A Phase 3 Study to Evaluate the Effect of Resmetirom on Clinical Outcomes in Patients With Well-compensated NASH Cirrhosis (MAESTRO-NASH-OUTCOMES)

A Randomized Double-blind Placebo-controlled Phase 3 Study to Evaluate the Effect of Resmetirom on Liver-related Outcomes in Patients With Well-compensated (Child-Pugh A) Non-alcoholic Steatohepatitis (NASH) Cirrhosis (MAESTRO-NASH-OUTCOMES)

This study will determine the effect of oral 80 mg resmetirom administered once daily on participants with well-compensated non-alcoholic steatohepatitis (NASH) cirrhosis by measuring the time to experiencing a Composite Clinical Outcome event.

Study Overview

• Status: Active, not recruiting
• Conditions: Cirrhosis, Liver; NASH
• Intervention / Treatment: Drug: Resmetirom; Drug: Placebo

Detailed Description

This is a multi-national, multicenter, double-blind, randomized, placebo-controlled study in participants with well-compensated NASH cirrhosis. Participants will be randomized 3:1 in a blinded manner to receive 80 mg resmetirom or matching placebo given orally once daily in the morning for the duration of the study (until the required number of Composite Clinical Outcome events are achieved). Composite Clinical Outcome events are defined as any of the following: all cause mortality, liver transplant, and significant hepatic events, including potential hepatic decompensation events (ascites, hepatic encephalopathy, or gastroesophageal variceal hemorrhage), and confirmed increase of Model for End-stage Liver Disease (MELD) score from <12 to ≥15. The study comprises an up to 60-day screening period and an approximately 3-year treatment period.

