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

NCT ID: NCT05500222

Last Updated: 2025-06-11

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 700 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-08-26
• Study Completion Date: 2027-01-31

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.

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: liver-related and CV 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.

Conditions

NASH; Cirrhosis, Liver

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Resmetirom

80 mg daily

Group Type: ACTIVE_COMPARATOR

Resmetirom

Intervention Type: DRUG

Randomized 80 mg

Placebo

matching placebo daily

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

randomized matching placebo

Interventions

Resmetirom

Randomized 80 mg

Intervention Type: DRUG

Placebo

randomized matching placebo

Intervention Type: DRUG

Other Intervention Names

MGL-3196

Eligibility Criteria

Inclusion Criteria

• 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.

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Madrigal Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thomas Hare

Role: STUDY_DIRECTOR

VP, Clinical Research

Locations

University of Alabama at Birmingham (UAB)

Birmingham, Alabama, United States

Arizona Liver Health - Chandler

Chandler, Arizona, United States

Arizona Liver Health - Peoria

Peoria, Arizona, United States

Adobe Clinical Research

Tucson, Arizona, United States

Arizona Liver Health - Tucson

Tucson, Arizona, United States

Arkansas Diagnostic Center/Liver Wellness Center

Little Rock, Arkansas, United States

Arkansas Gastroenterology

North Little Rock, Arkansas, United States

Southern California Research Center

Coronado, California, United States

University of California, San Francisco-Fresno

Fresno, California, United States

Univ. of California San Diego School of Medicine

La Jolla, California, United States

Keck School of Medicine of USC

Los Angeles, California, United States

California Liver Research Institute

Pasadena, California, United States

South Denver Gastroenterology

Englewood, Colorado, United States

Hi Tech and Global Research

Coral Gables, Florida, United States

Top Medical Research Inc

Cutler Bay, Florida, United States

Covenant Research - Fort Myers

Fort Myers, Florida, United States

Nature Coast Clinical Research - Inverness

Inverness, Florida, United States

Jacksonville Center for Clinical Research

Jacksonville, Florida, United States

Ocala GI Research DBA Lake Center for Clinical Research

Lady Lake, Florida, United States

Florida Research Institute

Lakewood Rch, Florida, United States

Sanchez Clinical Research

Miami, Florida, United States

Ocala GI Research

Ocala, Florida, United States

St Johns Center for Clinical Research

Saint Augustine, Florida, United States

Covenant Research

Sarasota, Florida, United States

International Center for Research

Tampa, Florida, United States

Florida Medical Clinic

Zephyrhills, Florida, United States

Summit Clinical Research

Athens, Georgia, United States

Gastrointestinal Specialists of Georgia

Marietta, Georgia, United States

Kansas Medical Clinic - Gastroenterology

Topeka, Kansas, United States

Delta Research Partners - Bastrop

Bastrop, Louisiana, United States

Louisiana Research Center

Shreveport, Louisiana, United States

Mercy Medical Center

Baltimore, Maryland, United States

Kansas City Research Institute

Kansas City, Missouri, United States

Premier Health Research

Sparta, New Jersey, United States

Lucas Research

Morehead City, North Carolina, United States

Regional Gastroenterology Associates of Lancaster

Flourtown, Pennsylvania, United States

Rapid City Medical Center

Rapid City, South Dakota, United States

Premier Medical Group

Clarksville, Tennessee, United States

Gastro One

Cordova, Tennessee, United States

Texas Clinical Research Institute

Arlington, Texas, United States

Pinnacle Clinical Research - Austin

Austin, Texas, United States

South Texas Research Institute - Brownsville

Brownsville, Texas, United States

The Liver Institute at Methodist Dallas Medical Center

Dallas, Texas, United States

Liver Center of Texas

Dallas, Texas, United States

South Texas Research Institute - Edinburg

Edinburg, Texas, United States

Pinnacle Clinical Research - Georgetown

Georgetown, Texas, United States

Houston Research Institute

Houston, Texas, United States

Pinnacle Clinical Research - San Antonio

San Antonio, Texas, United States

Impact Research Institute

Waco, Texas, United States

Digestive Health Research of Central Texas

Waco, Texas, United States

GI Select Health Research

Richmond, Virginia, United States

Hunter Holmes McGuire VA Medical Center

Richmond, Virginia, United States

Liver Institute Northwest

Seattle, Washington, United States

Latin Clinical Trials Center

San Juan, , Puerto Rico

FDI Clinical Research (Fundacion de Investigacion de Diego)

San Juan, , Puerto Rico

Countries

United States; Puerto Rico

References

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.

Reference Type: DERIVED

PMID: 37786277 (View on PubMed)

Other Identifiers

MGL-3196-19

Identifier Type: -

Identifier Source: org_study_id