A Phase III, Randomized, Open-label, Two-arm Trial in Japan to Investigate the Efficacy and Safety of TMC435 as Part of a Treatment Regimen Including Peginterferon Alfa-2a and Ribavirin in Hepatitis C, Genotype 1-Infected Subjects Who Failed to Respond to Previous IFN-based Therapy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 106
- 主要终点
- The Percentage of Participants With a Sustained Virologic Response at the End of Treatment (EOT) and 12 Weeks After the Last Dose of Treatment (SVR12)
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of TMC435 in combination with peginterferon alfa-2a (PegIFNα-2a) and ribavirin in genotype 1 hepatitis C virus (HCV)-infected participants who failed to respond to previous interferon (IFN)-based therapy in Japan.
详细描述
This is a randomized (study drug assigned by chance), 2-arm, open-label study to evaluate the efficacy and safety of TMC435 (also referred to as jnj-38733214-aaa) in combination with the standard of care (SoC) therapy consisting of peginterferon alfa-2a (PegIFNα-2a ) and ribavirin (RBV) administered according to the manufacturer's prescribing information in adult, genotype 1 hepatitis C virus (HCV)-infected participants who failed to respond to previous interferon (IFN)-based therapy in Japan. The study objective is to evaluate the efficacy of TMC435 by the proportion of participants with undetectable HCV ribonucleic acid (RNA). Participants will receive 12 weeks of treatment with TMC435 (100 mg) once daily plus PegIFNα-2a (P) and RBV P) followed by 12 or 36 weeks of treatment with PR OR participants will receive 24 weeks of treatment with TMC435 (100 mg) once daily plus PR followed by 24 weeks of treatment with PR. TMC435 is a 100-mg capsule and will be taken orally (via the mouth). Treatment with PR will last 24 or 48 weeks: Pegylated interferon is supplied as a vial containing 1.0 mL solution with 180 mcg PegIFNα-2a and will be injected by a syringe under the skin once weekly. Ribavirin is given as 200-mg tablets (daily dose: 600-1000 mg based on body weight), and taken orally by mouth two times a day after meals. Participants will receive oral capsules of TMC435 (100 mg) once daily up to Week 12 or 24.
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
- 20 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant must have chronic genotype 1 HCV infection with HCV RNA level >= 5.0 log10 IU/mL
- •Participant failed to respond to previous IFN-based therapy
- •Participant must be willing to use contraceptive measures from the time of informed consent to 6 months after last dose of study medication.
排除标准
- •Co-infection with any other HCV genotype or co-infection with the human immunodeficiency virus (HIV)
- •Diagnosed with hepatic cirrhosis or hepatic failure
- •A medical condition which is a contraindication to PegIFNα-2a or ribavirin therapy
- •History of, or any current medical condition which could impact the safety of the patient in the study
研究组 & 干预措施
TMC435 100 mg 12 Wks + PR24/48
Participants will receive TMC435 100 mg once daily with PegIFNα-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24. Treatment will be stopped at Week 24 if participants achieve plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels < 1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable plasma HCV RNA levels at Week 12. All other participants will continue PR until Week 48.
干预措施: TMC435 (Drug)
TMC435 100 mg 12 Wks + PR24/48
Participants will receive TMC435 100 mg once daily with PegIFNα-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24. Treatment will be stopped at Week 24 if participants achieve plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels < 1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable plasma HCV RNA levels at Week 12. All other participants will continue PR until Week 48.
干预措施: Peginterferon alfa-2a (PegIFNα-2a ) (Drug)
TMC435 100 mg 12 Wks + PR24/48
Participants will receive TMC435 100 mg once daily with PegIFNα-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24. Treatment will be stopped at Week 24 if participants achieve plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels < 1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable plasma HCV RNA levels at Week 12. All other participants will continue PR until Week 48.
干预措施: Ribavirin (RBV) (Drug)
TMC435 100 mg 24 Wks + PR24/48
Participants will receive TMC435 100 mg once daily with PegIFNα-2a and ribavirin ( PR) for 24 weeks (Wks). Treatment will be stopped at Week 24 if participants achieve plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels < 1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable plasma HCV RNA levels at Week 12. All other participants will continue PR until Week 48.
干预措施: TMC435 (Drug)
TMC435 100 mg 24 Wks + PR24/48
Participants will receive TMC435 100 mg once daily with PegIFNα-2a and ribavirin ( PR) for 24 weeks (Wks). Treatment will be stopped at Week 24 if participants achieve plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels < 1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable plasma HCV RNA levels at Week 12. All other participants will continue PR until Week 48.
干预措施: Peginterferon alfa-2a (PegIFNα-2a ) (Drug)
TMC435 100 mg 24 Wks + PR24/48
Participants will receive TMC435 100 mg once daily with PegIFNα-2a and ribavirin ( PR) for 24 weeks (Wks). Treatment will be stopped at Week 24 if participants achieve plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels < 1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable plasma HCV RNA levels at Week 12. All other participants will continue PR until Week 48.
干预措施: Ribavirin (RBV) (Drug)
结局指标
主要结局
The Percentage of Participants With a Sustained Virologic Response at the End of Treatment (EOT) and 12 Weeks After the Last Dose of Treatment (SVR12)
时间窗: EOT (Week 24 or 48) and Week 36 or 60
The table below shows the observed percentage of participants in each treatment group with a SVR12 defined as undetectable plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels at the EOT (Week 24 or 48) and at 12 weeks after the last dose of treatment (Week 36 or 60).
次要结局
- The Percentage of Participants With Undetectable Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) During Treatment and at the End of Treatment (EOT)(Weeks 4, 12, 24, 36, 48, 60, 72, and at EOT)
- The Number of Participants With Viral Breakthrough During the Study(Up to EOT (Week 24 or 48))
- The Percentage of Participants With a Sustained Virologic Response 24 Weeks After the End of Treatment (EOT) and 24 Weeks After the Last Dose of Treatment (SVR24)(EOT (Week 24 or 48) and Week 48 or 72)
- The Percentage of Participants Who Achieved a Greater Than or Equal to 2 log10 IU/mL Drop From Baseline in Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at Each Time Point During Treatment and Follow-up(Day 3, Day 7, and Weeks 2, 3, 4, 8, 12, 16, 20, 24, 28, 36, 48, 60, 72, EOT, and Follow-up (FU) Weeks 4, 12, and 24)
- The Number of Participants Demonstrating Viral Relapse During the Study(Up to 72 weeks)
- The Number Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normal ALT Levels at the End of Treatment (EOT)(EOT (Week 24 or 48))
- The Percentage of Participants Who Met Response Guided Treatment (RGT) Criteria and Completed Treatment With Peginterferon Alpha-2a (PegIFNα-2a) and Ribavirin (RBV) at Week 24(Week 24)
- The Percentage of Participants With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels During Treatment for Participants Who Did Not Achieve Undetectable Plasma HCV RNA Levels at Week 12(Weeks 24, 48, EOT (Weeks 24 or 48), SVR12 (Weeks 36 or 60), and SVR24 (Weeks 48 or 72))
- Plasma Concentrations of TMC435(Week 12, Week 24, and Overall (Weeks 4, 12, and 24))
- Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24h) for TMC435(Week 12, Week 24, and Overall (Weeks 4, 12, and 24))