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

NCT04197479 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: MGL-3196-14
• Study Type: interventional
• Target: 1,343
• Locations: 2 countries
• Sites: 77

Brief 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. 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).

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; Cirrhosis

Outcome Measures

Primary Outcomes (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.

  52 weeks

Secondary Outcomes (6)

• 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

  24 weeks

• 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

  24 weeks

• 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.

  16 weeks

• 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.

  24 weeks

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

  52 weeks

Study Arms (4)

Open label: resmetirom

EXPERIMENTAL

100 mg daily

Drug: Resmetirom

Double blinded: matching placebo

PLACEBO COMPARATOR

Placebo daily

Drug: Placebo

Double blinded: resmetirom 80 mg

EXPERIMENTAL

80 mg daily

Drug: Resmetirom

Double blinded: resmetirom 100 mg

EXPERIMENTAL

100 mg daily

Drug: Resmetirom

Interventions

Placebo DRUG

Matching tablets

Double blinded: matching placebo

Resmetirom DRUG

Tablet

Also known as: MGL-3196

Double blinded: resmetirom 100 mg; Double blinded: resmetirom 80 mg; Open label: resmetirom

Eligibility Criteria

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

You may qualify if:

• 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:
• 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)).

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• Madrigal Pharmaceuticals, Inc.: lead

Study Sites (77)

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

Arizona - Desert Clinical Research

Mesa, Arizona, 85213, 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

National Research Institute - Los Angeles

Los Angeles, California, 90057, United States

Location

Catalina Research Institute

Montclair, California, 91763, United States

Location

National Research Institute - Panorama City

Panorama City, California, 91402, United States

Location

Alliance Clinical Research

Poway, California, 92064, 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

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

Miami Dade Medical Research Institute

Miami, Florida, 33176, 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

Huron Gastroenterology

Ypsilanti, Michigan, 48197, 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

TMA - Wilmington Gastroenterology Accociates

Wilmington, North Carolina, 28403, United States

Location

Platinum - Sterling Research Group - Springdale

Cincinnati, Ohio, 45246, United States

Location

Aventiv Research Columbus

Columbus, Ohio, 43213, United States

Location

Awasty Research Network

Marion, Ohio, 43302, United States

Location

Northeast Clinical Research Center

Bethlehem, Pennsylvania, 18017, 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

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

Dallas, Texas, 75246, United States

Location

South Texas Research Institute

Edinburg, Texas, 78539, United States

Location

Texas Digestive Disease Consultants - Forth Worth - Downtown

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

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 (3)

• 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.

  PMID: 41142528 DERIVED

• 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.

  PMID: 37845512 DERIVED

• 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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2019
• First Posted: December 13, 2019
• Study Start: December 16, 2019
• Primary Completion: January 6, 2023
• Study Completion: January 6, 2023
• Last Updated: September 5, 2023

Record last verified: 2023-08

Locations

PR (1); US (76)