Abstract
BackgroundA Phase 2a, open-label study (NCT01724086) was conducted to assess the efficacy and safety of a once-daily, 2-direct-acting-antiviral-agent (2-DAA) combination of simeprevir + TMC647055/ritonavir ± ribavirin and of the 3-DAA combination of simeprevir + TMC647055/ritonavir + JNJ-56914845 in chronic hepatitis C virus genotype (GT)1-infected treatment-naïve and prior-relapse patients.MethodsThe study comprised four 12-week treatment panels: Panel 1 (n = 10; GT1a) and Panel 2-Arm 1 (n = 12; GT1b): simeprevir 75 mg once daily + TMC647055 450 mg once daily/ritonavir 30 mg once daily + ribavirin 1000–1200 mg/day; Panel 2-Arm 2 (n = 9; GT1b): simeprevir 75 mg + TMC647055 450 mg/ritonavir 30 mg without ribavirin; Panel 3: simeprevir 75 mg + TMC647055 600 mg/ritonavir 50 mg with (Arm 1: GT1a; n = 7) or without (Arm 2: GT1b; n = 8) ribavirin; Panel 4: simeprevir 75 mg + TMC647055 450 mg/ritonavir 30 mg + JNJ-56914845 30 mg once daily (Arm 1: n = 22; GT1a/GT1b) or 60 mg once daily (Arm 2: n = 22; GT1a/GT1b). Primary endpoint was sustained virologic response 12 weeks after end of treatment (12 weeks of combination treatment; SVR12).ResultsIn Panel 1 and Panel 2-Arm 1, 5/10 and 6/12 (50%) GT1a/GT1b + ribavirin patients achieved SVR12, versus 3/9 (33%) GT1b without ribavirin patients in Panel 2-Arm 2. In Panel 3-Arm 1 and Panel 3-Arm 2, 6/7 (86%) GT1a + ribavirin and 4/8 (50%) GT1b without ribavirin patients, respectively, achieved SVR12. In Panel 4, 10/14 (71%) and 14/15 (93%) GT1a patients in Arms 1 and 2 achieved SVR12 compared with 8/8 and 7/7 (100%) GT1b patients in each arm, respectively. No deaths, serious adverse events (AEs), Grade 4 AEs or AEs leading to treatment discontinuation occurred.ConclusionsThe 2- and 3-DAA combinations were well tolerated. High SVR rates of 93% and 100% in GT1a- and GT1b-infected patients, respectively, were achieved in this study by combining simeprevir with JNJ-56914845 60 mg and TMC647055/ritonavir.Trial registrationNCT01724086 (date of registration: September 26, 2012)
Highlights
A Phase 2a, open-label study (NCT01724086) was conducted to assess the efficacy and safety of a once-daily, 2-direct-acting-antiviral-agent (2-direct-acting antivirals (DAA)) combination of simeprevir + TMC647055/ritonavir ± ribavirin and of the 3-DAA combination of simeprevir + TMC647055/ritonavir + JNJ-56914845 in chronic hepatitis C virus genotype (GT)1-infected treatment-naïve and prior-relapse patients
Interferon (IFN)-free regimens comprising direct-acting antivirals (DAA) with different mechanisms of action can result in high sustained virologic response (SVR) rates in patients chronically infected with hepatitis C virus (HCV)
Combination regimens comprising an HCV NS3/4A protease inhibitor (PI), a non-nucleoside inhibitor (NNI) of the HCV NS5B polymerase and/or an HCV NS5A replication complex inhibitor with/without ribavirin have been shown to be successful in the treatment of chronic HCV infection [1]
Summary
A Phase 2a, open-label study (NCT01724086) was conducted to assess the efficacy and safety of a once-daily, 2-direct-acting-antiviral-agent (2-DAA) combination of simeprevir + TMC647055/ritonavir ± ribavirin and of the 3-DAA combination of simeprevir + TMC647055/ritonavir + JNJ-56914845 in chronic hepatitis C virus genotype (GT)1-infected treatment-naïve and prior-relapse patients. Interferon (IFN)-free regimens comprising direct-acting antivirals (DAA) with different mechanisms of action can result in high sustained virologic response (SVR) rates in patients chronically infected with hepatitis C virus (HCV). The combination of the PI paritaprevir, the NNI dasabuvir and the NS5A inhibitor ombitasvir, with ritonavir included as a pharmacologic booster for paritaprevir, is approved for the treatment of chronic HCV genotype (GT) 1 infection. Simeprevir is a once-daily, HCV NS3/4A PI approved as part of an IFN-free combination with sofosbuvir for HCV GT1 infection. Simeprevir inhibits organic anion transporting polypeptide (OATP) 1B1/3 and P-glycoprotein [4]
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