title: 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.
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).
authors.affiliation: Department of Medicine, Baylor University Medical Center, Dallas, TX, USA.
authors.forename: Jacqueline G
authors.initials: JG
authors.lastname: O'Leary
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fontana
authors.affiliation: Department of Medicine, Henry Ford Hospital, Detroit, MI, USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Brown
authors.affiliation: Department of Medicine, University of Colorado Denver, Aurora, CO, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Burton
authors.affiliation: Department of Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Firpi-Morell
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Muir
authors.affiliation: Department of Medicine, University of Miami School of Medicine, Miami, FL, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: O'Brien
authors.affiliation: Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Mordechai
authors.initials: M
authors.lastname: Rabinovitz
authors.affiliation: Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Rajender
authors.initials: R
authors.lastname: Reddy
authors.affiliation: Janssen Research & Development, Titusville, NJ, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Ryan
authors.affiliation: Janssen Scientific Affairs, Titusville, NJ, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Shprecher
authors.affiliation: Janssen Scientific Affairs, Titusville, NJ, USA.
authors.forename: Shirley
authors.initials: S
authors.lastname: Villadiego
authors.affiliation: Janssen Scientific Affairs, Titusville, NJ, USA.
authors.forename: Avinash
authors.initials: A
authors.lastname: Prabhakar
authors.affiliation: Department of Medicine, Weill Cornell Medical Center, New York, NY, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Brown
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D000071066:Patient Reported Outcome Measures; D011183:Postoperative Complications / Q000188:drug therapy* / Q000821:virology; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents
keywords: infection-hepatitis B, C; liver clinical-other