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)

Recruitment Status
ACTIVE, NOT RECRUITING
(See Contacts and Locations)Verified April 2026 by Madrigal Pharmaceuticals, Inc.
Sponsor
Madrigal Pharmaceuticals, Inc.
Information Provided by (Responsible Party)
Madrigal Pharmaceuticals, Inc.
Clinicaltrials.gov Identifier
NCT04951219
Other Study ID Numbers:
MGL-3196-18
First Submitted
June 17, 2021
First Posted
July 5, 2021
Last Update Posted
May 26, 2026
Last Verified
April 2026

ClinicalTrials.gov processed this data on May 2026. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

Condition or DiseaseIntervention/Treatment
Non-Alcoholic Fatty Liver Disease
Drug: ResmetiromDrug: ResmetiromDrug: ResmetiromDrug: ResmetiromDrug: ResmetiromDrug: Resmetirom

Study Design

Study TypeInterventional
Actual Enrollment810 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingTriple
Primary PurposeTreatment
Official TitleA 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)
Study Start DateJuly 8, 2021
Actual Primary Completion Date8mos 4d from now
Actual Study Completion Date9mos 1w from now

Groups and Cohorts

Group/CohortIntervention/Treatment
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
Drug: Resmetirom
Tablet
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
Drug: Resmetirom
Tablet
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 up to an additional 66 months (ie, 52 weeks in MGL-3196-14 and up to 66 months in MGL-3196-18).
Drug: Resmetirom
Tablet
Open-Label 80 mg
For patients with NASH cirrhosis who were screen failures from MGL-3196-11, open-label resmetirom 80 mg for up to 66 months.
Drug: Resmetirom
Tablet
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
Drug: Resmetirom
Tablet
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 up to 66 months.
Drug: Resmetirom
Tablet

Outcome Measures

Primary Outcome Measures
  1. The effect of once daily, oral administration of resmetirom on the incidence of adverse events.
Secondary Outcome Measures
  1. Percent change in the hepatic fat fraction as determined by MRI-PDFF from baseline
  2. Percent change in the hepatic fat fraction as determined by MRI-PDFF from baseline
  3. Percent change in LDL-C from baseline

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
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.

