A Phase 3 Study to Evaluate the Efficacy and Safety of MGL-3196 (Resmetirom) in Patients With NASH and Fibrosis (MAESTRO-NASH)
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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
Condition or disease
NASH - Nonalcoholic Steatohepatitis
Drug: MGL-3196Drug: Placebo
Primary and secondary endpoint population at Week 52 will be at least 900 patients, more than half F3, the remainder F2 and <10% F1B based on final liver biopsy baseline fibrosis score.
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
Actual Study Start Date :
March 28, 2019
Actual Primary Completion Date :
December 19, 2022
Estimated Study Completion Date :
Resource links provided by the National Library of Medicine
Week 52 Dual Primary Objectives: To determine the effect of 80 or 100 mg MGL-3196 vs matching placebo on liver biopsy (NASH CRN score) at Week 52 compared with Baseline [ Time Frame: 52 weeks ]
Proportion with resolution of NASH (ballooning 0, inflammation 0,1) associated with at least 2-point reduction in NAFLD Activity Score (NAS) without worsening of fibrosis stage OR
Proportion with at least a 1-point improvement in fibrosis stage with no worsening of NAS
Month 54 Primary Objective: Time to experiencing an adjudicated Composite Clinical Outcome event (Final Primary Endpoint, at 54 months) [ Time Frame: up to 54 months ]
The Composite Clinical Outcome is composed of all-cause mortality, liver transplant, and significant hepatic events (including hepatic decompensation events [ascites, encephalopathy, or gastroesophageal variceal hemorrhage], histological progression to cirrhosis, and a confirmed increase of MELD score from <12 to ≥15).
Secondary Outcome Measures :
Week 52 Key Secondary Objective: To determine the effect of once-daily, oral administration of MGL-3196 80 or 100 mg versus matching placebo on the percent change from Baseline at 24 weeks in directly measured low-density lipoprotein cholesterol (LDL-C) [ Time Frame: 24 weeks ]
Assess the effect of MGL-3196 80 mg or 100 mg compared to placebo on LDL-C measured by percent change from Baseline at 24 weeks.
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Layout table for eligibility information
Ages Eligible for Study:
18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:
Accepts Healthy Volunteers:
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:
Historical biochemical test for fibrosis: PRO-C3 >14 ng/mL or ELF ≥9
FibroScan with transient elastography ≥8.5 kPa and controlled attenuation parameter ≥280 dB.m-1
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.
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:
Steatosis (scored 0 to 3)
Ballooning degeneration (scored 0 to 2)
Lobular inflammation (scored 0 to 3)
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
Untreated clinical hypothyroidism defined by thyroid stimulating hormone (TSH) >7 IU/L with symptoms of hypothyroidism or >10 IU/L without symptoms.
Patients who have had a thyroidectomy and are on replacement thyroxine doses >75 µg per day are allowed.
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.
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.