A Phase 3 Study to Evaluate the Efficacy and Safety of MGL-3196 (Resmetirom) in Patients With NASH and Fibrosis (MAESTRO-NASH)

A Phase 3, Multinational, Double-Blind, Randomized, Placebo-Controlled Study of MGL-3196 (Resmetirom) in Patients With Non-Alcoholic Steatohepatitis (NASH) and Fibrosis to Resolve NASH and Reduce Progression to Cirrhosis and/or Hepatic Decompensation

A double-blind placebo controlled randomized Phase 3 study to determine if 80 or 100 mg of MGL-3196 as compared with placebo resolves NASH and/or reduces fibrosis on liver biopsy and prevents progression to cirrhosis and/or advanced liver disease

Study Overview

• Status: Active, not recruiting
• Conditions: NASH - Nonalcoholic Steatohepatitis
• Intervention / Treatment: Drug: Placebo; Drug: MGL-3196; Procedure: Liver Biopsy

Detailed Description

Primary and secondary endpoint population at Week 52 will be at least 900 patients, more than half fibrosis score 3 (F3), the remainder fibrosis score 2 (F2) and <10% fibrosis score F1B (F1B) based on final liver biopsy baseline fibrosis score.

• Study Type: Interventional
• Enrollment (Actual): 1759
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Kimberly Dorney, RN, MSN; Phone Number: 267-520-0252; Email: info@madrigalpharma.com

