Open AccessEfficacy 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
Author(s) -
O'Leary Jacqueline G.,
Fontana Robert J.,
Brown Kimberly,
Burton James R.,
FirpiMorell Roberto,
Muir Andrew,
O'Brien Christopher,
Rabinovitz Mordechai,
Reddy Rajender,
Ryan Robert,
Shprecher Adam,
Villadiego Shirley,
Prabhakar Avinash,
Brown Robert S.
Publication year - 2017
Publication title -
transplant international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.998
H-Index - 82
eISSN - 1432-2277
pISSN - 0934-0874
DOI - 10.1111/tri.12896
Subject(s) - simeprevir , sofosbuvir , medicine , ribavirin , gastroenterology , clinical endpoint , cirrhosis , hepatitis c virus , hepatitis c , adverse effect , randomized controlled trial , surgery , virology , virus
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 ( SVR 12). 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, SVR 12 was achieved by 81.8% in Arm 1, 100% in Arm 2, and 93.9% in Arm 3; two subjects did not achieve SVR 12: 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: NCT 02165189).