Phase 2, Open-Label Study to Investigate the Pharmacokinetics, Efficacy, Safety, and Tolerability of the Combination of Simeprevir (TMC435), Daclatasvir (BMS-790052) and Ribavirin (RBV) in Subjects With Recurrent Chronic Hepatitis C Genotype 1b Infection After Orthotopic Liver Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 35
- 主要终点
- Percentage of Participants With Sustained Virologic Response 12 Weeks After the End of Treatment (SVR 12)
研究概览
简要总结
The purpose of the study is to evaluate effect of steady-state (when the amount of drug administered (in a given time period is equal to the amount of drug eliminated in that same period) of simeprevir and daclatasvir on the steady-state pharmacokinetics (what a medication does to the body) of cyclosporine (applicable to Part 1 only) and tacrolimus when administered as a combinational regimen in post-orthotopic liver transplantation (OLT) participants with recurrent hepatitis C virus (HCV) genotype 1b infection and effectiveness of a 24-week treatment regimen containing simeprevir, daclatasvir, and ribavirin (RBV) with respect to the proportion of HCV genotype 1b infected post-OLT participants achieving sustained virologic response 12 weeks after end of treatment.
详细描述
This is an open-label (all participants of this study know the identity of the intervention) and multicenter (study conducted at multiple sites) study. This study will be conducted in 2 parts. Both the parts of the study will consist of screening phase (4 weeks), treatment period (24 weeks), and a post-treatment follow-up (24 weeks). A total of 30 participants will be enrolled in Part 1 and Part 2 of the study. A minimum of 9 participants were planned to receive cyclosporine as stable immunosuppressant therapy and a minimum of 9 participants were planned to receive tacrolimus as stable immunosuppressant therapy during Part 1. All participants will be receiving tacrolimus as stable immunosuppressant therapy during Part 2. In Part 1 of the study, participants with Metavir score of F1-F2, will receive a combination of study drugs - simeprevir, daclatasvir, and ribavirin for 24 weeks. In Part 2 of the study, participants with Metavir score F1-F4 will receive a dosing regimen of study drugs based on the data from Part 1 of the study. Safety evaluations will include assessments of adverse events, clinical laboratory tests, urinalysis, electrocardiogram, vital signs, and physical examination. The total study duration for each participant will be approximately 52 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Liver transplant between 6 months and 10 years prior to the screening visit
- •Hepatitis C virus (HCV) genotype 1 subtype b infection confirmed at screening
- •Screening HCV ribonucleic acid level greater than 10,000 IU/mL
- •HCV treatment-naïve participants must not have received post orthotopic liver transplant treatment with any approved or investigational drug for the treatment of HCV
- •Receiving stable immunosuppressant therapy (ie, no change in dose in the last month) with cyclosporine (only allowed in Part 1) or tacrolimus for more than 3 months prior to the screening visit
排除标准
- •Evidence of acute or chronic hepatic decompensation after the liver transplantation (including ascites, bleeding varices or hepatic encephalopathy)
- •Any liver disease of non-HCV etiology, including current evidence of graft rejection except the presence of liver steatosis
- •Any other clinically significant disease that in the opinion of the investigator would be exacerbated by the known effects of ribavirin
- •Coinfection with HCV of another genotype than genotype 1b, HIV type 1 or 2 (positive HIV-1 or HIV-2 antibodies test at screening), and hepatitis B virus (hepatitis B surface antigen positive)
- •Multi-organ transplant that included heart, lung, pancreas, or kidney
研究组 & 干预措施
Part 1
Participants with Metavir fibrosis score F1-F2 will receive treatment with combinational regimen of simeprevir, daclatasvir, and ribavirin along with cyclosporine or tacrolimus as stable immunosuppressant therapy.
干预措施: Simeprevir (Drug)
Part 1
Participants with Metavir fibrosis score F1-F2 will receive treatment with combinational regimen of simeprevir, daclatasvir, and ribavirin along with cyclosporine or tacrolimus as stable immunosuppressant therapy.
干预措施: Daclatasvir (Drug)
Part 1
Participants with Metavir fibrosis score F1-F2 will receive treatment with combinational regimen of simeprevir, daclatasvir, and ribavirin along with cyclosporine or tacrolimus as stable immunosuppressant therapy.
干预措施: Ribavirin (Drug)
Part 1
Participants with Metavir fibrosis score F1-F2 will receive treatment with combinational regimen of simeprevir, daclatasvir, and ribavirin along with cyclosporine or tacrolimus as stable immunosuppressant therapy.
干预措施: Cyclosporine (Drug)
Part 1
Participants with Metavir fibrosis score F1-F2 will receive treatment with combinational regimen of simeprevir, daclatasvir, and ribavirin along with cyclosporine or tacrolimus as stable immunosuppressant therapy.
干预措施: Tacrolimus (Drug)
Part 2
Participants with Metavir fibrosis score F1-F4 will receive treatment with combinational regimen of simeprevir, daclatasvir, and ribavirin along with tacrolimus as stable immunosuppressant therapy.
干预措施: Simeprevir (Drug)
Part 2
Participants with Metavir fibrosis score F1-F4 will receive treatment with combinational regimen of simeprevir, daclatasvir, and ribavirin along with tacrolimus as stable immunosuppressant therapy.
干预措施: Daclatasvir (Drug)
Part 2
Participants with Metavir fibrosis score F1-F4 will receive treatment with combinational regimen of simeprevir, daclatasvir, and ribavirin along with tacrolimus as stable immunosuppressant therapy.
干预措施: Ribavirin (Drug)
Part 2
Participants with Metavir fibrosis score F1-F4 will receive treatment with combinational regimen of simeprevir, daclatasvir, and ribavirin along with tacrolimus as stable immunosuppressant therapy.
干预措施: Tacrolimus (Drug)
结局指标
主要结局
Percentage of Participants With Sustained Virologic Response 12 Weeks After the End of Treatment (SVR 12)
时间窗: Week 36
Participants were considered to have achieved SVR12 if hepatitis C virus ribonucleic acid (HCV RNA) levels were less than (\<) 25 international unit per milliliter (IU/mL) detectable or undetectable at 12 weeks after the end of treatment.
次要结局
- Percentage of Participants With Sustained Virologic Response 4 Weeks After the End of Treatment (SVR 4)(Week 28)
- Percentage of Participants With Sustained Virologic Response 24 Weeks After the End of Treatment (SVR 24)(Week 48)
- Percentage of Participants With HCV RNA (< 25 IU/mL Undetectable) and HCV RNA < 25 IU/mL Detectable(Weeks 2, 4, 12, and 24)
- Percentage of Participants With HCV RNA (<) 100 IU/mL at Week 4(Week 4)
- Number of Participants With On-Treatment Failure(Up to Week 24 after actual EOT (week 24))
- Number of Participants With Viral Breakthrough(Up to week 24)
- Number of Participants With Viral Relapse(Up to Week 24 after actual EOT (week 24))