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

BMC Gastroenterology

Research Article

Thomas N. Kakuda¹  Stefan Bourgeois²  Hans Orlent³  Sven Francque⁴  Hans Van Vlierberghe⁵  Frederik Nevens⁶  Jörn M. Schattenberg⁷  Keikawus Arastéh⁸  Yves Horsmans⁹  Peter Buggisch^1,10  Bert Jacquemyn^1,11  Leen Vijgen^1,11  Donghan Luo^1,12  Pieter Van Remoortere^1,12  An Vandebosch^1,13  René Verloes^1,13  Eva Hoeben^1,13  Christophe Moreno^1,14 

[1] Alios BioPharma Inc, South San Francisco, CA, USA;Department of Gastroenterology & Hepatology, ZNA Antwerp, Antwerpen, Belgium;Department of Gastroenterology and Hepatology, AZ Sint-Jan AV Hospital, Bruges, Belgium;Department of Gastroenterology and Hepatology, Universitair Ziekenhuis Antwerpen, Antwerp, Belgium;Department of Hepatology and Gastroenterology, Universitair Ziekenhuis Gent, Ghent, Belgium;Department of Liver and Biliopancreatic Disorders, University Hospitals KU Leuven, Leuven, Belgium;Department of Medicine, University Medical Center Mainz, Mainz, Germany;EPIMED/Vivantes-Auguste-Viktoria-Klinikum, Berlin, Germany;Hepato-gastroenterology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium;IFI, Liver Center Hamburg, Asklepiosklinik St. Georg, Hamburg, Germany;Janssen Pharmaceutica NV, Beerse, Belgium;Janssen Pharmaceuticals LLC, Titusville, NJ, USA;Janssen Research & Development BVBA, Beerse, Belgium;Liver Unit, CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium;

关键词: Simeprevir;    TMC647055/ritonavir;    JNJ-56914845;    Ribavirin;    Direct-acting antiviral agents;    Hepatitis C virus;    genotype 1;    Efficacy;    Safety;   

DOI  :  10.1186/s12876-017-0580-2

 received in 2016-10-06, accepted in 2017-01-18,  发布年份 2017

来源: Springer

【 摘 要 】

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)

【 授权许可】

CC BY   
© The Author(s). 2017