Emricasan, a Caspase Inhibitor, for Evaluation in Subjects With Non-Alcoholic Steatohepatitis (NASH) Fibrosis
- Conditions
- Non-alcoholic SteatohepatitisLiver DiseasesFibrosis
- Interventions
- Registration Number
- NCT02686762
- Lead Sponsor
- Conatus Pharmaceuticals Inc.
- Brief Summary
This is a multicenter, double-blind, randomized, placebo-controlled trial involving subjects with a diagnosis of "definite NASH" with fibrosis (excluding cirrhosis) as determined by the central histopathologist. Upon successful screening, subjects will be randomized to receive either emricasan 50 mg BID or emricasan 5 mg BID or matching placebo BID.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 318
-
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
-
Histological evidence of definite NASH based on NASH CLinical Research Network (CRN) criteria, as confirmed by the central histopathologist, on a liver biopsy obtained no more than 6 months prior to Day 1
-
NAFLD Activity Score (NAS) of 4 or greater with a score of at least 1 in each component of the NAS (steatosis scored 0-3, lobular inflammation scored 0-3, ballooning scored 0-2)
-
Fibrosis stage 1 (limited to 20% of subjects), stage 2, or stage 3 using the NASH CRN Histologic Scoring System
a. Subjects with fibrosis stage 1 must also have diabetes mellitus or metabolic syndrome
-
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
-
If on vitamin E or pioglitazone, subjects must have been on a stable dose for at least 3 months prior to the biopsy (whether historical or qualifying biopsy)
-
Current or history of significant alcohol consumption, defined as more than 20 g/day for females and more than 30 g/day in males on average, or inability to reliably quantify alcohol consumption based on investigator's judgement
-
Use of the following drugs (which may have potential hepatotoxic effects) within 6 months prior to Day 1: amiodarone, methotrexate, tamoxifen, valproic acid, estrogens at doses greater than those used for hormone replacement or contraception, anabolic steroids, or systemic glucocorticoids for more than 4 weeks at doses greater than replacement doses
-
Uncontrolled diabetes (HbA1c ≥9%) within 60 days prior to Day 1
-
Presence of cirrhosis on liver biopsy (fibrosis stage 4 based on the central histopathologist reading)
-
Hepatitis and fibrosis more likely related to etiologies other than NASH such as:
- alcoholic steatohepatitis
- autoimmune hepatitis
- hepatitis B virus (HBV) infection
- hepatitis C virus (HCV) infection
- primary biliary cirrhosis
- primary sclerosing cholangitis
- Wilson's disease
- alpha-1-antitrypsin deficiency
- hemochromatosis or iron overload
- drug-induced liver disease
- other biliary liver disease
-
ALT or AST >5 times upper limit of normal (ULN) or total bilirubin >1.5 times ULN during screening (unless subject has elevated total bilirubin due to Gilbert's as documented in the medical records)
-
Alpha-fetoprotein >200 ng/mL
-
Hemoglobin <10 g/dL
-
White blood cell count <2.0 x 10^3/mm3
-
Estimated creatinine clearance <30 mL/min
-
Current use of the following medications that are considered significant inhibitors of OATP1B1 and OATP1B3 transporters: atazanavir, cyclosporine, eltrombopag, gemfibrozil, indinavir, lopinavir, ritonavir, rifampin, saquinavir, simeprevir, telaprevir, tipranovir, or some combination of these medications
-
Symptoms of biliary colic, e.g. due to symptomatic gallstones, within the last 6 months, unless resolved following cholecystectomy
-
Inability to safely obtain a liver biopsy
-
Known human immunodeficiency virus (HIV) infection
-
Weight loss ≥ 10% within 6 months of Day 1
-
Use of 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
-
History of or active malignancies, other than those successfully treated with curative intent and believed to be cured
-
Significant systemic or major illness other than liver disease that in the opinion of the investigator would preclude the subject from participating in and completing the study, including but not limited to acute coronary syndrome or stroke within 6 months of screening or major surgery within 3 months of screening
-
History or presence of clinically concerning cardiac arrhythmias, or prolongation of Screening (pre-treatment) QTcF interval >480 milliseconds (msec)
-
Prior or planned (during the time frame of the study) bariatric surgery
-
If female: planned or known pregnancy, positive urine or serum pregnancy test, or lactating/breastfeeding
-
Previous treatment with emricasan or active investigational medication in a clinical trial within 6 months prior to Day 1
-
Prior liver transplant
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Emricasan (50 mg) Emricasan (50 mg) Subjects with Non-alcoholic Steatohepatitis (NASH) Fibrosis will be administered orally with emricasan (50 mg) twice a day. Emricasan (5 mg) Emricasan (5 mg) Subjects with Non-alcoholic Steatohepatitis (NASH) Fibrosis will be administered orally with emricasan (5 mg) twice a day. Matching Placebo Placebo Subjects with Non-alcoholic Steatohepatitis (NASH) Fibrosis will be administered orally with a matching placebo twice a day.
