ACTIVE_NOT_RECRUITING

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

Conditions

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A Randomized Double-blind Placebo-controlled Phase 3 Study to Evaluate the Effect of Resmetirom on Liver-related Outcomes in Patients With Well-compensated (Child-Pugh A) Non-alcoholic Steatohepatitis (NASH) Cirrhosis (MAESTRO-NASH-OUTCOMES)

Quick Facts

Study Start:2022-08-26

Study Completion:2027-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT05500222

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.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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.	* 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.

Inclusion Criteria

Exclusion 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.

* 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.

Contacts and Locations

Principal Investigator

Thomas Hare

STUDY_DIRECTOR

VP, Clinical Research

Study Locations (Sites)

University of Alabama at Birmingham (UAB)

Birmingham, Alabama, 35249

United States

Arizona Liver Health - Chandler

Chandler, Arizona, 85224

United States

Arizona Liver Health - Peoria

Peoria, Arizona, 85381

United States

Adobe Clinical Research

Tucson, Arizona, 85712

United States

Arizona Liver Health - Tucson

Tucson, Arizona, 85712

United States

Arkansas Diagnostic Center/Liver Wellness Center

Little Rock, Arkansas, 72205-6414

United States

Arkansas Gastroenterology

North Little Rock, Arkansas, 72117

United States

Southern California Research Center

Coronado, California, 92118

United States

University of California, San Francisco-Fresno

Fresno, California, 93701

United States

Univ. of California San Diego School of Medicine

La Jolla, California, 92037

United States

Keck School of Medicine of USC

Los Angeles, California, 90033

United States

California Liver Research Institute

Pasadena, California, 91105

United States

South Denver Gastroenterology

Englewood, Colorado, 80113

United States

Hi Tech and Global Research

Coral Gables, Florida, 33134

United States

Top Medical Research Inc

Cutler Bay, Florida, 33189

United States

Covenant Research - Fort Myers

Fort Myers, Florida, 33912

United States

Nature Coast Clinical Research - Inverness

Inverness, Florida, 34452

United States

Jacksonville Center for Clinical Research

Jacksonville, Florida, 32216

United States

Ocala GI Research DBA Lake Center for Clinical Research

Lady Lake, Florida, 32159

United States

Florida Research Institute

Lakewood Ranch, Florida, 34238

United States

Sanchez Clinical Research

Miami, Florida, 33157

United States

Ocala GI Research

Ocala, Florida, 34471

United States

St Johns Center for Clinical Research

Saint Augustine, Florida, 32086

United States

Covenant Research

Sarasota, Florida, 34240

United States

International Center for Research

Tampa, Florida, 33614

United States

Florida Medical Clinic

Zephyrhills, Florida, 33542

United States

Summit Clinical Research

Athens, Georgia, 30607

United States

Gastrointestinal Specialists of Georgia

Marietta, Georgia, 30060

United States

Kansas Medical Clinic - Gastroenterology

Topeka, Kansas, 666006

United States

Delta Research Partners - Bastrop

Bastrop, Louisiana, 71220

United States

Louisiana Research Center

Shreveport, Louisiana, 71105

United States

Mercy Medical Center

Baltimore, Maryland, 21202

United States

Kansas City Research Institute

Kansas City, Missouri, 64131

United States

Premier Health Research

Sparta, New Jersey, 07871

United States

Lucas Research

Morehead City, North Carolina, 28557

United States

Regional Gastroenterology Associates of Lancaster

Flourtown, Pennsylvania, 19031

United States

Rapid City Medical Center

Rapid City, South Dakota, 57701

United States

Premier Medical Group

Clarksville, Tennessee, 37040

United States

Gastro One

Cordova, Tennessee, 38018

United States

Texas Clinical Research Institute

Arlington, Texas, 76012-3216

United States

Pinnacle Clinical Research - Austin

Austin, Texas, 78757

United States

South Texas Research Institute - Brownsville

Brownsville, Texas, 78520

United States

The Liver Institute at Methodist Dallas Medical Center

Dallas, Texas, 75203

United States

Liver Center of Texas

Dallas, Texas, 75234

United States

South Texas Research Institute - Edinburg

Edinburg, Texas, 78539

United States

Pinnacle Clinical Research - Georgetown

Georgetown, Texas, 78626

United States

Houston Research Institute

Houston, Texas, 77079

United States

Pinnacle Clinical Research - San Antonio

San Antonio, Texas, 78229

United States

Impact Research Institute

Waco, Texas, 76710

United States

Digestive Health Research of Central Texas

Waco, Texas, 76712

United States

GI Select Health Research

Richmond, Virginia, 23236

United States

Hunter Holmes McGuire VA Medical Center

Richmond, Virginia, 23249

United States

Liver Institute Northwest

Seattle, Washington, 98105

United States

Collaborators and Investigators

Sponsor: Madrigal Pharmaceuticals, Inc.

Thomas Hare, STUDY_DIRECTOR, VP, Clinical Research

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 Registration Dates

Study Start Date2022-08-26

Study Completion Date2027-01

Study Record Updates

Study Start Date2022-08-26

Study Completion Date2027-01

Terms related to this study

Additional Relevant MeSH Terms

NASH
Cirrhosis, Liver