A Study of TMC435 in Combination With Pegylated Interferon Alp\Fa-2a and Ribavirin in Patients Infected With Genotype 1 Hepatitis C Virus Who Never Received Treatment (PILLAR)
2014年5月19日 更新者：Tibotec Pharmaceuticals, Ireland
A Phase IIb, Randomized, Double-Blind, Placebo-Controlled Trial to Investigate the Efficacy, Tolerability, Safety and Pharmacokinetics of TMC435 as Part of a Treatment Regimen Including Peginterferon Alfa-2a and Ribavirin In Treatment-Naive Genotype 1 Hepatitis C-Infected Subjects
The purpose of this study is to evaluate the efficacy of 4 different regimens of TMC435 in combination with peginterferon alfa-2a (PegIFNα-2a) and ribavirin (RBV), defined as the proportion of patients with sustained virologic response at Week 72 (patients with undetectable plasma HCV RNA [less than 25 IU per mL undetectable] at the end of treatment and at Week 72), compared to the control group receiving PegIFN and RBV in combination with TMC435-matched placebo.
研究概览
详细说明
This is a randomized (study medication assigned by chance), 5-arm, double-blind (neither investigator nor the participant knows the treatment that the participant receives), placebo-controlled (an inactive substance that is compared with the study medication to test whether the study medication has a real effect in clinical study) study to compare the efficacy, tolerability and safety of different TMC435 regimens combined with peginterferon alfa-2a (PegIFNα-2a) and ribavirin (RBV) versus PegIFNα-2a plus RBV alone in adult treatment-naive patients with chronic genotype 1 HCV infection.
The study mainly consists of 3 phases: screening phase (approximately 6 weeks), treatment phase (up to 48 weeks), and follow up phase (up to 48 weeks).
In the treatment phase, patients will be divided in to 5 different arms in a 1:1:1:1:1 randomized ratio.
In treatment arms 1 and 2, patients will receive 12 weeks of therapy with TMC435 along with PegIFNα 2a and RBV followed by treatment with PegIFNα 2a, RBV, and TMC435-matched placebo.
In treatment arms 3 and 4, patients will receive 24 weeks of therapy with TMC435, PegIFNα 2a, and RBV.
In treatment arm 5 (control group), patients will receive PegIFNα 2a and RBV for 48 weeks and TMC435 matched placebo for the first 24 weeks.
Collection of blood samples for efficacy evaluations will be done at scheduled visits throughout the study.
Safety evaluations for adverse events, clinical laboratory tests, physical examination, vital signs and electrocardiogram will be monitored throughout the study.
The total duration of the study will be up to approximately 72 weeks after initiation of treatment.
研究类型
介入性
注册 (实际的)
386
阶段
- 阶段2
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
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Aarhus、丹麦
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Copenhagen、丹麦
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Hvidovre N/A、丹麦
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Kolding、丹麦
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Odense N/A、丹麦
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Moscow、俄罗斯联邦
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Nizhny Novgorod、俄罗斯联邦
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Saint-Petersburg、俄罗斯联邦
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Samara、俄罗斯联邦
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Smolensk、俄罗斯联邦
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St Petersburg、俄罗斯联邦
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Alberta
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Calgary、Alberta、加拿大
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Ontario
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Toronto、Ontario、加拿大
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Quebec
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Montreal、Quebec、加拿大
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Wien、奥地利
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Berlin、德国
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Düsseldorf、德国
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Frankfurt A. M.、德国
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Freiburg、德国
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Hamburg、德国
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Hannover、德国
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Köln、德国
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Stuttgart、德国
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Würzburg、德国
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Bergen、挪威
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Nordbyhagen、挪威
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Oslo、挪威
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Tromsø、挪威
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Auckland、新西兰
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Christchurch、新西兰
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Hamilton、新西兰
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Brugge、比利时
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Brussels、比利时
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Bruxelles、比利时
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Edegem、比利时
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Gent、比利时
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Leuven、比利时
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Roeselare、比利时
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Clichy、法国
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Creteil N/A、法国
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Grenoble、法国
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Lyon、法国
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Nice、法国
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Paris、法国
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Vandoeuvre Les Nancy、法国
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Bialystok、波兰
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Bydgoszcz、波兰
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Czeladz、波兰
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Kielce、波兰
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Lodz、波兰
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Warschau、波兰
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Concord、澳大利亚
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Darlinghurst、澳大利亚
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Fitzroy、澳大利亚
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Melbourne、澳大利亚
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Sydney、澳大利亚
