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)
Overview
- Phase
- Phase 3
- Intervention
- Resmetirom
- Conditions
- Non-Alcoholic Fatty Liver Disease
- Sponsor
- Madrigal Pharmaceuticals, Inc.
- Enrollment
- 1000
- Locations
- 70
- Primary Endpoint
- The effect of once daily, oral administration of resmetirom on the incidence of adverse events.
- Status
- Active, Not Recruiting
- Last Updated
- 9 months ago
Overview
Brief Summary
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)
Investigators
Eligibility Criteria
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
- •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.
Arms & Interventions
Double-blind 80 mg Daily
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
Intervention: Resmetirom
Double-blind 100 mg Daily
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
Intervention: Resmetirom
Open-label
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).
Intervention: Resmetirom
Open-Label 80 mg
For patients with NASH cirrhosis who were screen failures from MGL-3196-11, open-label resmetirom 80 mg for 104 weeks
Intervention: Resmetirom
Open Label 100 mg
For patients without NASH cirrhosis who were screen failures from MGL-3196-11, open-label resmetirom 100 mg for 52 weeks
Intervention: Resmetirom
Open-Label 40 mg
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
Intervention: Resmetirom
Outcomes
Primary Outcomes
The effect of once daily, oral administration of resmetirom on the incidence of adverse events.
Time Frame: 52 weeks
Secondary Outcomes
- Percent change in LDL-C from baseline(28 weeks)
- Percent change in the hepatic fat fraction as determined by MRI-PDFF from baseline(52 weeks)