- Primary Outcome Measures
Name Time Method Fibrosis improvement by at least one stage without worsening of steatohepatitis Week 72 Proportion of subjects who improve fibrosis on liver biopsy by at least one stage without worsening of steatohepatitis in the emricasan group compared to placebo
- Secondary Outcome Measures
Name Time Method Improvement in the Non-alcoholic fatty liver disease (NAFLD) Activity Score Baseline & Week 72 The proportion of subjects who improve the NAFLD Activity Score (NAS), its components (steatosis, lobular inflammation, ballooning), and portal inflammation, in the emricasan group compared to placebo
Steatohepatitis resolution (based on liver biopsy) Baseline & Week 72 The proportion of subjects who resolve steatohepatitis without worsening of fibrosis in the emricasan group compared to placebo
Caspase 3/7 Relative Light Units and Alanine aminotransferase (ALT) Day 1, week 4, 24, 48, and 72 To asses whether emricasan compared to placebo improves biomarkers Caspase 3/7 RLU and ALT Unit/Liter (U/L) in subjects with NASH fibrosis.
Trial Locations
- Locations (103)
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
UCLA The Pfleger Liver Institute
🇺🇸Los Angeles, California, United States
Gastrointestinal Biosciences
🇺🇸Los Angeles, California, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Surinder Singh Saini, M.D., Inc.
🇺🇸Newport Beach, California, United States
iResearch Atlanta LLC
🇺🇸Decatur, Georgia, United States
Inland Empire Liver Foundation
🇺🇸Rialto, California, United States
Fresno Clinical Research Center
🇺🇸Freestone, California, United States
Lahey Clinic Medical Center
🇺🇸Burlington, Massachusetts, United States
UnityPoint Clinic Center For Liver Disease
🇺🇸Des Moines, Iowa, United States
The University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Mercy Medical Center
🇺🇸Baltimore, Maryland, United States
McGuire VA Medical Center
🇺🇸Richmond, Virginia, United States
Options Health Research, LLC
🇺🇸Tulsa, Oklahoma, United States
State University of New York
🇺🇸Buffalo, New York, United States
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Northwestern Memorial Hospital
🇺🇸Chicago, Illinois, United States
Carolinas Healthcare System, Center for Liver Disease
🇺🇸Charlotte, North Carolina, United States
Universitätsklinikum Münster
🇩🇪Munster, North Rhine-Westphalia, Germany
Universitätsklinikum Hamburg Eppendorf
🇩🇪Hamburg, Germany
Rex Healthcare
🇺🇸Raleigh, North Carolina, United States
California Liver Research Institute
🇺🇸Pasadena, California, United States
Aquiant Research
🇺🇸New Albany, Indiana, United States
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Mount Sinai Beth Israel Medical Center
🇺🇸New York, New York, United States
Pinnacle Clinical Research, PLLC
🇺🇸Live Oak, Texas, United States
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
Hospital Universitario Puerta de Hierro - Majadahonda
🇪🇸Majadahonda, Spain
Hospital Universitario Marques de Valdecilla
🇪🇸Santander, Spain
Temple University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Methodist University Hospital
🇺🇸Memphis, Tennessee, United States
Texas Clinical Research Institute
🇺🇸Arlington, Texas, United States
Asheville Gastroenterology Associates, PA
🇺🇸Asheville, North Carolina, United States
Universitätsklinikum Freiburg
🇩🇪Freiburg, Germany
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Hospital Universitario de Donostia
🇪🇸San Sebastian, Spain
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Columbia University Medical Center (CUMC)
🇺🇸New York, New York, United States
Washington University School of Medicine-Infectious Disease Clinical Research Unit
🇺🇸Saint Louis, Missouri, United States
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
🇩🇪Mainz, Germany
Charité - Universitätsmedizin Berlin
🇩🇪Berlin, Germany
Eugastro GmbH
🇩🇪Leipzig, Germany
