Emricasan, an Oral Caspase Inhibitor, in Subjects With NASH Cirrhosis and Severe Portal Hypertension

Cirrhosis Clinical Trial

— ENCORE-PH  

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: NCT02960204
• Other study ID #: IDN-6556-41
• Status: Completed
• Phase: Phase 2
• Start date: October 17, 2016
• Est. completion date: April 8, 2019

Study information

• Verified date: December 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 ≥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.

Other known NCT identifiers

• NCT04806750

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, 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

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
Germany	Bonn	Bonn
Germany	Halle (Saale)	Halle (Saale)
Germany	Leipzig	Leipzig
Germany	Mainz	Mainz
Germany	Münster	Münster
Spain	Barcelona	Barcelona
Spain	Barcelona	Barcelona
Spain	Madrid	Madrid
Spain	Madrid	Madrid
Spain	Madrid	Madrid
Spain	Majadahonda	Majadahonda
Spain	San Sebastian	San Sebastian
Spain	Santander	Santander
Spain	Valencia	Valencia
Spain	Valencia	Valencia
United States	Arlington	Arlington	Texas
United States	Atlanta	Atlanta	Georgia
United States	Baltimore	Baltimore	Maryland
United States	Clive	Clive	Iowa
United States	Detroit	Detroit	Michigan
United States	Durham	Durham	North Carolina
United States	Germantown	Germantown	Tennessee
United States	Houston	Houston	Texas
United States	Kansas City	Kansas City	Missouri
United States	Norfolk	Norfolk	Virginia
United States	Palmetto Bay	Palmetto Bay	Florida
United States	Pasadena	Pasadena	California
United States	Philadelphia	Philadelphia	Pennsylvania
United States	Philadelphia	Philadelphia	Pennsylvania
United States	Rialto	Rialto	California
United States	Richmond	Richmond	Virginia
United States	Richmond	Richmond	Virginia
United States	Rochester	Rochester	Minnesota
United States	Saint Paul	Saint Paul	Minnesota
United States	San Antonio	San Antonio	Texas
United States	San Antonio	San Antonio	Texas
United States	Seattle, Washington	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Histogen

Countries where clinical trial is conducted

United States,  Germany,  Spain, 

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 to Week 24 in hepatic venous pressure gradient (HVPG)	Baseline to Week 24
Secondary	Improvement of HVPG Response Using a 20% Reduction From Baseline	To assess subjects who have at least a 20 percent reduction from baseline in HVPG	Baseline to Week 24
Secondary	Caspase 3/7	To assess whether number of Caspase 3/7 biomarkers is affected by emricasan as compared to placebo	Baseline to Week 24, Baseline to Week 48
Secondary	Alanine Aminotransferase (ALT)	To assess whether amount of non-specific (ALT) biomarkers are affected by emricasan compared to placebo	Baseline to Week 24 and Baseline to Week 48