Efficacy and safety of simeprevir and sofosbuvir with and without ribavirin in subjects with recurrent genotype 1 hepatitis C postorthotopic liver transplant: the randomized GALAXY study

Jacqueline G. O'Leary, Robert J. Fontana, Kimberly Brown, James R. Burton, Roberto Firpi-Morell, Andrew Muir, Christopher O'Brien, Mordechai Rabinovitz, Rajender Reddy, Robert Ryan, Adam Shprecher, Shirley Villadiego, Avinash Prabhakar, Robert S. Brown

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Abstract

This prospective, randomized, phase 2 study in subjects with recurrent hepatitis C virus (HCV) genotype 1 postorthotopic liver transplant evaluated once-daily simeprevir 150 mg + sofosbuvir 400 mg, with and without ribavirin 1000 mg. Primary endpoint was proportion of subjects with week 12 sustained virologic response (SVR12). Thirty-three subjects without cirrhosis were randomized 1:1:1 into three arms (stratified by genotype/subtype and Q80K): Arm 1, simeprevir + sofosbuvir + ribavirin, 12 weeks; Arm 2, simeprevir + sofosbuvir, 12 weeks; Arm 3, simeprevir + sofosbuvir, 24 weeks; 13 additional subjects (two with cirrhosis, 11 without cirrhosis) entered Arm 3. All 46 subjects received at least one dose of study drug; median age, 60 years; 73.9% male; 80.4% White; 71.7% genotype/subtype 1a [12 (36.4%) of these had Q80K]; median 4.5 years post-transplant. Among randomized subjects, SVR12 was achieved by 81.8% in Arm 1, 100% in Arm 2, and 93.9% in Arm 3; two subjects did not achieve SVR12: one viral relapse (follow-up week 4; Arm 1) and one missing follow-up week 12 data. In total, five subjects had a serious adverse event, considered unrelated to treatment per investigator. Simeprevir exposure was increased relative to the nontransplant setting, but not considered clinically relevant. Simeprevir + sofosbuvir treatment, with or without ribavirin, was efficacious and well tolerated (ClinicalTrials.gov Identifier: NCT02165189).

Original languageEnglish (US)
Pages (from-to)196-208
Number of pages13
JournalTransplant International
Volume30
Issue number2
DOIs
StatePublished - Feb 1 2017

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Keywords

  • infection–hepatitis B, C
  • liver clinical–other

ASJC Scopus subject areas

  • Transplantation

Cite this

O'Leary, J. G., Fontana, R. J., Brown, K., Burton, J. R., Firpi-Morell, R., Muir, A., O'Brien, C., Rabinovitz, M., Reddy, R., Ryan, R., Shprecher, A., Villadiego, S., Prabhakar, A., & Brown, R. S. (2017). Efficacy and safety of simeprevir and sofosbuvir with and without ribavirin in subjects with recurrent genotype 1 hepatitis C postorthotopic liver transplant: the randomized GALAXY study. Transplant International, 30(2), 196-208. https://doi.org/10.1111/tri.12896