A Phase 3 Study to Evaluate Safety and Biomarkers of Resmetirom (MGL-3196) in Patients With Non-alcoholic Fatty Liver Disease (NAFLD), MAESTRO-NAFLD-Open-Label-Extension (MAESTRO-NAFLD-OLE)

May 22, 2026 updated by: Madrigal Pharmaceuticals, Inc.

A 52-Week, Phase 3, Open-Label Extension Study, With a Double-blind Lead-in, to Evaluate Safety and Biomarkers of Resmetirom (MGL-3196) in Patients With Non-alcoholic Fatty Liver Disease (NAFLD), MAESTRO-NAFLD-Open-Label-Extension (MAESTRO-NAFLD-OLE)

A 52-Week, Multi-center, Open-label, Active Treatment Extension Study to Evaluate Safety and Tolerability of Once Daily, Oral Administration of Resmetirom (MGL-3196)

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

810

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Puerto Rico
      • San Juan, Puerto Rico
        • Fundacion de Investigacion de Diego
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35205
        • Central Research Associates
    • Arizona
      • Chandler, Arizona, United States, 85224
        • Arizona Liver Health - Chandler
      • Chandler, Arizona, United States, 85224
        • East Valley Family Physicians
      • Glendale, Arizona, United States, 85306
        • The Institute for Liver Health - Glendale
      • Tucson, Arizona, United States, 85711
        • The Institute for Liver Health - Tucson
      • Tucson, Arizona, United States, 85712
        • Adobe Gastroenterology
    • 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
      • Los Angeles, California, United States, 90048
        • Cedars-Sinai Medical Center
      • Los Angeles, California, United States, 90036
        • Ruane Clinical Research Group
      • Los Angeles, California, United States, 90057
        • National Research Institute - Los Angeles
      • Panorama City, California, United States, 91402
        • National Research Institute - Panorama City
      • West Hills, California, United States, 91307
        • San Fernando Valley Health Institute
    • Colorado
      • 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 Research
      • Hallandale, Florida, United States, 33009
        • Velocity Clinical Research, Hallandale Beach (MD Clinical)
      • Hialeah, Florida, United States, 33016
        • Floridian Clinical Research
      • Inverness, Florida, United States, 34452
        • Nature Coast Clinical Research - Inverness
      • Jacksonville, Florida, United States, 32216
        • Jacksonville Center for Clinical Research
      • Lakewood Rch, Florida, United States, 34211
        • Florida Research Institute
      • Miami Lakes, Florida, United States, 33016
        • Floridian Clinical Research
      • Orlando, Florida, United States, 32806
        • Orlando Research Center
      • Port Orange, Florida, United States, 32127
        • Progressive Medical Research
      • Sarasota, Florida, United States, 34240
        • Covenant Research
      • The Villages, Florida, United States, 32162
        • The Villages Research Center
    • Georgia
      • Marietta, Georgia, United States, 30060
        • Gastrointestinal Specialists of Georgia
    • Hawaii
      • Honolulu, Hawaii, United States, 96814
        • East-West Medical Research Institute
    • Illinois
      • Chicago, Illinois, United States, 60602
        • Chicago Research Center
      • Chicago, Illinois, United States, 60611
        • Northwestern Memorial Physicians Group
    • Iowa
      • West Des Moines, Iowa, United States, 50265
        • Iowa Diabetes Research
      • West Des Moines, Iowa, United States, 50266
        • Iowa Diabetes and Endocrinology Research Center
    • Kansas
