Emricasan, an Oral Caspase Inhibitor, in Subjects With Non-Alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension

Inclusion Criteria:

• Male or female subjects 18 years or older, able to provide written informed consentand 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 viralhepatitis, alcoholic liver disease, etc.)
• Compensated cirrhosis OR Decompensated cirrhosis with no more than 1 prior significantdecompensating event
• Severe portal hypertension defined as HVPG ≥12 mmHg
• Subjects who are on NSBB (non-selective beta-blockers), nitrates, diuretics,lactulose, rifaximin, or statins must be on a stable dose for at least 3 months priorto Day 1
• Willingness to utilize effective contraception (for both males and females ofchildbearing potential) from Screening to 4 weeks after the last dose of study drug

Exclusion Criteria:

• Evidence of severe decompensation
• Severe hepatic impairment defined as a Child-Pugh score ≥10
• ALT (alanine transaminase) > 3 times upper limit of normal (ULN) or AST (aspartatetransaminase) >5 times ULN during screening
• Estimated creatinine clearance <30 mL/min
• Prior transjugular intrahepatic portosystemic shunt or other porto-systemic bypassprocedure
• Known portal vein thrombosis
• Symptoms of biliary colic, e.g. due to symptomatic gallstones, within the last 6months, unless resolved following cholecystectomy
• Current use of medications that are considered inhibitors of OATP1B1 and OATP1B3transporters
• Alpha-fetoprotein >50 ng/mL
• History or presence of clinically concerning cardiac arrhythmias, or prolongation ofscreening (pre-treatment) QTcF interval (QT interval corrected by the FridericiaCorrection Formula) of >500 msec
• History of or active malignancies, other than those successfully treated with curativeintent and believed to be cured
• Prior liver transplant
• Change in diabetes medications or vitamin E within 3 months of screening
• Uncontrolled diabetes mellitus (HbA1c >9%) within 3 months of screening
• Significant systemic or major illness other than liver disease
• HIV infection
• Use of controlled substances (including inhaled or injected drugs) or non-prescribeduse of prescription drugs within 1 year of screening
• If female: planned or known pregnancy, positive urine or serum pregnancy test, orlactating/breastfeeding
• Previous treatment with emricasan or active investigational medication (exceptmethacetin) in a clinical trial within 3 months prior to Day 1