An Exploratory Phase IIa, Randomized, Open-Label Trial to Investigate the Efficacy and Safety of 12 Weeks or 24 Weeks of TMC435 in Combination With PSI-7977 (GS7977) With Or Without Ribavirin in Chronic Hepatitis C Genotype 1-Infected Prior Null Responders To Peginterferon/Ribavirin Therapy or HCV Treatment-Naive Subjects
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 168
- 主要终点
- Number of Participants With a Sustained Virologic Response (SVR) 12 Weeks After the Planned End of Treatment (EOT)
研究概览
简要总结
The purpose of this study is to investigate the efficacy and safety of TMC435 plus PSI-7977 (GS7977) with or without ribavirin in patients who are chronically infected with genotype 1 hepatitis C virus (HCV) and who did not respond to prior peginterferon/ribavirin therapy or are HCV treatment-naive (patients who never received treatment for HCV infection).
详细描述
This is a Phase IIa, randomized (the study medications are assigned by chance), open label (all people know the identity of the intervention) study of TMC435 plus PSI-7977 (GS7977) with or without ribavirin. The study consists of a screening phase (6 weeks); a treatment phase (12 or 24 week period); and a posttreatment phase (follow-up period up to Week 48). Approximately 180 patients will be enrolled in this study. Patients will be sequentially enrolled into two cohorts in this study. Cohort 1 (90 patients) will include patients without advanced hepatic fibrosis who did not respond to previous PegIFN/ribavirin therapy and Cohort 2 (90 patients) will include only patients with advanced hepatic fibrosis who did not respond to previous PegIFN/ribavirin therapy or are HCV treatment-naive. Safety will be evaluated throughout the study and will include evaluations of adverse events, clinical laboratory tests, electrocardiogram, vital signs, and physical examination. The entire study duration for each participant will be approximately 48 weeks.
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
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Chronic genotype 1 hepatitis C virus (HCV) infection
- •Plasma HCV RNA of more than 10,000 IU/mL at screening
- •Patients in Cohort 1 must be null responders to PegIFN/ribavirin with at least 1 documented previous course of PegIFN/ribavirin therapy for at least 12 consecutive weeks
- •Patients in Cohort 2 must be null responders to PegIFN/ribavirin with at least 1 documented previous course of PegIFN/ribavirin therapy for at least 12 consecutive weeks and could also be HCV treatment-naive, meaning never received treatment with any approved or investigational drug for the treatment of HCV
- •Null responders patients in Cohort 1 and Cohort 2 must meet the defined criterion for a null responder, defined as on-treatment less than 2 log10 IU/mL reduction in HCV RNA from baseline at Week 12 of the most recent PegIFN/ribavirin therapy
- •Patient must have had a liver biopsy within 3 years before screening (or between screening and baseline visit) or patient must have had a liver biopsy at any time in the past which showed Metavir F3 or F4 fibrosis
- •Must agree to use 2 forms of effective contraception throughout the study (male and female)
排除标准
- •Has evidence of hepatic decompensation
- •Has any liver disease of non-HCV etiology
- •Has an infection/co-infection with non-genotype 1 HCV
- •Has a co-infection with Human immunodeficiency virus (HIV) type 1 or type 2 (HIV-1 or HIV-2) (positive HIV-1 or HIV-2 antibody test at screening)
- •Has a co-infection with hepatitis B virus (hepatitis B surface antigen [HBsAg] positive)
- •Has a history of malignancy within 5 years of the screening visit
研究组 & 干预措施
Arm 1
30 patients will receive TMC435 (150 mg once a day) plus PSI-7977(GS7977) (400 mg once a day) with ribavirin (1000-1200 mg/day) for 24 weeks and followed by a 24-week follow-up phase.
干预措施: TMC435 (Drug)
Arm 1
30 patients will receive TMC435 (150 mg once a day) plus PSI-7977(GS7977) (400 mg once a day) with ribavirin (1000-1200 mg/day) for 24 weeks and followed by a 24-week follow-up phase.
