Peter Ferenci1, Tarik Asselah2, Graham R Foster3, Stefan Zeuzem4, Christoph Sarrazin4, Christophe Moreno5, Denis Ouzan6, Marina Maevskaya7, Filipe Calinas8, Luis E Morano9, Javier Crespo10, Jean-François Dufour11, Marc Bourlière12, Kosh Agarwal13, Daniel Forton14, Marcus Schuchmann15, Elmar Zehnter16, Shuhei Nishiguchi17, Masao Omata18, George Kukolj19, Yakov Datsenko20, Miguel Garcia19, Joseph Scherer19, Anne-Marie Quinson19, Jerry O Stern19. 1. Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria. Electronic address: peter.ferenci@meduniwien.ac.at. 2. Department of Hepatology, Hôpital Beaujon, APHP, University Paris-Diderot and INSERM CRB3, Clichy, France. 3. Department of Hepatology, Barts and the London School of Medicine and Dentistry, Queen Mary, University of London, London, UK. 4. Department of Internal Medicine, JW Goethe University Hospital, Frankfurt, Germany. 5. Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Hôpital Universitaire Erasme, Université Libre de Bruxelles, Brussels, Belgium. 6. Department of Hepato-gastroenterology, Institut Arnault Tzanck, St Laurent du Var, France. 7. Hepatology Department, First Moscow State Medical University, Moscow, Russia. 8. Gastroenterology Service, Centro Hospitalar de Lisboa Central, Lisbon, Portugal. 9. Department of Internal Medicine - Infectious Diseases, Hospital Meixoeiro, Vigo, Spain. 10. Department of Gastroenterology and Hepatology, Hospital Universitario Marqués de Valdecilla, Santander, Spain. 11. Department of Hepatology, University Clinic for Visceral Surgery and Medicine, Bern, Switzerland. 12. Département d'Hépato-gastroentérologie, Hôpital Saint Joseph, Marseille, France. 13. Institute of Liver Studies, King's College Hospital, London, UK. 14. Department of Gastroenterology and Hepatology, St George's Hospital, London, UK. 15. 1st Department of Medicine, University Hospital Mainz, Mainz, Germany. 16. Gastroenterological Practice, Schwerpunktpraxis Hepatologie, Dortmund, Germany. 17. Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan. 18. Department of Gastroenterology, Yamanishi Central and Kita Hospitals, Yamanishi, Japan. 19. Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA. 20. Boehringer Ingelheim Pharmaceuticals, GmbH & Co. KG, Biberach, Germany.
Abstract
BACKGROUND & 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.
RCT Entities:
BACKGROUND & 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.
Authors: K L Berger; J Scherer; M Ranga; N Sha; J O Stern; A-M Quinson; G Kukolj Journal: Antimicrob Agents Chemother Date: 2015-07-20 Impact factor: 5.191
Authors: Masao Omata; Tatsuo Kanda; Osamu Yokosuka; Darrell Crawford; Mamun Al-Mahtab; Lai Wei; Alaaeldin Ibrahim; George K K Lau; Barjesh C Sharma; Saeed S Hamid; Wan-Long Chuang; A Kadir Dokmeci Journal: Hepatol Int Date: 2015-05-05 Impact factor: 9.029
Authors: Tarik Asselah; Stefan Zeuzem; Vicente Soriano; Jean-Pierre Bronowicki; Ansgar W Lohse; Beat Müllhaupt; Marcus Schuchmann; Marc Bourlière; Maria Buti; Stuart K Roberts; Edward J Gane; Jerry O Stern; Florian Voss; Patrick Baum; John-Paul Gallivan; Wulf O Böcher; Federico J Mensa Journal: PLoS One Date: 2015-12-09 Impact factor: 3.240