A Study to Evaluate the Safety, Tolerability, and Effectiveness of a 12-Week Combination Therapy of TMC647055 and TMC435 With and Without GSK23336805 With a Pharmacokinetic Enhancer With and Without Ribavirin in Patients Infected With Chronic Genotype 1 Hepatitis C Virus
Condition: Chronic Hepatitis C
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to explore the efficacy and safety of TMC647055, TMC435, and
      low-dose ritonavir, administered together with and without ribavirin and of TMC647055,
      TMC435, low-dose ritonavir administered together with GSK233680k without ribavirin in a
      limited number of patients with chronic hepatitis C virus (HCV) infection.
    

Detailed description: 
      This study is an open-label study (all people know the identity of the intervention) in
      patients who are chronically infected with hepatitis C virus (HCV) genotype-1a (GT1a) or
      genotype-1b (GT1b) to assess the safety, tolerability and efficacy of the coadministration of
      TMC647055, TMC435 and low-dose ritonavir (RTV), with and without ribavirin (RBV) and of
      TMC647055, TMC435, RTV administered together with GSK233680k without RBV for 12 weeks.
      Approximately 86 patients will be enrolled in this study. Patients enrolled in the study will
      be chronically infected with HCV of GT1a (n=10) or GT1b (n=20), either treatment-naive
      patients (ie, patients never having received PegIFN [Pegylated interferon alpha-2a at 180 mcg
      subcutaneous once a week], RBV, or any other approved or investigational treatment for
      chronic HCV infection) or patients who are relapsers to prior treatment with PegIFN /RBV (ie,
      "relapsers" are patients with HCV ribonucleic acid [RNA] undetectable at the last on
      treatment measurement of a prior PegIFN based regimen of at least 24 weeks, but HCV RNA
      detectable within 1 year after the last medication intake). Patients in this first part of
      the study will be divided over 4 panels: Panel 1 will consist of 10 chronic HCV GT1a infected
      treatment-naive patients/prior relapsers who will receive 12 weeks of treatment with TMC435 +
      TMC647055 + low-dose ritonavir and ribavirin. Panel 2 will consist of 20 chronic HCV GT1b
      infected treatment-naive patients/ prior relapsers who will be randomly allocated to 2 arms
      in a 1:1 ratio. Arm 1 (N=10) will receive TMC435 + TMC647055 + low-dose ritonavir and
      ribavirin. Arm 2 (N=10) will receive TMC435 + TMC647055 + low-dose ritonavir. Panel 3 will
      consist of 16 chronic HCV GT1a or GT1b infected treatment-naïve patients/prior relapsers who
      will be allocated to 2 arms: 8 HCV GT1a patients in arm 1 and 8 HCV GT1b patients in arm 2.
      Patients in Arm 1 will receive 12 weeks of treatment with TMC435 + TMC647055 + low-dose RTV
      and RBV and patients in Arm 2 will receive 12 weeks of treatment with TMC435 + TMC647055 +
      low-dose RTV. Panel 4 will consist of 40 chronic HCV GT1a or GT1b infected treatment-naïve
      patients/prior relapsers who will be allocated to 2 arms: each arm will consist of 20
      patients of which at most 8 patients will be infected with HCV GT1b. Patients will be
      randomized in 1:1 ratio between the 2 arms whereby randomization will be stratified by
      genotype. Patients in Arm 1 will receive 12 weeks of treatment with TMC435 + TMC647055 +
      low-dose RTV + GSK2336805. Patients in Arm 2 will receive 12 weeks of treatment with TMC435 +
      TMC647055 + low-dose RTV + GSK2336805. The planned duration of the investigational treatment
      is 12 weeks. Patients in Panels 1, 2, and 3 may receive follow-up treatment with 12 weeks or
      36 weeks of PegIFNα + RBV; follow-up treatment principles will not apply to Panel 4 as based
      on available proof of concept data for such combinations, the need for an additional 12 or
      36-week PegIFN/RBV follow-up therapy is expected to be very low when evaluating a 12-week
      regimen of 3 direct acting antiviral agents for treatment of HCV genotype 1 infections.
      Safety will be monitored throughout the study
    

Intervention name(s): TMC647055; TMC435; Ritonavir; Ribavirin; Pegylated interferon alpha-2a (PegIFN); GSK2336805
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): Type=exact number, unit=mg, number=150, form=capsule, route=oral. 3 or 4 capsules of 150 mg will be administered once daily.; Type=exact number, unit=mg, number=75, form=capsule, route=oral. 1 capsule of 75 mg will be administered once daily.; Type=exact number, unit=mg, number=30 or 50, form=tablet or solution, route=oral. 0.375 mL or 0.625 ml (80 mg/mL) solution will be administered once daily.; Type=exact number, unit=mg, number=200, form=tablet, route=oral. 5 to 6 (1000 or 1200 mg) tablets will be administered once daily, divided in 2 daily doses. Patients meeting the Follow-UP (FU) treatment criteria specified in the protocol will receive treatment 5 or 6 (depending on bodyweight) tablets of ribavirin (equivalent to 200 mg/tablet) per day, divided in 2 daily doses for an additional 12 or 36 weeks.; Type=exact number, unit=mcg, number=180, form=solution, route=subcutaneous injection. PegIFN 0.5 mL prefilled syringe equivalent to 180 mcg will be administered as a subcutaneous (under the skin) injection as follow-up (FU) treatment for 12 or 36 weeks based on follow-up treatment principles as described in the protocol. Patients meeting the Follow-UP (FU) treatment criteria specified in the protocol will receive treatment with Pegylated interferon alpha-2a (PegIFN) 0.5 mL prefilled syringe equivalent to 180 mcg administered as a subcutaneous (under the skin) injection for an additional 12 or 36 weeks.; Type=exact number, unit=mg, number=30 or 60, form=tablet, route=subcutaneous injection. GSK2336805 one or two 30 mg tablet(s) taken orally (by mouth) once daily for 12 weeks.
Other intervention name(s): JNJ-42039556-AMR-G-001
Intervention MeSH terms: Interferons; Ritonavir; Ribavirin; Interferon-alpha; Interferon alpha-2; Peginterferon alfa-2a; Simeprevir
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Chronic hepatitis C; Chronic hepatitis C-infected patients; TMC647055; TMC435; Ritonavir; Ribavirin; Genotype 1a; Genotype 1b; GSK2336805