A Phase III Open-Label Study to Evaluate the Safety, Tolerability and Efficacy of TMC435 Plus PegIFNα-2a (Pegasys) and Ribavirin (Copegus) Triple Therapy in Chronic Hepatitis C Genotype-1 Infected Subjects Who Are Co-infected With Human Immunodeficiency Virus Type 1 (HIV-1)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 109
- 主要终点
- Percentage of Participants With Sustained Virologic Response at Week 12 (SVR 12)
研究概览
简要总结
The purpose of this study is to evaluate the safety and tolerability of TMC435 along with pegylated interferon alpha-2a (PegIFNα-2a) and ribavirin (RBV) triple therapy in hepatitis C virus genotype-1 infected subjects, co-infected with human immunodeficiency virus-type 1, and to evaluate the number of patients with sustained virologic response (SVR) at 12 weeks after the planned end of treatment.
详细描述
This is an open-label (all the people know the identity of the intervention), single arm (study will be conducted in a single group) clinical study, to evaluate the safety, tolerability and efficacy of TMC435 along with pegylated interferon alpha-2a (PegIFNα-2a) and ribavirin (RBV) triple therapy in adult chronic hepatitis C (CHC) genotype-1 infected patients who are co-infected with human immunodeficiency virus-type 1 (HIV-1). The study consists of 3 phases, screening phase (Week -6), treatment phase, and a follow-up phase (up to 24 weeks). In the treatment phase, patients will be classified based on their experience with previous hepatitis C virus (HCV) treatment as follows: 1) HCV treatment-naive (patients who never received medication for the treatment of HCV); 2) prior HCV relapsers (patients who received at least 24 weeks of a PegIFNα-2a and RBV-based therapy and relapsed within 1 year after the last medication intake); and 3) prior HCV non-responders (can be further classified as, null responders: patients having at least 1 prior documented course of PegIFNα-2a and RBV therapy for at least 12 consecutive weeks; or partial responders: patients having at least 20 consecutive weeks which has not been discontinued due to intolerability to PegIFNα-2a and RBV therapy). All patients will receive TMC435 once daily along with PegIFNα-2a and RBV for 12 weeks. Patients who are continuing treatment only with PegIFNα-2a and RBV will follow until 24 or 48 weeks. Pharmacokinetics will be measured after collection of blood samples. Safety evaluations for adverse events, clinical laboratory tests, electrocardiogram, vital signs, physical examinations, and specific toxicities will be performed throughout the study. The total duration of treatment is approximately of 24 weeks.
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
- •A liver biopsy required within 3 years prior to screening unless the patient has a contraindication for a liver biopsy
- •Patients with bridging fibrosis or cirrhosis and without a liver biopsy result within 2 years prior screening must have an ultrasound taken within 2 months prior to the screening visit or during screening with no findings suspicious for hepatocellular carcinoma (HCC)
- •Genotype-1 hepatitis C virus (HCV) infection
- •Plasma HCV ribonucleic acid (RNA) of more than 10,000 IU per mL
- •Documented human immunodeficiency virus-type 1 (HIV-1) infection at least 6 months prior to screening
排除标准
- •Patient showing evidence of hepatic decompensation (ie, history or current evidence of ascites, bleeding varices or hepatic encephalopathy, albumin serum concentration less than 3.3 gm per dL, prolonged prothrombin time [PT] expressed as international normalized ratio [INR] more than 1.5)
- •Any liver disease of non-HCV etiology
- •Co-infection with hepatitis B virus (hepatitis B surface antigen [HBsAg] positive)
- •An acute HIV-1 infection; or HIV-2 infection
- •Change in antiretroviral (ARV) regimen within the last 4 weeks prior screening
研究组 & 干预措施
TMC435 + pegylated interferon alpha-2a + ribavirin
Patients will be administered TMC435 150 mg along with pegylated interferon alpha-2a 180 microgram and ribavirin 1000 or 1200 mg for 12 weeks. Pegylated interferon alpha-2a and ribavirin will only be continued until 24 to 48 weeks.
干预措施: TMC435 (Drug)
TMC435 + pegylated interferon alpha-2a + ribavirin
Patients will be administered TMC435 150 mg along with pegylated interferon alpha-2a 180 microgram and ribavirin 1000 or 1200 mg for 12 weeks. Pegylated interferon alpha-2a and ribavirin will only be continued until 24 to 48 weeks.
干预措施: Pegylated interferon alpha-2a (Drug)
TMC435 + pegylated interferon alpha-2a + ribavirin
Patients will be administered TMC435 150 mg along with pegylated interferon alpha-2a 180 microgram and ribavirin 1000 or 1200 mg for 12 weeks. Pegylated interferon alpha-2a and ribavirin will only be continued until 24 to 48 weeks.
干预措施: Ribavirin (Drug)
结局指标
主要结局
Percentage of Participants With Sustained Virologic Response at Week 12 (SVR 12)
时间窗: 12 weeks after end of treatment (Week 24 or 48)
The SVR 12 was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) levels less than (\<) 25 international unit per milliliter (IU/mL) undetectable at the actual end of treatment (EOT), and HCV RNA levels \<25 IU/mL undetectable or HCV RNA levels \<25 IU/mL detectable at 12 Weeks after end of treatment.
次要结局
- Percentage of Participants With Viral Relapse(Week 1 to 72)
- Percentage of Participants With Sustained Virologic Response at Week 24 (SVR 24)(24 weeks after end of treatment (Week 24 or 48))
- Percentage of Participants With Viral Breakthrough(Week 1 to 48)
- Percentage of Participants With Hepatitis C Virus Ribonucleic Acid (HCV-RNA) Less Than (<) 25 International Units (IU/mL) Undetectable or Detectable/Undetectable(Week 4, 12, 24, 36, and 48)
- Percentage of Participants With On-treatment Failure(Week 1 to 48)
- Mean Change From Baseline in Log10 Plasma Human Immunodeficiency Virus (HIV) Viral Load(Baseline (Day 1), Week 2, 4, 8, 12, 16, 20, 24, 28, 36, 42, 48, 52, 60 and 72)
- Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)(Week 1 to Week 72)
- Percentage of Participants With Normalized Alanine Aminotransferase Levels(Baseline up to Week 72)
- Change From Baseline in CD4+ Cell Count in Percentage(Baseline (Day 1), Week 2, 4, 8, 12, 16, 20, 24, 28, 36, 42, 48, 52, 60 and 72)
- Percentage of Human Immunodeficiency Virus (HIV) Participants With Virologic Failure(Baseline to Week 72.)
- Mean Change From Baseline in CD4+ Cell Count(Baseline (Day 1), Week 2, 4, 8, 12, 16, 20, 24, 28, 36, 42, 48, 52, 60 and 72)