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

Prior treatment

• Weight gain or loss ≥5% total body weight within 12 weeks prior to randomization
• Use of high dose vitamin E (\>400 IU/day) unless stable for ≥6 months prior to randomization
• Glucagon-like peptide 1 (GLP-1) agonist therapy for diabetes treatment must be a stable dose for at least 12 weeks prior to randomization. GLP-1 agonists for weight loss must be at stable doses for at least 6 months (including body weight change ≥ 5% weight loss in the 12 weeks prior to randomization)

Other illness

• 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
• Participants with MELD score ≥12 due to liver disease are excluded.
• Participants with a history of hepatic decompensation or impairment are excluded
• No history of alcohol-related liver disease or history (within 5 years) of excessive alcohol consumption

Lab values

• HbA1c \>9.0%
• Platelet counts \<70,000/mm3 at either screening or baseline

Other

• Diagnosis of hepatocellular carcinoma (HCC) at Screening or historically
• Liver Imaging Reporting and Data System (LI-RADS) score ≥4 at Screening
• PEth value of ≥20 ng/mL measured at Screening
• Use of pioglitazone \>15 mg per day

• A clinical diagnosis of NASH cirrhosis
• At least 3 metabolic risk factors
• Historical liver biopsy read as consistent with NASH cirrhosis.
• Historical biopsy consistent with NASH with significant fibrosis, now with progression to cirrhosis. Or, no historical biopsy, with a clinical picture of NASH cirrhosis.
• Well-compensated Child-Pugh A (score of 5-6) cirrhosis at Screening and Baseline
• No history of a hepatic decompensation event.
• MRE ≥4.2 obtained during the screening period (if MRE is \<4.2 and ≥3.7, then an ELF ≥10.25 OR platelet counts \<140K obtained during the screening period is required for eligibility)