Presentation is loading. Please wait.

Presentation is loading. Please wait.

SILEN-C2: sustained virological response (SVR) and safety of BI 201335 combined with peginterferon alfa 2a and ribavirin (PegIFN/RBV) in chronic HCV genotype-1.

Similar presentations


Presentation on theme: "SILEN-C2: sustained virological response (SVR) and safety of BI 201335 combined with peginterferon alfa 2a and ribavirin (PegIFN/RBV) in chronic HCV genotype-1."— Presentation transcript:

1 SILEN-C2: sustained virological response (SVR) and safety of BI combined with peginterferon alfa 2a and ribavirin (PegIFN/RBV) in chronic HCV genotype-1 patients with nonresponse to PegIFN/RBV M.S. Sulkowski, 1 M. Bourlière, 2 J.-P. Bronowicki, 3 A. Streinu-Cercel, 4 L. Preotescu, 4 T. Asselah, 5 J.-M. Pawlotsky, 6 S. Shafran, 7 S. Pol, 8 F.A. Caruntu, 4 S. Mauss, 9 D. Larrey, 10 C. Häfner, 11 Y. Datsenko, 11 J.O. Stern, 12 R. Kubiak, 11 W. Böcher, 11 G. Steinmann 11 On behalf of the SILEN-C2 study group 1 Johns Hopkins University, Baltimore, MD, USA; 2 Hôpital Saint Joseph, Marseille, France; 3 Hôpital de Brabois, Vandoeuvre Cedex, France; 4 Prof. Dr. Matei Bals Institute of Infectious Diseases, Bucharest, Romania; 5 Hôpital Beaujon, Clichy Cedex, France; 6 Hôpital Henri Mondor, Créteil, France; 7 University of Alberta, Edmonton, AB, Canada; 8 Hôpital Cochin, Paris, France; 9 Center for HIV and Hepatogastroenterology, Düsseldorf, Germany; 10 Hôpital Saint-Eloi, Montpellier Cedex, France; 11 Boehringer Ingelheim Pharma, Biberach, Germany; 12 Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT, USA

2 Speaker declaration I have financial relationships within the last 12 months relevant to my presentation with Boehringer Ingelheim Pharmaceuticals. The terms of this arrangement are being managed by the Johns Hopkins University in accordance with its conflict of interest policies and my presentation includes discussion of off-label or investigational use of: BI Peginterferon alfa 2a Ribavirin

3 SILEN-C2 trial Double-blind, placebo-controlled, phase IIb study in HCV genotype-1 (GT-1) patients with nonresponse to previous PegIFN/RBV *3-day lead-in period (LI) of PegIFN alfa 2a (180 μg/week) plus ribavirin (1,000 mg or 1,200 mg/day); Re-randomisation 1:1 of patients with eRVR (extended rapid virological response) to 24 versus 48 weeks of PegIFN/RBV QD, once daily; BID, twice daily n = 142 n = 76 n = 70 PegIFN/RBV240 mg BID LI BI PegIFN/RBV* PegIFN/RBV 240 mg QD BI PegIFN/RBV D1D4Week 24Week 48 * PegIFN/RBV 240 mg QD LI BI PegIFN/RBV

4 Main inclusion criteria Age 18 to 65 years Chronic hepatitis C GT-1 infection Confirmed nonresponse during previous PegIFN/RBV treatment – 12 weeks of an approved dose of PegIFN/RBV –Null response: < 1 log 10 maximum HCV RNA reduction any time during treatment –Partial response: > 1 log 10 maximum HCV RNA reduction, but never undetectable (with a sensitive assay) –Relapsers were excluded HCV RNA 100,000 IU/mL at screening Liver biopsy within 2 years without evidence of cirrhosis

5 Baseline characteristics 240 mg QD LI n = mg QD n = mg BID LI n = 70 Mean age (years) Male gender (%) Ethnicity (%) White Black Asian Mean HCV RNA (log 10 ) Genotype a (%) 1a 1b 1, other subtypes b Prior response to PegIFN/RBV (%) Null response Partial response Nonresponse Others a Based on NS3/4A sequencing; b Other genotypes were 1C (n=1), 1D (n=1) and 1G (n=1). 1 patient was GT-1 but subgenotype could not be determined

6 Virological response 61/14234/7633/70 31/76 39/14222/70 eRVR: HCV RNA < 25 IU/mL at Week 4 and undetected at Weeks 8 to 20 Proportion of patients (%)

7 SVR in partial- and null-responders 16/5413/2610/24 14/40 12/5711/38 Null response, <1 log 10 maximum HCV RNA reduction any time during treatment; Partial response, > 1 log 10 maximum HCV RNA reduction, but never undetectable (with a sensitive assay) Proportion of patients (%)

