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: Jacqueline G O'Leary, Robert J Fontana, Kimberly Brown, James R Burton Jr, Roberto Firpi-Morell, Andrew Muir, Christopher O'Brien, Mordechai Rabinovitz, Rajender Reddy, Robert Ryan, Adam Shprecher, Shirley Villadiego, Avinash Prabhakar, Robert S Brown Jr
• Journal: Transplant international : official journal of the European Society for Organ Transplantation (Transpl Int) Vol. 30 Issue 2 Pg. 196-208 (Feb 2017) ISSN: 1432-2277 [Electronic] Switzerland
• PMID: 27896858 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: © 2016 Steunstichting ESOT.

Chemical References

• Antiviral Agents

Topics

• Aged
• Antiviral Agents (pharmacokinetics, therapeutic use)
• Female
• Hepacivirus (genetics)
• Hepatitis C (drug therapy, virology)
• Humans
• Liver Transplantation (adverse effects)
• Male
• Middle Aged
• Patient Reported Outcome Measures
• Postoperative Complications (drug therapy, virology)
• Treatment Outcome