Efficacy and Safety of Simeprevir and Sofosbuvir With and Without Ribavirin in Subjects With Recurrent Genotype 1 Hepatitis C Post-Orthotopic Liver Transplant: The Randomized GALAXY Study.
O'Leary JG, Fontana RJ, et al.Transplant International 2016 [record in progress]
Aims
To evaluate the efficacy and safety of simeprevir in combination with sofosbuvir, with or without ribavirin, on recurrent hepatitis C virus (HCV) genotype 1 infection post-orthotopic liver transplant.
Interventions
Participants without cirrhosis were randomized into one of three treatment arms and received either once-daily simeprevir 150 mg + once-daily sofosbuvir 400 mg + weight-based ribavirin for 12 weeks (Arm 1), once-daily simeprevir 150 mg + once-daily sofosbuvir 400 mg for 12 weeks (Arm 2) or once-daily simeprevir 150 mg + once-daily sofosbuvir 400 mg for 24 weeks (Arm 3). Upon completion of randomization, enrolment into Arm 3 was opened to all eligible subjects, regardless of the presence of cirrhosis, until the total 46 participants were enrolled.
Participants
46 non-pregnant recipients of an orthotopic liver transplant ≥6 months to 15 years before enrolment, aged ≥18 years, with recurrent HCV genotype 1 infection, an HCV RNA level >10,000 IU/mL at baseline, and on stable immunosuppression for ≥3 months before screening.
Outcomes
The primary outcome measured was the proportion of subjects with sustained virologic response (SVR) at week 12. Secondary measured outcomes were on-treatment virologic response at Weeks 2, 4, 8, and 12, for all subjects and Weeks 16, 20, and 24 for subjects in Arm 3, the proportion of subjects who achieved SVR four weeks after the end of treatment, and the the incidence of virologic breakthrough and relapse. Resistance, pharmacokinetic, safety and patient-reported outcomes were also measurerd.
Follow-up
12 weeks
CET Conclusions
This is a phase II trial of simeprevir + sofosbuvir for recurrent Hepatitis C Virus (Type 1) post liver transplantation. The randomisation changed whether ribavirin was also prescribed and the duration of treatment from 12 to 24 weeks. The randomised patients did not have cirrhosis, however after the inclusion of 11 to each arm a further 13 (some with cirrhosis) were allocated to Arm 3 (simeprevir + sofosbuvir for 24 weeks). The study was randomised adequately, was assessed as intention to treat, but not blinded.The primary outcome was SVR12 (sustained virologic response at 12 weeks after the end of treatment) and the rates were 81-100% depending on the arm (Arm 1 had a rate of 81% due to the loss of data for one patient only). No subjects had viral breakthrough, although 1 had relapse. The most common adverse events were headache (37%) and fatigue (35%). 98% reported at least one adverse event. 5 patients (11%) had a serious adverse event, including one fatality (suicide). The results are consistent with those in a non-transplant setting and the drug combination was generally well tolerated.
Data analysis
Available case analysis
Trial registration
ClinicalTrials.gov - NCT02165189