Emricasan, a Caspase Inhibitor, for Treatment of Subjects With Decompensated NASH Cirrhosis
- Conditions
- Decompensated Cirrhosis
- Interventions
- Registration Number
- NCT03205345
- Lead Sponsor
- 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.
- 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 210
- 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.)
- 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.
- MELD score ≥12 and ≤20 during screening
- Albumin ≥2.5 g/dL during screening
- Serum creatinine ≤1.5 mg/dL during screening
Key
- Evidence of severe decompensation
- Non-cirrhotic portal hypertension
- Child-Pugh score ≥10
- Current use of anticoagulants that affect prothrombin time or international normalized ratio
- ALT >3 times upper limit of normal (ULN) or AST >5 times ULN during screening
- Initiation or discontinuation of non-selective beta blockers within 1 month of screening
- Transjugular intrahepatic portosystemic shunt or other porto-systemic bypass procedure within 1 year of screening or previously requiring revision
- Alpha-fetoprotein >50 ng/mL in the last year
- History of hepatocellular carcinoma (HCC) or evidence of HCC
- History of malignancies other than HCC, unless successfully treated with curative intent and believed to be cured
- Prior liver transplant
- Uncontrolled diabetes mellitus (HbA1c >9%)
- Change in diabetes medications or vitamin E within 3 months of screening
- Restrictive bariatric surgery or bariatric device within 1 year of screening or prior malabsorptive bariatric surgery
- Symptoms of biliary colic unless resolved following cholecystectomy
- History of significant alcohol consumption within the past 5 years
- Current use of medications that are considered inhibitors of organic anion transporting polypeptide OATP1B1 and OATP1B3 transporters
- Prolongation of screening (pre-treatment) QTcF interval of >500 msecs, or history or presence of clinically concerning cardiac arrhythmias
- Significant systemic or major illness other than liver disease
- Human immunodeficiency virus infection
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Emricasan (5 mg) Emricasan (5 mg) Emricasan 5mg Placebo Placebo Matching placebo Emricasan (25 mg) Emricasan (25 mg) Emricasan 25 mg
- Primary Outcome Measures
Name Time Method Comparison of the effect of emricasan on improving event-free survival relative to placebo, based on a composite clinical endpoint Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks)
- Secondary Outcome Measures
Name Time Method Reduction of the proportion of subjects with MELD score progression 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
Improvement in health-related quality of life (QOL) as measured by Short Form-36 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) Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks) Decrease in all-cause and liver specific mortality 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 MELD score 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 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
Decrease in new decompensation events 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 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
Trial Locations
- Locations (75)
Cedars Sinai Medical Center
🇺🇸Los Angeles, California, United States
Stanford University
🇺🇸Redwood City, California, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Swedish Organ Transplant and Liver Center
🇺🇸Seattle, Washington, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
GHS Gastroenterology and Liver Center
🇺🇸Greenville, South Carolina, United States
Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States
Scripps Clinic - Torrey Pines
🇺🇸San Diego, California, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
American Research Corporation at the Texas Liver Institue
🇺🇸San Antonio, Texas, United States
Methodist Specialty & Transplant Hospital
🇺🇸San Antonio, Texas, United States
San Antonio Military Medical Center
🇺🇸San Antonio, Texas, United States
California Pacific Medical Center
🇺🇸San Francisco, California, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
Peak Enterology Associates
🇺🇸Colorado Springs, Colorado, United States
Mayo Clinic Arizona
🇺🇸Phoenix, Arizona, United States
St. Joseph's Hospital & Medical Center
🇺🇸Phoenix, Arizona, United States
University of Colorado Denver
🇺🇸Aurora, Colorado, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Tampa General Hospital
🇺🇸Tampa, Florida, United States
Walter Reed National Military Medical Center (WRNMMC)
🇺🇸Bethesda, Maryland, United States
University of Arizona Liver Research Institute
🇺🇸Tucson, Arizona, United States
University of California, San Francisco-Fresno
🇺🇸Fresno, California, United States
The Institute for Liver Health
🇺🇸Chandler, Arizona, United States
UC Davis GI/Hepatology Clinical Trials Unit
🇺🇸Sacramento, California, United States
California Liver Research Institute
🇺🇸Pasadena, California, United States
UCLA Pfleger Liver Institute
🇺🇸Los Angeles, California, United States
Inland Empire Liver Foundation
🇺🇸Rialto, California, United States
West Haven VA Medical Center
🇺🇸West Haven, Connecticut, United States
UF Hepatology Research at CTRB
🇺🇸Gainesville, Florida, United States
Florida Research Institute
🇺🇸Lakewood Ranch, Florida, United States
Florida Hospital Transplant Institute
🇺🇸Orlando, Florida, United States
Schiff Center for Liver Disease/University of Miami
🇺🇸Miami, Florida, United States
IMIC Inc.
🇺🇸Palmetto Bay, Florida, United States
Piedmont Transplant Institute
🇺🇸Atlanta, Georgia, United States
Gastrointestinal Specialists of Georgia
🇺🇸Marietta, Georgia, United States
Aquiant Research
🇺🇸Albany, Indiana, United States
University of Iowa Hospitals and Clinics/ Internal Medicine
🇺🇸Iowa City, Iowa, United States
Mercy Medical Center
🇺🇸Baltimore, Maryland, United States
Delta Research Partners
🇺🇸Bastrop, Louisiana, United States
Digestive Disease Associates, PA
🇺🇸Catonsville, Maryland, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Kansas City Research Institute
🇺🇸Kansas City, Missouri, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
University of Mississippi Medical Center, Division of Digestive Diseases
🇺🇸Jackson, Mississippi, United States
Rutgers New Jersey Medical School
🇺🇸Newark, New Jersey, United States
Northwell Health Inc., Sandra Atlas Bass Center for Liver Diseases.
🇺🇸Manhasset, New York, United States
NYU Medical Center
🇺🇸New York, New York, United States
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
Columbia University Medical Center - Center for Liver Disease and Transplantation
🇺🇸New York, New York, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
Carolinas Healthcare System, Center for Liver Disease
🇺🇸Charlotte, North Carolina, United States
Diabetes & Endocrinology Consultants, PC
🇺🇸Morehead City, North Carolina, United States
UC Health/ UCPC LLC
🇺🇸Cincinnati, Ohio, United States
Options Health Research, LLC
🇺🇸Tulsa, Oklahoma, United States
Hospital of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
ClinSearch, LLC
🇺🇸Chattanooga, Tennessee, United States
Texas Clinical Research Institute
🇺🇸Arlington, Texas, United States
Methodist Health System Clinical Research Institute
🇺🇸Dallas, Texas, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Baylor College of Medicine - Advanced Liver Therapies
🇺🇸Houston, Texas, United States
Liver Associates of Texas, P.A.
🇺🇸Houston, Texas, United States
Emeritas Research Group LLC
🇺🇸Leesburg, Virginia, United States
Banner University Medical Center - Phoenix Transplant Institute
🇺🇸Newport News, Virginia, United States
Bon Secours Liver Institute of Virginia
🇺🇸Richmond, Virginia, United States
University of Washington Harborview Medical Center
🇺🇸Seattle, Washington, United States
University of Washington
🇺🇸Seattle, Washington, United States
Baylor Scott & White Research Institute
🇺🇸Fort Worth, Texas, United States