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

Non-Alcoholic Fatty Liver Disease Clinical Trial

— MAESTRO-NAFLD1  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04197479
• Other study ID #: MGL-3196-14
• Status: Completed
• Phase: Phase 3
• Start date: December 16, 2019
• Est. completion date: January 6, 2023

Study information

• Verified date: August 2023
• Source: Madrigal Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1343
• Est. completion date: January 6, 2023
• Est. primary completion date: January 6, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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)).
• 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.

Exclusion Criteria:

• 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).
• 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.

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• Non-Alcoholic Fatty Liver Disease

Intervention

Drug:
• Placebo
Matching tablets
• Resmetirom
Tablet

Locations

Country	Name	City	State
Puerto Rico	Fundacion de Investigacion de Diego	San Juan
United States	Pinnacle Clinical Research - Austin	Austin	Texas
United States	Digestive Health Center of Louisiana	Baton Rouge	Louisiana
United States	Northeast Clinical Research Center	Bethlehem	Pennsylvania
United States	Central Research Associates	Birmingham	Alabama
United States	Excel Medical Clinical Trials	Boca Raton	Florida
United States	Arizona Liver Health - Chandler	Chandler	Arizona
United States	East Valley Family Physicians	Chandler	Arizona
United States	Chicago Research Center	Chicago	Illinois
United States	Northwestern Memorial Physicians Group	Chicago	Illinois
United States	Platinum - Sterling Research Group - Springdale	Cincinnati	Ohio
United States	Premier Medical Group - Clarksville - Dunlop Lane	Clarksville	Tennessee
United States	Aventiv Research Columbus	Columbus	Ohio
United States	Dallas Research Center	Dallas	Texas
United States	Liver Center of Texas	Dallas	Texas
United States	Texas Digestive Disease Consultants - Dallas - Baylor University Medical Center Gaston Ave	Dallas	Texas
United States	The Liver Institute At Methodist Dallas	Dallas	Texas
United States	Duke University Medical Center	Durham	North Carolina
United States	Clarity Clinical Research	East Syracuse	New York
United States	South Texas Research Institute	Edinburg	Texas
United States	South Denver Gastroenterology - Swedish Medical Center Office	Englewood	Colorado
United States	Cumberland Research Associates	Fayetteville	North Carolina
United States	Gastrointestinal Associates & Endoscopy Center - Flowood	Flowood	Mississippi
United States	Texas Digestive Disease Consultants - Forth Worth - Downtown	Fort Worth	Texas
United States	Fresno Clinical Research Center	Fresno	California
United States	Gastro One - Germantown Office - Wolf Park Drive	Germantown	Tennessee
United States	The Institute For Liver Health - Glendale	Glendale	Arizona
United States	Velocity Clinical Research, Hallandale Beach (MD Clinical)	Hallandale Beach	Florida
United States	Henderson Research Center	Henderson	Nevada
United States	Floridian Clinical Research	Hialeah	Florida
United States	East-West Medical Research Institute	Honolulu	Hawaii
United States	Liver Associates of Texas	Houston	Texas
United States	National Research Institute - Huntington Park	Huntington Park	California
United States	Nature Coast Clinical Research - Inverness	Inverness	Florida
United States	Southern Therapy and Advanced Research	Jackson	Mississippi
United States	Jacksonville Center for Clinical Research	Jacksonville	Florida
United States	Kansas City Research Institute	Kansas City	Missouri
United States	Florida Research Institute	Lakewood Ranch	Florida
United States	Wasatch Peak Family Practice	Layton	Utah
United States	National Research Institute - Los Angeles	Los Angeles	California
United States	Ruane Clinical Research Group	Los Angeles	California
United States	L-MARC Research Center	Louisville	Kentucky
United States	Gastrointestinal Specialists of Georgia	Marietta	Georgia
United States	Awasty Research Network	Marion	Ohio
United States	Tandem Clinical Research - New Orleans Area Site	Marrero	Louisiana
United States	Doctor's Hospital at Renaissance	McAllen	Texas
United States	Arizona - Desert Clinical Research	Mesa	Arizona
United States	Miami Dade Medical Research Institute	Miami	Florida
United States	Catalina Research Institute	Montclair	California
United States	Diabetes and Endocrinology Consultants	Morehead City	North Carolina
United States	Salt Lake City Research Center	Murray	Utah
United States	Mount Sinai Health System	New York	New York
United States	Arkansas Gastroenterology	North Little Rock	Arkansas
United States	Orlando Research Center	Orlando	Florida
United States	National Research Institute - Panorama City	Panorama City	California
United States	Plano Research Center	Plano	Texas
United States	Progressive Medical Research	Port Orange	Florida
United States	Alliance Clinical Research	Poway	California
United States	Bon Secours Liver Institute of Richmond	Richmond	Virginia
United States	National Clinical Research - Richmond	Richmond	Virginia
United States	Virginia Commonwealth University School of Medicine	Richmond	Virginia
United States	Pinnacle Clinical Research - San Antonio	San Antonio	Texas
United States	San Antonio Research Center	San Antonio	Texas
United States	Texas Liver Institute/American Research Corporation	San Antonio	Texas
United States	Texas Digestive Disease Consultants - San Marcos	San Marcos	Texas
United States	Covenant Research	Sarasota	Florida
United States	Liver Institute Northwest	Seattle	Washington
United States	The Villages Research Center	The Villages	Florida
United States	Kansas Medical Clinic - Gastroenterology	Topeka	Kansas
United States	Adobe Gastroenterology	Tucson	Arizona
United States	The Institute For Liver Health - Tucson	Tucson	Arizona
United States	Texas Digestive Disease Consultants - Bay Area Houston Endoscopy Center	Webster	Texas
United States	Iowa Diabetes Research	West Des Moines	Iowa
United States	San Fernando Valley Health Institute	West Hills	California
United States	Clinical Trials of America	West Monroe	Louisiana
United States	TMA - Wilmington Gastroenterology Accociates	Wilmington	North Carolina
United States	Huron Gastroenterology	Ypsilanti	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Madrigal Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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	24 weeks
Secondary	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	24 weeks
Secondary	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.	16 weeks
Secondary	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.	24 weeks
Secondary	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)	52 weeks
Secondary	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)	52 weeks