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
    • Darlinghurst, New South Wales, Australia, 2010
      • Saint Vincent's Hospital Sydney
    • Kingswood, New South Wales, Australia, 2747
      • Nepean Hospital
    • New Lambton, New South Wales, Australia, 2305
      • John Hunter Hospital
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane and Women's Hospital
    • South Brisbane, Queensland, Australia, 4101
      • Mater Misericordiae
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Medical Centre
    • Heidelberg, Victoria, Australia, 3084
      • Austin Health
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
    • Parkville, Victoria, Australia, 3050
      • The Royal Melbourne Hospital
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Sir Charles Gairdner Hospital
    • Perth, Western Australia, Australia, 6000
      • Royal Perth Hospital
• Austria
  • Salzburg, Austria
    • Landesklinik St. Veit
  • St. Pölten, Austria, 3100
    • Universitätsklinikum St. Pölten
  • Vienna, Austria
    • Medizinische Universitat Wien
  • Wels, Austria
    • Klinikum Wels-Grieskirchen
  • Carinthia
    • Klagenfurt, Carinthia, Austria
      • Klinikum Klagenfurt am Wörthersee
  • Upper Austria
    • Linz, Upper Austria, Austria
      • Ordensklinikum Linz GmbH Barmherzige Schwestern
  • Vienna
    • Wien, Vienna, Austria
      • Krankenanstalt Rudolfstiftung
• Belgium
  • Brussel, Belgium, 1090
    • Universitair Ziekenhuis Brussel
  • Brussels, Belgium
    • Cliniques universitaires Saint-Luc
  • Laeken, Belgium
    • Centre Hospitalier Universitaire Brugmann
  • Leuven, Belgium
    • Universitair Ziekenhuis Leuven
  • Antwerpen
    • Edegem, Antwerpen, Belgium
      • Universitair Ziekenhuis Antwerpen
  • Brussels
    • Bruxelles, Brussels, Belgium
      • Hopital Erasme
  • Flemish Brabant
    • Leuven, Flemish Brabant, Belgium
      • Universitair Ziekenhuis Leuven
  • Limburg
    • Genk, Limburg, Belgium
      • Ziekenhuis Oost-Limburg'
  • Oost-Vlaanderen
    • Gent, Oost-Vlaanderen, Belgium
      • Universitair Ziekenhuis Gent
    • Gent, Oost-Vlaanderen, Belgium
      • Algemeen ziekenhuis Maria Middelares
  • West-Vlaanderen
    • Roeselare, West-Vlaanderen, Belgium
      • AZ Delta Campus Wilgenstraat
• Canada
  • Vancouver, Canada
    • GI Research Institute
  • Vancouver, Canada, V5Z 1J4
    • Lair Centre
  • Alberta
    • Calgary, Alberta, Canada
      • University of Calgary Liver Unit
    • Edmonton, Alberta, Canada
      • University of Alberta
  • Nova Scotia
    • Bridgewater, Nova Scotia, Canada
      • South Shore Medical Arts
  • Ontario
    • Brampton, Ontario, Canada
      • William Osler Health System
    • Brampton, Ontario, Canada
      • LMC/ Manna Research - Brampton
    • Hamilton, Ontario, Canada
      • McMaster University
    • Toronto, Ontario, Canada
      • Toronto Liver Center
    • Toronto, Ontario, Canada
      • Toronto General Hospital - Clinical Trials Pharmacy
• France
  • Amiens, France
    • Centre Hospitalier Universitaire Amiens-Picardie
  • Clichy, France
    • Hopital Beaujon
  • Paris Cedex 13, France
    • Hopital Universitaire Pitie Salpetriere
  • Vandœuvre-lès-Nancy, France
    • Centre Hospitalier Universitaire de Nancy - Hôpital de Brabois
  • Alsace
    • Strasbourg, Alsace, France
      • Les Hôpitaux Universitaires de Strasbourg - Hôpital Hautepierre
    • Strasbourg Cedex, Alsace, France
      • Nouvel Hopital Civil
  • Auvergne
    • Clermont-Ferrand, Auvergne, France
      • Centre Hospitalier Universitaire Estaing
  • Bretagne
    • Rennes Cedex 9, Bretagne, France
      • Centre Hospitalier Universitaire de Rennes
  • Franche-Comte
    • Besançon, Franche-Comte, France
      • Hôpital Jean-Minjoz
  • Ile-de-France
    • Bobigny Cedex, Ile-de-France, France
      • Hôpital Avicenne
    • Créteil Cedex, Ile-de-France, France
      • Centre Hospitalier Universitaire Henri Mondor
    • Paris Cedex 14, Ile-de-France, France
      • Assistance Publique-Hôpitaux de Paris Hôpital Cochin
  • Languedoc-Roussillon
    • Montpellier Cedex 5, Languedoc-Roussillon, France
      • Centre Hospitalier Universitaire de Montpellier
  • Limousin
    • Limoges, Limousin, France
      • Hôpital Dupuytren
  • Midi-Pyrenees
    • Toulouse Cedex, Midi-Pyrenees, France
      • Centre Hospitalier Universitaire de Toulouse - Hôpital Rangueil
  • Nord Pas-de-Calais
    • Lille, Nord Pas-de-Calais, France
      • Centre Hospitalier Regional Universitaire de Lille
  • Pays De La Loire
    • Angers, Pays De La Loire, France
      • Center Hospitalier Universitaire d'Angers
  • Provence Alpes Cote D'Azur
    • Nice Cedex 3, Provence Alpes Cote D'Azur, France
      • Centre Hospitalier Universitaire de Nice Hôpital l'Archet
  • Rhone-Alpes
    • Lyon Cedex 04, Rhone-Alpes, France
      • Hopital de La Croix Rousse
• Germany
  • Berlin, Germany
    • Charite Universitatsmedizin Berlin
  • Berlin, Germany
    • EPIMED
  • Berlin, Germany
    • Berlin Clinical Research Center
