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)

Phase 3

Recruiting

• Conditions: Non-Alcoholic Fatty Liver Disease
• Interventions: Drug: Resmetirom

• Registration Number: NCT04951219
• Lead Sponsor: Madrigal Pharmaceuticals, Inc.

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)

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-06-18
• Study First Submitted QC: 2021-07-02
• Study First Posted: 2021-07-06
• Study Start: 2021-07-09
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-28
• Last Update Posted: 2023-12-04
• Primary Completion: 2026-03
• Study Completion: 2026-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1000

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Open-label	Resmetirom	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).
Open Label 100 mg	Resmetirom	For patients without NASH cirrhosis who were screen failures from MGL-3196-11, open-label resmetirom 100 mg for 52 weeks
Double-blind 100 mg Daily	Resmetirom	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
Open-Label 40 mg	Resmetirom	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
Open-Label 80 mg	Resmetirom	For patients with NASH cirrhosis who were screen failures from MGL-3196-11, open-label resmetirom 80 mg for 104 weeks
Double-blind 80 mg Daily	Resmetirom	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

Primary Outcome Measures

Name	Time	Method
The effect of once daily, oral administration of resmetirom on the incidence of adverse events.	52 weeks

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (73)

Central Research Associates; 🇺🇸 Birmingham, Alabama, United States

Arizona Liver Health - Chandler; 🇺🇸 Chandler, Arizona, United States

East Valley Family Physicians; 🇺🇸 Chandler, Arizona, United States

The Institute For Liver Health - Glendale; 🇺🇸 Glendale, Arizona, United States

The Institute For Liver Health - Tucson; 🇺🇸 Tucson, Arizona, United States

Adobe Gastroenterology; 🇺🇸 Tucson, Arizona, United States

Arkansas Gastroenterology; 🇺🇸 North Little Rock, Arkansas, United States

Fresno Clinical Research Center; 🇺🇸 Fresno, California, United States

National Research Institute - Huntington Park; 🇺🇸 Huntington Park, California, United States

Ruane Clinical Research Group; 🇺🇸 Los Angeles, California, United States

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