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Non-Alcoholic Fatty Liver DiseasePhase 3MAESTRO-NAFLD1NCT04197479

A Phase 3 Study to Evaluate Safety and Biomarkers of Resmetirom (MGL-3196) in Non Alcoholic Fatty Liver Disease Patients

A Phase 3 study testing Resmetirom in people with Non-Alcoholic Fatty Liver Disease, run by Madrigal Pharmaceuticals, Inc. at 77 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

A double-blind placebo controlled randomized Phase 3 study to evaluate the safety and tolerability of once-daily, oral administration of 80 or 100 mg resmetirom versus matching placebo. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-Alcoholic Fatty Liver Disease
What is being tested?
Resmetirom
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
1,343 participants
Where
77 sitesin 2 countries
Study dates
16 Dec 2019to 6 Jan 2023
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Must be willing to participate in the study and provide written informed consent.
  • Male and female adults ≥18 years of age.
  • Suspected or confirmed diagnosis of NASH or NAFLD (presumed NASH):
  • Fibroscan with kPa ≥5.5 and <8.5; CAP ≥280 dB.m-1 OR
  • MRE ≥2 and <4.0; MRI-PDFF ≥8% liver fat consistent with steatosis and fibrosis stage ≥1 and <4. OR
  • Recent liver biopsy (within past 2 years) documenting NASH/NAFLD with steatosis showing one of the following:
Show all 20Show fewer
  • NAS ≥4, steatosis ≥1, fibrosis stage 0 or F1A/1C with PRO-C3 <14
  • NAS <4, steatosis ≥1, with fibrosis stage ≤3
  • NAS ≥4, steatosis ≥1, fibrosis stage ≤3 without ballooning
  • NOTE: Since the completion of enrollment of the double-blind arms, patients meeting all other criteria who have a liver biopsy result from MGL-3196-11 with the following may be enrolled in the open-label active treatment arm of MGL-3196-14 (100 mg dose):
  • NAS = 3, steatosis 1, ballooning 1, inflammation 1 with F2 or F3
  • NAS = 3, ballooning 0 with F2 or F3
  • For the compensated NASH cirrhosis arm, eligible patients must have compensated NASH cirrhosis diagnosed by liver biopsy showing NASH with F4 stage fibrosis (either historic or recent biopsy) or a historic biopsy with NASH F2-F3 fibrosis with subsequent progression to NASH cirrhosis as diagnosed by an expert hepatologist/gastroenterologist.
  • Compensated NASH cirrhosis at screening and baseline includes
  • Child Pugh-A (score 5-6) ( may have either mild hepatic encephalopathy OR mild diuretic responsive ascites OR albumin < 3.5 and ≥ 3.2 (not any two of these, unless explained by Gilbert's Syndrome or non-hepatic causes)).
  • MELD < 12 at screening/baseline unless MELD ≥ 12 based on non-cirrhotic parameters (e.g., elevated INR due to anticoagulation, bilirubin elevation due to documented Gilbert's Syndrome, elevated creatine due to renal disease (non-hepatic)).
  • Albumin ≥ 3.2.
  • Bilirubin < 2 (unless documented Gilbert's Syndrome).
  • MRI-PDFF fat fraction ≥8% obtained during the Screening Period (baseline MRI-PDFF) or a historic MRI-PDFF ≤8 weeks old at the time of randomization.
  • Stable dyslipidemia therapy for ≥30 days prior to randomization.

Who cannot join

  • History of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to Screening.
  • Regular use of drugs historically associated with NAFLD.
  • History of bariatric surgery or intestinal bypass surgery within the 5 years prior to randomization or planned during the conduct of the study.
  • Weight gain or loss ≥5% total body weight within 12 weeks prior to randomization.
  • HbA1c >9.0%.
  • Glucagon-like peptide 1 [GLP-1] agonist therapy or high dose vitamin E (>400 IU/day) unless stable for 24 weeks prior to biopsy.
Show all 18Show fewer
  • Presence of cirrhosis on liver biopsy defined as stage 4 fibrosis.
  • Diagnosis of hepatocellular carcinoma (HCC).
  • Model for End-stage Liver Disease (MELD) score ≥12, as determined at Screening, unless due to therapeutic anti coagulation or Gilbert syndrome.
  • Hepatic decompensation.
  • Chronic liver diseases.
  • Has an active autoimmune disease.
  • Serum ALT >250 U/L.
  • History of biliary diversion.
  • Uncontrolled hypertension (either treated or untreated).
  • Active, serious medical disease with a likely life expectancy <2 years.
  • Participation in an investigational new drug trial in the 60 days or 5 half-lives, whichever is longer, prior to randomization.
  • 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.

