Ferenci, PAsselah, TFoster, GZeuzem, SSarrazin, CMoreno, COuzan, DMaevskaya, MCalinas, FMorano, LCrespo, JDufour, JFBourlière, MAgarwal, KForton, DSchuchmann, MZehnter, ENishiguchi, SOmata, MKukolj, GDatsenko, YGarcia, MScherer, JQuinson, AMStern, J2016-06-072016-06-072015-06J Hepatol. 2015 Jun;62(6):1246-55http://hdl.handle.net/10400.17/2513BACKGROUND & AIMS: The efficacy and tolerability of faldaprevir, a potent hepatitis C virus (HCV) NS3/4A protease inhibitor, plus peginterferon (PegIFN) and ribavirin (RBV) was assessed in a double-blind, placebo-controlled phase 3 study of treatment-naïve patients with HCV genotype-1 infection. METHODS: Patients were randomly assigned (1:2:2) to PegIFN/RBV plus: placebo (arm 1, n = 132) for 24 weeks; faldaprevir (120 mg, once daily) for 12 or 24 weeks (arm 2, n = 259); or faldaprevir (240 mg, once daily) for 12 weeks (arm 3, n = 261). In arms 2 and 3, patients with early treatment success (HCV-RNA <25 IU/ml at week 4 and undetectable at week 8) stopped all treatment at week 24. Other patients received PegIFN/RBV until week 48 unless they met futility criteria. The primary endpoint was sustained virologic response 12 weeks post-treatment (SVR12). RESULTS: SVR12 was achieved by 52%, 79%, and 80% of patients in arms 1, 2, and 3, respectively (estimated difference for arms 2 and 3 vs. arm 1: 27%, 95% confidence interval 17%-36%; and 29%, 95% confidence interval, 19%-38%, respectively; p < 0.0001 for both). Early treatment success was achieved by 87% (arm 2) and 89% (arm 3) of patients, of whom 86% and 89% achieved SVR12. Adverse event rates were similar among groups; few adverse events led to discontinuation of all regimen components. CONCLUSIONS: Faldaprevir plus PegIFN/RBV significantly increased SVR12, compared with PegIFN/RBV, in treatment-naïve patients with HCV genotype-1 infection. No differences were seen in responses of patients given faldaprevir once daily at 120 or 240 mg.engAdultAntiviral Agents/administration & dosageDouble-Blind MethodDrug Therapy, CombinationFemaleGenotypeHepacivirus/classificationHepatitis C, Chronic/virologyHumansInterferon-alpha/administration & dosageMaleMiddle AgedOligopeptides/administration & dosagePolyethylene Glycols/administration & dosageRNA, Viral/bloodRecombinant Proteins/administration & dosageRibavirin/administration & dosageThiazoles/administration & dosageCHLC GASAntiviral Agents/adverse effectsHepacivirus/drug effectsHepacivirus/geneticsHepatitis C, Chronic/drug therapyInterferon-alpha/adverse effectsOligopeptides/adverse effectsPolyethylene Glycols/adverse effectsRecombinant Proteins/adverse effectsRibavirin/adverse effectsThiazoles/adverse effectsjournal article10.1016/j.jhep.2014.12.024