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)

NCT04951219 | Active Not Recruiting Phase 3 FDA Drug

• 1 other identifier: MGL-3196-18
• Study Type: interventional
• Target: 1,000
• Locations: 2 countries
• Sites: 71

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)

Conditions

Non-Alcoholic Fatty Liver Disease

Keywords

NAFLD; NASH; Hyperlipidemia; Resmetirom; Thyroid hormone receptor beta; Hepatic; Fibrosis; NASH resolution; Thyroid hormone receptor agonist; Cardiovascular; Dyslipidemia; Fatty liver disease; Nonalcoholic steatohepatitis

Outcome Measures

Primary Outcomes (1)

• The effect of once daily, oral administration of resmetirom on the incidence of adverse events.

  52 weeks

Secondary Outcomes (3)

• 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

Study Arms (6)

Double-blind 80 mg Daily

EXPERIMENTAL

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

Double-blind 100 mg Daily

EXPERIMENTAL

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

Open-label

EXPERIMENTAL

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

Open-Label 80 mg

EXPERIMENTAL

For patients with NASH cirrhosis who were screen failures from MGL-3196-11, open-label resmetirom 80 mg for 104 weeks

Drug: Resmetirom

Open Label 100 mg

EXPERIMENTAL

For patients without NASH cirrhosis who were screen failures from MGL-3196-11, open-label resmetirom 100 mg for 52 weeks

Drug: Resmetirom

Open-Label 40 mg

EXPERIMENTAL

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

Interventions

Resmetirom DRUG

Tablet

Also known as: MGL-3196

Double-blind 100 mg Daily; Double-blind 80 mg Daily; Open Label 100 mg; Open-Label 40 mg; Open-Label 80 mg; Open-label

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 .

You may not qualify if:

• 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.

Sponsors & Collaborators

• Madrigal Pharmaceuticals, Inc.: lead

Study Sites (71)

Central Research Associates

Birmingham, Alabama, 35205, United States

Location

Arizona Liver Health - Chandler

Chandler, Arizona, 85224, United States

Location

East Valley Family Physicians

Chandler, Arizona, 85224, United States

Location

The Institute For Liver Health - Glendale

Glendale, Arizona, 85306, United States

Location

The Institute For Liver Health - Tucson

Tucson, Arizona, 85711, United States

Location

Adobe Gastroenterology

Tucson, Arizona, 85712, United States

Location

Arkansas Gastroenterology

North Little Rock, Arkansas, 72117, United States

Location

Fresno Clinical Research Center

Fresno, California, 93720, United States

Location

National Research Institute - Huntington Park

Huntington Park, California, 90255, United States

Location

Ruane Clinical Research Group

Los Angeles, California, 90036, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

National Research Institute - Los Angeles

Los Angeles, California, 90057, United States

Location

National Research Institute - Panorama City

Panorama City, California, 91402, United States

Location

San Fernando Valley Health Institute

West Hills, California, 91307, United States

Location

South Denver Gastroenterology - Swedish Medical Center Office

Englewood, Colorado, 80113, United States

Location

Excel Medical Clinical Trials

Boca Raton, Florida, 33434, United States

Location

Covenant Research

Fort Myers, Florida, 33912, United States

Location

Velocity Clinical Research, Hallandale Beach (MD Clinical)

