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Non-alcoholic SteatohepatitisPhase 2ENCORE-NFNCT02686762

Emricasan, a Caspase Inhibitor, for Evaluation in Subjects With Non-Alcoholic Steatohepatitis (NASH) Fibrosis

A Phase 2 study testing Emricasan (5 mg) and Emricasan (50 mg) in people with Non-alcoholic Steatohepatitis and Fibrosis, run by Conatus Pharmaceuticals Inc. at 103 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Emricasan (5 mg) and Emricasan (50 mg)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
318 participants
Where
103 sitesin 3 countries
Study dates
26 Jan 2016to 28 Feb 2019
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
  • 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)

Who cannot join

  • 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
Show all 34Show fewer
  • 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

Trial locations and contacts

103 sites in 3 countries.

103 sites in 3 countries

United States83 sites

  • Texas Clinical Research Institute

    Arlington, Texas, 76012

  • Asheville Gastroenterology Associates, PA

    Asheville, North Carolina, 28801

  • Mercy Medical Center

    Baltimore, Maryland, 21202

  • Walter Reed National Military Medical Center

    Bethesda, Maryland, 20889

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35233

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • State University of New York

    Buffalo, New York, 14203

  • Lahey Clinic Medical Center

    Burlington, Massachusetts, 01803

  • University of Vermont

    Burlington, Vermont, 05405

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • PMG Research at Charleston

    Charleston, South Carolina, 29461

  • Carolinas Healthcare System, Center for Liver Disease

    Charlotte, North Carolina, 28204

  • ClinSearch, LLC

    Chattanooga, Tennessee, 37421

  • Northwestern Memorial Hospital

    Chicago, Illinois, 60611

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • The University of Chicago Medical Center

    Chicago, Illinois, 60637

  • Consultants for Clinical Research

    Cincinnati, Ohio, 45249

  • University Hospitals Case Medical Center

    Cleveland, Ohio, 44106

  • Iowa Digestive Disease Center, P.C

    Clive, Iowa, 50325

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

  • iResearch Atlanta LLC

    Decatur, Georgia, 30030

  • UnityPoint Clinic Center For Liver Disease

    Des Moines, Iowa, 50309

  • Henry Ford Health System

    Detroit, Michigan, 48202

  • Duke University Medical Center, Duke South Clinics

    Durham, North Carolina, 27710

  • Baylor All Saints Medical Center

    Fort Worth, Texas, 76104

  • Fresno Clinical Research Center

    Freestone, California, 93701

  • UF Hepatology Research at CTRB

    Gainesville, Florida, 32610

  • Gastro One

    Germantown, Tennessee, 38138

  • Baylor College of Medicine

    Houston, Texas, 77030

  • Liver Associates of Texas, P.A.

    Houston, Texas, 77030

  • Research Specialists of Texas

    Houston, Texas, 77030

  • Kansas City VA Medical Center

    Kansas City, Missouri, 64128

  • Kansas City Research Institute

    Kansas City, Missouri, 64131

  • Florida Digestive Health Specialist

    Lakewood Rch, Florida, 34211

  • Preferred Research Partners, Inc.

    Little Rock, Arkansas, 72211

  • Pinnacle Clinical Research, PLLC

    Live Oak, Texas, 78233

  • UCLA The Pfleger Liver Institute

    Los Angeles, California, 90024

  • Gastrointestinal Biosciences

    Los Angeles, California, 90067

  • University of Louisville

    Louisville, Kentucky, 40202

  • Northwell Health, Inc.

    Manhasset, New York, 11030

  • Gastrointestinal Specialists of Georgia

    Marietta, Georgia, 30060

  • Methodist University Hospital

    Memphis, Tennessee, 38104

  • Miami Veterans Administration Healthcare System

    Miami, Florida, 33125

  • University of Miami/Schiff Center for Liver Diseases

    Miami, Florida, 33136

  • Vanderbilt University Medical Center - Digestive Disease Center

    Nashville, Tennessee, 37232

  • Aquiant Research

    New Albany, Indiana, 47150

  • Yale University School of Medicine

    New Haven, Connecticut, 06510

  • Ochsner Clinic Foundation

    New Orleans, Louisiana, 70121

  • Mount Sinai Beth Israel Medical Center

    New York, New York, 10003

  • NYU Langone Medical Center

    New York, New York, 10016

  • Columbia University Medical Center (CUMC)

    New York, New York, 10032

  • Weill Cornell Medical College

    New York, New York, 10065

  • Doctors Office Center

    Newark, New Jersey, 07103

  • Surinder Singh Saini, M.D., Inc.

