临床试验/NCT01724086

NCT01724086已完成2 期

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

Janssen R&D Ireland0 个研究点目标入组 90 人开始时间: 2012年10月最近更新: 2016年1月11日

适应症

干预措施

试验速览

阶段: 2 期
状态: 已完成
发起方
入组人数: 90
主要终点: Number of patients with adverse events

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者记录与标识符相似试验

研究概览

简要总结

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.

详细描述

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

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Parallel
主要目的: Treatment
盲法: None

入排标准

年龄范围: 18 Years 至 70 Years（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•Documented chronic genotype 1a or genotype 1b hepatitis C virus (HCV) infection with HCV ribonucleic acid (RNA) level >100,000 IU/mL at screening
•Treatment-naive or documented prior relapser to previous treatment regimens and has stopped treatment at least 3 months before screening
•Liver biopsy within 3 years before the screening visit or elastography results available prior to first study drug dosing
•Medically stable based on physical examination, medical history, vital signs, and electrocardiogram performed at screening
•Body mass index of 18.0 to 32.0 kg/m2 and body weight more than 50 kg

排除标准

•Evidence of liver cirrhosis by liver biopsy or the presence of esophageal varices or a transient elastography result of >14.6 kPa within 2 years prior to first dosing
•Evidence of decompensated liver disease defined as prior history or current evidence of ascites, hepatic encephalopathy, bleeding oesophageal or gastric varices
•Evidence of any significant liver disease in addition to hepatitis C (including but not limited to hepatitis B, drug- or alcohol-related cirrhosis, autoimmune hepatitis, hemochromatosis, Wilson's disease, non-alcoholic steatohepatitis, or primary biliary cirrhosis)
•Receiving or has received any HCV-specific direct antiviral agent (HCV protease inhibitors, HCV nucleoside polymerase inhibitors, HCV non-nucleoside polymerase inhibitors, HCV NS5a inhibitors or any other HCV inhibitor targeting an HCV protein or a target involved in the HCV replication cycle
•Co-infected with human immunovirus (HIV)-1 or HIV-2, with non-genotype 1a/1b HCV, or hepatitis A or B virus infection

研究组 & 干预措施

Panel 1

Experimental

10 chronic HCV genotype 1a (GT1a) infected treatment-naive patients/prior relapsers who will receive 12 weeks of treatment with TMC435 + TMC647055 + low-dose ritonavir and ribavirin.

干预措施: TMC647055 (Drug)

Panel 1

Experimental

10 chronic HCV genotype 1a (GT1a) infected treatment-naive patients/prior relapsers who will receive 12 weeks of treatment with TMC435 + TMC647055 + low-dose ritonavir and ribavirin.

干预措施: TMC435 (Drug)

Panel 1

Experimental

10 chronic HCV genotype 1a (GT1a) infected treatment-naive patients/prior relapsers who will receive 12 weeks of treatment with TMC435 + TMC647055 + low-dose ritonavir and ribavirin.

干预措施: Ritonavir (Drug)

Panel 1

Experimental

10 chronic HCV genotype 1a (GT1a) infected treatment-naive patients/prior relapsers who will receive 12 weeks of treatment with TMC435 + TMC647055 + low-dose ritonavir and ribavirin.

干预措施: Ribavirin (Drug)

Panel 1

Experimental

10 chronic HCV genotype 1a (GT1a) infected treatment-naive patients/prior relapsers who will receive 12 weeks of treatment with TMC435 + TMC647055 + low-dose ritonavir and ribavirin.

干预措施: Pegylated interferon alpha-2a (PegIFN) (Drug)

Panel 2 Arm 1

Experimental

10 chronic HCV GT1b infected treatment-naive patients/ prior relapsers will receive TMC435 + TMC647055 + low-dose ritonavir and ribavirin.

干预措施: TMC647055 (Drug)

Panel 2 Arm 1

Experimental

10 chronic HCV GT1b infected treatment-naive patients/ prior relapsers will receive TMC435 + TMC647055 + low-dose ritonavir and ribavirin.

干预措施: TMC435 (Drug)

Panel 2 Arm 1

Experimental

10 chronic HCV GT1b infected treatment-naive patients/ prior relapsers will receive TMC435 + TMC647055 + low-dose ritonavir and ribavirin.

干预措施: Ritonavir (Drug)

Panel 2 Arm 1

Experimental

10 chronic HCV GT1b infected treatment-naive patients/ prior relapsers will receive TMC435 + TMC647055 + low-dose ritonavir and ribavirin.

干预措施: Ribavirin (Drug)

Panel 2 Arm 1

Experimental

10 chronic HCV GT1b infected treatment-naive patients/ prior relapsers will receive TMC435 + TMC647055 + low-dose ritonavir and ribavirin.

干预措施: Pegylated interferon alpha-2a (PegIFN) (Drug)