NCT03205345Unknown2 期
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Emricasan, an Oral Caspase Inhibitor, in Subjects With Decompensated Non-Alcoholic Steatohepatitis (NASH) Cirrhosis
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 入组人数
- 210
- 试验地点
- 75
- 主要终点
- Comparison of the effect of emricasan on improving event-free survival relative to placebo, based on a composite clinical endpoint
研究概览
简要总结
This is a multicenter, double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of emricasan in improving event-free survival based on a composite clinical endpoint (where all-cause mortality, new decompensation events, and MELD score progression are events) in subjects with decompensated NASH cirrhosis.
详细描述
The study treatment duration will be at least 48 weeks with study visits every 4 weeks up to Week 48 and every 8 weeks after Week 48. All subjects will continue treatment until the last subject in the study reaches 48 weeks in the study. At least 30% of subjects randomized should have baseline MELD score ≥15 and ≤20.
For each subject, the study will consist of:
- Screening period of up to 4 weeks
- Randomized, double-blind treatment period of at least 48 weeks
- A follow-up visit 2 weeks after completion of study drug treatment
The duration of each subject's participation will be at least 54 weeks for those completing the entire study.
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)
盲法说明
Study drug will be double-blind with matching placebo. Emricasan at 25 mg or 5 mg or matching placebo will be administered orally twice a day.
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.)
- •At least one of the following: a) history of variceal hemorrhage (more than 3 months prior to day 1) documented on endoscopy and requiring blood transfusion, b) history of at least moderate ascites (on physical exam or imaging) currently treated with diuretics.
- •MELD score ≥12 and ≤20 during screening
- •Albumin ≥2.5 g/dL during screening
- •Serum creatinine ≤1.5 mg/dL during screening
排除标准
- •Evidence of severe decompensation
- •Non-cirrhotic portal hypertension
- •Child-Pugh score ≥10
- •Current use of anticoagulants that affect prothrombin time or international normalized ratio
- •ALT >3 times upper limit of normal (ULN) or AST >5 times ULN during screening
- •Initiation or discontinuation of non-selective beta blockers within 1 month of screening
- •Transjugular intrahepatic portosystemic shunt or other porto-systemic bypass procedure within 1 year of screening or previously requiring revision
- •Alpha-fetoprotein >50 ng/mL in the last year
- •History of hepatocellular carcinoma (HCC) or evidence of HCC
- •History of malignancies other than HCC, unless successfully treated with curative intent and believed to be cured
- •Prior liver transplant
- •Uncontrolled diabetes mellitus (HbA1c >9%)
- •Change in diabetes medications or vitamin E within 3 months of screening
- •Restrictive bariatric surgery or bariatric device within 1 year of screening or prior malabsorptive bariatric surgery
- •Symptoms of biliary colic unless resolved following cholecystectomy
- •History of significant alcohol consumption within the past 5 years
- •Current use of medications that are considered inhibitors of organic anion transporting polypeptide OATP1B1 and OATP1B3 transporters
- •Prolongation of screening (pre-treatment) QTcF interval of >500 msecs, or history or presence of clinically concerning cardiac arrhythmias
- •Significant systemic or major illness other than liver disease
- •Human immunodeficiency virus infection
- •Use of alcohol, controlled substances (including inhaled or injected drugs), or non-prescribed use of prescription drugs within 1 year of screening to the point of interfering with the subject's ability to comply with study procedures and study drug administration in the investigator's judgement
研究组 & 干预措施
Emricasan (25 mg)
Active Comparator
Emricasan 25 mg
干预措施: Emricasan (25 mg) (Drug)
Emricasan (5 mg)
Active Comparator
Emricasan 5mg
干预措施: Emricasan (5 mg) (Drug)
Placebo
Placebo Comparator
Matching placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Comparison of the effect of emricasan on improving event-free survival relative to placebo, based on a composite clinical endpoint
时间窗: Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks)
次要结局
- Reduction of the proportion of subjects with MELD score progression(Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks))
- Improvement in health-related quality of life (QOL) as measured by Short Form-36(Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks))
- Improvement in liver metabolic function as measured by Methacetin Breath Test (MBT)(Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks))
- Decrease in all-cause and liver specific mortality(Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks))
- Improvement in MELD score(Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks))
- Improvement in Child-Pugh scores(Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks))
- Decrease in new decompensation events(Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks))
- Decrease in liver transplantation rates(Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks))
研究者
研究点 (75)
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