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Woolloongabba N/A、澳大利亚
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California
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Los Angeles、California、美国
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Florida
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Jacksonville、Florida、美国
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Orlando、Florida、美国
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Palm Harbor、Florida、美国
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Illinois
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Chicago、Illinois、美国
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Louisiana
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New Orleans、Louisiana、美国
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Minnesota
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Saint Paul、Minnesota、美国
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New York
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New York、New York、美国
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North Carolina
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Chapel Hill、North Carolina、美国
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Ohio
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Cincinnati、Ohio、美国
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Tennessee
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Germantown、Tennessee、美国
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Virginia
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Charlottesville、Virginia、美国
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Barcelona、西班牙
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Madrid、西班牙
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Sevilla N/A、西班牙
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Valencia、西班牙
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参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 至 70年 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion Criteria:
- Patients with documented chronic genotype-1 hepatitis C infection and with plasma HCV RNA of > 100,000 IU/mL at screening
- Patients that have not been treated before for HCV
- Patients that are of childbearing potential or have a partner of childbearing potential should agree to use 2 effective methods of contraception
Exclusion Criteria:
- Patients with cirrhosis or evidence of hepatic decompensation
- Co-infection with the human immunodeficiency virus (HIV)
- Any contraindication to Pegasys or Copegus therapy
- History of, or any current medical condition which could impact the safety of the patient in the study
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：四人间
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的：TMC435 75 mg 12 Wks + PR 24/48
Participants will receive TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo once daily and PR for 12 weeks.
Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria.
All other participants continued PR until Week 48.
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TMC435 will be administered as one or two 75 mg capsules orally, once daily, for 12 or 24 weeks.
其他名称：
Ribavirin (R) will be administered as 200 mg tablets (5 to 6 tablets) orally, twice daily, for 48 weeks.
其他名称：
PegIFNα-2a (P) 180 micrograms will be administered as a subcutaneous (under the skin) injection, once weekly for 48 weeks.
其他名称：
Placebo capsules identical in appearance to TMC435 capsule will be administered orally, once daily, for 48 weeks.
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实验性的：TMC435 75 mg 24 Wks + PR 24/48
Participants will receive TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks.
Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria.
All other participants continued PR until Week 48.
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TMC435 will be administered as one or two 75 mg capsules orally, once daily, for 12 or 24 weeks.
其他名称：
Ribavirin (R) will be administered as 200 mg tablets (5 to 6 tablets) orally, twice daily, for 48 weeks.
其他名称：
PegIFNα-2a (P) 180 micrograms will be administered as a subcutaneous (under the skin) injection, once weekly for 48 weeks.
其他名称：
Placebo capsules identical in appearance to TMC435 capsule will be administered orally, once daily, for 48 weeks.
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实验性的：TMC435 150 mg 12 Wks + PR 24/48
Participants will receive TMC435 150 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed Placebo and PR for 12 weeks.
Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria.
All other participants continued PR until Week 48.
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TMC435 will be administered as one or two 75 mg capsules orally, once daily, for 12 or 24 weeks.
其他名称：
Ribavirin (R) will be administered as 200 mg tablets (5 to 6 tablets) orally, twice daily, for 48 weeks.
其他名称：
PegIFNα-2a (P) 180 micrograms will be administered as a subcutaneous (under the skin) injection, once weekly for 48 weeks.
其他名称：
Placebo capsules identical in appearance to TMC435 capsule will be administered orally, once daily, for 48 weeks.
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实验性的：TMC435 150 mg 24 Wks + PR 24/48
Participants will receive TMC435 150 mg once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks.
Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria.
All other participants continued PR until Week 48.
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TMC435 will be administered as one or two 75 mg capsules orally, once daily, for 12 or 24 weeks.
其他名称：
Ribavirin (R) will be administered as 200 mg tablets (5 to 6 tablets) orally, twice daily, for 48 weeks.
其他名称：
PegIFNα-2a (P) 180 micrograms will be administered as a subcutaneous (under the skin) injection, once weekly for 48 weeks.
其他名称：
Placebo capsules identical in appearance to TMC435 capsule will be administered orally, once daily, for 48 weeks.
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安慰剂比较：Placebo 24 Wks + PR48
Participants will receive Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
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Ribavirin (R) will be administered as 200 mg tablets (5 to 6 tablets) orally, twice daily, for 48 weeks.
其他名称：
PegIFNα-2a (P) 180 micrograms will be administered as a subcutaneous (under the skin) injection, once weekly for 48 weeks.
其他名称：
Placebo capsules identical in appearance to TMC435 capsule will be administered orally, once daily, for 48 weeks.
