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

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:
4. Historical biochemical test for fibrosis: PRO-C3 >14 ng/mL or ELF ≥9
5. FibroScan with transient elastography ≥8.5 kPa and controlled attenuationparameter ≥280 dB.m-1
6. Historical liver biopsy obtained <2 years before expected randomization showingStage 1B, 2 or 3 fibrosis with NASH based on existing pathology review, with nosignificant change in body weight >5% or medication that might affect NAS orfibrosis stage.
7. MRI-PDFF fat fraction ≥8% obtained during the screening period
8. Biopsy-proven NASH (baseline liver biopsy) based on a liver biopsy obtained ≤6 monthsbefore anticipated date of randomization (if the biopsy is deemed acceptable forinterpretation by the central reader) with fibrosis stage 1A/1C, 1B, 2, or 3 on liverbiopsy and NAS of ≥4 with a score of at least 1 in each of the following NAScomponents:
9. Steatosis (scored 0 to 3)
10. Ballooning degeneration (scored 0 to 2)
11. Lobular inflammation (scored 0 to 3)

Exclusion Criteria:

1. History of significant alcohol consumption for a period of more than 3 consecutivemonths within 1 year prior to Screening.
2. Regular use of drugs historically associated with NAFLD
3. Thyroid diseases:
4. Active hyperthyroidism.
5. Untreated clinical hypothyroidism defined by thyroid stimulating hormone (TSH) >7IU/L with symptoms of hypothyroidism or >10 IU/L without symptoms.
6. Patients who have had a thyroidectomy and are on replacement thyroxine doses >75 µg per day are allowed.
7. History of bariatric surgery or intestinal bypass surgery within the 5 years prior torandomization or planned during the conduct of the study.
8. Recent significant weight gain or loss
9. HbA1c ≥ 9.0%.
10. Glucagon-like peptide 1 [GLP-1] agonist, high dose Vitamin E (> 400 IU/day), orpioglitazone therapy unless stable dose for 24 weeks prior to biopsy.
11. Presence of cirrhosis on liver biopsy defined as stage 4 fibrosis.
12. Diagnosis of hepatocellular carcinoma (HCC).
13. MELD score ≥12, as determined at Screening, unless due to therapeutic anticoagulation.
14. Hepatic decompensation
15. Chronic liver diseases other than NASH
16. Active autoimmune disease
17. Serum ALT > 250 U/L.
18. Active, serious medical disease with a likely life expectancy < 2 years.
19. Participation in an investigational new drug trial in the 60 days or 5 half-lives,whichever is longer.
20. Any other condition which, in the opinion of the Investigator, would impedecompliance, hinder completion of the study, compromise the well-being of the patient,or interfere with the study outcomes.