Trial locations and contacts

77 sites in 2 countries.

77 sites in 2 countries

United States76 sites

  • Pinnacle Clinical Research - Austin

    Austin, Texas, 78746

  • Digestive Health Center of Louisiana

    Baton Rouge, Louisiana, 70809

  • Northeast Clinical Research Center

    Bethlehem, Pennsylvania, 18017

  • Central Research Associates

    Birmingham, Alabama, 35205

  • Excel Medical Clinical Trials

    Boca Raton, Florida, 33434

  • Arizona Liver Health - Chandler

    Chandler, Arizona, 85224

  • East Valley Family Physicians

    Chandler, Arizona, 85224

  • Chicago Research Center

    Chicago, Illinois, 60602

  • Northwestern Memorial Physicians Group

    Chicago, Illinois, 60611

  • Platinum - Sterling Research Group - Springdale

    Cincinnati, Ohio, 45246

  • Premier Medical Group - Clarksville - Dunlop Lane

    Clarksville, Tennessee, 37040

  • Aventiv Research Columbus

    Columbus, Ohio, 43213

  • The Liver Institute At Methodist Dallas

    Dallas, Texas, 75203

  • Dallas Research Center

    Dallas, Texas, 75234

  • Liver Center of Texas

    Dallas, Texas, 75234

  • Texas Digestive Disease Consultants - Dallas - Baylor University Medical Center Gaston Ave

    Dallas, Texas, 75246

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Clarity Clinical Research

    East Syracuse, New York, 13057

  • South Texas Research Institute

    Edinburg, Texas, 78539

  • South Denver Gastroenterology - Swedish Medical Center Office

    Englewood, Colorado, 80113

  • Cumberland Research Associates

    Fayetteville, North Carolina, 28304

  • Gastrointestinal Associates & Endoscopy Center - Flowood

    Flowood, Mississippi, 39232

  • Texas Digestive Disease Consultants - Forth Worth - Downtown

    Fort Worth, Texas, 76104

  • Fresno Clinical Research Center

    Fresno, California, 93720

  • Gastro One - Germantown Office - Wolf Park Drive

    Germantown, Tennessee, 38138

  • The Institute For Liver Health - Glendale

    Glendale, Arizona, 85306

  • Velocity Clinical Research, Hallandale Beach (MD Clinical)

