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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02960204
Recruitment Status : Completed
First Posted : November 9, 2016
Results First Posted : January 14, 2022
Last Update Posted : February 11, 2022
Sponsor:
Information provided by (Responsible Party):
Histogen

Brief 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.

Condition or disease Intervention/treatment Phase
Cirrhosis Portal Hypertension Non-alcoholic Steatohepatitis Drug: Emricasan Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 263 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : October 17, 2016
Actual Primary Completion Date : October 2, 2018
Actual Study Completion Date : April 8, 2019


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



Primary Outcome Measures :
  1. 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)


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02960204


Locations
Show Show 37 study locations
Sponsors and Collaborators
Histogen
Investigators
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Study Director: Jeanette M Wetzel Histogen
Study Director: Samuel Mboggo Histogen
Study Director: Ruqayyah Abdulrahoof Histogen
  Study Documents (Full-Text)

Documents provided by Histogen:
Study Protocol  [PDF] March 14, 2018
Statistical Analysis Plan  [PDF] July 10, 2018

Publications of Results:
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Responsible Party: Histogen
ClinicalTrials.gov Identifier: NCT02960204    
Obsolete Identifiers: NCT04806750
Other Study ID Numbers: IDN-6556-41
First Posted: November 9, 2016    Key Record Dates
Results First Posted: January 14, 2022
Last Update Posted: February 11, 2022
Last Verified: December 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: There is no plan to share this data with outside researchers

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Histogen:
cirrhosis
Portal Hypertension
Non-alcoholic Steatohepatitis
Liver cirrhosis
Additional relevant MeSH terms:
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Liver Cirrhosis
Fatty Liver
Hypertension, Portal
Non-alcoholic Fatty Liver Disease
Hypertension
Fibrosis
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Liver Diseases
Digestive System Diseases