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital General Universitario de Valencia
🇪🇸Valencia, Spain
Miami Veterans Administration Healthcare System
🇺🇸Miami, Florida, United States
University of Miami/Schiff Center for Liver Diseases
🇺🇸Miami, Florida, United States
Duke University Medical Center, Duke South Clinics
🇺🇸Durham, North Carolina, United States
Consultants for Clinical Research
🇺🇸Cincinnati, Ohio, United States
Vanderbilt University Medical Center - Digestive Disease Center
🇺🇸Nashville, Tennessee, United States
American Research Corporation at the Texas Liver Institue
🇺🇸San Antonio, Texas, United States
University of Utah Health Sciences Center
🇺🇸Salt Lake City, Utah, United States
Universitätsklinikum Bonn
🇩🇪Bonning, North Rhine-Westphalia, Germany
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
University of California San Diego Medical Center
🇺🇸San Diego, California, United States
Florida Digestive Health Specialist
🇺🇸Lakewood Ranch, Florida, United States
UF Hepatology Research at CTRB
🇺🇸Gainesville, Florida, United States
University Hospitals Case Medical Center
🇺🇸Cleveland, Ohio, United States
Hospital of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Brooke Army Medical Center
🇺🇸San Antonio, Texas, United States
Bon Secours Richmond Health System
🇺🇸Newport News, Virginia, United States
Digestive and Liver Disease Specialists
🇺🇸Norfolk, Virginia, United States
Universitätsklinikum der RWTH Aachen
🇩🇪Aachen, North Rhine-Westphalia, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital Universitario de La Princesa
🇪🇸Madrid, Spain
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Preferred Research Partners, Inc.
🇺🇸Little Rock, Arkansas, United States
Sibley Memorial Hospital
🇺🇸Washington, District of Columbia, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Doctors Office Center
🇺🇸Newark, New Jersey, United States
Howard University
🇺🇸Washington, District of Columbia, United States
Cedars Sinai Medical Center
🇺🇸West Hollywood, California, United States
University of Arizona Clinical and Translational Sciences Research Center
🇺🇸Tucson, Arizona, United States
NYU Langone Medical Center
🇺🇸New York, New York, United States
ClinSearch, LLC
🇺🇸Chattanooga, Tennessee, United States
Louisiana Research Center, LLC
🇺🇸Shreveport, Louisiana, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
Gastro One
🇺🇸Germantown, Tennessee, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
University of Vermont
🇺🇸Burlington, Vermont, United States
Gastrointestinal Specialists of Georgia
🇺🇸Marietta, Georgia, United States
Baylor All Saints Medical Center
🇺🇸Fort Worth, Texas, United States
Liver Associates of Texas, P.A.
🇺🇸Houston, Texas, United States
Research Specialists of Texas
🇺🇸Houston, Texas, United States
University of Washington Harborview Medical Center
🇺🇸Seattle, Washington, United States
Albert Einstein Medical Center
🇺🇸Philadelphia, Pennsylvania, United States
Northwell Health, Inc.
🇺🇸Manhasset, New York, United States
University of California Davis Medical Center
🇺🇸Sacramento, California, United States
Yale University School of Medicine
🇺🇸New Haven, Connecticut, United States
Florida Hospital Orlando Transplant Institute
🇺🇸Orlando, Florida, United States
Tampa General Medical Group
🇺🇸Tampa, Florida, United States
University of Louisville
🇺🇸Louisville, Kentucky, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
PMG Research at Charleston
🇺🇸Charleston, South Carolina, United States
Kansas City VA Medical Center
🇺🇸Kansas City, Missouri, United States
Kansas City Research Institute
🇺🇸Kansas City, Missouri, United States
Walter Reed National Military Medical Center
🇺🇸Bethesda, Maryland, United States
Iowa Digestive Disease Center, P.C
🇺🇸Clive, Iowa, United States
University Gastroenterology
🇺🇸Providence, Rhode Island, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States