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. (20th January 2017)

• Record Type: Journal Article
• Authors: O'Leary, Jacqueline G.; Fontana, Robert J.; Brown, Kimberly; Burton, James R.; Firpi‐Morell, Roberto; Muir, Andrew; O'Brien, Christopher; Rabinovitz, Mordechai; Reddy, Rajender; Ryan, Robert; Shprecher, Adam; Villadiego, Shirley; Prabhakar, Avinash; Brown, Robert S.
• Is Part Of: Transplant international. Volume 30:Number 2(2017)
• Page Start: 196
• Page End: 208
• Publication Date: 2017-01-20
• Subjects: infection–hepatitis B, C -- liver clinical–other; Transplantation of organs, tissues, etc -- Periodicals; 617.95405
• DOI: 10.1111/tri.12896
• Languages: English
• ISSNs: 0934-0874

Abstract

Summary: 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).