Simeprevir (TMC435) once daily with peginterferon-α-2b and ribavirin in patients with genotype 1 hepatitis C virus infection: The CONCERTO-4 study

Aim The efficacy and safety of simeprevir in combination with peginterferon‐α‐2b and ribavirin (PEG IFN‐α‐2b/RBV) were investigated in patients infected with hepatitis C virus (HCV) genotype 1 who were treatment‐naïve or had previously received interferon (IFN)‐based therapy. Methods CONCERTO‐4 (NCT01366638) was an open‐label, non‐comparative, multicenter study of once‐daily simeprevir (TMC435) 100 mg in combination with PEG IFN‐α‐2b/RBV in treatment‐naïve and ‐experienced patients (prior relapsers or non‐responders to IFN‐based therapy) with chronic HCV genotype 1 infection. Twelve‐week combination treatment was followed by 24/48‐week response‐guided PEG IFN‐α‐2b/RBV therapy for treatment‐naïve patients and prior relapsers, and 48‐week PEG IFN‐α‐2b/RBV therapy for prior non‐responders. Patients were followed for 72 weeks after treatment initiation. The proportions of patients with sustained viral response (SVR; undetectable HCV RNA) at treatment end and 12 weeks after the last treatment (SVR12) were among the major efficacy end‐points. Safety, including adverse events (AE), was monitored. Results Of the 79 patients treated, the proportion achieving SVR12 was highest among treatment‐naïve patients (91.7%) and prior relapsers (100%) versus 38.5% of prior non‐responders. All treatment‐naïve patients and prior non‐responders who achieved SVR12 also achieved SVR at treatment end and 24 weeks after last dose; 96.6% of prior relapsers achieved both end‐points. Most AE were of grade 1 or 2 severity. Grade 3 AE occurred in 17 patients, most frequently neutropenia (6.3%). Conclusion Simeprevir combined with PEG IFN‐α‐2b/RBV was effective in patients infected with HCV genotype 1, both for initial treatment of naïve patients and for retreatment of patients in whom previous IFN‐based therapy had failed.