Efficacy and safety of glecaprevir/pibrentasvir in patients with chronic hepatitis C virus genotype 5 or 6 infection (ENDURANCE-5,6): an open-label, multicentre, phase 3b trial.

Background The pangenotypic direct-acting antiviral regimen of glecaprevir coformulated with pibrentasvir is approved to treat chronic hepatitis C virus (HCV) genotype 1-6 infection in adults. In registrational studies, 84 (99%) of 85 patients with HCV genotype 5 or 6 infection achieved a sustained virological response (SVR) with glecaprevir/pibrentasvir, with no virological failures. To increase the body of data for these less prevalent genotypes, ENDURANCE-5,6 evaluated the efficacy and safety of glecaprevir/pibrentasvir exclusively in patients infected with HCV genotype 5 or 6. Methods ENDURANCE-5,6 was a phase 3b, single-arm, open-label, multicentre trial done in 24 hospitals or clinics in Europe, Oceania, North America, South Africa, and southeast Asia. Adults with chronic HCV genotype 5 or 6 infection who were previously untreated or treatment-experienced were eligible to be enrolled. Glecaprevir/pibrentasvir (300 mg/120 mg) was given orally once daily for 8 weeks (for patients without cirrhosis) or 12 weeks (for patients with compensated cirrhosis). The primary efficacy endpoint was SVR12 (ie, HCV RNA <15 IU/mL at 12 weeks post-treatment), assessed within each HCV genotype, and analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov , number NCT02966795. Findings Between Feb 9, 2017, and Aug 28, 2018, 84 patients were enrolled: 23 with genotype 5 infection and 61 with genotype 6 infection. Overall, 82 (97.6%, 95% CI 94. 4-100. 0) of the 84 patients achieved SVR12. 22 (95.7%, 95% CI 87.3-100.0) of 23 patients with genotype 5 infection achieved SVR12, as did 60 (98.4%, CI 95 2-100. 0) of 61 with genotype 6 infection. One patient with an HCV genotype 6f infection and cirrhosis had on-treatment virological failure at treatment week 12, and one patient with HCV genotype 5a without cirrhosis who had achieved SVR at post-treatment week 4 relapsed at post-treatment week 12. Five (6%) patients had serious adverse events, none of which were deemed related to glecaprevir/pibrentsavir or led to discontinuation. Fatigue (11 [13%] patients) and headache (11 [13%]) were the only adverse events that occurred in 10% or more of patients. No post-baseline grade 3 or higher increases in aminotransferase concentrations were reported. Interpretation Glecaprevir/pibrentasvir achieved high SVR12 rates, comparable with data reported in registrational studies, and was well tolerated in patients with HCV genotype 5 or 6 infection with compensated liver disease. Copyright (C) 2018 Elsevier Ltd. All rights reserved.