a phase 3 study to evaluate the efficacy and safety of mgl-3196 (resmetirom) in patients with nash and fibrosis

Conditions: NASH - Nonalcoholic Steatohepatitis

Summary: 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.

Eligibility criteria:
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 \ 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.