  • Berlin, Germany
    • Charité Universitätsmedizin Berlin - Campus Mitte
  • Berlin, Germany
    • Zentrum für Infektiologie Berlin Prenzlauer Berg
  • Frankfurt am main, Germany
    • Frankfurt Clinical Research Center
  • Frankfurt am main, Germany
    • Universitatsklinikum Frankfurt
  • Homburg, Germany
    • Universitätsklinikum des Saarlandes
  • Leipzig, Germany
    • Eugastro
  • Leipzig, Germany
    • Leipzig Research Center
  • Leipzig, Germany
    • SIBAmed Studienzentrum
  • Mainz, Germany, 55131
    • Universitätsmedizin der Johannes Gutenberg Universität Mainz
  • Würzburg, Germany
    • Universitätsklinikum Würzburg
• Hungary
  • Budapest, Hungary
    • Dél-Pesti Centrumkórház - Országos Hematológiai És Infektológiai Intézet
  • Budapest, Hungary
    • Magyarország Research Center
  • Bekes
    • Békéscsaba, Bekes, Hungary
      • Békés Megyei Központi Kórház Dr. Réthy Pál Tagkórház
    • Gyula, Bekes, Hungary
      • Magyarország Egészségügyi Szolgáltató - Gyula
  • Hajdu-Bihar
    • Debrecen, Hajdu-Bihar, Hungary
      • Debreceni Egyetem Kenezy Gyula Egyetemi Korhaz
    • Debrecen, Hajdu-Bihar, Hungary
      • Magyarország Research Center
  • Szabolcs-Szatmar-Bereg
    • Nyíregyháza, Szabolcs-Szatmar-Bereg, Hungary
      • Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz
• Israel
  • Afula, Israel
    • Emek Medical Center
  • Be'er Sheva, Israel
    • Soroka University Medical Center
  • Haifa, Israel
    • The Lady Davis Carmel Medical Center
  • Haifa, Israel
    • Rambam Health Care Campus - Rambam Medical Center
  • Jerusalem, Israel
    • Shaare Zedek Medical Center
  • Jerusalem, Israel
    • Hadassah University Hospital Ein Kerem
  • Nahariya, Israel
    • Western Galilee Hospital-Nahariya
  • Nazareth, Israel
    • Holy Family Hospital
  • Petah Tikva, Israel
    • Rabin Medical Center
  • Tel Aviv, Israel
    • Tel Aviv Sourasky Medical Center
  • Tel Aviv
    • Ramat Gan, Tel Aviv, Israel
      • The Chaim Sheba Medical Center
• Italy
  • Bergamo, Italy
    • Azienda Ospedaliera Papa Giovanni Xxiii
  • Firenze, Italy
    • Azienda Ospedaliero - Universitaria Careggi
  • Messina, Italy
    • Azienda Ospedaliera Universitaria Policlinico Gaetano Martino
  • Milano, Italy
    • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
  • Milano, Italy
    • Polo Universitario - L'Azienda Ospedaliera Luigi Sacco
  • Novara, Italy
    • Azienda Ospedaliera Universitaria-Maggiore della Carità di Novara
  • Palermo, Italy
    • Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone
  • Palermo, Italy
    • Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (ISMETT)
  • Pisa, Italy, 56124
    • Azienda Ospedaliero-Universitaria Pisana Ospedale Cisanello
  • Roma, Italy
    • Universita degli Studi di Roma La Sapienza - Umberto I Policlinico di Roma
  • Roma, Italy
    • Fondazione Policlinico Universitario Agostino Gemelli
  • San Giovanni Rotondo, Italy
    • Ospedale Casa Sollievo della Sofferenza
• Mexico
  • Distrito Federal
    • Ciudad de México, Distrito Federal, Mexico, 06100
      • Centro Mexicano de Desarrollo de Estudios Clinicos
    • Ciudad de México, Distrito Federal, Mexico, 06700
      • Centro de Investigación y Gastroenterología
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44160
      • Centro Integral en Reumatologia
  • Morelos
    • Cuernavaca, Morelos, Mexico, 62290
      • JM Research
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64000
      • Investigaciones Médicas Cisneros
• Poland
  • Częstochowa, Poland
    • Polska Oddział w Częstochowie
  • Gdańsk, Poland
    • Polska Oddział w Gdansk
  • Gdynia, Poland
    • Polska Oddział w Gdyni
  • Katowice, Poland
    • Polska Oddział w Katowicach
  • Poznań, Poland
    • Polska Oddział w Poznaniu
  • Skórzewo, Poland, 60-185
    • Centrum Medyczne Pratia Poznań
  • Warszawa, Poland
    • Polska Oddział w Warszawie
  • Wrocław, Poland
    • Polska Oddział w Wrocław
  • Łódź, Poland
    • Polska Oddział w Łodz
• Puerto Rico
  • San Juan, Puerto Rico
    • Fundacion de Investigacion de Diego
• Spain
  • Almeria, Spain
    • Complejo Hospitalario Torrecárdenas
  • Barcelona, Spain
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain
    • Hospital de la Santa Creu i de Sant Pau
  • Barcelona, Spain
    • Hospital del Mar - Parc de Salut Mar
  • Madrid, Spain
    • Hospital General Universitario Gregorio Maranon
  • Madrid, Spain
    • Hospital Universitario Ramon Y Cajal
  • Pontevedra, Spain
    • Complejo Hospitalario de Pontevedra
  • Santander, Spain
    • Hospital Universitario Marques de Valdecilla
  • Sevilla, Spain
    • Hospital Universitario Virgen del Rocío
  • Valencia, Spain
    • Consorci Hospital General Universitari de València
  • Valencia, Spain
    • Hospital Universitari i Politecnic La Fe de Valencia
  • Madrid
    • Majadahonda, Madrid, Spain
      • Hospital Universitario Puerta de Hierro - Majadahonda
• Switzerland
  • Bern, Switzerland
    • Universitätsspital Bern
  • Lugano, Switzerland
