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

Cirrhosis, Liver Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05500222
• Other study ID #: MGL-3196-19
• Status: Recruiting
• Phase: Phase 3
• Start date: August 26, 2022
• Est. completion date: January 2027

Study information

• Verified date: March 2024
• Source: Madrigal Pharmaceuticals, Inc.
• Contact: Thomas Hare
• Phone: 267-520-0252
• Email: info[@]madrigalpharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 700
• Est. completion date: January 2027
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cirrhosis, Liver
• Fibrosis
• Liver Cirrhosis
• NASH

Intervention

Drug:
• Resmetirom
Randomized 80 mg
• Placebo
randomized matching placebo

Locations

Country	Name	City	State
Puerto Rico	FDI Clinical Research (Fundacion de Investigacion de Diego)	San Juan
Puerto Rico	Latin Clinical Trials Center	San Juan
United States	Texas Clinical Research Institute	Arlington	Texas
United States	Summit Clinical Research	Athens	Georgia
United States	Pinnacle Clinical Research - Austin	Austin	Texas
United States	Mercy Medical Center	Baltimore	Maryland
United States	Delta Research Partners - Bastrop	Bastrop	Louisiana
United States	University of Alabama at Birmingham (UAB)	Birmingham	Alabama
United States	South Texas Research Institute - Brownsville	Brownsville	Texas
United States	Arizona Liver Health - Chandler	Chandler	Arizona
United States	Premier Medical Group	Clarksville	Tennessee
United States	Hi Tech and Global Research	Coral Gables	Florida
United States	Gastro One	Cordova	Tennessee
United States	Southern California Research Center	Coronado	California
United States	Top Medical Research Inc	Cutler Bay	Florida
United States	Liver Center of Texas	Dallas	Texas
United States	The Liver Institute at Methodist Dallas Medical Center	Dallas	Texas
United States	South Texas Research Institute - Edinburg	Edinburg	Texas
United States	South Denver Gastroenterology	Englewood	Colorado
United States	Regional Gastroenterology Associates of Lancaster	Flourtown	Pennsylvania
United States	Covenant Research - Fort Myers	Fort Myers	Florida
United States	University of California, San Francisco-Fresno	Fresno	California
United States	Pinnacle Clinical Research - Georgetown	Georgetown	Texas
United States	Houston Research Institute	Houston	Texas
United States	Nature Coast Clinical Research - Inverness	Inverness	Florida
United States	Jacksonville Center for Clinical Research	Jacksonville	Florida
United States	Kansas City Research Institute	Kansas City	Missouri
United States	Univ. of California San Diego School of Medicine	La Jolla	California
United States	Ocala GI Research DBA Lake Center for Clinical Research	Lady Lake	Florida
United States	Florida Research Institute	Lakewood Ranch	Florida
United States	Arkansas Diagnostic Center/Liver Wellness Center	Little Rock	Arkansas
United States	Keck School of Medicine of USC	Los Angeles	California
United States	Gastrointestinal Specialists of Georgia	Marietta	Georgia
United States	Sanchez Clinical Research	Miami	Florida
United States	Lucas Research	Morehead City	North Carolina
United States	Arkansas Gastroenterology	North Little Rock	Arkansas
United States	Ocala GI Research	Ocala	Florida
United States	California Liver Research Institute	Pasadena	California
United States	Arizona Liver Health - Peoria	Peoria	Arizona
United States	Rapid City Medical Center	Rapid City	South Dakota
United States	GI Select Health Research	Richmond	Virginia
United States	Hunter Holmes McGuire VA Medical Center	Richmond	Virginia
United States	St Johns Center for Clinical Research	Saint Augustine	Florida
United States	Pinnacle Clinical Research - San Antonio	San Antonio	Texas
United States	Covenant Research	Sarasota	Florida
United States	Liver Institute Northwest	Seattle	Washington
United States	Louisiana Research Center	Shreveport	Louisiana
United States	Premier Health Research	Sparta	New Jersey
United States	International Center for Research	Tampa	Florida
United States	Kansas Medical Clinic - Gastroenterology	Topeka	Kansas
United States	Adobe Clinical Research	Tucson	Arizona
United States	Arizona Liver Health - Tucson	Tucson	Arizona
United States	Digestive Health Research of Central Texas	Waco	Texas
United States	Impact Research Institute	Waco	Texas
United States	Florida Medical Clinic	Zephyrhills	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Madrigal Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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