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

Inclusion Criteria:

• Definitive (by histologic documentation) or probable NASH as causative agent forcirrhosis, following a modified version of the NASH Cirrhosis: Liver Forum ConsensusDefinitions for Clinical Trials.
• a. Most recent biopsy (within last 5 years) shows cirrhosis with a NAS of ≥ 2, and atleast 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, eligiblewith an MRI-PDFF >5%. If steatosis and ballooning and/or steatosis and inflammationare noted by the local pathologist, then the biopsy qualifies even if a NAS is notprovided (Approximately 70% of the study patient population) b. Historical biopsy (within last 5 years) showed NASH with significant fibrosis with pathology reportdocumenting "F2" or "F3", with at least steatosis either by biopsy with no minimalpercentage required or by MRI-PDFF >5%, AND inflammation or ballooning. Now withcirrhosis, 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 documentssteatosis with no minimal percentage required. Now with cirrhosis, either by clinicalhistory or current features, imaging, noninvasive tests, or biopsy (see Appendix 7).Prescreening metabolic risk factors must include obesity and/or T2D. (Up toapproximately 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 obtainedduring the Screening period or a historic MRI-PDFF at ≤8 weeks old at the time ofrandomization 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 primarybiliary cholangitis, primary sclerosing cholangitis, Hepatitis B positive, HepatitisC, history or evidence of current active autoimmune hepatitis, history or evidence ofWilson's disease, history or evidence of alpha-1-antitrypsin deficiency, history orevidence of genetic hemochromatosis (hereditary, primary), evidence of drug-inducedliver disease, as defined on the basis of typical exposure and history, known bileduct 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.