• Study Type: Interventional
• Enrollment (Estimated): 845
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1200
    • Cliniques Universitaires Saint Luc
  • Brussels, Belgium, 1070
    • CUB Hôpital Erasme
  • Oost-Vlaanderen
    • Ghent, Oost-Vlaanderen, Belgium
      • Algemeen Ziekenhuis Maria Middelares
    • Ghent, Oost-Vlaanderen, Belgium
      • Universitair Ziekenhuis Gent
  • West-Vlaanderen
    • Roeselare, West-Vlaanderen, Belgium, 8800
      • Algemeen Ziekenhuis Delta
• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • University of Calgary Liver Unit
  • Ontario
    • Brampton, Ontario, Canada, L6R 3J7
      • William Osler Health System - Brampton Civic Hospital
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital
    • Toronto, Ontario, Canada, M6H 3M1
      • Toronto Liver Center
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre
• France
  • Clichy, France
    • Hôpital Beaujon
  • Créteil, France, 94010
    • Hopital Henri Mondor
  • Nice, France, 06202
    • CHU de Nice - Hopital de l'Archet 2
  • Paris, France
    • Hôpital Universitaire Pitié Salpêtrière
  • Strasbourg, France, 67091
    • Nouvel Hôpital Civil- Hôpitaux Universitaires de Strasbourg
  • Toulouse, France, 31059
    • Hopital Rangueil - CHU Toulouse
  • Auvergne-Rhône-Alpes
    • Lyon, Auvergne-Rhône-Alpes, France
      • Hopital de la croix rousse
  • Grand Est
    • Vandœuvre-lès-Nancy, Grand Est, France, 54511
      • Hôpital Brabois Adultes - CHU de Nancy
  • Hauts-de-France
    • Lille, Hauts-de-France, France, 59037
      • CHU de LILLE - Hopital Claude Huriez
• Germany
  • Berlin, Germany, 13353
    • Charite - Universitatsmedizin Berlin CVK
  • Hesse
    • Leipzig, Hesse, Germany, 04103
      • University Hospital of Leipzig
  • Rhineland-Palatinate
    • Mainz, Rhineland-Palatinate, Germany, 55131
      • Universitätsmedizin Mainz
  • Saxony
    • Leipzig, Saxony, Germany, 04103
      • Eugastro Clinical Studies GmbH
• Italy
  • Florence, Italy
    • Azienda Ospedaliero - Universitaria Careggi
  • Palermo, Italy
    • Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (ISMETT)
  • Pisa, Italy, 56124
    • Azienda Ospedaliero-Universitaria Pisana Ospedale Cisanello
  • Foggia
    • San Giovanni Rotondo, Foggia, Italy, 71013
      • IRCCS Ospedale Casa Sollievo della Sofferenza
  • Milan
    • Rozzano, Milan, Italy, 20089
      • Istituto Clinico Humanitas
  • Milano
    • Milan, Milano, Italy
      • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
  • Roma
    • Roma, Roma, Italy
      • Fondazione Policlinico Universitario Agostino Gemelli
  • Turin
    • Torino, Turin, Italy, 10126
      • Istituto Mediterraneo e della Scienza di Torino
• Puerto Rico
  • Puerto Rico
    • San Juan, Puerto Rico, Puerto Rico, 00909
      • Latin Clinical Trials Center
    • San Juan, Puerto Rico, Puerto Rico, 00927
      • FDI Clinical Research (Fundacion de Investigacion de Diego)
• Spain
  • Barcelona, Spain
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08036
    • Hospital Clinic De Barcelona
  • Madrid, Spain
    • Hospital General Universitario Gregorio Marañon
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Seville, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • Madrid
    • Majadahonda, Madrid, Spain
      • Hospital Universitario Puerta de Hierro - Majadahonda
• United Kingdom
  • England
    • Birmingham, England, United Kingdom
      • University Hospitals Birmingham NHS Foundation Trust
    • Cambridge, England, United Kingdom
      • Cambridge University Hospitals NHS Foundation Trust
    • London, England, United Kingdom, SE5 9RS
      • King's College Hospital NHS Foundation Trust
    • London, England, United Kingdom
      • Barts Health NHS Trust
    • London, England, United Kingdom
      • Imperial College Healthcare NHS Trust
    • London, England, United Kingdom
      • Royal Free London NHS Foundation Trust
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • University of Alabama at Birmingham (UAB)
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Arizona Liver Health - Chandler
    • Peoria, Arizona, United States, 85381
      • Arizona Liver Health - Peoria
    • Tucson, Arizona, United States, 85712
      • Adobe Clinical Research
    • Tucson, Arizona, United States, 85712
      • Arizona Liver Health - Tucson
  • Arkansas
    • Little Rock, Arkansas, United States, 72205-6414
      • Arkansas Diagnostic Center/Liver Wellness Center
    • North Little Rock, Arkansas, United States, 72117
      • Arkansas Gastroenterology
  • California
    • Coronado, California, United States, 92118
      • Southern California Research Center
    • Fresno, California, United States, 93701
      • University of California, San Francisco-Fresno
    • La Jolla, California, United States, 92037
      • Univ. of California San Diego School of Medicine
    • Los Angeles, California, United States, 90033
      • Keck School of Medicine of USC
    • Orange, California, United States, 92868
      • Knowledge Research Center
    • Pasadena, California, United States, 91105
      • California Liver Research Institute
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
    • Engelwood, Colorado, United States, 80113
      • South Denver Gastroenterology
  • Florida
    • Clearwater, Florida, United States, 33761
      • Tampa Bay Medical Research
    • Coral Gables, Florida, United States, 33134
      • Hi Tech and Global Research
    • Cutler Bay, Florida, United States, 33189
      • Top Medical Research Inc
    • Fort Myers, Florida, United States, 33912
      • Covenant Research - Fort Myers
    • Inverness, Florida, United States, 34452
      • Nature Coast Clinical Research - Inverness
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
    • Lady Lake, Florida, United States, 32159
      • Ocala GI Research DBA Lake Center for Clinical Research
    • Lakewood Rch, Florida, United States, 34238
      • Florida Research Institute
    • Miami, Florida, United States, 33157
      • Sanchez Clinical Research
    • Miami, Florida, United States, 33136
      • Schiff Center for Liver Diseases/Univ of Miami
    • Ocala, Florida, United States, 34471
      • Ocala GI Research
    • Orlando, Florida, United States, 32804
      • AdventHealth Orlando th Investigational Drug Services
    • Saint Augustine, Florida, United States, 32086
      • St Johns Center for Clinical Research
    • Sarasota, Florida, United States, 34240
      • Covenant Research
    • Tampa, Florida, United States, 33614
      • International Center for Research
    • Zephyrhills, Florida, United States, 33542
      • Florida Medical Clinic
  • Georgia
    • Athens, Georgia, United States, 30607
      • Summit Clinical Research
    • Marietta, Georgia, United States, 30060
      • Gastrointestinal Specialists of Georgia
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60208
      • Northwestern University
  • Kansas
    • Topeka, Kansas, United States, 666006
      • Kansas Medical Clinic - Gastroenterology
  • Louisiana
    • Bastrop, Louisiana, United States, 71220
      • Delta Research Partners - Bastrop
    • Marrero, Louisiana, United States, 70072
      • Tandem Clinical Research
    • New Orleans, Louisiana, United States, 70112
      • Tulane University School of Medicine
    • Shreveport, Louisiana, United States, 71105
      • Louisiana Research Center
  • Maryland
    • Baltimore, Maryland, United States, 21202
      • Mercy Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • Kansas City Research Institute
    • St Louis, Missouri, United States, 63104
      • Saint Louis University
  • New Jersey
    • Sparta, New Jersey, United States, 07871
      • Premier Health Research
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai Health System
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center
    • Morehead City, North Carolina, United States, 28557
      • Lucas Research
  • Pennsylvania
    • Flourtown, Pennsylvania, United States, 19031
      • Regional Gastroenterology Associates of Lancaster
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Rapid City Medical Center
  • Tennessee
    • Clarksville, Tennessee, United States, 37040
      • Premier Medical Group
    • Cordova, Tennessee, United States, 38018
      • Gastro One
  • Texas
    • Arlington, Texas, United States, 76012-3216
      • Texas Clinical Research Institute
    • Austin, Texas, United States, 78757
      • Pinnacle Clinical Research - Austin
    • Brownsville, Texas, United States, 78520
      • South Texas Research Institute - Brownsville
    • Dallas, Texas, United States, 75203
      • The Liver Institute at Methodist Dallas Medical Center
    • Dallas, Texas, United States, 75234
      • Liver Center of Texas
    • Edinburg, Texas, United States, 78539
      • South Texas Research Institute - Edinburg
    • Georgetown, Texas, United States, 78626
      • Pinnacle Clinical Research - Georgetown
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
    • Houston, Texas, United States, 77079
      • Houston Research Institute
    • San Antonio, Texas, United States, 78229
      • Pinnacle Clinical Research - San Antonio
    • Waco, Texas, United States, 76710
      • Impact Research Institute
    • Waco, Texas, United States, 76712
      • Digestive Health Research of Central Texas
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia Health System
    • Richmond, Virginia, United States, 23249
      • Hunter Holmes McGuire VA Medical Center
    • Richmond, Virginia, United States, 23226
      • Bon Secours Liver Institute of Richmond
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University School of Medicine
    • Richmond, Virginia, United States, 23236
      • GI Select Health Research
  • Washington
    • Seattle, Washington, United States, 98105
      • Liver Institute Northwest