    • Fondazione Epatocentro Ticino
  • Zürich, Switzerland
    • Universitätsspital Zürich
• United Kingdom
  • Liverpool, United Kingdom
    • Aintree University Hospitals NHS Foundation Trust
  • London, United Kingdom
    • Saint George's University Hospitals NHS Foundation Trust
  • Plymouth, United Kingdom
    • Plymouth Hospitals Nhs Trust
  • Portsmouth, United Kingdom
    • Portsmouth Hospitals NHS Trust
  • England
    • Birmingham, England, United Kingdom
      • Midlands Clinical Research Centre
    • Birmingham, England, United Kingdom
      • University Hospitals Birmingham NHS Foundation Trust
    • Cambridge, England, United Kingdom
      • Cambridge University Hospitals NHS Foundation Trust
    • Chorley, England, United Kingdom
      • Lancashire Clinical Research Centre
    • Hardwick, England, United Kingdom
      • North Teesside Clinical Research Centre
    • Liverpool, England, United Kingdom
      • Merseyside Clinical Research Centre
    • London, England, United Kingdom
      • Barts Health Nhs Trust
    • London, England, United Kingdom
      • Chelsea And Westminster Hospital NHS Foundation Trust
    • London, England, United Kingdom
      • Imperial College Healthcare NHS Trust
    • London, England, United Kingdom
      • Royal Free London NHS Foundation Trust
    • Manchester, England, United Kingdom
      • Manchester Clinical Research Centre
    • Newcastle Upon Tyne, England, United Kingdom
      • The Newcastle upon Tyne Hospitals NHS Foundation Trust
    • Norwich, England, United Kingdom
      • Norfolk and Norwich University Hospital
    • Nottingham, England, United Kingdom
      • Nottingham University Hospitals Nhs Trust
    • Reading, England, United Kingdom
      • Thames Valley Dedicated Research Centre
  • Northern Ireland
    • Belfast, Northern Ireland, United Kingdom
      • Belfast Health and Social Care Trust
  • Northumberland, England
    • Hexham, Northumberland, England, United Kingdom
      • The Hexham Clinic
  • Wales
    • Cardiff, Wales, United Kingdom
      • The Wales Clinic
    • Swansea, Wales, United Kingdom
      • Abertawe Bro Morgannwg University Health Board
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • University of Alabama at Birmingham
  • Arizona
    • Chandler, Arizona, United States, 85224
      • East Valley Family Physicians
    • Chandler, Arizona, United States, 85224
      • The Institute for Liver Health - Chandler
    • Glendale, Arizona, United States, 85306
      • The Institute for Liver Health - Glendale
    • Mesa, Arizona, United States, 85213
      • Desert Clinical Research
    • Tucson, Arizona, United States, 85712
      • Adobe Gastroenterology
    • Tucson, Arizona, United States, 85712
      • The Institute for Liver Health - Tucson
  • Arkansas
    • North Little Rock, Arkansas, United States, 72117
      • Arkansas Gastroenterology
  • California
    • Fresno, California, United States, 93720
      • Fresno Clinical Research Center
    • Huntington Park, California, United States, 90255
      • National Research Institute - Huntington Park
    • La Jolla, California, United States, 92037
      • University of California San Diego
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Los Angeles, California, United States, 90057
      • National Research Institute - Los Angeles
    • Los Angeles, California, United States, 90057
      • Ruane Clinical Research
    • Palo Alto, California, United States, 94304
      • Stanford University School of Medicine
    • Panorama City, California, United States, 91402
      • National Research Institute - Panorama City
    • Poway, California, United States, 92064
      • Alliance Clinical Research
    • Van Nuys, California, United States, 91405
      • San Fernando Valley Health Institute
  • Colorado
    • Colorado Springs, Colorado, United States, 80909
      • Colorado Springs Family Practice
    • Englewood, Colorado, United States, 80113
      • South Denver Gastroenterology - Swedish Medical Center Office
  • Florida
    • Boca Raton, Florida, United States, 33434
      • Excel Medical Clinical Trials
    • Fort Myers, Florida, United States, 33912
      • Covenant Metabolic Specialists - Fort Myers
    • Gainesville, Florida, United States, 32610
      • University of Florida Hepatology Research at CTRB
    • Inverness, Florida, United States, 34452
      • Nature Coast Clinical Research
    • Lakewood Ranch, Florida, United States, 34211
      • Florida Research Institute
    • Miami, Florida, United States, 33136
      • University of Miami
    • Miami, Florida, United States, 33176
      • Miami Dade Medical Research Institute
    • Orlando, Florida, United States, 32806
      • Bioclinica Research - Orlando
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
    • Sarasota, Florida, United States, 34240
      • Covenant Research
    • The Villages, Florida, United States, 32162
      • Bioclinica Research - The Villages
  • Georgia
    • Marietta, Georgia, United States, 30060
