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

Objective: 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%).

Conclusions: 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.