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

NCT05500222 | Active Not Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: MGL-3196-19
• Study Type: interventional
• Target: 845
• Locations: 9 countries
• Sites: 141

Brief Summary

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.

Conditions

NASH; Cirrhosis, Liver

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

Resmetirom

ACTIVE COMPARATOR

80 mg daily

Drug: Resmetirom

Placebo

PLACEBO COMPARATOR

matching placebo daily

Drug: Placebo

Interventions

Resmetirom DRUG

Randomized 80 mg

Also known as: MGL-3196

Resmetirom

Placebo DRUG

randomized matching placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Madrigal Pharmaceuticals, Inc.: lead

Study Sites (141)

University of Alabama at Birmingham (UAB)

Birmingham, Alabama, 35249, United States

Location

Arizona Liver Health - Chandler

Chandler, Arizona, 85224, United States

Location

Arizona Liver Health - Peoria

Peoria, Arizona, 85381, United States

Location

Adobe Clinical Research

Tucson, Arizona, 85712, United States

Location

Arizona Liver Health - Tucson

Tucson, Arizona, 85712, United States

Location

Arkansas Diagnostic Center/Liver Wellness Center

Little Rock, Arkansas, 72205-6414, United States

Location

Arkansas Gastroenterology

North Little Rock, Arkansas, 72117, United States

Location

Southern California Research Center

Coronado, California, 92118, United States

Location

University of California, San Francisco-Fresno

Fresno, California, 93701, United States

Location

Univ. of California San Diego School of Medicine

La Jolla, California, 92037, United States

Location

Keck School of Medicine of USC

Los Angeles, California, 90033, United States

Location

Knowledge Research Center

Orange, California, 92868, United States

Location

California Liver Research Institute

Pasadena, California, 91105, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

South Denver Gastroenterology

Engelwood, Colorado, 80113, United States

Location

Tampa Bay Medical Research

Clearwater, Florida, 33761, United States

Location

Hi Tech and Global Research

Coral Gables, Florida, 33134, United States

Location

Top Medical Research Inc

Cutler Bay, Florida, 33189, United States

Location

Covenant Research - Fort Myers

Fort Myers, Florida, 33912, United States

Location

Nature Coast Clinical Research - Inverness

Inverness, Florida, 34452, United States

Location

Jacksonville Center for Clinical Research

Jacksonville, Florida, 32216, United States

Location

Ocala GI Research DBA Lake Center for Clinical Research

Lady Lake, Florida, 32159, United States

Location

Florida Research Institute

Lakewood Rch, Florida, 34238, United States

Location

Schiff Center for Liver Diseases/Univ of Miami

Miami, Florida, 33136, United States

Location

Sanchez Clinical Research

Miami, Florida, 33157, United States

Location

Ocala GI Research

Ocala, Florida, 34471, United States

Location

AdventHealth Orlando th Investigational Drug Services

Orlando, Florida, 32804, United States

Location

St Johns Center for Clinical Research

Saint Augustine, Florida, 32086, United States

Location

Covenant Research

Sarasota, Florida, 34240, United States

Location

International Center for Research

Tampa, Florida, 33614, United States

Location

Florida Medical Clinic

Zephyrhills, Florida, 33542, United States

Location

Summit Clinical Research

Athens, Georgia, 30607, United States

Location

Gastrointestinal Specialists of Georgia

Marietta, Georgia, 30060, United States

Location

Northwestern University

Chicago, Illinois, 60208, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Kansas Medical Clinic - Gastroenterology

Topeka, Kansas, 666006, United States

Location

Delta Research Partners - Bastrop

Bastrop, Louisiana, 71220, United States

Location

Tandem Clinical Research

Marrero, Louisiana, 70072, United States

Location

Tulane University School of Medicine

New Orleans, Louisiana, 70112, United States

Location

Louisiana Research Center

Shreveport, Louisiana, 71105, United States

Location

Mercy Medical Center

Baltimore, Maryland, 21202, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Umass Chan Medical School

Worcester, Massachusetts, 01655, United States

Location

Henry Ford Columbus Center

Novi, Michigan, 48377, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Kansas City Research Institute

Kansas City, Missouri, 64131, United States

Location

Saint Louis University

St Louis, Missouri, 63104, United States

Location

Premier Health Research

Sparta, New Jersey, 07871, United States

Location

NYU Langone Health Gastroenterology and Hepatology Associates

New York, New York, 10016, United States

Location

Weill Cornell Medical College

New York, New York, 10021, United States

Location

Mount Sinai Health System

New York, New York, 10029, United States

Location

Atrium Health CMC Liver Disease Research

Charlotte, North Carolina, 28204, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

Coastal Research Institute

Fayetteville, North Carolina, 28304, United States

Location

Lucas Research

Morehead City, North Carolina, 28557, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Clinical Research Institute of Ohio

Westlake, Ohio, 44145, United States

Location

Regional Gastroenterology Associates of Lancaster

Flourtown, Pennsylvania, 19031, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

UPMC - Center for Liver Diseases

Pittsburgh, Pennsylvania, 15213, United States

Location

Velocity Clinical Research - Providence

East Greenwich, Rhode Island, 02818, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Columbia Digestive Health Research

