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

Chronic Hepatitis C Clinical Trial

Official title: A Phase IIa, Open-label Trial to Evaluate the Safety, Tolerability and Efficacy of a 12 Weeks Combination Therapy of TMC647055 and TMC435 With and Without GSK23336805 With a Pharmacokinetic Enhancer With and Without Ribavirin in Chronic Genotype 1 Hepatitis C Infected Patients

Status Completed

Clinical Trial 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.

Clinical Trial 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 ;

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Hepatitis C
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic

• NCT number: NCT01724086
• Study type: Interventional
• Source: Janssen R&D Ireland
• Status: Completed
• Phase: Phase 2
• Start date: October 2012
• Completion date: December 2014