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• A clinical diagnosis of NASH cirrhosis
• At least 3 metabolic risk factors
• Historical liver biopsy read as consistent with NASH cirrhosis.
• Historical biopsy consistent with NASH with significant fibrosis, now with progression to cirrhosis. Or, no historical biopsy, with a clinical picture of NASH cirrhosis.
• Well-compensated Child-Pugh A (score of 5-6) cirrhosis at Screening and Baseline
• No history of a hepatic decompensation event.
• MRE ≥4.2 obtained during the screening period (if MRE is <4.2 and ≥3.7, then an ELF ≥10.25 OR platelet counts <140K obtained during the screening period is required for eligibility)

Exclusion Criteria:

• Participants with a chronic liver diseases other than NASH cirrhosis, such as primary biliary cholangitis, primary sclerosing cholangitis, Hepatitis B positive, Hepatitis C, history or evidence of current active autoimmune hepatitis, history or evidence of Wilson's disease, history or evidence of alpha-1 -antitrypsin deficiency, history or evidence of genetic hemochromatosis (hereditary, primary), evidence of drug-induced liver disease, as defined on the basis of typical exposure and history, known bile duct obstruction, or suspected or confirmed liver cancer
• Participants with MELD score ≥12 due to liver disease are excluded.
• Participants with a history of hepatic decompensation or impairment are excluded
• Diagnosis of hepatocellular carcinoma (HCC) at Screening or historically
• Liver Imaging Reporting and Data System (LI-RADS) score ≥4 at Screening
• No history of alcohol-related liver disease or history (within 5 years) of excessive alcohol consumption
• Weight gain or loss ≥5% total body weight within 12 weeks prior to randomization
• PEth value of ≥20 ng/mL measured at Screening
• HbA1c >9.0%
• Platelet counts <70,000/mm3 at either screening or baseline
• Use of high dose vitamin E (>400 IU/day) unless stable for ≥6 months prior to randomization
• Use of pioglitazone >15 mg per day
• Glucagon-like peptide 1 (GLP-1) agonist therapy for diabetes treatment must be a stable dose for at least 12 weeks prior to randomization. GLP-1 agonists for weight loss must be at stable doses for at least 6 months (including body weight change ≥ 5% weight loss in the 12 weeks prior to randomization)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Resmetirom; 80 mg daily	Drug: Resmetirom; Randomized 80 mg; Other Names: MGL-3196
Placebo Comparator: Placebo; matching placebo daily	Drug: Placebo; randomized matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence Of adjudicated Composite Clinical Outcome event	Any event of all-cause mortality, liver transplant, ascites, hepatic encephalopathy, gastroesophageal variceal hemorrhage, and confirmed increase of MELD score from <12 to >/= 15 due to liver disease	Baseline up to Month 36

Collaborators and Investigators

• Sponsor: Madrigal Pharmaceuticals, Inc.
• Investigators: Study Director: Thomas Hare, SVP, Clinical Research

Publications and helpful links

General Publications

• Harrison SA, Ratziu V, Anstee QM, Noureddin M, Sanyal AJ, Schattenberg JM, Bedossa P, Bashir MR, Schneider D, Taub R, Bansal M, Kowdley KV, Younossi ZM, Loomba R. Design of the phase 3 MAESTRO clinical program to evaluate resmetirom for the treatment of nonalcoholic steatohepatitis. Aliment Pharmacol Ther. 2024 Jan;59(1):51-63. doi: 10.1111/apt.17734. Epub 2023 Oct 2.

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: August 11, 2022
• First Submitted That Met QC Criteria: August 11, 2022
• First Posted (Actual): August 15, 2022

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Digestive System Diseases; Liver Diseases; Fibrosis; Pathological Conditions, Signs and Symptoms; Liver Cirrhosis; resmetirom
• Other Study ID Numbers: MGL-3196-19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No