A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Emricasan, an Oral Caspase Inhibitor, in Subjects With Non-Alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 263
- 试验地点
- 30
- 主要终点
- Mean Change in Hepatic Venous Pressure Gradient (HVPG)
研究概览
简要总结
This is a multicenter, randomized, double-blind, placebo-controlled trial involving subjects with NASH cirrhosis and severe portal hypertension (defined as HVPG ≥12 mmHg as determined by the central reader assigned to this study). Upon successful screening, subjects will be randomized to receive either emricasan 50 mg BID, 25 mg BID, or 5 mg BID or matching placebo BID.
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
- Triple (Participant, 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 18 years or older, able to provide written informed consent and able to understand and willing to comply with the requirements of the study.
- •Cirrhosis due to NASH with exclusion of other causes of cirrhosis (e.g. chronic viral hepatitis, alcoholic liver disease, etc.)
- •Compensated cirrhosis OR Decompensated cirrhosis with no more than 1 prior significant decompensating event
- •Severe portal hypertension defined as HVPG ≥12 mmHg
- •Subjects who are on NSBB, nitrates, diuretics, lactulose, rifaximin, or statins must be on a stable dose for at least 3 months prior to Day 1
- •Willingness to utilize effective contraception (for both males and females of childbearing potential) from Screening to 4 weeks after the last dose of study drug
排除标准
- •Evidence of severe decompensation
- •Severe hepatic impairment defined as a Child-Pugh score ≥10
- •ALT (alanine transaminase) > 3 times upper limit of normal (ULN) or AST (aspartate transaminase) >5 times ULN during screening
- •Estimated creatinine clearance <30 mL/min
- •Prior transjugular intrahepatic portosystemic shunt or other porto-systemic bypass procedure
- •Known portal vein thrombosis
- •Symptoms of biliary colic, e.g. due to symptomatic gallstones, within the last 6 months, unless resolved following cholecystectomy
- •Current use of medications that are considered inhibitors of OATP1B1 and OATP1B3 transporters
- •Alpha-fetoprotein >50 ng/mL
- •History or presence of clinically concerning cardiac arrhythmias, or prolongation of screening (pre-treatment) QTcF interval of >500 msec
- •History of or active malignancies, other than those successfully treated with curative intent and believed to be cured
- •Prior liver transplant
- •Change in diabetes medications or vitamin E within 3 months of screening
- •Uncontrolled diabetes mellitus (HbA1c >9%) within 3 months of screening
- •Significant systemic or major illness other than liver disease
- •HIV infection
- •Use of controlled substances (including inhaled or injected drugs) or non-prescribed use of prescription drugs within 1 year of screening
- •If female: planned or known pregnancy, positive urine or serum pregnancy test, or lactating/breastfeeding
- •Previous treatment with emricasan or active investigational medication (except methacetin) in a clinical trial within 3 months prior to Day 1
研究组 & 干预措施
Emricasan (5 mg)
Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (5 mg) twice a day.
干预措施: Emricasan (Drug)
Emricasan (25 mg)
Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (25 mg) twice a day.
干预措施: Emricasan (Drug)
Emricasan (50 mg)
Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (50 mg) twice a day.
干预措施: Emricasan (Drug)
Matching Placebo
Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with a matching placebo twice a day.
干预措施: Placebo (Drug)
结局指标
主要结局
Mean Change in Hepatic Venous Pressure Gradient (HVPG)
时间窗: Baseline to Week 24
To assess the mean change from baseline to Week 24 in hepatic venous pressure gradient (HVPG)
次要结局
- Improvement of HVPG Response Using a 20% Reduction From Baseline(Baseline to Week 24)
- Caspase 3/7(Baseline to Week 24, Baseline to Week 48)
- Alanine Aminotransferase (ALT)(Baseline to Week 24 and Baseline to Week 48)