A Phase 3 Study to Evaluate Safety and Biomarkers of Resmetirom (MGL-3196) in Patients With Non-alcoholic Fatty Liver Disease (NAFLD), MAESTRO-NAFLD-Open-Label-Extension (MAESTRO-NAFLD-OLE)

Study Overview
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Brief Summary
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A 52-Week, Multi-center, Open-label, Active Treatment Extension Study to Evaluate Safety and Tolerability of Once Daily, Oral Administration of Resmetirom (MGL-3196)

Official Title
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A 52-Week, Phase 3, Open-Label Extension Study, With a Double-blind Lead-in, to Evaluate Safety and Biomarkers of Resmetirom (MGL-3196) in Patients With Non-alcoholic Fatty Liver Disease (NAFLD), MAESTRO-NAFLD-Open-Label-Extension (MAESTRO-NAFLD-OLE)

Conditions
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Non-Alcoholic Fatty Liver Disease

Intervention / Treatment
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* Drug: Resmetirom


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For patients who completed MAESTRO-NAFLD-1, completed the Week 52 visit, and completed the Week 56 visit within 90 days of the Extension Day 1 visit, and are willing to participate in MAESTRO-NAFLD-OLE and provide written informed consent. For patients who screen failed MAESTRO-NASH, must provide written informed consent for MAESTRO-NAFLD-OLE and must have screened and met all eligibility requirements for MAESTRO-NASH within 90 days of the Extension Day 1 visit for MAESTRO-NAFLD-OLE and have a liver biopsy that is ineligible for MAESTRO-NASH within 6 months of the Extension Day 1 visit. Eligible liver biopsy for MAESTRO-NAFLD-OLE must have one of the following results: NAS = 3, steatosis 1, ballooning 1, inflammation 1, OR NAS = 3, ballooning 0, with F1B, F2 or F3 NAS ≥ 4, at least 1 in all NAS components, F1A or F1C, PRO-C3 ≤ 14 (NASH, but ineligible for MAESTRO-NASH) Compensated NASH cirrhosis based on biopsy at screening of MAESTRO-NASH and baseline of MAESTRO-NAFLD-OLE, including Child Pugh-A (score 5-6), MELD <12, albumin ≥3.2, and bilirubin <2 For patients who screen failed from MAESTRO-NASH OUTCOMES and de novo patients, must have documented CP-A/B (score <8) NASH cirrhosis (including minimal decompensation) and MELD <15 unless MELD >=15 based on non-cirrhotic parameters. MAESTRO-NASH OUTCOMES screen failures must have screened and met all eligibility requirements for MAESTRO-NASH OUTCOMES within 90 days of the Extension Day 1 visit for MAESTRO-NAFLD-OLE . Exclusion Criteria: A history of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to Extension Day 1. Diagnosis of hepatocellular carcinoma or other carcinomas that may prevent participation in the Extension study. Chronic liver diseases Has an active autoimmune disease 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Double-blind 80 mg Daily<br>For patients assigned to double-blind treatment and who completed Week 52 and 56 of MAESTRO-NAFLD-1, double-blind resmetirom 80 mg for first 12 weeks followed by open-label resmetirom 100 mg for weeks 12-52 | Drug: Resmetirom<br>* Tablet<br>* Other names: MGL-3196;|
| Experimental: Double-blind 100 mg Daily<br>For patients assigned to double-blind treatment and who completed Week 52 and 56 of MAESTRO-NAFLD-1, double-blind resmetirom 100 mg for first 12 weeks followed by open-label resmetirom 100 mg for weeks 12-52 | Drug: Resmetirom<br>* Tablet<br>* Other names: MGL-3196;|
| Experimental: Open-label<br>For patients assigned to open-label treatment and who completed Week 52 and 56 of MAESTRO-NAFLD-1, open-label resmetirom at same dose as MGL-3196-14 for an additional 52 weeks. NASH cirrhosis patients may receive open-label resmetirom for an additional 52 weeks (ie, 52 weeks in MGL-3196-14 and 104 weeks in MGL-3196-18). | Drug: Resmetirom<br>* Tablet<br>* Other names: MGL-3196;|
| Experimental: Open-Label 80 mg<br>For patients with NASH cirrhosis who were screen failures from MGL-3196-11, open-label resmetirom 80 mg for 104 weeks | Drug: Resmetirom<br>* Tablet<br>* Other names: MGL-3196;|
| Experimental: Open Label 100 mg<br>For patients without NASH cirrhosis who were screen failures from MGL-3196-11, open-label resmetirom 100 mg for 52 weeks | Drug: Resmetirom<br>* Tablet<br>* Other names: MGL-3196;|
| Experimental: Open-Label 40 mg<br>For NASH cirrhosis patients who enter MGL-3196-18 directly or were screen failures from MGL-3196-19, open-label resmetirom 40 mg for 104 weeks | Drug: Resmetirom<br>* Tablet<br>* Other names: MGL-3196;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effect of once daily, oral administration of resmetirom on the incidence of adverse events. |  | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change in the hepatic fat fraction as determined by MRI-PDFF from baseline |  | 16 weeks | 
| Percent change in the hepatic fat fraction as determined by MRI-PDFF from baseline |  | 52 weeks | 
| Percent change in LDL-C from baseline |  | 28 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NAFLD, NASH, Hyperlipidemia, Resmetirom, Thyroid hormone receptor beta, Hepatic, Fibrosis, NASH resolution, Thyroid hormone receptor agonist, Cardiovascular, Dyslipidemia, Fatty liver disease, Nonalcoholic steatohepatitis