Emricasan, a Caspase Inhibitor, for Treatment of Subjects With Decompensated NASH Cirrhosis
- Conditions
- Decompensated Cirrhosis
- Interventions
- Registration Number
- NCT03205345
- Lead Sponsor
- Conatus Pharmaceuticals Inc.
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 210
- 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
Key
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Emricasan (5 mg) Emricasan (5 mg) Emricasan 5mg Placebo Placebo Matching placebo Emricasan (25 mg) Emricasan (25 mg) Emricasan 25 mg
- Primary Outcome Measures
Name Time Method Comparison of the effect of emricasan on improving event-free survival relative to placebo, based on a composite clinical endpoint Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks)
- Secondary Outcome Measures
Name Time Method Decrease in all-cause and liver specific mortality Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks) The effect of emricasan on decreasing all-cause and liver specific mortality relative to placebo
Improvement in MELD score Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks) The effect of emricasan on improving MELD score relative to placebo
Improvement in Child-Pugh scores Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks) The effect of emricasan on improving the Child-Pugh score relative to placebo
Decrease in new decompensation events Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks) The effect of emricasan on decreasing new decompensation events relative to placebo
Decrease in liver transplantation rates Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks) The effect of emricasan on decreasing liver transplantation rates (in association with MELD score ≥25) relative to placebo
Reduction of the proportion of subjects with MELD score progression Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks) The effect of emricasan on reducing the proportion of patients with MELD score progression (≥4 point increase at any study visit) relative to placebo
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)
Trial Locations
- Locations (75)
The Institute for Liver Health
🇺🇸Chandler, Arizona, United States
St. Joseph's Hospital & Medical Center
🇺🇸Phoenix, Arizona, United States
Mayo Clinic Arizona
🇺🇸Phoenix, Arizona, United States
University of Arizona Liver Research Institute
🇺🇸Tucson, Arizona, United States
University of California, San Francisco-Fresno
🇺🇸Fresno, California, United States
Cedars Sinai Medical Center
🇺🇸Los Angeles, California, United States
UCLA Pfleger Liver Institute
🇺🇸Los Angeles, California, United States
California Liver Research Institute
🇺🇸Pasadena, California, United States
Stanford University
🇺🇸Redwood City, California, United States
Inland Empire Liver Foundation
🇺🇸Rialto, California, United States
Scroll for more (65 remaining)The Institute for Liver Health🇺🇸Chandler, Arizona, United States