Summary

for people ages 18 years and up (full criteria)
at Fresno, California and other locations
study started
estimated completion:
Danielle Brandman

Description

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.

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

Details

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.

Keywords

Decompensated Cirrhosis Cirrhosis NASH Cirrhosis Decompensated NASH cirrhosis Cirrhosis, Liver Non-Alcoholic Fatty Liver Disease Fibrosis Liver Cirrhosis Caspase Inhibitors Emricasan (25 mg) Emricasan (5 mg)

Eligibility

For people ages 18 years and up

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

Locations

  • University of California, San Francisco-Fresno accepting new patients
    Fresno California 93701 United States
  • University of California San Francisco accepting new patients
    San Francisco California 94143 United States
  • California Pacific Medical Center accepting new patients
    San Francisco California 94115 United States

Lead Scientist

  • Danielle Brandman
    Associate Professor, Medicine. Authored (or co-authored) 9 research publications

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Conatus Pharmaceuticals Inc.
ID
NCT03205345
Phase
Phase 2
Study Type
Interventional
Last Updated