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

January 13, 2022 updated by: Histogen

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

263

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Bonn, Germany, 53127
        • Bonn
      • Halle (Saale), Germany, 06120
        • Halle (Saale)
      • Leipzig, Germany, 04103
        • Leipzig
      • Mainz, Germany, 55131
        • Mainz
      • Münster, Germany, 48149
        • Munster
  • Spain
      • Barcelona, Spain, 08035
        • Barcelona
      • Barcelona, Spain, 08036
        • Barcelona
      • Madrid, Spain, 28006
        • Madrid
      • Madrid, Spain, 28034
        • Madrid
      • Madrid, Spain, 28046
        • Madrid
      • Majadahonda, Spain, 28222
        • Majadahonda
      • San Sebastian, Spain, 20014
        • San Sebastian
      • Santander, Spain, 39008
        • Santander
      • Valencia, Spain, 46010
        • Valencia
      • Valencia, Spain, 46104
        • Valencia
  • United States
    • California
      • Pasadena, California, United States, 91105
        • Pasadena
      • Rialto, California, United States, 92377
        • Rialto
    • Florida
      • Palmetto Bay, Florida, United States, 33157
        • Palmetto Bay
    • Georgia
      • Atlanta, Georgia, United States, 30309
        • Atlanta
    • Iowa
      • Clive, Iowa, United States, 50325
        • Clive
    • Maryland
      • Baltimore, Maryland, United States, 21202
        • Baltimore
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Detroit
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Rochester
      • Saint Paul, Minnesota, United States, 55114
        • Saint Paul
    • Missouri
      • Kansas City, Missouri, United States, 64131
        • Kansas City
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Durham
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Philadelphia
      • Philadelphia, Pennsylvania, United States, 19141
        • Philadelphia
    • Tennessee
      • Germantown, Tennessee, United States, 38138
        • Germantown
    • Texas
      • Arlington, Texas, United States, 76012
        • Arlington
      • Houston, Texas, United States, 77030
        • Houston
      • San Antonio, Texas, United States, 78215
        • San Antonio
      • San Antonio, Texas, United States, 78233
        • San Antonio
    • Virginia
      • Norfolk, Virginia, United States, 23502
        • Norfolk
      • Richmond, Virginia, United States, 23226
        • Richmond
      • Richmond, Virginia, United States, 23249
        • Richmond
    • Washington
      • Seattle, Washington, United States, 98104
        • Seattle, Washington

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Emricasan (5 mg)
Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (5 mg) twice a day.
Drug: Emricasan
Active Comparator: Emricasan (25 mg)
Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (25 mg) twice a day.
Drug: Emricasan
Active Comparator: Emricasan (50 mg)
Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (50 mg) twice a day.
Drug: Emricasan
Placebo Comparator: Matching Placebo
Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with a matching placebo twice a day.
Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean Change in Hepatic Venous Pressure Gradient (HVPG)
Time Frame: Baseline to Week 24
To assess the mean change from baseline to Week 24 in hepatic venous pressure gradient (HVPG)
Baseline to Week 24

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Improvement of HVPG Response Using a 20% Reduction From Baseline
Time Frame: Baseline to Week 24
To assess subjects who have at least a 20 percent reduction from baseline in HVPG
Baseline to Week 24
Caspase 3/7
Time Frame: Baseline to Week 24, Baseline to Week 48
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
Alanine Aminotransferase (ALT)
Time Frame: Baseline to Week 24 and Baseline to Week 48
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Histogen

Investigators

  • Study Director: Jeanette M Wetzel, Histogen
  • Study Director: Samuel Mboggo, Histogen
  • Study Director: Ruqayyah Abdulrahoof, Histogen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 17, 2016

Primary Completion (Actual)

October 2, 2018

Study Completion (Actual)

April 8, 2019

Study Registration Dates

First Submitted

July 29, 2016

First Submitted That Met QC Criteria

November 7, 2016

First Posted (Estimate)

November 9, 2016

Study Record Updates

Last Update Posted (Actual)

February 11, 2022

Last Update Submitted That Met QC Criteria

January 13, 2022

Last Verified

December 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IDN-6556-41

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

There is no plan to share this data with outside researchers

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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