    Hallandale, Florida, 33009

  • Henderson Research Center

    Henderson, Nevada, 89052

  • Floridian Clinical Research

    Hialeah, Florida, 33016

  • East-West Medical Research Institute

    Honolulu, Hawaii, 96814

  • Liver Associates of Texas

    Houston, Texas, 77030

  • National Research Institute - Huntington Park

    Huntington Park, California, 90255

  • Nature Coast Clinical Research - Inverness

    Inverness, Florida, 34452

  • Southern Therapy and Advanced Research

    Jackson, Mississippi, 39216

  • Jacksonville Center for Clinical Research

    Jacksonville, Florida, 32216

  • Kansas City Research Institute

    Kansas City, Missouri, 64131

  • Florida Research Institute

    Lakewood Rch, Florida, 34211

  • Wasatch Peak Family Practice

    Layton, Utah, 84041

  • Ruane Clinical Research Group

    Los Angeles, California, 90036

  • National Research Institute - Los Angeles

    Los Angeles, California, 90057

  • L-MARC Research Center

    Louisville, Kentucky, 40213

  • Gastrointestinal Specialists of Georgia

    Marietta, Georgia, 30060

  • Awasty Research Network

    Marion, Ohio, 43302

  • Tandem Clinical Research - New Orleans Area Site

    Marrero, Louisiana, 70072

  • Doctor's Hospital at Renaissance

    McAllen, Texas, 78504

  • Arizona - Desert Clinical Research

    Mesa, Arizona, 85213

  • Miami Dade Medical Research Institute

    Miami, Florida, 33176

  • Catalina Research Institute

    Montclair, California, 91763

  • Diabetes and Endocrinology Consultants

    Morehead City, North Carolina, 28557

  • Salt Lake City Research Center

    Murray, Utah, 84123

  • Mount Sinai Health System

    New York, New York, 10029

  • Arkansas Gastroenterology

    North Little Rock, Arkansas, 72117

  • Orlando Research Center

    Orlando, Florida, 32806

  • National Research Institute - Panorama City

    Panorama City, California, 91402

  • Plano Research Center

    Plano, Texas, 75093

  • Progressive Medical Research

    Port Orange, Florida, 32127

  • Alliance Clinical Research

    Poway, California, 92064

  • Bon Secours Liver Institute of Richmond

    Richmond, Virginia, 23226

  • National Clinical Research - Richmond

    Richmond, Virginia, 23294

  • Virginia Commonwealth University School of Medicine

    Richmond, Virginia, 23298

  • Texas Liver Institute/American Research Corporation

    San Antonio, Texas, 78215

  • Pinnacle Clinical Research - San Antonio

    San Antonio, Texas, 78229

  • San Antonio Research Center

    San Antonio, Texas, 78229

  • Texas Digestive Disease Consultants - San Marcos

    San Marcos, Texas, 78666

  • Covenant Research

    Sarasota, Florida, 34240

  • Liver Institute Northwest

    Seattle, Washington, 98105

  • The Villages Research Center

    The Villages, Florida, 32162

  • Kansas Medical Clinic - Gastroenterology

    Topeka, Kansas, 66606

  • The Institute For Liver Health - Tucson

    Tucson, Arizona, 85711

  • Adobe Gastroenterology

    Tucson, Arizona, 85712

  • Texas Digestive Disease Consultants - Bay Area Houston Endoscopy Center

    Webster, Texas, 77598

  • Iowa Diabetes Research

    West Des Moines, Iowa, 50265

  • San Fernando Valley Health Institute

    West Hills, California, 91307

  • Clinical Trials of America

    West Monroe, Louisiana, 71291

  • TMA - Wilmington Gastroenterology Accociates

    Wilmington, North Carolina, 28403

  • Huron Gastroenterology

    Ypsilanti, Michigan, 48197

Other trials in United States

Puerto Rico1 site

  • Fundacion de Investigacion de Diego

    San Juan

Other trials in Puerto Rico

About this study

Official title: A 52-Week, Phase 3 Study to Evaluate Safety and Biomarkers of Resmetirom (MGL-3196) in Patients With Non-alcoholic Fatty Liver Disease (NAFLD) (MAESTRO-NAFLD-1)

A double-blind placebo controlled randomized Phase 3 study to evaluate the safety and tolerability of once-daily, oral administration of 80 or 100 mg resmetirom versus matching placebo. At least 100 patients will be enrolled in a 100 mg open-label arm and will include a special safety population (eg, patients with compensated NASH cirrhosis).

Being tested
Placebo, Resmetirom
Keywords
NAFLD, NASH, Hyperlipidemia, Resmetirom, Thyroid hormone receptor beta, Hepatic, Fibrosis, NASH resolution, Thyroid hormone receptor agonist, Cardiovascular, Dyslipidemia, Fatty liver disease, Nonalcoholic steatohepatitis, Cirrhosis
Medical subject headings
Non-alcoholic Fatty Liver Disease, Hyperlipidemias, Thyroid Hormone Resistance Syndrome, Fibrosis, Dyslipidemias

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PlaceboDrug

    Matching tablets

  • ResmetiromDrug

    Also called MGL-3196

    Tablet

Study groups in NCT04197479
Study groupRoleWhat they receive
Open label: resmetiromExperimental100 mg daily
Receives: Drug: Resmetirom
Double blinded: matching placeboPlacebo comparatorPlacebo daily
Receives: Drug: Placebo
Double blinded: resmetirom 80 mgExperimental80 mg daily
Receives: Drug: Resmetirom
Double blinded: resmetirom 100 mgExperimental100 mg daily
Receives: Drug: Resmetirom

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The effect of once daily, oral administration of 80 or 100 mg resmetirom versus placebo on the incidence of adverse events.

    The effect of once daily, oral administration of 80 or 100 mg resmetirom versus placebo on the incidence of adverse events.