      • GI Specialists of Georgia
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Medical Faculty Foundation
    • Chicago, Illinois, United States, 60637
      • The University of Chicago Medicine
    • Chicago, Illinois, United States, 60602
      • Clinical Research - Chicago
  • Kansas
    • Fairway, Kansas, United States, 66205
      • University of Kansas Medical Center Research Institute
    • Topeka, Kansas, United States, 66606
      • Kansas Medical Clinic - Gastroenterology
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Texas Digestive Disease Consultants - Gastroenterology Associates - Baton Rouge
    • Marrero, Louisiana, United States, 70072
      • Tandem Clinical Research
    • New Orleans, Louisiana, United States, 70112
      • Tulane University School of Medicine
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Medical Center
    • West Monroe, Louisiana, United States, 71291
      • Clinical Trials of America
  • Maryland
    • Bethesda, Maryland, United States, 20889
      • Walter Reed National Military Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Gastrointestinal Associates and Endoscopy Center - Madison
    • Jackson, Mississippi, United States, 39216
      • Southern Therapy and Advanced Research
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Hospital of Kansas City
    • Kansas City, Missouri, United States, 64131
      • Kansas City Research Institute
    • Saint Louis, Missouri, United States, 63104
      • Saint Louis University
  • Nevada
    • Henderson, Nevada, United States, 89052
      • Clinical Research US - Henderson
  • New York
    • New York, New York, United States, 10065
      • New York Presbyterian Hospital
    • New York, New York, United States, 10029
      • Mt. Sinai Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 27599
      • University of North Carolina Medical Center - Chapel Hill
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center
    • Fayetteville, North Carolina, United States, 28304
      • Cumberland Research Associates
    • Morehead City, North Carolina, United States, 28557
      • Lucas Research
  • Ohio
    • Cincinnati, Ohio, United States, 45249
      • Consultants for Clinical Research
    • Columbus, Ohio, United States, 43213
      • Aventiv Research - Columbus
    • Marion, Ohio, United States, 43302
      • Awasty Research Network
  • Tennessee
    • Clarksville, Tennessee, United States, 37040
      • Premier Medical Group - Clarksville
    • Germantown, Tennessee, United States, 38138
      • Gastro One - Germantown - Centre Oak Way
    • Hermitage, Tennessee, United States, 37076
      • Associates in Gastroenterology
    • Knoxville, Tennessee, United States, 37909
      • Gastrointestinal Associates - Knoxville
  • Texas
    • Brownsville, Texas, United States, 78520
      • South Texas Research Institute - Brownsville
    • Dallas, Texas, United States, 75234
      • Dallas Research Center
    • Dallas, Texas, United States, 75234
      • Liver Center of Texas
    • Dallas, Texas, United States, 75234
      • Texas Digestive Disease Consultants - Dallas
    • Dallas, Texas, United States, 75234
      • The Liver Institute At Methodist Dallas Medical Center
    • Edinburg, Texas, United States, 78539
      • South Texas Research Institute
    • Fort Sam Houston, Texas, United States, 78234
      • Brooke Army Medical Center
    • Fort Worth, Texas, United States, 76104
      • Texas Digestive Disease Consultants - Fort Worth
    • Houston, Texas, United States, 77030
      • Liver Associates of Texas
    • McAllen, Texas, United States, 78504
      • Doctor's Hospital at Renaissance
    • Plano, Texas, United States, 75093
      • Plano Research Center
    • Rollingwood, Texas, United States, 78746
      • Pinnacle Clinical Research - Austin
    • San Antonio, Texas, United States, 78229
      • San Antonio Research Center
    • San Antonio, Texas, United States, 78229
      • Pinnacle Clinical Research
    • San Antonio, Texas, United States, 78229
      • The Texas Liver Institute
    • San Marcos, Texas, United States, 78666
      • Texas Digestive Disease Consultants - San Marcos
    • Waco, Texas, United States, 76710
      • Impact Research Institute
    • Webster, Texas, United States, 77598
      • Texas Digestive Disease Consultants - Bay Area Gastroenterology
  • Utah
    • Layton, Utah, United States, 84041
      • Wasatch Peak Family Practice
    • Murray, Utah, United States, 84123
      • Salt Lake City Research Center
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Hospital
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia Health System
    • Richmond, Virginia, United States, 23249
      • Virginia Commonwealth University
    • Richmond, Virginia, United States, 23249
      • Hunter Holmes McGuire Veterans Administration Medical Center
    • Richmond, Virginia, United States, 23226
      • Bon Secours St. Mary's Hospital of Richmond
  • 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:

