Faldaprevir combined with peginterferon alfa-2a and ribavirin in chronic hepatitis C virus genotype-1 patients with prior nonresponse: SILEN-C2 trial

Mark S. Sulkowski, Marc Bourlière, Jean Pierre Bronowicki, Tarik Asselah, Jean Michel Pawlotsky, Stephen D. Shafran, Stanislas Pol, Stefan Mauss, Dominique Larrey, Yakov Datsenko, Jerry O. Stern, George Kukolj, Joseph Scherer, Gerhard Nehmiz, Gerhard G. Steinmann, Wulf O. Böcher

Research output: Contribution to journalArticle

Abstract

Faldaprevir (BI 201335) is a potent, hepatitis C virus (HCV) NS3/4A protease inhibitor. In all, 290 noncirrhotic HCV genotype (GT)-1 patients with prior null (<1 log10 viral load [VL] drop at any time on treatment) or partial response (≥1 log10 VL drop but never undetectable on treatment) were randomized 2:1:1 to receive 48 weeks of peginterferon alfa-2a and ribavirin (PegIFN/RBV) in combination with faldaprevir 240 mg once daily (QD) with 3 days PegIFN/RBV lead-in (LI), 240 mg QD without LI, or 240 mg twice daily (BID) with LI. Patients in the 240 mg QD/LI group achieving maintained rapid virologic response (mRVR; VL <25 IU/mL [Roche TaqMan] at week 4 and undetectable at weeks 8 to 20) were rerandomized to cease all treatment at week 24 or continue PegIFN/RBV up to week 48. Sustained virologic response (SVR) rates were 32%, 50%, and 42% in prior partial responders, and 21%, 35%, and 29% in prior null responders in the faldaprevir 240 mg QD/LI, 240 mg QD, and 240 mg BID/LI groups, respectively. In the 240 mg QD/LI group, a significantly higher proportion of mRVR patients rerandomized to 48 weeks' treatment achieved SVR compared with those assigned to 24 weeks treatment (72% versus 43%; P = 0.035). Rates of gastrointestinal disorders, jaundice, dry skin, and photosensitivity were increased at 240 mg BID compared with the 240 mg QD dose. Faldaprevir discontinuations owing to adverse events occurred in 6%, 4%, and 23% of patients in the 240 mg QD/LI, 240 mg QD, and 240 mg BID/LI groups, respectively. Conclusion: Faldaprevir 240 mg QD with PegIFN/RBV was safe and tolerable and produced substantial SVR rates in prior null and partial responders. The 240 mg QD dose is currently undergoing phase 3 evaluation.

Original languageEnglish (US)
Pages (from-to)2155-2163
Number of pages9
JournalHepatology
Volume57
Issue number6
DOIs
StatePublished - Jun 1 2013

ASJC Scopus subject areas

  • Hepatology

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    Sulkowski, M. S., Bourlière, M., Bronowicki, J. P., Asselah, T., Pawlotsky, J. M., Shafran, S. D., Pol, S., Mauss, S., Larrey, D., Datsenko, Y., Stern, J. O., Kukolj, G., Scherer, J., Nehmiz, G., Steinmann, G. G., & Böcher, W. O. (2013). Faldaprevir combined with peginterferon alfa-2a and ribavirin in chronic hepatitis C virus genotype-1 patients with prior nonresponse: SILEN-C2 trial. Hepatology, 57(6), 2155-2163. https://doi.org/10.1002/hep.26386