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

Open to people ages 18 years and up

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)

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.