Emricasan, a Caspase Inhibitor, for Treatment of Subjects With Decompensated NASH Cirrhosis(ENCORE-LF)

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.

Eligibility Criteria

Key Inclusion Criteria:

1. 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

Key Exclusion Criteria:

1. 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

Principal Investigator

Ryan M Taylor, MD

Study Contact

Baljit Kaur, bkaur@kumc.edu, 913-588-3708

Estimated Completion Date

Thursday, August 1, 2019

ClinicalTrials.gov #

NCT03205345
07/23/2018