Hallandale, Florida, 33009, United States

Location

Floridian Clinical Research

Hialeah, Florida, 33016, United States

Location

Nature Coast Clinical Research - Inverness

Inverness, Florida, 34452, United States

Location

Jacksonville Center for Clinical Research

Jacksonville, Florida, 32216, United States

Location

Florida Research Institute

Lakewood Rch, Florida, 34211, United States

Location

Orlando Research Center

Orlando, Florida, 32806, United States

Location

Progressive Medical Research

Port Orange, Florida, 32127, United States

Location

Covenant Research

Sarasota, Florida, 34240, United States

Location

The Villages Research Center

The Villages, Florida, 32162, United States

Location

Gastrointestinal Specialists of Georgia

Marietta, Georgia, 30060, United States

Location

East-West Medical Research Institute

Honolulu, Hawaii, 96814, United States

Location

Chicago Research Center

Chicago, Illinois, 60602, United States

Location

Northwestern Memorial Physicians Group

Chicago, Illinois, 60611, United States

Location

Iowa Diabetes Research

West Des Moines, Iowa, 50265, United States

Location

Kansas Medical Clinic - Gastroenterology

Topeka, Kansas, 66606, United States

Location

L-MARC Research Center

Louisville, Kentucky, 40213, United States

Location

Digestive Health Center of Louisiana

Baton Rouge, Louisiana, 70809, United States

Location

Tandem Clinical Research - New Orleans Area Site

Marrero, Louisiana, 70072, United States

Location

Clinical Trials of America

West Monroe, Louisiana, 71291, United States

Location

Gastrointestinal Associates & Endoscopy Center - Flowood

Flowood, Mississippi, 39232, United States

Location

Southern Therapy and Advanced Research

Jackson, Mississippi, 39216, United States

Location

Kansas City Research Institute

Kansas City, Missouri, 64131, United States

Location

Henderson Research Center

Henderson, Nevada, 89052, United States

Location

Clarity Clinical Research

East Syracuse, New York, 13057, United States

Location

Mount Sinai Health System

New York, New York, 10029, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cumberland Research Associates

Fayetteville, North Carolina, 28304, United States

Location

Diabetes and Endocrinology Consultants

Morehead City, North Carolina, 28557, United States

Location

Aventiv Research Columbus

Columbus, Ohio, 43213, United States

Location

Awasty Research Network

Marion, Ohio, 43302, United States

Location

Premier Medical Group - Clarksville - Dunlop Lane

Clarksville, Tennessee, 37040, United States

Location

Gastro One - Germantown Office - Wolf Park Drive

Germantown, Tennessee, 38138, United States

Location

Pinnacle Clinical Research - Austin

Austin, Texas, 78746, United States

Location

The Liver Institute At Methodist Dallas

Dallas, Texas, 75203, United States

Location

Dallas Research Center

Dallas, Texas, 75234, United States

Location

Liver Center of Texas

Dallas, Texas, 75234, United States

Location

South Texas Research Institute

Edinburg, Texas, 78539, United States

Location

Texas Digestive Disease Consultants

Fort Worth, Texas, 76104, United States

Location

Liver Associates of Texas

Houston, Texas, 77030, United States

Location

Doctor's Hospital at Renaissance

McAllen, Texas, 78504, United States

Location

Plano Research Center

Plano, Texas, 75093, United States

Location

Texas Liver Institute/American Research Corporation

San Antonio, Texas, 78215, United States

Location

Pinnacle Clinical Research - San Antonio

San Antonio, Texas, 78229, United States

Location

San Antonio Research Center

San Antonio, Texas, 78229, United States

Location

Texas Digestive Disease Consultants - San Marcos

San Marcos, Texas, 78666, United States

Location

Impact Research Institute

Waco, Texas, 76710, United States

Location

Texas Digestive Disease Consultants - Bay Area Houston Endoscopy Center

Webster, Texas, 77598, United States

Location

Wasatch Peak Family Practice

Layton, Utah, 84041, United States

Location

Salt Lake City Research Center

Murray, Utah, 84123, United States

Location

Bon Secours Liver Institute of Richmond

Richmond, Virginia, 23226, United States

Location

National Clinical Research - Richmond

Richmond, Virginia, 23294, United States

Location

Virginia Commonwealth University School of Medicine

Richmond, Virginia, 23298, United States

Location

Liver Institute Northwest

Seattle, Washington, 98105, United States

Location

Fundacion de Investigacion de Diego

San Juan, Puerto Rico

Location

Related Publications (1)

• Harrison SA, Ratziu V, Anstee QM, Noureddin M, Sanyal AJ, Schattenberg JM, Bedossa P, Bashir MR, Schneider D, Taub R, Bansal M, Kowdley KV, Younossi ZM, Loomba R. Design of the phase 3 MAESTRO clinical program to evaluate resmetirom for the treatment of nonalcoholic steatohepatitis. Aliment Pharmacol Ther. 2024 Jan;59(1):51-63. doi: 10.1111/apt.17734. Epub 2023 Oct 2.

  PMID: 37786277 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Hyperlipidemias; Thyroid Hormone Resistance Syndrome; Fibrosis; Dyslipidemias

Interventions

resmetirom

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Hyperthyroxinemia; Thyroid Diseases; Endocrine System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Rebecca Taub, MD

  Madrigal Pharmaceuticals, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Select patients will be randomized in 1:1 manner to a double-blind, 12-week lead-in treatment period. Only investigators, patients, and the Sponsor will be blinded to treatment assignment during the double-blind treatment period.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2021
• First Posted: July 6, 2021
• Study Start: July 9, 2021
• Primary Completion: March 1, 2026
• Study Completion: April 1, 2026
• Last Updated: August 3, 2025

Record last verified: 2025-07

Locations

US (70); PR (1)