    Newport Beach, California, 92660

  • Bon Secours Richmond Health System

    Newport News, Virginia, 23602

  • Digestive and Liver Disease Specialists

    Norfolk, Virginia, 23502

  • Florida Hospital Orlando Transplant Institute

    Orlando, Florida, 32804

  • California Liver Research Institute

    Pasadena, California, 91105

  • Hospital of the University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

  • Temple University Hospital

    Philadelphia, Pennsylvania, 19140

  • Albert Einstein Medical Center

    Philadelphia, Pennsylvania, 19141

  • University Gastroenterology

    Providence, Rhode Island, 02905

  • Rex Healthcare

    Raleigh, North Carolina, 27607

  • Inland Empire Liver Foundation

    Rialto, California, 92377

  • McGuire VA Medical Center

    Richmond, Virginia, 23249

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • University of California Davis Medical Center

    Sacramento, California, 95817

  • University of Utah Health Sciences Center

    Salt Lake City, Utah, 84132

  • American Research Corporation at the Texas Liver Institue

    San Antonio, Texas, 78215

  • Brooke Army Medical Center

    San Antonio, Texas, 78219

  • University of California San Diego Medical Center

    San Diego, California, 92103

  • University of Washington Harborview Medical Center

    Seattle, Washington, 98104

  • Louisiana Research Center, LLC

    Shreveport, Louisiana, 71105

  • Washington University School of Medicine-Infectious Disease Clinical Research Unit

    St Louis, Missouri, 63110

  • Tampa General Medical Group

    Tampa, Florida, 33606

  • Montefiore Medical Center

    The Bronx, New York, 10467

  • University of Arizona Clinical and Translational Sciences Research Center

    Tucson, Arizona, 85724

  • Options Health Research, LLC

    Tulsa, Oklahoma, 74104

  • Sibley Memorial Hospital

    Washington D.C., District of Columbia, 20016

  • Howard University

    Washington D.C., District of Columbia, 20059

  • Cedars Sinai Medical Center

    West Hollywood, California, 90048

Other trials in United States

Spain11 sites

  • Hospital Universitario Vall d'Hebron

    Barcelona, 08035

  • Hospital Clinic de Barcelona

    Barcelona, 08036

  • Hospital Universitario de Donostia

    Donostia / San Sebastian, 20014

  • Hospital Universitario de La Princesa

    Madrid, 28006

  • Hospital General Universitario Gregorio Marañon

    Madrid, 28007

  • Hospital Universitario Ramon y Cajal

    Madrid, 28034

  • Hospital Universitario La Paz

    Madrid, 28046

  • Hospital Universitario Puerta de Hierro - Majadahonda

    Majadahonda, 28222

  • Hospital Universitario Marques de Valdecilla

    Santander, 39008

  • Hospital Clinico Universitario de Valencia

    Valencia, 46010

  • Hospital General Universitario de Valencia

    Valencia, 46104

Other trials in Spain

Germany9 sites

  • Universitätsklinikum der RWTH Aachen

    Aachen, North Rhine-Westphalia, 52074

  • Charité - Universitätsmedizin Berlin

    Berlin, 13353

  • Universitätsklinikum Bonn

    Bönning, North Rhine-Westphalia, 53127

  • Universitätsklinikum Freiburg

    Freiburg im Breisgau, 79106

  • Universitätsklinikum Hamburg Eppendorf

    Hamburg, 20246

  • Medizinische Hochschule Hannover

    Hanover, 30625

  • Eugastro GmbH

    Leipzig, 04103

  • Universitätsmedizin der Johannes Gutenberg-Universität Mainz

    Mainz, 55131

  • Universitätsklinikum Münster

    Münster, North Rhine-Westphalia, 48149

Other trials in Germany

About this study

Official title: A Multicenter, Randomized, Double-Blind, Placebo-controlled Trial of Emricasan (IDN-6556-12), an Oral Caspase Inhibitor, in Subjects With Non-alcoholic Steatohepatitis (NASH) Fibrosis

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.

