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: 700
• Locations: 2 countries
• Sites: 55

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:

• Definitive (by histologic documentation) or probable NASH as causative agent for cirrhosis, following a modified version of the NASH Cirrhosis: Liver Forum Consensus Definitions for Clinical Trials.
• a. Most recent biopsy (within last 5 years) shows cirrhosis with a NAS of ≥ 2, and at least two components: one being steatosis and at least one other component; OR NAS of ≥ 2, if steatosis = 0 or is ungraded with inflammation and/or ballooning, eligible with an MRI-PDFF \>5%. If steatosis and ballooning and/or steatosis and inflammation are noted by the local pathologist, then the biopsy qualifies even if a NAS is not provided (Approximately 70% of the study patient population) b. Historical biopsy (within last 5 years) showed NASH with significant fibrosis with pathology report documenting "F2" or "F3", with at least steatosis either by biopsy with no minimal percentage required or by MRI-PDFF \>5%, AND inflammation or ballooning. Now with cirrhosis, either by clinical history or current features, imaging, noninvasive tests, or biopsy (see Appendix 7) (Up to approximately 20% of study patient population) c. Historical biopsy (within last 5 years) shows steatosis. Pathology report documents steatosis with no minimal percentage required. Now with cirrhosis, either by clinical history or current features, imaging, noninvasive tests, or biopsy (see Appendix 7). Prescreening metabolic risk factors must include obesity and/or T2D. (Up to approximately 10% of study patient population.)
• Well-compensated NASH cirrhosis at screening and baseline with Child-Pugh A (score of 5-6) (no history of hepatic decompensation event).
• At least 3 metabolic risk factors
• Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) that is obtained during the Screening period or a historic MRI-PDFF at ≤8 weeks old at the time of randomization with no weight change ≥5% weight change in that interval.
• MRE ≥4.2 where MRE is available.
• Enhanced liver function (ELF) ≥9.8, only if MRE is unavailable or contraindicated.

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, are excluded.
• Participants with MELD score ≥12 due to liver disease are excluded.
• Participants with a history of hepatic decompensation or impairment are excluded.

Sponsors & Collaborators

• Madrigal Pharmaceuticals, Inc.: lead

Study Sites (55)

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

California Liver Research Institute

Pasadena, California, 91105, United States

Location

South Denver Gastroenterology

Englewood, Colorado, 80113, 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

Sanchez Clinical Research

Miami, Florida, 33157, United States

Location

Ocala GI Research

Ocala, Florida, 34471, 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

Kansas Medical Clinic - Gastroenterology

Topeka, Kansas, 666006, United States

Location

Delta Research Partners - Bastrop

Bastrop, Louisiana, 71220, United States

Location

Louisiana Research Center

Shreveport, Louisiana, 71105, United States

Location

Mercy Medical Center

Baltimore, Maryland, 21202, United States

Location

Kansas City Research Institute

Kansas City, Missouri, 64131, United States

Location

Premier Health Research

Sparta, New Jersey, 07871, United States

Location

Lucas Research

Morehead City, North Carolina, 28557, United States

Location

Regional Gastroenterology Associates of Lancaster

Flourtown, Pennsylvania, 19031, 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

Texas Clinical Research Institute

Arlington, Texas, 76012-3216, United States

Location

Pinnacle Clinical Research - Austin

Austin, Texas, 78757, 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

Liver Center of Texas

Dallas, Texas, 75234, United States

Location

South Texas Research Institute - Edinburg

Edinburg, Texas, 78539, United States

Location

Pinnacle Clinical Research - Georgetown

Georgetown, Texas, 78626, United States

Location

Houston Research Institute

Houston, Texas, 77079, 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

GI Select Health Research

Richmond, Virginia, 23236, United States

Location

Hunter Holmes McGuire VA Medical Center

Richmond, Virginia, 23249, United States

Location

Liver Institute Northwest

Seattle, Washington, 98105, United States

Location

Latin Clinical Trials Center

San Juan, 00909, Puerto Rico

Location

FDI Clinical Research (Fundacion de Investigacion de Diego)

San Juan, 00927, Puerto Rico

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

  VP, 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: June 11, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (53); PR (2)