A Phase 3 Study to Evaluate the Efficacy and Safety of MGL-3196 (Resmetirom) in Patients With NASH and Fibrosis

A double-blind placebo controlled randomized Phase 3 study to determine if 80 or 100 mg of MGL-3196 as compared with placebo resolves NASH and/or reduces fibrosis on liver biopsy and prevents progression to cirrhosis and/or advanced liver disease

Primary and secondary endpoint population at Week 52 will be at least 900 patients, more than half fibrosis score 3 (F3), the remainder fibrosis score 2 (F2) and \<10% fibrosis score F1B (F1B) based on final liver biopsy baseline fibrosis score.

Inclusion Criteria: 1. Must be willing to participate in the study and provide written informed consent. 2. Male and female adults ≥ 18 years of age. 3. Suspected or confirmed diagnosis of NASH fibrosis suggested by the historical data. Meet one of the following criteria that is consistent with NASH liver fibrosis: 1. Historical biochemical test for fibrosis: PRO-C3 \>14 ng/mL or ELF ≥9 2. FibroScan with transient elastography ≥8.5 kPa and controlled attenuation parameter ≥280 dB.m-1 3. Historical liver biopsy obtained \<2 years before expected randomization showing Stage 1B, 2 or 3 fibrosis with NASH based on existing pathology review, with no significant change in body weight \>5% or medication that might affect NAS or fibrosis stage. 4. MRI-PDFF fat fraction ≥8% obtained during the screening period 5. Biopsy-proven NASH (baseline liver biopsy) based on a liver biopsy obtained ≤6 months before anticipated date of randomization (if the biopsy is deemed acceptable for interpretation by the central reader) with fibrosis stage 1A/1C, 1B, 2, or 3 on liver biopsy and NAS of ≥4 with a score of at least 1 in each of the following NAS components: 1. Steatosis (scored 0 to 3) 2. Ballooning degeneration (scored 0 to 2) 3. Lobular inflammation (scored 0 to 3) Exclusion Criteria: 1. History of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to Screening. 2. Regular use of drugs historically associated with NAFLD 3. Thyroid diseases: 1. Active hyperthyroidism. 2. Untreated clinical hypothyroidism defined by thyroid stimulating hormone (TSH) \>7 IU/L with symptoms of hypothyroidism or \>10 IU/L without symptoms. 3. Patients who have had a thyroidectomy and are on replacement thyroxine doses \>75 µg per day are allowed. 4. History of bariatric surgery or intestinal bypass surgery within the 5 years prior to randomization or planned during the conduct of the study. 5. Recent significant weight gain or loss 6. HbA1c ≥ 9.0%. 7. Glucagon-like peptide 1 \[GLP-1\] agonist, high dose Vitamin E (\> 400 IU/day), or pioglitazone therapy unless stable dose for 24 weeks prior to biopsy. 8. Presence of cirrhosis on liver biopsy defined as stage 4 fibrosis. 9. Diagnosis of hepatocellular carcinoma (HCC). 10. MELD score ≥12, as determined at Screening, unless due to therapeutic anti coagulation. 11. Hepatic decompensation 12. Chronic liver diseases other than NASH 13. Active autoimmune disease 14. Serum ALT \> 250 U/L. 15. Active, serious medical disease with a likely life expectancy \< 2 years. 16. Participation in an investigational new drug trial in the 60 days or 5 half-lives, whichever is longer. 17. Any other condition which, in the opinion of the Investigator, would impede compliance, hinder completion of the study, compromise the well-being of the patient, or interfere with the study outcomes.