A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Emricasan, an Oral Caspase Inhibitor, in Subjects With Decompensated Non-Alcoholic Steatohepatitis (NASH) Cirrhosis
Overview
- Phase
- Phase 2
- Intervention
- Emricasan (25 mg)
- Conditions
- Decompensated Cirrhosis
- Sponsor
- Conatus Pharmaceuticals Inc.
- Enrollment
- 210
- Locations
- 75
- Primary Endpoint
- Comparison of the effect of emricasan on improving event-free survival relative to placebo, based on a composite clinical endpoint
- Last Updated
- 7 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
Emricasan (25 mg)
Emricasan 25 mg
Intervention: Emricasan (25 mg)
Emricasan (5 mg)
Emricasan 5mg
Intervention: Emricasan (5 mg)
Placebo
Matching placebo
Intervention: Placebo
Outcomes
Primary Outcomes
Comparison of the effect of emricasan on improving event-free survival relative to placebo, based on a composite clinical endpoint
Time Frame: Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks)
Secondary Outcomes
- 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))