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

Overview

About this study

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.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

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

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status

Rochester, Minn.

Mayo Clinic principal investigator

Douglas Simonetto, M.D.

Closed for enrollment

More information

Publications

Publications are currently not available

Additional contact information

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