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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第 72 周时达到持续病毒学应答的参与者百分比 (SVRW72)
大体时间：第 72 周
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下表显示了每个治疗组中达到 SVRW72 的参与者百分比，定义为在治疗结束 (EOT) 和第 72 周时血浆丙型肝炎病毒核糖核酸水平检测不到的参与者百分比。
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第 72 周
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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参与者实现快速病毒学反应 (RVR) 的百分比
大体时间：第四周
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下表显示了每个治疗组中达到 RVR 的参与者百分比，RVR 定义为接受 4 周治疗后血浆丙型肝炎病毒核糖核酸水平检测不到。
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第四周
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参与者实现完全早期病毒学应答 (cEVR) 的百分比
大体时间：第 12 周
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下表显示了每个治疗组中达到 cEVR 的参与者百分比，cEVR 定义为在第 12 周时血浆丙型肝炎病毒核糖核酸水平检测不到。
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第 12 周
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The Percentage of Participants Achieving Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels of Less Than 25 IU/mL Undetectable During Treatment and Follow-up
大体时间：Weeks, 2, 4, 8, 12, 24, 36, 48, 60, 72, and at EOT (up to Week 24 or 48)
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The table below shows the percentage of participants in each treatment group who achieved plasma HCV RNA levels of less than 25 IU/mL undetectable at selected time points during treatment, follow-up, and at end of treatment (EOT).
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Weeks, 2, 4, 8, 12, 24, 36, 48, 60, 72, and at EOT (up to Week 24 or 48)
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The Percentage of Participants Who Achieved Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels of Less Than 25 IU/mL Detectable or Undetectable During Treatment and Follow-up
大体时间：Weeks 2, 4, 8, 12, 24, 36, 48, 60, 72, and at EOT (up to Week 24 or 48)
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The table below shows the percentage of participants in each treatment group who achieved plasma levels of HCV RNA less than 25 IU/mL detectable or undetectable at selected time points during treatment, follow-up, and at end of treatment (EOT).
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Weeks 2, 4, 8, 12, 24, 36, 48, 60, 72, and at EOT (up to Week 24 or 48)
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The Percentage of Participants Achieving Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels of Greater Than or Equal to 2 log10 Drop During Treatment
大体时间：Baseline (Day 1) and Weeks, 2, 4, 8, and 12
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The table below shows the percentage of participants in each treatment group who achieved plasma levels of HCV RNA greater than or equal to 2 log10 drop from Baseline at selected time points during treatment.
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Baseline (Day 1) and Weeks, 2, 4, 8, and 12
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The Percentage of Participants Who Achieved a Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24)
大体时间：Week 48 or 72
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The table below shows the percentage of participants in each treatment group who achieved a SVR24, defined as having undetectable plasma Hepatitis C virus ribonucleic acid levels at the end of treatment (EOT) and 24 weeks after the EOT.
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Week 48 or 72
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The Percentage of Participants Achieving an Early Virologic Response (EVR)
大体时间：Baseline (Day 1) and Week 12
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The table below shows the percentage of participants who achieved an EVR, defined as having a change from baseline in plasma Hepatitis C virus ribonucleic acid of 2 log10 at Week 12.
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Baseline (Day 1) and Week 12
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The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12)
大体时间：Up to Week 36 or 52
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The table below shows the percentage of participants who achieved undetectable plasma Hepatitis C virus ribonucleic acid levels at the end of treatment (EOT) and 12 Weeks after the EOT.
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Up to Week 36 or 52
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Number of Participants With Viral Breakthrough
大体时间：Week 24 or 48
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The table below shows the number of participants in each treatment group who experienced viral breakthrough during the TMC435 treatment period of the study, defined as a confirmed increase of more than 1 log10 IU/mL in plasma Hepatitis C virus (HCV) ribonucleic acid (RNA) level from the lowest level reached or a confirmed value of plasma HCV RNA more than 100 IU/mL in participants whose plasma HCV RNA level had previously been below the limit of quantification (less than 25 IU/mL detectable or undetectable).
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Week 24 or 48
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The Number of Participants With Viral Relapse
大体时间：Up to Week 72
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The table below shows the number of participants who experienced viral relapse, defined as a confirmed detectable plasma Hepatitis C virus (HCV) ribonucleic acid (RNA) level during the follow-up period in participants with undetectable plasma HCV RNA (less than 25 IU/mL undetectable) at the end of treatment.
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Up to Week 72
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The Number of Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normalized ALT Levels at the End of Treatment (EOT)
大体时间：Baseline (Day 1) up to Week 24 or 48
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The table below shows the number of participants with abnormal ALT levels at Baseline who achieved ALT levels within the normal range at the EOT.
