Emricasan, an Oral Caspase Inhibitor, in Subjects With NASH Cirrhosis and Severe Portal Hypertension (ENCORE-PH)

Histogen

Status and phase: Completed; Phase 2

Conditions: Portal Hypertension; Cirrhosis; Non-alcoholic Steatohepatitis

Treatments: Drug: Emricasan; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02960204

IDN-6556-41

Details and patient eligibility

About

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.

Enrollment: 263 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 (alanine transaminase) > 3 times upper limit of normal (ULN) or AST (aspartate transaminase) >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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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263 participants in 4 patient groups, including a placebo group

Emricasan (5 mg)

Active Comparator group

Description:

Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (5 mg) twice a day.

Treatment:

Drug: Emricasan

Emricasan (25 mg)

Active Comparator group

Description:

Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (25 mg) twice a day.

Treatment:

Drug: Emricasan

Emricasan (50 mg)

Active Comparator group

Description:

Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (50 mg) twice a day.

Treatment:

Drug: Emricasan

Matching Placebo

Placebo Comparator group

Description:

Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with a matching placebo twice a day.

Treatment:

Drug: Placebo