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

Cirrhosis Clinical Trial

Official title:

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Emricasan, an Oral Caspase Inhibitor, in Subjects With Non-Alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04806750
• Other study ID #: IDN-6556-14
• Status: Completed
• Phase: Phase 2
• Start date: October 17, 2016
• Est. completion date: April 8, 2019

Study information

• Verified date: April 2021
• Source: Histogen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a multicenter, randomized, double-blind, placebo-controlled trial involving subjects with NASH cirrhosis and severe portal hypertension (defined as HVPG [hepatic venous pressure gradient] ≥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 (Bis in die, twice daily), 25 mg BID, or 5 mg BID or matching placebo BID.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 263
• Est. completion date: April 8, 2019
• Est. primary completion date: October 2, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 (non-selective beta-blockers), 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 (QT interval corrected by the Fridericia Correction Formula) 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

Related Conditions & MeSH terms

• Cirrhosis
• Fatty Liver
• Fibrosis
• Hypertension
• Hypertension, Portal
• Liver Cirrhosis
• Non-alcoholic Fatty Liver Disease
• Non-alcoholic Steatohepatitis
• Portal Hypertension

Intervention

Drug:
• Emricasan

• Placebo

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Histogen

References & Publications (1)

Garcia-Tsao G, Bosch J, Kayali Z, Harrison SA, Abdelmalek MF, Lawitz E, Satapathy SK, Ghabril M, Shiffman ML, Younes ZH, Thuluvath PJ, Berzigotti A, Albillos A, Robinson JM, Hagerty DT, Chan JL, Sanyal AJ; IDN-6556-14 Investigators(‡). Randomized placebo- — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change in Hepatic Venous Pressure Gradient (HVPG)	To assess the mean change from baseline in hepatic venous pressure gradient (HVPG)	Baseline to Week 24
Secondary	Improvement of HVPG Response Using a 20 Percent Reduction From Baseline	To assess the proportion of subjects who have at least a 20 percent reduction from baseline in HVPG	Baseline to Week 24
Secondary	Caspase 3/7	To assess whether emricasan compared to placebo decreases Caspase 3/7 biomarkers	Baseline to Week 24, Baseline to Week 48
Secondary	Alanine Aminotransferase (ALT)	To assess whether emricasan compared to placebo decreases non-specific (ALT) biomarkers	Baseline to Week 24 and Baseline to Week 48

External Links

•   ClinicalTrials.gov listing (NCT02960204) by previous sponsor: Conatus Pharmaceuticals Inc.