:1:1) to receive one of three once-daily doses of oral sofosbuvir (100, 200, or 400 mg) or placebo plus PegIFN/RBV for 28 days, after which all patients continued to receive PegIFN/RBV alone for a further 44 weeks. Results Patients in the sofosbuvir/PegIFN/RBV groups experienced mean reductions in HCV RNA >5 log10 IU/ml (-5.3 for 100 mg, -5.1 for 200 mg and -5.3 for 400 mg) vs. -2.8 log10 IU/ml for placebo/PegIFN/RBV after 28 days. Rapid virologic response (RVR) rates were markedly higher after sofosbuvir treatment (88-94%) than placebo (21%), as were rates of sustained virologic response (SVR) at post-treatment Week 24 (56%, 83%, and 80% for sofosbuvir 100, 200, and 400 mg, respectively, vs. 43% for placebo). The number of patients experiencing virologic breakthrough and post-treatment relapse was higher in the sofosbuvir 100 mg group than sofosbuvir 200 and 400 mg groups. Sofosbuvir was well tolerated; the most frequent adverse events were fatigue and nausea. Conclusions These results support further studies with sofosbuvir at 200 mg and 400 mg to determine the optimal dose and treatment duration of sofosbuvir in HCV genotype 1.

Original languageEnglish (US)
Pages (from-to)663-668
Number of pages6
JournalJournal of Hepatology
Volume58
Issue number4
DOIs
StatePublished - Apr 1 2013
Externally publishedYes

Keywords

  • Antiviral
  • Hepatitis C virus
  • Rapid virologic response
  • Sofosbuvir
  • Sustained virologic response

ASJC Scopus subject areas

  • Hepatology

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    Rodriguez-Torres, M., Lawitz, E., Kowdley, K. V., Nelson, D. R., Dejesus, E., McHutchison, J. G., Cornpropst, M. T., Mader, M., Albanis, E., Jiang, D., Hebner, C. M., Symonds, W. T., Berrey, M. M., & Lalezari, J. (2013). Sofosbuvir (GS-7977) plus peginterferon/ribavirin in treatment-naïve patients with HCV genotype 1: A randomized, 28-day, dose-ranging trial. Journal of Hepatology, 58(4), 663-668. https://doi.org/10.1016/j.jhep.2012.11.018