Author information
1
Queen Mary University, London, United Kingdom.
2
Institute of Liver Studies, Kings College Hospital, London, United Kingdom.
3
South West Liver Unit, Derriford Hospital and Peninsula Schools of Medicine and Dentistry, Plymouth, United Kingdom.
4
Bradford Teaching Hospitals Foundation Trust, Bradford, United Kingdom.
5
Glasgow Royal Campus, Glasgow, United Kingdom.
6
John Radcliffe Hospital, Oxford, United Kingdom.
7
Imperial College Healthcare NHS Trust, London, United Kingdom.
8
NIHR Biomedical Unit in Gastrointestinal and Liver Diseases at Nottingham University Hospital NHS Trust and The University of Nottingham, Nottingham, United Kingdom.
9
North Manchester General Hospital, Manchester, United Kingdom.
10
St. Georges University of London, London, United Kingdom.
11
Gartnavel General Hospital, Glasgow, United Kingdom.
12
Hepatology Joint Clinical Research Unit, Bristol, United Kingdom.
13
Institute for Liver and Digestive Health, University College London, London, United Kingdom.
14
QE Hospital, Birmingham, United Kingdom.
15
Merck & Co., Inc., Kenilworth, New Jersey.
Abstract
Many direct-acting antiviral regimens have reduced activity in people with hepatitis C virus (HCV) genotype (GT)3 infection and cirrhosis. The C-ISLE study assessed the efficacy and safety of elbasvir/grazoprevir (EBR/GZR) plus sofosbuvir (SOF) with and without ribavirin (RBV) in compensated cirrhotic participants with GT3 infection. This was a phase 2, randomized, open-label study. Treatment-naive participants received EBR/GZR + SOF + RBV for 8 weeks or EBR/GZR + SOF for 12 weeks and peginterferon/RBV treatment-experienced participants received EBR/GZR + SOF ± RBV for 12 weeks or EBR/GZR + SOF for 16 weeks. The primary end point was HCV RNA <15 IU/mL 12 weeks after end of treatment (SVR12). Among treatment-naive participants, SVR12 was 91% (21/23) in those treated with RBV for 8 weeks and 96% (23/24) in those treated for 12 weeks. Among treatment-experienced participants, SVR12 was 94% (17/18) and 100% (17/17) in the 12-week arm, with and without RBV, respectively, and 94% (17/18) in the 16-week arm. Five participants failed to achieve SVR: 2 relapsed (both in the 8-week arm); 1 discontinued due to vomiting/cellulitis (16-week arm); and 2 discontinued (consent withdrawn/lost to follow-up). SVR12 was not affected by the presence of resistance-associated substitutions (RASs). There was no consistent change in insulin resistance, and 5 participants reported serious adverse events (pneumonia, chest pain, opiate overdose, cellulitis, decreased creatinine).
CONCLUSION:
High efficacy was demonstrated in participants with HCV GT3 infection and cirrhosis. Treatment beyond 12 weeks was not required, and efficacy was maintained regardless of baseline RASs. Data from this study support the use of EBR/GZR plus SOF for 12 weeks without RBV for treatment-naive and peginterferon/RBV-experienced people with GT3 infection and cirrhosis. ClinicalTrials.gov no: NCT02601573.