Emricasan, a Caspase Inhibitor, for Treatment of Subjects With Decompensated NASH Cirrhosis
Purpose
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.
Condition
- Decompensated Cirrhosis
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
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. 2. Cirrhosis due to NASH with exclusion of other causes of cirrhosis (e.g. chronic viral hepatitis, alcoholic liver disease, etc.) 3. 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. 4. MELD score ≥12 and ≤20 during screening 5. Albumin ≥2.5 g/dL during screening 6. Serum creatinine ≤1.5 mg/dL during screening
Exclusion Criteria
- Evidence of severe decompensation 2. Non-cirrhotic portal hypertension 3. Child-Pugh score ≥10 4. Current use of anticoagulants that affect prothrombin time or international normalized ratio 5. ALT >3 times upper limit of normal (ULN) or AST >5 times ULN during screening 6. Initiation or discontinuation of non-selective beta blockers within 1 month of screening 7. Transjugular intrahepatic portosystemic shunt or other porto-systemic bypass procedure within 1 year of screening or previously requiring revision 8. Alpha-fetoprotein >50 ng/mL in the last year 9. History of hepatocellular carcinoma (HCC) or evidence of HCC 10. History of malignancies other than HCC, unless successfully treated with curative intent and believed to be cured 11. Prior liver transplant 12. Uncontrolled diabetes mellitus (HbA1c >9%) 13. Change in diabetes medications or vitamin E within 3 months of screening 14. Restrictive bariatric surgery or bariatric device within 1 year of screening or prior malabsorptive bariatric surgery 15. Symptoms of biliary colic unless resolved following cholecystectomy 16. History of significant alcohol consumption within the past 5 years 17. Current use of medications that are considered inhibitors of organic anion transporting polypeptide OATP1B1 and OATP1B3 transporters 18. Prolongation of screening (pre-treatment) QTcF interval of >500 msecs, or history or presence of clinically concerning cardiac arrhythmias 19. Significant systemic or major illness other than liver disease 20. Human immunodeficiency virus infection 21. 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
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Investigator, Outcomes Assessor)
- Masking Description
- 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.
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Active Comparator Emricasan (25 mg) |
Emricasan 25 mg |
|
|
Active Comparator Emricasan (5 mg) |
Emricasan 5mg |
|
|
Placebo Comparator Placebo |
Matching placebo |
|
More Details
- Status
- Unknown status
- Sponsor
- Conatus Pharmaceuticals Inc.
Study Contact
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.