8 SVR and relapse in eRVR patients by duration of PegIFN/RBV Relapse: rebound from undetectable at end of all treatment 12/3021/2918/306/29 P = Proportion of patients (%)

9 Virological failures a 1 log 10 rebound from nadir, or rebound to 100 IU/mL if nadir < lower limit of detection (LLOD) on treatment, confirmed in a second sample; b Rebound after end of all treatment from nadir < LLOD after end of treatment Proportion of patients (%) Breakthrough a on BI Breakthrough a on PegIFN/RBV Relapse b 240 mg QD LI240 mg QD240 mg BID LI

10 Adverse events a 240 mg QD LI (%) 240 mg QD (%) 240 mg BID LI (%) All patients (n b ) Rash c Mild Moderate Severe Jaundice Severe Nausea Diarrhoea Vomiting a Adverse events > 10% compared with PegIFN/RBV; b Number quoted is according to given treatment; c No cases of Stevens-Johnson syndrome, erythema multiforme or drug rash with eosinophilia and systemic symptoms

11 Adverse events: overall summary 240 mg QD LI (%) 240 mg QD (%) 240 mg BID LI (%) All patients (n a ) With severe adverse events Fatalities000 Discontinuations for adverse events Discontinuations for Rash Photosensitivity Jaundice Others b a Number quoted is according to given treatment; b Other discontinuations mainly due to general disorders and administration site conditions, gastrointestinal and others

12 BLDay 4Week 1Week 2Week 4Week 8Week 10 Week 12 Week 16 Week 20 Week 24 Week 28 Mean total bilirubin (mg/dL) Effect of BI on bilirubin and haemoglobin Mean haemoglobin (g/dL) 240 mg QD LI240 mg QD240 mg BID LI BL, baseline

13 Discussion and conclusion Virological response –robust SVR rates up to 41% at 240 mg QD dose selected for phase III –response-guided therapy was not effective for nonresponsive patients achieving eRVR –3-day PegIFN/RBV lead-in did not increase SVR Safety and tolerability –most adverse events were those commonly related to PegIFN/RBV therapy no excess effect on haemoglobin –mild-to-moderate jaundice and rash are the main BI related adverse events and are dose-dependent jaundice is due to isolated indirect hyperbilirubinaemia In treatment-experienced patients, BI mg QD appears to offer the best safety/efficacy balance –phase III trial in preparation

14 Acknowledgements Patients and study investigators at study centres in the following countries: Australia Jacob George William Sievert Barbara Leggett Graeme MacDonald Stephen Riordan Sally Bell Amany Zekry Austria Peter Ferenci Michael Gschwantler Andreas Maieron Canada Jenny Heathcote Stephen Shafran Bernard Willems Brian Conway Netherlands Henk Reesink Bart van Hoek Portugal Armando Carvalho Fernando Ramalho Filipe Calinas José Sarmento Rui Sarmento e Castro Republic of Korea Jeong Heo DoYoung Kim Young Oh Kweon SeungWoon Paik YounJae Lee Mong Cho Romania Adrian Streinu-Cercel Liliana Preotescu Florin Alexandru Caruntu Ceasu Emanoil Spain Jose Luis Calleja Javier García-Samaniego María Luisa Gracía Buey Jaime Enriquez Vicente Soriano Switzerland Enos Bernasconi Jürg Reichen France Tarik Asselah Yves Benhamou Stanislas Pol Marc Bourlière Jean-Pierre Bronowicki Dominique Larrey Jean-Michel Pawlotsky Christophe Hezode Christian Trepo Germany Thomas Berg Dieter Häussinger Ansgar Lohse Marcus Schuchmann Johannes Wiegand Stefan Mauss Ulrich Spengler Wolfgang E. Schmidt Elmar Zehnter United Kingdom Janice Main William Rosenberg Mark Wright Fiona Gordon Graham Foster Stephen Ryder Kosh Agarwal Mark Nelson United States Maurizio Bonacini Douglas Dieterich Ira Jacobson David Wright Donald Jensen Rajender Reddy Jacob Lalezari Ira Stein Lawrence Wruble Boehringer Ingelheim for sponsoring the study and their clinical and statistical teams for study monitoring, data collection and analysis Editorial support provided by StemScientific


Download ppt "SILEN-C2: sustained virological response (SVR) and safety of BI 201335 combined with peginterferon alfa 2a and ribavirin (PegIFN/RBV) in chronic HCV genotype-1."

Similar presentations


Ads by Google