A Phase 3, Open-Label, Single-Arm Study to Evaluate the Safety and Efficacy of TMC435 Plus Pegylated Interferon Alfa-2a and Ribavirin Administered for 12 Weeks in Treatment-Naïve Subjects With Chronic Genotype 1 or Genotype 4 HCV Infection
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 232
- 主要终点
- The proportion (percentage) of participants infected wtih genotype 1 HCV with a sustained virologic response 12 weeks after planned end of treatment (SVR12)
研究概览
简要总结
The purpose of this study is to evaluate the efficacy, tolerability, and safety of 12-weeks of treatment with TMC435 plus pegylated interferon alfa-2a (PegIFNα-2a) and ribavirin (RBV) in previously untreated adult participants with genotype 1 or genotype 4 chronic Hepatitis C Virus (HCV) infection.
详细描述
This is a multicenter, international study where all participants will receive triple therapy with the following 3 medications: TMC435 also referred to as simeprevir (formerly known as TMC435350) which is an investigational medication in development for the treatment of chronic hepatitis C virus (HCV) infection, pegylated interferon alfa-2a (PegIFNα-2a), and ribavirin (RBV). PegIFNα-2a and RBV are commercially available therapies for HCV infection. Participants will receive treatment with TMC435, PegIFNα-2a, and RBV for 12 weeks. If blood levels of HCV ribonucleic acid (RNA) monitored at Weeks 2, 4, and 8 are below 25 IU/mL, all treatment will be stopped at Week 12. If HCV RNA values are above 25 IU/mL at Weeks 2, 4, or 8, treatment with PegIFNα-2a and RBV will continue for an additional 12 weeks (up to Week 24) unless protocol-specified stopping criteria are met at Week 4 or 12, at which time all treatment will be discontinued. The study will be conducted in 3 phases: a screening phase of maximum 6 weeks, a treatment phase extending from Day 1 (baseline) up to 12 or 24 weeks depending on the response to treatment, and a posttreatment follow-up period of 24 weeks after the participant's last planned dose of study drug. The duration of the participation (excluding screening phase) for each participant will vary between 36 and 48 weeks, depending on the response to treatment. Blood samples for laboratory analysis will be obtained from participants at protocol-specified time points during the study and participant safety will be monitored throughout the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •treatment-naïve with confirmed chronic Hepatitis C Virus (HCV) infection
- •liver biopsy performed within 2 years prior to screening or non-invasive confirmation of the liver disease stage (by transient elastography) performed within 6 months prior to screening
- •liver disease stage equivalent to Metavir Score F0-F2 (no fibrosis, or portal fibrosis without or with few septa)
排除标准
- •Participants with advanced liver disease equivalent to Metavir score F3-F4 (bridging fibrosis or cirrhosis), with hepatic decompensation, with any liver disease of non-HCV etiology, and/or with a non-genotype 1 or non-genotype 4 hepatitis C, hepatitis B or HIV co-infection will be excluded from the study
研究组 & 干预措施
TMC435 + PegIFNα-2a + RBV
TMC435 will be administered as triple therapy with pegylated interferon alfa-2a (PegIFNα-2a) and ribavirin (RBV).
干预措施: TMC435 (Drug)
TMC435 + PegIFNα-2a + RBV
TMC435 will be administered as triple therapy with pegylated interferon alfa-2a (PegIFNα-2a) and ribavirin (RBV).
干预措施: Pegylated interferon alfa-2a (PegIFNα-2a) (Drug)
TMC435 + PegIFNα-2a + RBV
TMC435 will be administered as triple therapy with pegylated interferon alfa-2a (PegIFNα-2a) and ribavirin (RBV).
干预措施: Ribavirin (RBV) (Drug)
结局指标
主要结局
The proportion (percentage) of participants infected wtih genotype 1 HCV with a sustained virologic response 12 weeks after planned end of treatment (SVR12)
时间窗: Week 24
Participants are considered to have reached SVR12 if at the actual end of treatment hepatitis C virus (HCV) ribonucleic acid (RNA) levels \< 25 IU/mL undetectable, AND at the time point of SVR12 (i.e., 12 weeks after the planned end of treatment \[EOT\]), HCV RNA levels \< 25 IU/mL undetectable.
次要结局
- The proportion (percentage) of participants who achieve rapid virologic response (RVR)(Week 4)
- The proportion (percentage) of participants with sustained virologic response 12 weeks after planned end of treatment (SVR12)(Week 24)
- The proportion (percentage) of participants with > or = 2 log decrease in hepatitis C virus (HCV) RNA at each time point(Up to Week 48)
- The proportion (percentage) of participants who achieve virologic response at Week 2 (W2VR)(Week 2)
- Change from Baseline in The Work Productivity and Activity Index (WPAI) for Hepatitis C missed work time, daily activity impairment, and productivity scores(Day 1 and at each study visit up to Week 48)
- The proportion (percentage) of participants infected wtih genotype 4 HCV with a sustained virologic response 12 weeks after planned end of treatment (SVR12)(Week 24)
- The proportion (percentage) of participants with hepatitis C virus (HCV) RNA < 25 IU/mL undetectable at each time point(Up to Week 48)
- The proportion (percentage) of participants with viral breakthrough(Up to Week 48)
- Change from Screening in liver disease stage assessment(Week -6; Week 48)
- The number of participants reporting adverse events as a measure of safety and tolerability(Up to Week 48)
- The proportion (percentage) of participants with viral relapse(Up to Week 48)
- The proportion (percentage) of participants with sustained virologic response 24 weeks after planned end of treatment (SVR24)(Week 48)
- Change from Baseline in the Hepatitis C Treatment Symptom & Impact Questionnaire (HCV SIQ) symptom and impact scores(Day 1 and at each study visit up to Week 48)
- The proportion (percentage) of participants with normalized alanine aminotransferase (ALT) levels(Up to Week 48)
- Change from Baseline in The Fatigue Severity Scale (FSS) total score(Day 1 and at each study visit up to Week 48)
- Change from Baseline in The Center for Epidemiologic Studies Depression Scale (CES-D) score(Day 1 and at each study visit up to Week 48)
- Change from Baseline in The EuroQol 5 Dimension (EQ5D) Visual Analog Scale (VAS) valuation index, and Descriptive System scores(Day 1 and at each study visit up to Week 48)