Companion Protocol for the ¹³C-Methacetin Breath Test Using the BreathID® MCS System for Conatus Phase 2 Study of Emricasan, an Oral Caspase Inhibitor, Under Protocol IDN-6556-17
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 199
- 试验地点
- 1
- 主要终点
- Number of Subjects Experiencing a High Risk Event Based on a 5.5%/Hour Cut-off
研究概览
简要总结
This study is a companion protocol that will use the data generated by Conatus' study of emricasan under protocol IDN-6556-17.The IDN-6556-17 study is a Phase 2, multicenter, double-blind, placebo-controlled trial of Emricasan in subjects with decompensated non-alcoholic steatohepatitis (NASH) cirrhosis.
详细描述
The protocol is intended to validate the ability of the MBT to predict deterioration by 48 weeks for all subjects, and at later time points for those followed longer, for subjects with decompensated NASH cirrhosis in the placebo treatment arm of Conatus' study IDN-6556-17.
As one of the Conatus' study secondary objectives, this companion protocol is designed to assess improvement in liver metabolic function as measured by Methacetin Breath Test (MBT) [ Time Frame: Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks) ].
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
The collaborator is responsible for the masking process.
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 25mg
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.
干预措施: Methacetin Breath Test (Combination Product)
Emricasan 25mg
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.
干预措施: Emricasan (Drug)
Emricasan 5mg
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.
干预措施: Methacetin Breath Test (Combination Product)
Emricasan 5mg
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.
干预措施: Emricasan (Drug)
Placebo
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.
干预措施: Methacetin Breath Test (Combination Product)
Placebo
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.
干预措施: Placebo oral capsule (Drug)
结局指标
主要结局
Number of Subjects Experiencing a High Risk Event Based on a 5.5%/Hour Cut-off
时间窗: 1 hour for MBT for assessment of this diagnostic outcome assessed during screening
Binary diagnosis of subjects that are at high risk to develop a deterioration event as determined by the Methacetin Breath Test (MBT) derived from an algorithm developed under other Exalenz clinical studies using a pre-designed cutoff of Percentage Dose Recovery (PDR) peak of \< 5.5%/hour. The data was collected and analyzed agnostic to the intervention.
次要结局
- Number of Subjects Experiencing a High Risk Event Based on a 7.5 %/Hour Cut-off(1 hour for MBT for assessment of this diagnostic outcome assessed during screening)