A Phase III, Randomized, Double-blind, Placebo-controlled Trial in Japan to Investigate the Efficacy and Safety of TMC435 vs. Placebo as Part of a Treatment Regimen Including Peginterferon Alfa-2a and Ribavirin in Treatment-Naive, Genotype 1, Hepatitis C-infected Subjects
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 183
- 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 compared with placebo in combination with peginterferon alfa-2a (pegIFN alfa-2a) and ribavirin in treatment-naive patients with chronic genotype 1 hepatitis C virus (HCV) infection in Japan.
详细描述
This is a randomized (study drug assigned by chance), 2-arm, double-blind study to evaluate the efficacy and safety of TMC435 (also referred to as jnj-38733214-aaa) versus placebo in combination with the standard of care (SoC) therapy (peginterferon alfa-2a [pegIFN alfa-2a] and ribavirin) in adult treatment-naïve patients (who never received treatment for HCV) with chronic genotype 1 HCV infection in Japan. The study objective is to evaluate and compare the efficacy of TMC435 vs placebo by the proportion of the patients with undetectable HCV ribonucleic acid (RNA). In the TMC435 treatment group, patients will receive 12 weeks of treatment with TMC435 (100 mg) once daily plus SoC followed by an additional 12 or 36 weeks of treatment with SoC. In the placebo treatment group, patients will receive 12 weeks of treatment with placebo once daily plus SoC followed by an additional 36 weeks of treatment with SoC. TMC435 is a 100-mg capsule and will be taken orally by mouth. The SoC treatment will be given for 24 or 48 weeks. Pegylated interferon is supplied as a vial containing 1.0 mL solution with 180 mcg pegIFN alpha-2a and administered subcutaneously (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.
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
- Double (Participant, Investigator)
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
- •Patient must have chronic genotype 1 HCV infection with HCV RNA level >= 5.0 log10 IU/mL
- •Patient has never received treatment for HCV
- •Patient 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 pegIFN 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 + PR 24/48
Participants received TMC435 100 mg once daily with PegIFNα-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24. Treatment was stopped at Week 24 for participants who achieved HCV RNA < 1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable HCV RNA at Week 12. All other participants continued PR until Week 48.
干预措施: TMC435 (Drug)
TMC435 100 mg 12 Wks + PR 24/48
Participants received TMC435 100 mg once daily with PegIFNα-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24. Treatment was stopped at Week 24 for participants who achieved HCV RNA < 1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable HCV RNA at Week 12. All other participants continued PR until Week 48.
干预措施: Peginterferon alfa-2a (pegIFN alfa-2a) (Drug)
TMC435 100 mg 12 Wks + PR 24/48
Participants received TMC435 100 mg once daily with PegIFNα-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24. Treatment was stopped at Week 24 for participants who achieved HCV RNA < 1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable HCV RNA at Week 12. All other participants continued PR until Week 48.
干预措施: Ribavirin (RBV) (Drug)
PBO 12 Wks + PR 48
Participants received placebo (PBO) once daily with PegIFNα-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 48.
干预措施: Placebo (Drug)
PBO 12 Wks + PR 48
Participants received placebo (PBO) once daily with PegIFNα-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 48.
干预措施: Peginterferon alfa-2a (pegIFN alfa-2a) (Drug)
PBO 12 Wks + PR 48
Participants received placebo (PBO) once daily with PegIFNα-2a and ribavirin (PR) for 12 weeks (Wks) followed by 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 (up to Week 24 or 48) and 12 weeks after the EOT (up to Week 36 or 60)
The table below shows the observed percentage of participants with a SVR12 defined as undetectable plasma hepatitis C virus (HCV) ribonucleic acid (RNA) at 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 a Sustained Virologic Response at the End of Treatment (EOT) and 24 Weeks After the Last Dose of Treatment (SVR24)(EOT (up to Week 24 or 48) and 24 weeks after the after the last dose of treatment (up to 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, 42, 48, 52, 60, 72, EOT (up to Week 24 or 48), FU Week 4, 12, and 24)
- The Percentage of Participants With Undetectable Plasma Levels of 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 (up to Week 24 or 48))
- The Number of Participants With Viral Breakthrough(Up to EOT (up to Week 24 or 48))
- The Number of Participants Demonstrating Viral Relapse(Up to Week 72)
- The Number of Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normal ALT Levels at the End of Treatment (EOT)(Baseline (Day 1) to EOT (up to Week 24 or 48))
- The Percentage of Participants in the TMC435 Treatment Group Who Met Response Guided Treatment (RGT) Criteria and Completed Treatment With Peginterferon Alpha-2a (PegIFN Alpha-2a) and Ribavirin (RBV) at Week 24(Week 24)
- Plasma Concentrations of TMC435(Overall (ie, Up to Week 12))
- Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24h) for TMC435(Overall (Up to Week 12))