    Measured: 52 weeks

Secondary outcomes (6)

  1. The effect of once daily, oral administration of 80 or 100 mg resmetirom versus placebo on the percent change in low density lipoprotein C (LDL-C) from baseline to Week 24

    The effect of once daily, oral administration of 80 or 100 mg resmetirom versus placebo on the percent change in low density lipoprotein C (LDL-C) from baseline to Week 24

    Measured: 24 weeks

  2. The effect of once daily, oral administration of 80 or 100 mg resmetirom versus placebo on the percent change in apolipoprotein B (ApoB) from baseline to Week 24

    The effect of once daily, oral administration of 80 or 100 mg resmetirom versus placebo on the percent change in apolipoprotein B (ApoB) from baseline to Week 24

    Measured: 24 weeks

  3. The effect of once daily, oral administration of 80 or 100 mg resmetirom versus placebo on the percent change in hepatic fat fraction as determined by MRI-PDFF from baseline to Week 16.

    The effect of once daily, oral administration of 80 or 100 mg resmetirom versus placebo on the percent change in hepatic fat fraction as determined by MRI-PDFF from baseline to Week 16.

    Measured: 16 weeks

  4. The effect of once daily, oral administration of 80 or 100 mg resmetirom versus placebo on the percent change in triglycerides (TGs) from baseline to Week 24 in patients with baseline TG > 150 mg/dL.

    The effect of once daily, oral administration of 80 or 100 mg resmetirom versus placebo on the percent change in triglycerides (TGs) from baseline to Week 24 in patients with baseline TG > 150 mg/dL.

    Measured: 24 weeks

  5. The effect of once daily, oral administration of 80 or 100 mg resmetirom versus placebo after 52 weeks on FibroScan controlled attenuation parameter (CAP)

    The effect of once daily, oral administration of 80 or 100 mg resmetirom versus placebo after 52 weeks on FibroScan controlled attenuation parameter (CAP)

    Measured: 52 weeks

  6. The change from baseline to Week 52 in FibroScan vibration controlled transient elastography (kPa)

    The change from baseline to Week 52 in FibroScan vibration controlled transient elastography (VCTE) (kPa) in patients with baseline kPa >/=7.2 and a Week 52 or end of treatment FibroScan (VCTE)

    Measured: 52 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Dec 2019
  2. Study start16 Dec 2019
  3. Primary completion6 Jan 2023
  4. Study completion6 Jan 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
1,343 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04197479
Sponsor's protocol ID
MGL-3196-14
Acronym
MAESTRO-NAFLD1
Status last verified
Aug 2023
First submitted
11 Dec 2019
Last updated
5 Sep 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Younossi ZM, Nader F, Labriola D, Taub R, Racila A, Henry L, Stepanova M. Self-Reported Cognitive Function in Metabolic Dysfunction-associated Steatotic Liver Disease and Metabolic Dysfunction-associated Steatohepatitis: A Post-hoc Analysis of the MAESTRO Resmetirom Trials. J Clin Exp Hepatol. 2026 Jul-Aug;16(4):103531. doi: 10.1016/j.jceh.2026.103531. Epub 2026 Mar 5.

    PubMed 41953252

  • Alkhouri N, McRae MP, Taub R, Hill B, Imperial JC, Kittelson J, Moussa SE, Everson GT. The Cholate Challenge Test Quantified Baseline Functional Heterogeneity and Improvement in Response to Resmetirom in MASH-related Child-Pugh A Cirrhosis. Gastro Hep Adv. 2025 Aug 29;4(10):100785. doi: 10.1016/j.gastha.2025.100785. eCollection 2025.

    PubMed 41142528

  • Harrison SA, Taub R, Neff GW, Lucas KJ, Labriola D, Moussa SE, Alkhouri N, Bashir MR. Resmetirom for nonalcoholic fatty liver disease: a randomized, double-blind, placebo-controlled phase 3 trial. Nat Med. 2023 Nov;29(11):2919-2928. doi: 10.1038/s41591-023-02603-1. Epub 2023 Oct 16.

    PubMed 37845512

  • 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.

    PubMed 37786277

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Resmetirom in people with Non-Alcoholic Fatty Liver Disease, run by Madrigal Pharmaceuticals, Inc. at 77 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 77 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The effect of once daily, oral administration of 80 or 100 mg resmetirom versus placebo on the incidence of adverse events. (time frame: 52 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04197479, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Sep 2023.

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