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

This study is currently recruiting participants.
Verified May 2017 by Conatus Pharmaceuticals Inc.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02960204
First Posted: November 9, 2016
Last Update Posted: May 19, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Conatus Pharmaceuticals Inc.
  Purpose
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 Intervention Phase
Cirrhosis Portal Hypertension Non-alcoholic Steatohepatitis Drug: Emricasan Drug: Placebo Phase 2

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Conatus Pharmaceuticals Inc.:

Primary Outcome Measures:
  • Mean Change in Hepatic Venous Pressure Gradient (HVPG) [ Time Frame: Week 24 ]
    To assess the mean change from baseline in hepatic venous pressure gradient (HVPG)


Secondary Outcome Measures:
  • Improvement of HVPG response using a 20% reduction from baseline [ Time Frame: Week 24 ]
    To assess the proportion of subjects who have at least a 20% reduction from baseline in HVPG

  • Caspase 3/7 [ Time Frame: Baseline, Weeks 24 and 48 ]
    To assess whether emricasan compared to placebo decreases Caspase 3/7 biomarkers

  • Alanine aminotransferase (ALT) [ Time Frame: Baseline, Weeks 24 and 48 ]
    To assess whether emricasan compared to placebo decreases non-specific (ALT) biomarkers

  • The Number of Subjects with Treatment Emergent Adverse Events [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 32, 40 and 48 ]
    To assess the differences in adverse events between emricasan and placebo


Estimated Enrollment: 240
Actual Study Start Date: October 17, 2016
Estimated Study Completion Date: April 2019
Estimated Primary Completion Date: October 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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 > 3 times upper limit of normal (ULN) or AST >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
  Contacts and Locations
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


Contacts
Contact: Lisa Grubbs (858) 376-2627 lgrubbs@conatuspharma.com

  Show 38 Study Locations
Sponsors and Collaborators
Conatus Pharmaceuticals Inc.
Investigators
Study Chair: David Hagerty, MD Conatus Pharmaceuticals Inc.
  More Information

Responsible Party: Conatus Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT02960204     History of Changes
Other Study ID Numbers: IDN-6556-14
First Submitted: July 29, 2016
First Posted: November 9, 2016
Last Update Posted: May 19, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: There is no plan to share this data with outside researchers

Keywords provided by Conatus Pharmaceuticals Inc.:
cirrhosis
Portal Hypertension
Non-alcoholic Steatohepatitis
Liver cirrhosis

Additional relevant MeSH terms:
Hypertension
Fibrosis
Liver Cirrhosis
Fatty Liver
Hypertension, Portal
Non-alcoholic Fatty Liver Disease
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Liver Diseases
Digestive System Diseases
Caspase Inhibitors
Cysteine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action