1. Must be willing to participate in the study and provide written informed consent.
2. Male and female adults ≥ 18 years of age.

3. Suspected or confirmed diagnosis of NASH fibrosis suggested by the historical data. Meet one of the following criteria that is consistent with NASH liver fibrosis:

   1. Historical biochemical test for fibrosis: PRO-C3 >14 ng/mL or ELF ≥9
   2. FibroScan with transient elastography ≥8.5 kPa and controlled attenuation parameter ≥280 dB.m-1
   3. Historical liver biopsy obtained <2 years before expected randomization showing Stage 1B, 2 or 3 fibrosis with NASH based on existing pathology review, with no significant change in body weight >5% or medication that might affect NAS or fibrosis stage.
4. MRI-PDFF fat fraction ≥8% obtained during the screening period

5. Biopsy-proven NASH (baseline liver biopsy) based on a liver biopsy obtained ≤6 months before anticipated date of randomization (if the biopsy is deemed acceptable for interpretation by the central reader) with fibrosis stage 1A/1C, 1B, 2, or 3 on liver biopsy and NAS of ≥4 with a score of at least 1 in each of the following NAS components:

   1. Steatosis (scored 0 to 3)
   2. Ballooning degeneration (scored 0 to 2)
   3. Lobular inflammation (scored 0 to 3)

Exclusion Criteria:

1. History of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to Screening.
2. Regular use of drugs historically associated with NAFLD

