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

• Status: Completed
• Trial end date: 2019-05-07
• Target enrollment: 0
• Participant gender: All

Summary

This is a multicenter, randomized, double-blind, placebo-controlled trial involving subjects with NASH cirrhosis and severe portal hypertension (defined as HVPG ≥12 mmHg as determined by the central reader assigned to this study). Upon successful screening, subjects will be randomized to receive either emricasan 50 mg BID, 25 mg BID, or 5 mg BID or matching placebo BID.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Conatus Pharmaceuticals Inc.; Histogen

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.)

• Compensated cirrhosis OR Decompensated cirrhosis with no more than 1 prior significant decompensating event

• Severe portal hypertension defined as HVPG ≥12 mmHg

• Subjects who are on NSBB, nitrates, diuretics, lactulose, rifaximin, or statins must be on a stable dose for at least 3 months prior to Day 1

• Willingness to utilize effective contraception (for both males and females of childbearing 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 > 3 times upper limit of normal (ULN) or AST >5 times ULN during screening

• Estimated creatinine clearance <30 mL/min

• Prior transjugular intrahepatic portosystemic shunt or other porto-systemic bypass procedure

• Known portal vein thrombosis

• Symptoms of biliary colic, e.g. due to symptomatic gallstones, within the last 6 months, unless resolved following cholecystectomy

• Current use of medications that are considered inhibitors of OATP1B1 and OATP1B3 transporters

• Alpha-fetoprotein >50 ng/mL

• History or presence of clinically concerning cardiac arrhythmias, or prolongation of screening (pre-treatment) QTcF interval of >500 msec

• History of or active malignancies, other than those successfully treated with curative intent 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-prescribed use of prescription drugs within 1 year of screening

• If female: planned or known pregnancy, positive urine or serum pregnancy test, or lactating/breastfeeding

• Previous treatment with emricasan or active investigational medication (except methacetin) in a clinical trial within 3 months prior to Day 1