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Trial record 2 of 6 for:    nash emricasan

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

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ClinicalTrials.gov Identifier: NCT03205345
Recruitment Status : Unknown
Verified March 2019 by Conatus Pharmaceuticals Inc..
Recruitment status was:  Active, not recruiting
First Posted : July 2, 2017
Last Update Posted : March 19, 2019
Sponsor:
Information provided by (Responsible Party):
Conatus Pharmaceuticals Inc.

Tracking Information
First Submitted Date  ICMJE June 20, 2017
First Posted Date  ICMJE July 2, 2017
Last Update Posted Date March 19, 2019
Actual Study Start Date  ICMJE June 28, 2017
Estimated Primary Completion Date August 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 29, 2017)
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) ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 29, 2017)
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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) ]
  • 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) ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Emricasan, a Caspase Inhibitor, for Treatment of Subjects With Decompensated NASH Cirrhosis
Official Title  ICMJE A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Emricasan, an Oral Caspase Inhibitor, in Subjects With Decompensated Non-Alcoholic Steatohepatitis (NASH) Cirrhosis
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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
Condition  ICMJE Decompensated Cirrhosis
Intervention  ICMJE
  • Drug: Emricasan (25 mg)
    25 mg emricasan
    Other Name: IDN-6556
  • Drug: Emricasan (5 mg)
    5 mg emricasan
    Other Name: IDN-6556
  • Drug: Placebo
    Matching Placebo
    Other Name: Matching placebo
Study Arms  ICMJE
  • Active Comparator: Emricasan (25 mg)
    Emricasan 25 mg
    Intervention: Drug: Emricasan (25 mg)
  • Active Comparator: Emricasan (5 mg)
    Emricasan 5mg
    Intervention: Drug: Emricasan (5 mg)
  • Placebo Comparator: Placebo
    Matching placebo
    Intervention: Drug: Placebo
Publications * Frenette C, Kayali Z, Mena E, Mantry PS, Lucas KJ, Neff G, Rodriguez M, Thuluvath PJ, Weinberg E, Bhandari BR, Robinson J, Wedick N, Chan JL, Hagerty DT, Kowdley KV; IDN-6556-17 Study Investigators. Emricasan to prevent new decompensation in patients with NASH-related decompensated cirrhosis. J Hepatol. 2021 Feb;74(2):274-282. doi: 10.1016/j.jhep.2020.09.029. Epub 2020 Oct 8.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: June 29, 2017)
210
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2019
Estimated Primary Completion Date August 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03205345
Other Study ID Numbers  ICMJE IDN-6556-17
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Conatus Pharmaceuticals Inc.
Study Sponsor  ICMJE Conatus Pharmaceuticals Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Jean L Chan, MD Conatus Pharmaceuticals
PRS Account Conatus Pharmaceuticals Inc.
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP