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, andat least two components: one being steatosis and at least one other component; ORNAS 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 andinflammation are noted by the local pathologist, then the biopsy qualifies even if aNAS is not provided (Approximately 70% of the study patient population) b.Historical biopsy (within last 5 years) showed NASH with significant fibrosis withpathology report documenting "F2" or "F3", with at least steatosis either by biopsywith no minimal percentage required or by MRI-PDFF >5%, AND inflammation orballooning. Now with cirrhosis, either by clinical history or current features,imaging, noninvasive tests, or biopsy (see Appendix 7) (Up to approximately 20% ofstudy patient population) c. Historical biopsy (within last 5 years) showssteatosis. 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 factorsmust include obesity and/or T2D. (Up to approximately 10% of study patientpopulation.)

• Well-compensated NASH cirrhosis at screening and baseline with Child-Pugh A (scoreof 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 asprimary biliary cholangitis, primary sclerosing cholangitis, Hepatitis B positive,Hepatitis C, history or evidence of current active autoimmune hepatitis, history orevidence of Wilson's disease, history or evidence of alpha-1-antitrypsin deficiency,history or evidence of genetic hemochromatosis (hereditary, primary), evidence ofdrug-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.