A Multicenter, Double-Blind, Randomized Trial of IDN-6556 in Subjects Who Had Hepatitis C Virus (HCV) Reinfection and Liver Fibrosis Following Orthotopic Liver Transplantation for Chronic HCV Infection and Who Subsequently Achieved a Sustained Virologic Response Following Anti-HCV Therapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 64
- 试验地点
- 35
- 主要终点
- Number of Participants With At Least a One Stage Reduction From Baseline in Ishak Fibrosis Score
研究概览
简要总结
This is a double-blind, multicenter study involving patients with chronic HCV infection who had a liver transplantation; developed HCV-related liver fibrosis and/or incomplete cirrhosis; achieved a sustained virologic response (SVR) following anti-HCV therapy; but still have fibrosis and/or incomplete cirrhosis on liver biopsy to see if treatment with IDN-6556 is better than placebo in reversing or stopping the progression of the damage to the new liver caused by HCV.
详细描述
There are data to suggest that with eradication of the HCV virus, improvements in liver fibrosis can be seen in the post-transplant population. However, amelioration of inflammatory activity, and deceleration of fibrosis progression is a gradual process over the course of many years. This placebo-controlled study is designed to evaluate the effects of IDN-6556, compared to placebo, on markers of apoptosis and inflammation, and liver histology.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Male or female subjects of minimum adult legal age (according to local laws for signing the informed consent document), able to provide written informed consent, and able to understand and willing to comply with the requirements of the study
- •History of orthotopic liver transplantation for HCV-induced liver disease
- •Diagnosis of HCV infection (HCV-RNA detectable in serum) and liver fibrosis and/or incomplete cirrhosis status post liver transplantation, and achieved a sustained virologic response (SVR) with anti-viral HCV treatment within 18 months of Day 1
- •Liver fibrosis on liver histology as read by central histopathologist of Ishak F2 to F6 within three months of Day 1 (Up to 15 subjects with an Ishak score of F6 can be enrolled)
- •Willingness to utilize two reliable forms of contraception (for both males and females of childbearing potential) from Screening to one month after the last dose of study drug
排除标准
- •Known infection with hepatitis B virus (HBV) and/or human immunodeficiency virus (HIV)
- •History of renal transplant and/or severe renal impairment defined as eGFR (estimated glomerular filtration rate) of less than 30 mL/min/1.73 m2
- •Evidence of tumor burden >Milan criteria, or evidence of micro- or macrovascular invasion in explanted liver
- •Hepatocellular carcinoma (HCC) at entry into the study
- •Concurrent sirolimus (rapamycin) use
- •History or presence of clinically concerning cardiac arrhythmias, or prolongation of Screening (pre-treatment) QT or QTc interval of > 480 milliseconds (msec)
- •Subjects with diagnosed or suspected systemic lupus erythematosus (SLE) and/or rheumatoid arthritis (RA)
- •If female: known pregnancy, positive urine or serum pregnancy test, or lactating/breastfeeding
研究组 & 干预措施
IDN-6556
IDN-6556 25 mg BID
干预措施: IDN-6556 (Drug)
Placebo
Placebo BID
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With At Least a One Stage Reduction From Baseline in Ishak Fibrosis Score
时间窗: 24 months
At least a one stage reduction from baseline in Ishak Fibrosis Stage. Score F0 No fibrosis F1 Fibrous expansion of some portal areas, with or without short fibrous septa F2 Fibrous expansion of most portal areas, with or without short fibrous septa F3 Fibrous expansion of most portal areas, with occasional portal to portal bridging F4 Fibrous expansion of portal areas, with marked bridging (portal to portal as well as portal to central) F5 Marked bridging (portal to portal and/or portal to central) with occasional nodules (incomplete cirrhosis) F6 Cirrhosis probable or definite Since the primary analysis used multiple imputation methodology, the numerator and denominator varied across 20 imputations.
次要结局
- Number of Participants With At Least a One Stage Reduction From Baseline in Ishak Fibrosis Score (Observed Cases Only)(24 months)
- Number of Participants With At Least a One Stage Reduction From Baseline in Ishak Fibrosis Score(12 months)
- Alanine Aminotransferase (ALT) - Change From Baseline(Baseline and 24 months)
- Aspartate Aminotransferase (AST) Change From Baseline(Baseline and 24 months)
- Caspase 3/7 Change From Baseline(Baseline and 24 months)
- cCK18/M30 Change From Baseline(Baseline and 24 months)
- flCK18/M65 Change From Baseline(Baseline and 24 months)
- Ishak Modification of Knodell Histological Activity Index - Interface Hepatitis(24 months)
- Ishak Modification of Knodell Histological Index - Confluent Necrosis(24 months)
- Ishak Modification of Knodell Histological Index - Parenchymal Injury(24 months)
- Ishak Modification of Knodell Histological Index - Portal Inflammation(24 months)