3. Thyroid diseases:

   1. Active hyperthyroidism.
   2. Untreated clinical hypothyroidism defined by thyroid stimulating hormone (TSH) >7 IU/L with symptoms of hypothyroidism or >10 IU/L without symptoms.
   3. Patients who have had a thyroidectomy and are on replacement thyroxine doses >75 µg per day are allowed.
4. History of bariatric surgery or intestinal bypass surgery within the 5 years prior to randomization or planned during the conduct of the study.
5. Recent significant weight gain or loss
6. HbA1c ≥ 9.0%.
7. Glucagon-like peptide 1 [GLP-1] agonist, high dose Vitamin E (> 400 IU/day), or pioglitazone therapy unless stable dose for 24 weeks prior to biopsy.
8. Presence of cirrhosis on liver biopsy defined as stage 4 fibrosis.
9. Diagnosis of hepatocellular carcinoma (HCC).
10. MELD score ≥12, as determined at Screening, unless due to therapeutic anti coagulation.
11. Hepatic decompensation
12. Chronic liver diseases other than NASH
13. Active autoimmune disease
14. Serum ALT > 250 U/L.
15. Active, serious medical disease with a likely life expectancy < 2 years.
16. Participation in an investigational new drug trial in the 60 days or 5 half-lives, whichever is longer.
17. Any other condition which, in the opinion of the Investigator, would impede compliance, hinder completion of the study, compromise the well-being of the patient, or interfere with the study outcomes.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Matching Placebo; Placebo Daily	Drug: Placebo; Matching Tablets; Procedure: Liver Biopsy; A procedure in which a needle is inserted into the liver to collect a tissue sample
Active Comparator: 80 mg MGL-3196; 80 mg daily	Drug: MGL-3196; Tablet; Other Names: Resmetirom; Procedure: Liver Biopsy; A procedure in which a needle is inserted into the liver to collect a tissue sample
Active Comparator: 100 mg MGL-3196; 100 mg daily	Drug: MGL-3196; Tablet; Other Names: Resmetirom; Procedure: Liver Biopsy; A procedure in which a needle is inserted into the liver to collect a tissue sample

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Week 52 Dual Primary Objectives: To determine the effect of 80 or 100 mg MGL-3196 vs matching placebo on liver biopsy (NASH CRN score) at Week 52 compared with Baseline	Proportion with resolution of NASH (ballooning 0, inflammation 0,1) associated with at least 2-point reduction in NAFLD Activity Score (NAS) without worsening of fibrosis stage OR; Proportion with at least a 1-point improvement in fibrosis stage with no worsening of NAS	52 weeks
Month 54 Primary Objective: Time to experiencing an adjudicated Composite Clinical Outcome event (Final Primary Endpoint, at 54 months)	The Composite Clinical Outcome is composed of all-cause mortality, liver transplant, and significant hepatic events (including hepatic decompensation events [ascites, encephalopathy, or gastroesophageal variceal hemorrhage], histological progression to cirrhosis, and a confirmed increase of MELD score from <12 to ≥15).	up to 54 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Week 52 Key Secondary Objective: To determine the effect of once-daily, oral administration of MGL-3196 80 or 100 mg versus matching placebo on the percent change from Baseline at 24 weeks in directly measured low-density lipoprotein cholesterol (LDL-C)	Assess the effect of MGL-3196 80 mg or 100 mg compared to placebo on LDL-C measured by percent change from Baseline at 24 weeks.	24 weeks

Collaborators and Investigators

• Sponsor: Madrigal Pharmaceuticals, Inc.
• Investigators: Study Director: Rebecca Taub, MD, Madrigal Pharmaceuticals, Inc.

Publications and helpful links

General Publications

• Harrison SA, Bashir M, Moussa SE, McCarty K, Pablo Frias J, Taub R, Alkhouri N. Effects of Resmetirom on Noninvasive Endpoints in a 36-Week Phase 2 Active Treatment Extension Study in Patients With NASH. Hepatol Commun. 2021 Jan 4;5(4):573-588. doi: 10.1002/hep4.1657. eCollection 2021 Apr.

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2019
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: March 26, 2019
• First Submitted That Met QC Criteria: March 30, 2019
• First Posted (Actual): April 3, 2019

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 15, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: MGL-3196-11

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No