Efficacy, safety and pharmacokinetics of simeprevir and TMC647055/ritonavir with or without ribavirin and JNJ-56914845 in HCV genotype 1 infection

Bourgeois, Stefan;Van Vlierberghe, Hans;Moreno, Christophe;Orlent, Hans;Verloes, René;et.al.
(2017) BMC Gastroenterology — Vol. 17, n° 1, p. 1-10 (2017)

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Authors
  • Bourgeois, Stefan
    Author
  • Van Vlierberghe, Hans
    Author
  • Moreno, Christophe
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  • Orlent, Hans
    Author
  • Horsmans, YvesUCLouvain
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  • Verloes, René
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Abstract
A Phase 2a, open-label study (NCT01724086) was conducted to assess the efficacy and safety of aonce-daily, 2-direct-acting-antiviral-agent (2-DAA) combination of simeprevir + TMC647055/ritonavir ± ribavirin andof the 3-DAA combination of simeprevir + TMC647055/ritonavir + JNJ-56914845 in chronic hepatitis C virusgenotype (GT)1-infected treatment-naïve and prior-relapse patients.Methods:The 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: simeprevir75 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)or60 mg once daily (Arm 2:n= 22; GT1a/GT1b). Primary endpoint was sustained virologic response 12 weeks after end oftreatment (12 weeks of combination treatment; SVR12).Results:In 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 + ribavirinand 4/8 (50%) GT1b without ribavirin patients, respectively, achieved SVR12. In Panel 4, 10/14 (71%) and 14/15 (93%) GT1apatients in Arms 1 and 2 achieved SVR12 compared with 8/8 and 7/7 (100%) GT1b patients in each arm, respectively. Nodeaths,seriousadverseevents(AEs),Grade4AEsorAEs leading to treatment discontinuation occurred.Conclusions:The 2- and 3-DAA combinations were well tolerated.HighSVRratesof93%and100%inGT1a-andGT1b-infected patients, respectively, were achieved in this study by combining simeprevir with JNJ-56914845 60 mg andTMC647055/ritonavir.
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Bourgeois, S., Van Vlierberghe, H., Moreno, C., Orlent, H., Nevens, F., Arastéh, K., Horsmans, Y., Schattenberg, J. M., Buggisch, P., Francque, S., Vijgen, L., Kakuda, T. N., Hoeben, E., Luo, D., Vandebosch, A., Jacquemyn, B., Van Remoortere, P., & Verloes, R. (2017). Efficacy, safety and pharmacokinetics of simeprevir and TMC647055/ritonavir with or without ribavirin and JNJ-56914845 in HCV genotype 1 infection. BMC Gastroenterology, 17(1), 1-10. https://doi.org/10.1186/s12876-017-0580-2 (Original work published 2017)