ClinicalTrials.gov
ClinicalTrials.gov Menu

Emricasan, a Caspase Inhibitor, for Treatment of Subjects With Decompensated NASH Cirrhosis (ENCORE-LF)

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.
ClinicalTrials.gov Identifier: NCT03205345
Recruitment Status : Recruiting
First Posted : July 2, 2017
Last Update Posted : April 30, 2018
Sponsor:
Information provided by (Responsible Party):
Conatus Pharmaceuticals Inc.

Brief Summary:
This is a multicenter, double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of emricasan in improving event-free survival based on a composite clinical endpoint (where all-cause mortality, new decompensation events, and MELD score progression are events) in subjects with decompensated NASH cirrhosis.

Condition or disease Intervention/treatment Phase
Decompensated Cirrhosis Drug: Emricasan (25 mg) Drug: Emricasan (5 mg) Drug: Placebo Phase 2

Detailed Description:

The study treatment duration will be at least 48 weeks with study visits every 4 weeks up to Week 48 and every 8 weeks after Week 48. All subjects will continue treatment until the last subject in the study reaches 48 weeks in the study. At least 30% of subjects randomized should have baseline MELD score ≥15 and ≤20.

For each subject, the study will consist of:

  • Screening period of up to 4 weeks
  • Randomized, double-blind treatment period of at least 48 weeks
  • A follow-up visit 2 weeks after completion of study drug treatment

The duration of each subject's participation will be at least 54 weeks for those completing the entire study.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 210 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description: Study drug will be double-blind with matching placebo. Emricasan at 25 mg or 5 mg or matching placebo will be administered orally twice a day.
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Emricasan, an Oral Caspase Inhibitor, in Subjects With Decompensated Non-Alcoholic Steatohepatitis (NASH) Cirrhosis
Actual Study Start Date : June 28, 2017
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : August 2019


Arm Intervention/treatment
Active Comparator: Emricasan (25 mg)
Emricasan 25 mg
Drug: Emricasan (25 mg)
25 mg emricasan
Other Name: IDN-6556

Active Comparator: Emricasan (5 mg)
Emricasan 5mg
Drug: Emricasan (5 mg)
5 mg emricasan
Other Name: IDN-6556

Placebo Comparator: Placebo
Matching placebo
Drug: Placebo
Matching Placebo
Other Name: Matching placebo




Primary Outcome Measures :
  1. Comparison of the effect of emricasan on improving event-free survival relative to placebo, based on a composite clinical endpoint [ Time Frame: Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks) ]

Secondary Outcome Measures :
  1. Improvement in MELD score [ Time Frame: Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks) ]
    The effect of emricasan on improving MELD score relative to placebo

  2. Improvement in Child-Pugh scores [ Time Frame: Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks) ]
    The effect of emricasan on improving the Child-Pugh score relative to placebo

  3. Reduction of the proportion of subjects with MELD score progression [ Time Frame: Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks) ]
    The effect of emricasan on reducing the proportion of patients with MELD score progression (≥4 point increase at any study visit) relative to placebo

  4. Decrease in new decompensation events [ Time Frame: Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks) ]
    The effect of emricasan on decreasing new decompensation events relative to placebo

  5. Decrease in liver transplantation rates [ Time Frame: Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks) ]
    The effect of emricasan on decreasing liver transplantation rates (in association with MELD score ≥25) relative to placebo

  6. Decrease in all-cause and liver specific mortality [ Time Frame: Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks) ]
    The effect of emricasan on decreasing all-cause and liver specific mortality relative to placebo

  7. Improvement in health-related quality of life (QOL) as measured by Short Form-36 [ Time Frame: Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks) ]
  8. Improvement in liver metabolic function as measured by Methacetin Breath Test (MBT) [ Time Frame: Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Key Inclusion Criteria:

  1. 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.
  2. Cirrhosis due to NASH with exclusion of other causes of cirrhosis (e.g. chronic viral hepatitis, alcoholic liver disease, etc.)
  3. At least one of the following: a) history of variceal hemorrhage (more than 3 months prior to day 1) documented on endoscopy and requiring blood transfusion, b) history of at least moderate ascites (on physical exam or imaging) currently treated with diuretics.
  4. MELD score ≥12 and ≤20 during screening
  5. Albumin ≥2.5 g/dL during screening
  6. Serum creatinine ≤1.5 mg/dL during screening

Key Exclusion Criteria:

  1. Evidence of severe decompensation
  2. Non-cirrhotic portal hypertension
  3. Child-Pugh score ≥10
  4. Current use of anticoagulants that affect prothrombin time or international normalized ratio
  5. ALT >3 times upper limit of normal (ULN) or AST >5 times ULN during screening
  6. Initiation or discontinuation of non-selective beta blockers within 1 month of screening
  7. Transjugular intrahepatic portosystemic shunt or other porto-systemic bypass procedure within 1 year of screening or previously requiring revision
  8. Alpha-fetoprotein >50 ng/mL in the last year
  9. History of hepatocellular carcinoma (HCC) or evidence of HCC
  10. History of malignancies other than HCC, unless successfully treated with curative intent and believed to be cured
  11. Prior liver transplant
  12. Uncontrolled diabetes mellitus (HbA1c >9%)
  13. Change in diabetes medications or vitamin E within 3 months of screening
  14. Restrictive bariatric surgery or bariatric device within 1 year of screening or prior malabsorptive bariatric surgery
  15. Symptoms of biliary colic unless resolved following cholecystectomy
  16. History of significant alcohol consumption within the past 5 years
  17. Current use of medications that are considered inhibitors of organic anion transporting polypeptide OATP1B1 and OATP1B3 transporters
  18. Prolongation of screening (pre-treatment) QTcF interval of >500 msecs, or history or presence of clinically concerning cardiac arrhythmias
  19. Significant systemic or major illness other than liver disease
  20. Human immunodeficiency virus infection
  21. Use of alcohol, controlled substances (including inhaled or injected drugs), or non-prescribed use of prescription drugs within 1 year of screening to the point of interfering with the subject's ability to comply with study procedures and study drug administration in the investigator's judgement

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): NCT03205345


Contacts
Contact: Cathryn Bennett, BN 858-376-2627 cbennett@conatuspharma.com
Contact: Joanne C Imperial, MD, FAASLD jimperial@conatuspharma.com

  Show 22 Study Locations
Sponsors and Collaborators
Conatus Pharmaceuticals Inc.
Investigators
Study Director: Jean L Chan, MD Conatus Pharmaceuticals

Responsible Party: Conatus Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT03205345     History of Changes
Other Study ID Numbers: IDN-6556-17
First Posted: July 2, 2017    Key Record Dates
Last Update Posted: April 30, 2018
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Conatus Pharmaceuticals Inc.:
Cirrhosis
NASH Cirrhosis
Decompensated NASH cirrhosis
Cirrhosis, Liver
Non-Alcoholic Fatty Liver Disease

Additional relevant MeSH terms:
Fibrosis
Liver Cirrhosis
Pathologic Processes
Liver Diseases
Digestive System Diseases
Caspase Inhibitors
Cysteine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action