干预措施: PSI-7977 (GS7977) (Drug)
Arm 1
30 patients will receive TMC435 (150 mg once a day) plus PSI-7977(GS7977) (400 mg once a day) with ribavirin (1000-1200 mg/day) for 24 weeks and followed by a 24-week follow-up phase.
干预措施: Ribavirin (Drug)
Arm 2
15 patients wiil receive TMC435 (150 mg once a day) plus PSI-7977 (GS7977) (400 mg once a day) for 24 weeks of and followed by a 24-week follow-up phase.
干预措施: TMC435 (Drug)
Arm 2
15 patients wiil receive TMC435 (150 mg once a day) plus PSI-7977 (GS7977) (400 mg once a day) for 24 weeks of and followed by a 24-week follow-up phase.
干预措施: PSI-7977 (GS7977) (Drug)
Arm 3
30 patients will receive TMC435 (150 mg once a day) plus PSI-7977 (GS7977) (400 mg once a day) with ribavirin (1000-1200 mg/day) for 12 weeks and followed by a 36-week follow-up phase.
干预措施: TMC435 (Drug)
Arm 3
30 patients will receive TMC435 (150 mg once a day) plus PSI-7977 (GS7977) (400 mg once a day) with ribavirin (1000-1200 mg/day) for 12 weeks and followed by a 36-week follow-up phase.
干预措施: PSI-7977 (GS7977) (Drug)
Arm 3
30 patients will receive TMC435 (150 mg once a day) plus PSI-7977 (GS7977) (400 mg once a day) with ribavirin (1000-1200 mg/day) for 12 weeks and followed by a 36-week follow-up phase.
干预措施: Ribavirin (Drug)
Arm 4
15 patients will receive TMC435 (150 mg once a day) plus PSI-7977 (GS7977) (400 mg once a day) for 12 weeks and followed by a 36-week follow-up phase.
干预措施: TMC435 (Drug)
Arm 4
15 patients will receive TMC435 (150 mg once a day) plus PSI-7977 (GS7977) (400 mg once a day) for 12 weeks and followed by a 36-week follow-up phase.
干预措施: PSI-7977 (GS7977) (Drug)
结局指标
主要结局
Number of Participants With a Sustained Virologic Response (SVR) 12 Weeks After the Planned End of Treatment (EOT)
时间窗: Week 12 and 24 (for the arms treated for 12 weeks) or Week 24 and 36 (for the arms treated for 24 weeks)
Participants with hepatitis C virus (HCV) ribonucleic acid (RNA) undetectable at end of treatment and HCV RNA less than (\<) 25 international unit per milliliter (IU/mL) (detectable or undetectable) at 12 weeks after the planned end of treatment.
次要结局
- Number of Participants With a Sustained Virologic Response (SVR) 24 Weeks After the Planned End of Treatment (EOT)(Week 12 and 36 (for the arms treated for 12 weeks) or Week 24 and 48 (for the arms treated for 24 weeks))
- Number of Participants With a Sustained Virologic Response (SVR) at Week 48(Week 48)
- Number of Participants With Viral Breakthrough(Up to End of Treatment [Week 12 (for the arms treated for 12 weeks) or Week 24 (for the arms treated for 24 weeks)])
- Number of Participants With a Sustained Virologic Response (SVR) 4 Weeks After the Planned End of Treatment (EOT)(Week 12 and 16 (for the arms treated for 12 weeks) or Week 24 and 28 (for the arms treated for 24 weeks))
- Number of Participants With Inadequate Virologic Response(Week 8 and End of Treatment [Week 12 (for the arms treated for 12 weeks) or Week 24 (for the arms treated for 24 weeks)])
- Number of Participants With Viral Relapse(During the Follow-up [Week 36 (for the arms treated for 12 weeks) or Week 24 (for the arms treated for 24 weeks)])