A Phase 3, Multinational, Double-Blind, Randomized, Placebo-Controlled Study of MGL-3196 (Resmetirom) in Patients With Non-Alcoholic Steatohepatitis (NASH) and Fibrosis to Resolve NASH and Reduce Progression to Cirrhosis and/or Hepatic Decompensation
A Phase 3, Multinational, Double-Blind, Randomized, Placebo-Controlled Study of MGL-3196 (Resmetirom) in Patients With Non-Alcoholic Steatohepatitis (NASH) and Fibrosis to Resolve NASH and Reduce Progression to Cirrhosis and/or Hepatic Decompensation
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:
Must be willing to participate in the study and provide written informed consent.
Male and female adults ≥ 18 years of age.
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:
MRI-PDFF fat fraction ≥8% obtained during the screening period
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:
Exclusion Criteria:
History of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to Screening.
Regular use of drugs historically associated with NAFLD
Thyroid diseases:
History of bariatric surgery or intestinal bypass surgery within the 5 years prior to randomization or planned during the conduct of the study.
Recent significant weight gain or loss
HbA1c ≥ 9.0%.
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.
Presence of cirrhosis on liver biopsy defined as stage 4 fibrosis.
Diagnosis of hepatocellular carcinoma (HCC).
MELD score ≥12, as determined at Screening, unless due to therapeutic anti coagulation.
Hepatic decompensation
Chronic liver diseases other than NASH
Active autoimmune disease
Serum ALT > 250 U/L.
Active, serious medical disease with a likely life expectancy < 2 years.
Participation in an investigational new drug trial in the 60 days or 5 half-lives, whichever is longer.
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.
Englewood, Colorado 80113, United States
Baton Rouge, Louisiana 70809, United States
Charlotte, North Carolina 27599, United States
Nice, Provence-Alpes-Côte d'Azur Region, France
Nyíregyháza, Szabolcs-Szatmár-Bereg, Hungary