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Baseline (Day 1) up to Week 24 or 48
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Plasma Concentrations of TMC435
大体时间：Two random blood samples taken at least 2 hours apart at Weeks 2, 4, 8, 12, 16, and 24
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The table below shows median (range) predose plasma concentration (C0h) values and median (range) average steady-state plasma concentration (Css,av) values for participants in each of the 4 TMC435 treatment groups.
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Two random blood samples taken at least 2 hours apart at Weeks 2, 4, 8, 12, 16, and 24
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Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24h) for TMC435
大体时间：Two random blood samples taken at least 2 hours apart at Weeks 2, 4, 8, 12, 16, and 24
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The table below shows the median (range) AUC24h values for TMC435 for participants in each of the 4 TMC435 treatment groups.
Two blood samples taken at least 2 hours apart from each other for determination of TMC435 plasma pharmacokinetics were obtained in all participants on Weeks 2, 4, 8, 12, 16, and 24 to obtain Bayesian estimates of TMC435 AUC24h (overall exposure).
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Two random blood samples taken at least 2 hours apart at Weeks 2, 4, 8, 12, 16, and 24
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
一般刊物
- Lenz O, Verbinnen T, Fevery B, Tambuyzer L, Vijgen L, Peeters M, Buelens A, Ceulemans H, Beumont M, Picchio G, De Meyer S. Virology analyses of HCV isolates from genotype 1-infected patients treated with simeprevir plus peginterferon/ribavirin in Phase IIb/III studies. J Hepatol. 2015 May;62(5):1008-14. doi: 10.1016/j.jhep.2014.11.032. Epub 2014 Nov 28.
- Scott J, Rosa K, Fu M, Cerri K, Peeters M, Beumont M, Zeuzem S, Evon DM, Gilles L. Fatigue during treatment for hepatitis C virus: results of self-reported fatigue severity in two Phase IIb studies of simeprevir treatment in patients with hepatitis C virus genotype 1 infection. BMC Infect Dis. 2014 Aug 26;14:465. doi: 10.1186/1471-2334-14-465.
- Fried MW, Buti M, Dore GJ, Flisiak R, Ferenci P, Jacobson I, Marcellin P, Manns M, Nikitin I, Poordad F, Sherman M, Zeuzem S, Scott J, Gilles L, Lenz O, Peeters M, Sekar V, De Smedt G, Beumont-Mauviel M. Once-daily simeprevir (TMC435) with pegylated interferon and ribavirin in treatment-naive genotype 1 hepatitis C: the randomized PILLAR study. Hepatology. 2013 Dec;58(6):1918-29. doi: 10.1002/hep.26641. Epub 2013 Oct 11.
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
2009年6月1日
初级完成 (实际的)
2010年4月1日
研究完成 (实际的)
2011年4月1日
研究注册日期
首次提交
2009年4月16日
首先提交符合 QC 标准的
2009年4月16日
首次发布 (估计)
2009年4月17日
研究记录更新
最后更新发布 (估计)
2014年6月16日
上次提交的符合 QC 标准的更新
2014年5月19日
最后验证
2014年5月1日
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- CR015799
- TMC435-TiDP16-C205 (其他标识符：Tibotec Pharmaceuticals, Ireland)
- 2008-007147-13 (EudraCT编号)
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.
丙型肝炎的临床试验
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Meir Medical Center完全的开发从数字立体光盘图像测量 C/D 比的新技术 | C/D 测量的观察者内再现性 | C/D 测量的观察者间变异性
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University Hospital, GrenobleClinical Investigation Centre for Innovative Technology Network完全的
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Haisco Pharmaceutical Group Co., Ltd.完全的
TMC435的临床试验
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Tibotec Pharmaceuticals, Ireland完全的
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Tibotec Pharmaceuticals, Ireland完全的
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Janssen R&D Ireland完全的
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Janssen R&D Ireland完全的丙型肝炎美国, 澳大利亚, 法国, 乌克兰, 英国, 比利时, 德国, 西班牙, 以色列, 葡萄牙, 保加利亚, 荷兰, 加拿大, 新西兰, 俄罗斯联邦, 阿根廷, 巴西, 波多黎各, 奥地利, 波兰, 罗马尼亚, 墨西哥
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Tibotec Pharmaceuticals, Ireland完全的
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Tibotec Pharmaceuticals, Ireland完全的
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Tibotec Pharmaceuticals, Ireland完全的
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Janssen R&D Ireland完全的