TY - JOUR
T1 - Efficacy and safety of simeprevir and sofosbuvir with and without ribavirin in subjects with recurrent genotype 1 hepatitis C postorthotopic liver transplant
T2 - the randomized GALAXY study
AU - O'Leary, Jacqueline G.
AU - Fontana, Robert J.
AU - Brown, Kimberly
AU - Burton, James R.
AU - Firpi-Morell, Roberto
AU - Muir, Andrew
AU - O'Brien, Christopher
AU - Rabinovitz, Mordechai
AU - Reddy, Rajender
AU - Ryan, Robert
AU - Shprecher, Adam
AU - Villadiego, Shirley
AU - Prabhakar, Avinash
AU - Brown, Robert S.
N1 - Funding Information:
This study was funded by Janssen Scientific Affairs, LLC. Medical writing support was provided by Courtney St. Amour, PhD, of MedErgy, and was funded by Janssen Scientific Affairs, LLC. This study was funded by Janssen Scientific Affairs, LLC. The authors would like to thank the patients and their families, study investigators and the study team. The authors would also like to acknowledge Greg Everson (University of Colorado Denver), Joy Peter and Dave Nelson (University of Florida, Gainesville) and Adrianne Padilla (Janssen Scientific Affairs, LLC) for their contributions to the original design of the study. Medical writing support was provided by Courtney St. Amour, PhD, of MedErgy, and was funded by Janssen Scientific Affairs, LLC.
Publisher Copyright:
© 2016 Steunstichting ESOT
PY - 2017/2/1
Y1 - 2017/2/1
N2 - 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).
AB - 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).
KW - infection–hepatitis B, C
KW - liver clinical–other
UR - http://www.scopus.com/inward/record.url?scp=85011805292&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85011805292&partnerID=8YFLogxK
U2 - 10.1111/tri.12896
DO - 10.1111/tri.12896
M3 - Article
C2 - 27896858
AN - SCOPUS:85011805292
SN - 0934-0874
VL - 30
SP - 196
EP - 208
JO - Transplant International
JF - Transplant International
IS - 2
ER -