Clinical trial NCT04951219: 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)
Official title: A 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 type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
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
Lead sponsor: Madrigal Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2021-07-06
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)


Eligibility criteria: 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.

Primary outcomes:
measure: The effect of once daily, oral administration of resmetirom on the incidence of adverse events.
timeFrame: 52 weeks
Secondary outcomes:
measure: Percent change in the hepatic fat fraction as determined by MRI-PDFF from baseline
timeFrame: 16 weeks
measure: Percent change in the hepatic fat fraction as determined by MRI-PDFF from baseline
timeFrame: 52 weeks
measure: Percent change in LDL-C from baseline
timeFrame: 28 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Central Research Associates
state: Alabama
city: Chandler
country: United States
facility: Arizona Liver Health - Chandler
state: Arizona
city: Chandler
country: United States
facility: East Valley Family Physicians
state: Arizona
city: Glendale
country: United States
facility: The Institute For Liver Health - Glendale
state: Arizona
city: Tucson
country: United States
facility: The Institute For Liver Health - Tucson
state: Arizona
city: Tucson
country: United States
facility: Adobe Gastroenterology
state: Arizona
city: North Little Rock
country: United States
facility: Arkansas Gastroenterology
state: Arkansas
city: Fresno
country: United States
facility: Fresno Clinical Research Center
state: California
city: Huntington Park
country: United States
facility: National Research Institute - Huntington Park
state: California
city: Los Angeles
country: United States
facility: Ruane Clinical Research Group
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: National Research Institute - Los Angeles
state: California
city: Montclair
country: United States
facility: Catalina Research Institute
state: California
city: Panorama City
country: United States
facility: National Research Institute - Panorama City
state: California
city: West Hills
country: United States
facility: San Fernando Valley Health Institute
state: California
city: Englewood
country: United States
facility: South Denver Gastroenterology - Swedish Medical Center Office
state: Colorado
city: Boca Raton
country: United States
facility: Excel Medical Clinical Trials
state: Florida
city: Fort Myers
country: United States
facility: Covenant Research
state: Florida
city: Hallandale Beach
country: United States
facility: Velocity Clinical Research, Hallandale Beach (MD Clinical)
state: Florida
city: Hialeah
country: United States
facility: Floridian Clinical Research
state: Florida
city: Inverness
country: United States
facility: Nature Coast Clinical Research - Inverness
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: Lakewood Ranch
country: United States
facility: Florida Research Institute
state: Florida
city: Miami
country: United States
facility: Miami Dade Medical Research Institute
state: Florida
city: Orlando
country: United States
facility: Orlando Research Center
state: Florida
city: Port Orange
country: United States
facility: Progressive Medical Research
state: Florida
city: Sarasota
country: United States
facility: Covenant Research
state: Florida
city: The Villages
country: United States
facility: The Villages Research Center
state: Florida
city: Marietta
country: United States
facility: Gastrointestinal Specialists of Georgia
state: Georgia
city: Honolulu
country: United States
facility: East-West Medical Research Institute
state: Hawaii
city: Chicago
country: United States
facility: Chicago Research Center
state: Illinois
city: Chicago
country: United States
facility: Northwestern Memorial Physicians Group
state: Illinois
city: West Des Moines
country: United States
facility: Iowa Diabetes Research
state: Iowa
city: Topeka
country: United States
facility: Kansas Medical Clinic - Gastroenterology
state: Kansas
city: Louisville
country: United States
facility: L-MARC Research Center
state: Kentucky
city: Baton Rouge
country: United States
facility: Digestive Health Center of Louisiana
state: Louisiana
city: Marrero
country: United States
facility: Tandem Clinical Research - New Orleans Area Site
state: Louisiana
city: West Monroe
country: United States
facility: Clinical Trials of America
state: Louisiana
city: Flowood
country: United States
facility: Gastrointestinal Associates & Endoscopy Center - Flowood
state: Mississippi
city: Jackson
country: United States
facility: Southern Therapy and Advanced Research
state: Mississippi
city: Kansas City
country: United States
facility: Kansas City Research Institute
state: Missouri
city: Henderson
country: United States
facility: Henderson Research Center
state: Nevada
city: East Syracuse
country: United States
facility: Clarity Clinical Research
state: New York
city: New York
country: United States
facility: Mount Sinai Health System
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Fayetteville
country: United States
facility: Cumberland Research Associates
state: North Carolina
city: Morehead City
country: United States
facility: Diabetes and Endocrinology Consultants
state: North Carolina
city: Cincinnati
country: United States
facility: Platinum - Sterling Research Group - Springdale
state: Ohio
city: Columbus
country: United States
facility: Aventiv Research Columbus
state: Ohio
city: Marion
country: United States
facility: Awasty Research Network
state: Ohio
city: Clarksville
country: United States
facility: Premier Medical Group - Clarksville - Dunlop Lane
state: Tennessee
city: Germantown
country: United States
facility: Gastro One - Germantown Office - Wolf Park Drive
state: Tennessee
city: Austin
country: United States
facility: Pinnacle Clinical Research - Austin
state: Texas
city: Dallas
country: United States
facility: The Liver Institute At Methodist Dallas
state: Texas
city: Dallas
country: United States
facility: Dallas Research Center
state: Texas
city: Dallas
country: United States
facility: Liver Center of Texas
state: Texas
city: Edinburg
country: United States
facility: South Texas Research Institute
state: Texas
city: Fort Worth
country: United States
facility: Texas Digestive Disease Consultants
state: Texas
city: Houston
country: United States
facility: Liver Associates of Texas
state: Texas
city: McAllen
country: United States
facility: Doctor's Hospital at Renaissance
state: Texas
city: Plano
country: United States
facility: Plano Research Center
state: Texas
city: San Antonio
country: United States
facility: Texas Liver Institute/American Research Corporation
state: Texas
city: San Antonio
country: United States
facility: Pinnacle Clinical Research - San Antonio
state: Texas
city: San Antonio
country: United States
facility: San Antonio Research Center
state: Texas
city: San Marcos
country: United States
facility: Texas Digestive Disease Consultants - San Marcos
state: Texas
city: Waco
country: United States
facility: Impact Research Institute
state: Texas
city: Webster
country: United States
facility: Texas Digestive Disease Consultants - Bay Area Houston Endoscopy Center
state: Texas
city: Layton
country: United States
facility: Wasatch Peak Family Practice
state: Utah
city: Murray
country: United States
facility: Salt Lake City Research Center
state: Utah
city: Richmond
country: United States
facility: Bon Secours Liver Institute of Richmond
state: Virginia
city: Richmond
country: United States
facility: National Clinical Research - Richmond
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University School of Medicine
state: Virginia
city: Seattle
country: United States
facility: Liver Institute Northwest
state: Washington
city: San Juan
country: Puerto Rico
facility: Fundacion de Investigacion de Diego
Study officials:
affiliation: Madrigal Pharmaceuticals, Inc.
name: Rebecca Taub, MD
role: STUDY_DIRECTOR
References: