1JW Goethe University Hospital, Frankfurt, Germany. Electronic address: Zeuzem@em.uni-frankfurt.de.
2University Clinic Leipzig, Leipzig, Germany.
3Auckland Clinical Studies, Auckland, New Zealand.
4Universitätsklinik für Innere Medizin III, Wien, Austria.
5Queen Mary's University of London, London, United Kingdom.
6University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
7Hôpital Henri-Mondor, Université Paris-Est, Créteil, France.
8NIHR Biomedical Research Unit, Centre for Liver Research, University of Birmingham, United Kingdom.
9Weill Cornell Medical College, New York, New York.
10Russian State Medical University, Moscow, Russia.
11Scripps Clinic, La Jolla, California.
12The Texas Liver Institute/University of Texas Health Science Center, San Antonio, Texas.
13Janssen Global Services LLC, High Wycombe, Buckinghamshire, United Kingdom.
14Janssen Infectious Diseases BVBA, Beerse, Belgium.
15Janssen Research & Development, Titusville, New Jersey.
BACKGROUND & AIMS:
Simeprevir (TMC435) is an oral NS3/4 protease inhibitor in phase III trials for chronic hepatitis C virus (HCV) infection. We performed a phase IIb, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of the combination of simeprevir, peginterferon-α2a (PegIFN), and ribavirin (RBV) in patients with HCV genotype-1 infection previously treated with PegIFN and RBV.
We analyzed data from patients who did not respond (null response), had a partial response, or relapsed after treatment with PegIFN and RBV, randomly assigned to receive simeprevir (100 or 150 mg, once daily) for 12, 24, or 48 weeks plus PegIFN and RBV for 48 weeks (n = 396), or placebo plus PegIFN and RBV for 48 weeks (n = 66). All patients were followed for 24 weeks after planned end of treatment; the primary end point was the proportion of patients with sustained virologic response (SVR; undetectable HCV RNA) at that time point.
Overall, rates of SVR at 24 weeks were significantly higher in the groups given simeprevir than those given placebo (61%-80% vs 23%; P < .001), regardless of prior response to PegIFN and RBV (simeprevir vs placebo: prior null response, 38%-59% vs 19%; prior partial response, 48%-86% vs 9%; prior relapse, 77%-89% vs 37%). All groups had comparable numbers of adverse events; these led to discontinuation of simeprevir or placebo and/or PegIFN and RBV in 8.8% of patients given simeprevir and 4.5% of those given placebo.
In treatment-experienced patients, 12, 24, or 48 weeks simeprevir (100 mg or 150 mg once daily) in combination with 48 weeks PegIFN and RBV significantly increased rates of SVR at 24 weeks compared with patients given placebo, PegIFN, and RBV and was generally well tolerated. ClinicalTrials.gov number: NCT00980330.