Columbia, South Carolina, 29204, United States

Location

Rapid City Medical Center

Rapid City, South Dakota, 57701, United States

Location

Premier Medical Group

Clarksville, Tennessee, 37040, United States

Location

Gastro One

Cordova, Tennessee, 38018, United States

Location

Quality Medical Reseach, PLLC

Nashville, Tennessee, 37211, United States

Location

Texas Clinical Research Institute

Arlington, Texas, 76012-3216, United States

Location

Pinnacle Clinical Research - Austin

Austin, Texas, 78757, United States

Location

Apex Mobile Clinical Research, LLC

Bellaire, Texas, 77401, United States

Location

South Texas Research Institute - Brownsville

Brownsville, Texas, 78520, United States

Location

The Liver Institute at Methodist Dallas Medical Center

Dallas, Texas, 75203, United States

Location

Dallas VA Medical Center

Dallas, Texas, 75216, United States

Location

Liver Center of Texas

Dallas, Texas, 75234, United States

Location

GI Alliance, Texas Digestive Disease Consultants

Dallas, Texas, 75246, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

South Texas Research Institute - Edinburg

Edinburg, Texas, 78539, United States

Location

GI Alliance

Fort Worth, Texas, 76104, United States

Location

Pinnacle Clinical Research - Georgetown

Georgetown, Texas, 78626, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Houston Research Institute

Houston, Texas, 77079, United States

Location

DHR Health Institute for Research & Development

McAllen, Texas, 78504, United States

Location

Pinnacle Clinical Research - San Antonio

San Antonio, Texas, 78229, United States

Location

Impact Research Institute

Waco, Texas, 76710, United States

Location

Digestive Health Research of Central Texas

Waco, Texas, 76712, United States

Location

University of Vermont Medical Center

Burlington, Vermont, 05401, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22903, United States

Location

Bon Secours Liver Institute of Richmond

Richmond, Virginia, 23226, United States

Location

GI Select Health Research

Richmond, Virginia, 23236, United States

Location

Hunter Holmes McGuire VA Medical Center

Richmond, Virginia, 23249, United States

Location

Virginia Commonwealth University School of Medicine

Richmond, Virginia, 23298, United States

Location

Harborview Medical Center

Seattle, Washington, 98104, United States

Location

Liver Institute Northwest

Seattle, Washington, 98105, United States

Location

Algemeen Ziekenhuis Maria Middelares

Ghent, Oost-Vlaanderen, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, Oost-Vlaanderen, Belgium

Location

Algemeen Ziekenhuis Delta

Roeselare, West-Vlaanderen, 8800, Belgium

Location

CUB Hôpital Erasme

Brussels, 1070, Belgium

Location

Cliniques Universitaires Saint Luc

Brussels, 1200, Belgium

Location

University of Calgary Liver Unit

Calgary, Alberta, Canada

Location

William Osler Health System - Brampton Civic Hospital

Brampton, Ontario, L6R 3J7, Canada

Location

Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

Toronto Liver Center

Toronto, Ontario, M6H 3M1, Canada

Location

McGill University Health Centre

Montreal, Quebec, H4A 3J1, Canada

Location

Hôpital de la Croix Rousse

Lyon, Auvergne-Rhône-Alpes, France

Location

Hôpital Brabois Adultes - CHU de Nancy

Vandœuvre-lès-Nancy, Grand Est, 54511, France

Location

CHU de LILLE - Hopital Claude Huriez

Lille, Hauts-de-France, 59037, France

Location

Hôpital Beaujon

Clichy, France

Location

Hopital Henri Mondor

Créteil, 94010, France

Location

CHU de Nice - Hopital de l'Archet 2

Nice, 06202, France

Location

Hôpital Universitaire Pitié Salpêtrière

Paris, France

Location

Nouvel Hôpital Civil- Hôpitaux Universitaires de Strasbourg

Strasbourg, 67091, France

Location

Hopital Rangueil - CHU Toulouse

Toulouse, 31059, France

Location

University Hospital of Leipzig

Leipzig, Hesse, 04103, Germany

Location

Universitätsmedizin Mainz

Mainz, Rhineland-Palatinate, 55131, Germany

Location

Eugastro Clinical Studies GmbH

Leipzig, Saxony, 04103, Germany

Location

Charite - Universitatsmedizin Berlin CVK

Berlin, 13353, Germany

Location

IRCCS Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, Foggia, 71013, Italy

Location

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, Milano, Italy

Location

Istituto Clinico Humanitas

Rozzano, Milan, 20089, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli

Roma, Roma, Italy

Location

Istituto Mediterraneo e della Scienza di Torino

Torino, Turin, 10126, Italy

Location

Azienda Ospedaliero - Universitaria Careggi

Florence, Italy

Location

Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (ISMETT)

Palermo, Italy

Location

Azienda Ospedaliero-Universitaria Pisana Ospedale Cisanello

Pisa, 56124, Italy

Location

Latin Clinical Trials Center

San Juan, Puerto Rico, 00909, Puerto Rico

Location

FDI Clinical Research (Fundacion de Investigacion de Diego)

San Juan, Puerto Rico, 00927, Puerto Rico

Location

Hospital Universitario Puerta de Hierro - Majadahonda

Majadahonda, Madrid, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitari Vall d'Hebrón

Barcelona, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

University Hospitals Birmingham NHS Foundation Trust

Birmingham, England, United Kingdom

Location

Cambridge University Hospitals NHS Foundation Trust

Cambridge, England, United Kingdom

Location

King's College Hospital NHS Foundation Trust

London, England, SE5 9RS, United Kingdom

Location

Barts Health NHS Trust

London, England, United Kingdom

Location

Imperial College Healthcare NHS Trust

London, England, United Kingdom

Location

Royal Free London NHS Foundation Trust

London, England, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 37786277 DERIVED

MeSH Terms

Conditions

Liver Cirrhosis

Interventions

resmetirom

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Thomas Hare

  SVP, Clinical Research

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2022
• First Posted: August 15, 2022
• Study Start: August 26, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: July 8, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (5); GB (6); BE (5); ES (6); DE (4); IT (8); US (96); PR (2); FR (9)