Contacts and Locations

Sponsors and CollaboratorsMadrigal Pharmaceuticals, Inc.
Locations
Central Research Associates | Birmingham Alabama, United States, 35205Arizona Liver Health - Chandler | Chandler Arizona, United States, 85224East Valley Family Physicians | Chandler Arizona, United States, 85224The Institute For Liver Health - Glendale | Glendale Arizona, United States, 85306The Institute For Liver Health - Tucson | Tucson Arizona, United States, 85711Adobe Gastroenterology | Tucson Arizona, United States, 85712Arkansas Gastroenterology | North Little Rock Arkansas, United States, 72117Fresno Clinical Research Center | Fresno California, United States, 93720National Research Institute - Huntington Park | Huntington Park California, United States, 90255Ruane Clinical Research Group | Los Angeles California, United States, 90036Cedars-Sinai Medical Center | Los Angeles California, United States, 90048National Research Institute - Los Angeles | Los Angeles California, United States, 90057National Research Institute - Panorama City | Panorama City California, United States, 91402San Fernando Valley Health Institute | West Hills California, United States, 91307South Denver Gastroenterology - Swedish Medical Center Office | Englewood Colorado, United States, 80113Excel Medical Clinical Trials | Boca Raton Florida, United States, 33434Covenant Research | Fort Myers Florida, United States, 33912Velocity Clinical Research, Hallandale Beach (MD Clinical) | Hallandale Florida, United States, 33009Floridian Clinical Research | Hialeah Florida, United States, 33016Nature Coast Clinical Research - Inverness | Inverness Florida, United States, 34452Jacksonville Center for Clinical Research | Jacksonville Florida, United States, 32216Florida Research Institute | Lakewood Rch Florida, United States, 34211Floridian Clinical Research | Miami Lakes Florida, United States, 33016Orlando Research Center | Orlando Florida, United States, 32806Progressive Medical Research | Port Orange Florida, United States, 32127Covenant Research | Sarasota Florida, United States, 34240The Villages Research Center | The Villages Florida, United States, 32162Gastrointestinal Specialists of Georgia | Marietta Georgia, United States, 30060East-West Medical Research Institute | Honolulu Hawaii, United States, 96814Chicago Research Center | Chicago Illinois, United States, 60602Northwestern Memorial Physicians Group | Chicago Illinois, United States, 60611Iowa Diabetes Research | West Des Moines Iowa, United States, 50265Iowa Diabetes and Endocrinology Research Center | West Des Moines Iowa, United States, 50266Kansas Medical Clinic - Gastroenterology | Topeka Kansas, United States, 66606L-MARC Research Center | Louisville Kentucky, United States, 40213Rovia Clinical Research | Bastrop Louisiana, United States, 71220Digestive Health Center of Louisiana | Baton Rouge Louisiana, United States, 70809Tandem Clinical Research - New Orleans Area Site | Marrero Louisiana, United States, 70072Clinical Trials of America | West Monroe Louisiana, United States, 71291Gastrointestinal Associates & Endoscopy Center - Flowood | Flowood Mississippi, United States, 39232Southern Therapy and Advanced Research | Jackson Mississippi, United States, 39216Kansas City Research Institute | Kansas City Missouri, United States, 64131Henderson Research Center | Henderson Nevada, United States, 89052Clarity Clinical Research | East Syracuse New York, United States, 13057Velocity Clinical Research | East Syracuse New York, United States, 13057Mount Sinai Health System | New York New York, United States, 10029Duke University Medical Center | Durham North Carolina, United States, 27710Cumberland Research Associates | Fayetteville North Carolina, United States, 28304Lucas Research | Moorehead City North Carolina, United States, 28557Diabetes and Endocrinology Consultants | Morehead City North Carolina, United States, 28557Aventiv Research Columbus | Columbus Ohio, United States, 43213Awasty Research Network | Marion Ohio, United States, 43302Innovative Clinical Research | Clarksville Tennessee, United States, 37040Gastro One - Germantown Office - Wolf Park Drive | Germantown Tennessee, United States, 38138Pinnacle Clinical Research - Austin | Austin Texas, United States, 78746The Liver Institute At Methodist Dallas | Dallas Texas, United States, 75203Dallas Research Center | Dallas Texas, United States, 75234Liver Center of Texas | Dallas Texas, United States, 75234South Texas Research Institute | Edinburg Texas, United States, 78539Texas Digestive Disease Consultants | Fort Worth Texas, United States, 76104Liver Associates of Texas | Houston Texas, United States, 77030Doctor's Hospital at Renaissance | McAllen Texas, United States, 78504Plano Research Center | Plano Texas, United States, 75093Texas Liver Institute/American Research Corporation | San Antonio Texas, United States, 78215Pinnacle Clinical Research - San Antonio | San Antonio Texas, United States, 78229San Antonio Research Center | San Antonio Texas, United States, 78229Texas Digestive Disease Consultants - San Marcos | San Marcos Texas, United States, 78666Impact Research Institute | Waco Texas, United States, 76710Texas Digestive Disease Consultants - Bay Area Houston Endoscopy Center | Webster Texas, United States, 77598Wasatch Peak Family Practice | Layton Utah, United States, 84041Salt Lake City Research Center | Murray Utah, United States, 84123Bon Secours Liver Institute of Richmond | Richmond Virginia, United States, 23226National Clinical Research - Richmond | Richmond Virginia, United States, 23294Virginia Commonwealth University School of Medicine | Richmond Virginia, United States, 23298Liver Institute Northwest | Seattle Washington, United States, 98105Fundacion de Investigacion de Diego | San Juan , Puerto Rico,
Investigators
Study Director: Tom Hare, MD, Madrigal Pharmaceuticals, Inc.