Being tested
Emricasan (5 mg), Emricasan (50 mg), Placebo
Keywords
NASH
Medical subject headings
Non-alcoholic Fatty Liver Disease, Fibrosis, Liver Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Emricasan (5 mg)Drug

    Also called IDN-6556

    Subjects with Non-alcoholic Steatohepatitis (NASH) Fibrosis will be administered orally with emricasan (5 mg) twice a day.

  • Emricasan (50 mg)Drug

    Also called IDN-6556

    Subjects with Non-alcoholic Steatohepatitis (NASH) Fibrosis will be administered orally with emricasan (50 mg) twice a day.

  • PlaceboDrug

    Subjects with Non-alcoholic Steatohepatitis (NASH) Fibrosis will be administered orally with a matching placebo twice a day.

Study groups in NCT02686762
Study groupRoleWhat they receive
Emricasan (5 mg)Active comparatorSubjects with Non-alcoholic Steatohepatitis (NASH) Fibrosis will be administered orally with emricasan (5 mg) twice a day.
Receives: Drug: Emricasan (5 mg)
Emricasan (50 mg)Active comparatorSubjects with Non-alcoholic Steatohepatitis (NASH) Fibrosis will be administered orally with emricasan (50 mg) twice a day.
Receives: Drug: Emricasan (50 mg)
Matching PlaceboPlacebo comparatorSubjects with Non-alcoholic Steatohepatitis (NASH) Fibrosis will be administered orally with a matching placebo twice a day.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Fibrosis improvement by at least one stage without worsening of steatohepatitis

    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

    Measured: Week 72

Secondary outcomes (3)

  1. Steatohepatitis resolution (based on liver biopsy)

    The proportion of subjects who resolve steatohepatitis without worsening of fibrosis in the emricasan group compared to placebo

    Measured: Baseline & Week 72

  2. Improvement in the Non-alcoholic fatty liver disease (NAFLD) Activity Score

    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

    Measured: Baseline & Week 72

  3. Caspase 3/7 Relative Light Units and Alanine aminotransferase (ALT)

    To asses whether emricasan compared to placebo improves biomarkers Caspase 3/7 RLU and ALT Unit/Liter (U/L) in subjects with NASH fibrosis.

    Measured: Day 1, week 4, 24, 48, and 72

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Feb 2016 (estimated)
  2. Study start26 Jan 2016
  3. Primary completion29 Jan 2019
  4. Study completion28 Feb 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
318 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02686762
Sponsor's protocol ID
IDN-6556-12
Acronym
ENCORE-NF
Status last verified
Aug 2019
First submitted
10 Feb 2016
Last updated
19 Aug 2019
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Harrison SA, Goodman Z, Jabbar A, Vemulapalli R, Younes ZH, Freilich B, Sheikh MY, Schattenberg JM, Kayali Z, Zivony A, Sheikh A, Garcia-Samaniego J, Satapathy SK, Therapondos G, Mena E, Schuppan D, Robinson J, Chan JL, Hagerty DT, Sanyal AJ. A randomized, placebo-controlled trial of emricasan in patients with NASH and F1-F3 fibrosis. J Hepatol. 2020 May;72(5):816-827. doi: 10.1016/j.jhep.2019.11.024. Epub 2019 Dec 27.

    PubMed 31887369

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Emricasan (5 mg) and Emricasan (50 mg) in people with Non-alcoholic Steatohepatitis and Fibrosis, run by Conatus Pharmaceuticals Inc. at 103 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 103 sites in United States, Spain, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Fibrosis improvement by at least one stage without worsening of steatohepatitis (time frame: Week 72). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02686762, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2019.

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