Open‐label study of faldaprevir plus peginterferon and ribavirin in hepatitis C virus genotype 1‐infected patients who failed placebo plus peginterferon and ribavirin |
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| Authors: | G. R. Foster P. Ferenci T. Asselah P. Mantry J.‐F. Dufour M. Bourlière D. Forton M. Maevskaya D. Wright E. M. Yoshida J. García‐Samaniego C. Oliveira M. Wright N. Warner N. Sha A.‐M. Quinson J. O. Stern |
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| Affiliation: | 1. Department of Hepatology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK;2. Department of Medicine III, University Hospital Vienna, Vienna, Austria;3. Service d'Hépatologie, AP‐HP, University Paris‐Diderot and INSERM U773, CRB3, H?pital Beaujon, Clichy, France;4. Department of Hepatology, The Liver Institute at Methodist Dallas Medical Center, Dallas, TX, USA;5. Department of Hepatology, University Clinic for Visceral Surgery and Medicine and University of Bern, Bern, Switzerland;6. Département d'Hépato‐gastroentérologie, H?pital Saint Joseph, Marseille, France;7. Department of Gastroenterology and Hepatology, St George's Hospital, London, UK;8. Hepatology Department, First Moscow State Medical University, Moscow, Russia;9. Central Texas Clinical Research, Austin, TX, USA;10. University of British Columbia, Vancouver, BC, Canada;11. Liver Unit, Hospital Universitario La Paz/Carlos III CIBERehd, Madrid, Spain;12. Department of Radiology, Hospital Infante D. Pedro, Aveiro, Portugal;13. Wellcome Trust Clinical Research Facility, Southampton, UK;14. Boehringer Ingelheim Ltd., Bracknell, UK;15. Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA |
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| Abstract: | Faldaprevir, a hepatitis C virus (HCV) NS3/4A protease inhibitor, was evaluated in HCV genotype 1‐infected patients who failed peginterferon and ribavirin (PegIFN/RBV) treatment during one of three prior faldaprevir trials. Patients who received placebo plus PegIFN/RBV and had virological failure during a prior trial were enrolled and treated in two cohorts: prior relapsers (n = 43) and prior nonresponders (null responders, partial responders and patients with breakthrough; n = 75). Both cohorts received faldaprevir 240 mg once daily plus PegIFN/RBV for 24 weeks. Prior relapsers with early treatment success (ETS; HCV RNA <25 IU/mL detectable or undetectable at week 4 and <25 IU/mL undetectable at week 8) stopped treatment at week 24. Others received PegIFN/RBV through week 48. The primary efficacy endpoint was sustained virological response (HCV RNA <25 IU/mL undetectable) 12 weeks post treatment (SVR12). More prior nonresponders than prior relapsers had baseline HCV RNA ≥800 000 IU/mL (80% vs 58%) and a non‐CC IL28B genotype (91% vs 70%). Rates of SVR12 (95% CI) were 95.3% (89.1, 100.0) among prior relapsers and 54.7% (43.4, 65.9) among prior nonresponders; corresponding ETS rates were 97.7% and 65.3%. Adverse events led to faldaprevir discontinuations in 3% of patients. The most common Division of AIDS Grade ≥2 adverse events were anaemia (13%), nausea (10%) and hyperbilirubinaemia (9%). In conclusion, faldaprevir plus PegIFN/RBV achieved clinically meaningful SVR12 rates in patients who failed PegIFN/RBV in a prior trial, with response rates higher among prior relapsers than among prior nonresponders. The adverse event profile was consistent with the known safety profile of faldaprevir. |
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| Keywords: | faldaprevir hepatitis C virus NS3/4A protease inhibitor sustained virological response treatment‐experienced |
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