      • Topeka, Kansas, United States, 66606
        • Kansas Medical Clinic - Gastroenterology
    • Kentucky
      • Louisville, Kentucky, United States, 40213
        • L-MARC Research Center
    • Louisiana
      • Bastrop, Louisiana, United States, 71220
        • Rovia Clinical Research
      • Baton Rouge, Louisiana, United States, 70809
        • Digestive Health Center of Louisiana
      • Marrero, Louisiana, United States, 70072
        • Tandem Clinical Research - New Orleans Area Site
      • West Monroe, Louisiana, United States, 71291
        • Clinical Trials of America
    • Mississippi
      • Flowood, Mississippi, United States, 39232
        • Gastrointestinal Associates & Endoscopy Center - Flowood
      • Jackson, Mississippi, United States, 39216
        • Southern Therapy and Advanced Research
    • Missouri
      • Kansas City, Missouri, United States, 64131
        • Kansas City Research Institute
    • Nevada
      • Henderson, Nevada, United States, 89052
        • Henderson Research Center
    • New York
      • East Syracuse, New York, United States, 13057
        • Clarity Clinical Research
      • East Syracuse, New York, United States, 13057
        • Velocity Clinical Research
      • New York, New York, United States, 10029
        • Mount Sinai Health System
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
      • Fayetteville, North Carolina, United States, 28304
        • Cumberland Research Associates
      • Moorehead City, North Carolina, United States, 28557
        • Lucas Research
      • Morehead City, North Carolina, United States, 28557
        • Diabetes and Endocrinology Consultants
    • Ohio
      • Columbus, Ohio, United States, 43213
        • Aventiv Research Columbus
      • Marion, Ohio, United States, 43302
        • Awasty Research Network
    • Tennessee
      • Clarksville, Tennessee, United States, 37040
        • Innovative Clinical Research
      • Germantown, Tennessee, United States, 38138
        • Gastro One - Germantown Office - Wolf Park Drive
    • Texas
      • Austin, Texas, United States, 78746
        • Pinnacle Clinical Research - Austin
      • Dallas, Texas, United States, 75203
        • The Liver Institute At Methodist Dallas
      • Dallas, Texas, United States, 75234
        • Dallas Research Center
      • Dallas, Texas, United States, 75234
        • Liver Center of Texas
      • Edinburg, Texas, United States, 78539
        • South Texas Research Institute
      • Fort Worth, Texas, United States, 76104
        • Texas Digestive Disease Consultants
      • 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
      • San Antonio, Texas, United States, 78215
        • Texas Liver Institute/American Research Corporation
      • San Antonio, Texas, United States, 78229
        • Pinnacle Clinical Research - San Antonio
      • San Antonio, Texas, United States, 78229
        • San Antonio Research Center
      • 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 Houston Endoscopy Center
    • Utah
      • Layton, Utah, United States, 84041
        • Wasatch Peak Family Practice
      • Murray, Utah, United States, 84123
        • Salt Lake City Research Center
    • Virginia
      • Richmond, Virginia, United States, 23226
        • Bon Secours Liver Institute of Richmond
      • Richmond, Virginia, United States, 23294
        • National Clinical Research - Richmond
      • Richmond, Virginia, United States, 23298
        • Virginia Commonwealth University School of Medicine
    • Washington
      • Seattle, Washington, United States, 98105
        • Liver Institute Northwest

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • For patients who completed MAESTRO-NAFLD-1, completed the Week 52 visit, and completed the Week 56 visit within 90 days of the Extension Day 1 visit, and are willing to participate in MAESTRO-NAFLD-OLE and provide written informed consent.

  • For patients who screen failed MAESTRO-NASH, must provide written informed consent for MAESTRO-NAFLD-OLE and must have screened and met all eligibility requirements for MAESTRO-NASH within 90 days of the Extension Day 1 visit for MAESTRO-NAFLD-OLE and have a liver biopsy that is ineligible for MAESTRO-NASH within 6 months of the Extension Day 1 visit. Eligible liver biopsy for MAESTRO-NAFLD-OLE must have one of the following results:

    • NAS = 3, steatosis 1, ballooning 1, inflammation 1, OR NAS = 3, ballooning 0, with F1B, F2 or F3
    • NAS ≥ 4, at least 1 in all NAS components, F1A or F1C, PRO-C3 ≤ 14 (NASH, but ineligible for MAESTRO-NASH)
    • Compensated NASH cirrhosis based on biopsy at screening of MAESTRO-NASH and baseline of MAESTRO-NAFLD-OLE, including Child Pugh-A (score 5-6), MELD <12, albumin ≥3.2, and bilirubin <2
  • For patients who screen failed from MAESTRO-NASH OUTCOMES and de novo patients, must have documented CP-A/B (score <8) NASH cirrhosis (including minimal decompensation) and MELD <15 unless MELD >=15 based on non-cirrhotic parameters. MAESTRO-NASH OUTCOMES screen failures must have screened and met all eligibility requirements for MAESTRO-NASH OUTCOMES within 90 days of the Extension Day 1 visit for MAESTRO-NAFLD-OLE .

Exclusion Criteria:

  • A history of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to Extension Day 1.
  • Diagnosis of hepatocellular carcinoma or other carcinomas that may prevent participation in the Extension study.
  • Chronic liver diseases
  • Has an active autoimmune disease
  • 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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Double-blind 80 mg Daily
For patients assigned to double-blind treatment and who completed Week 52 and 56 of MAESTRO-NAFLD-1, double-blind resmetirom 80 mg for first 12 weeks followed by open-label resmetirom 100 mg for weeks 12-52
Drug: Resmetirom
Tablet
Other Names:
  • MGL-3196
Experimental: Double-blind 100 mg Daily
For patients assigned to double-blind treatment and who completed Week 52 and 56 of MAESTRO-NAFLD-1, double-blind resmetirom 100 mg for first 12 weeks followed by open-label resmetirom 100 mg for weeks 12-52
Drug: Resmetirom
Tablet
Other Names:
  • MGL-3196
Experimental: Open Label 100 mg
For patients without NASH cirrhosis who were screen failures from MGL-3196-11, open-label resmetirom 100 mg for 52 weeks
Drug: Resmetirom
Tablet
Other Names:
  • MGL-3196
Experimental: Open-label
For patients assigned to open-label treatment and who completed Week 52 and 56 of MAESTRO-NAFLD-1, open-label resmetirom at same dose as MGL-3196-14 for an additional 52 weeks. NASH cirrhosis patients may receive open-label resmetirom for up to an additional 66 months (ie, 52 weeks in MGL-3196-14 and up to 66 months in MGL-3196-18).
Drug: Resmetirom
Tablet
Other Names:
  • MGL-3196
Experimental: Open-Label 80 mg
For patients with NASH cirrhosis who were screen failures from MGL-3196-11, open-label resmetirom 80 mg for up to 66 months.
Drug: Resmetirom
Tablet
Other Names:
  • MGL-3196
Experimental: Open-Label 40 mg
For NASH cirrhosis patients who enter MGL-3196-18 directly or were screen failures from MGL-3196-19, open-label resmetirom 40 mg for up to 66 months.
Drug: Resmetirom
Tablet
Other Names:
  • MGL-3196

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The effect of once daily, oral administration of resmetirom on the incidence of adverse events.
Time Frame: 52 weeks
52 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Percent change in the hepatic fat fraction as determined by MRI-PDFF from baseline
Time Frame: 16 weeks
16 weeks
Percent change in the hepatic fat fraction as determined by MRI-PDFF from baseline
Time Frame: 52 weeks
52 weeks
Percent change in LDL-C from baseline
Time Frame: 28 weeks
28 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Madrigal Pharmaceuticals, Inc.

Investigators

  • Study Director: Tom Hare, MD, Madrigal Pharmaceuticals, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 9, 2021

Primary Completion (Estimated)

March 1, 2027

Study Completion (Estimated)

April 1, 2027

Study Registration Dates

First Submitted

June 18, 2021

First Submitted That Met QC Criteria

July 2, 2021

First Posted (Actual)

July 6, 2021

Study Record Updates

Last Update Posted (Actual)

May 27, 2026

Last Update Submitted That Met QC Criteria

May 22, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MGL-3196-18

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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