A Phase 3 Study to Evaluate Safety and Biomarkers of Resmetirom (MGL-3196) in Non Alcoholic Fatty Liver Disease Patients
- Conditions
- Non-Alcoholic Fatty Liver Disease
- Interventions
- Drug: Placebo
- Registration Number
- NCT04197479
- Lead Sponsor
- Madrigal Pharmaceuticals, Inc.
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1343
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Must be willing to participate in the study and provide written informed consent.
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Male and female adults ≥18 years of age.
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Suspected or confirmed diagnosis of NASH or NAFLD (presumed NASH):
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Fibroscan with kPa ≥5.5 and <8.5; CAP ≥280 dB.m-1 OR
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MRE ≥2 and <4.0; MRI-PDFF ≥8% liver fat consistent with steatosis and fibrosis stage ≥1 and <4. OR
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Recent liver biopsy (within past 2 years) documenting NASH/NAFLD with steatosis showing one of the following:
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NAS ≥4, steatosis ≥1, fibrosis stage 0 or F1A/1C with PRO-C3 <14
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NAS <4, steatosis ≥1, with fibrosis stage ≤3
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NAS ≥4, steatosis ≥1, fibrosis stage ≤3 without ballooning
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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
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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.
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-
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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).
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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.
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Stable dyslipidemia therapy for ≥30 days prior to randomization.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Double blinded: matching placebo Placebo Placebo daily Open label: resmetirom Resmetirom 100 mg daily Double blinded: resmetirom 100 mg Resmetirom 100 mg daily Double blinded: resmetirom 80 mg Resmetirom 80 mg daily
- Primary Outcome Measures
Name Time Method The effect of once daily, oral administration of 80 or 100 mg resmetirom versus placebo on the incidence of adverse events. 52 weeks The effect of once daily, oral administration of 80 or 100 mg resmetirom versus placebo on the incidence of adverse events.
- Secondary Outcome Measures
Name Time Method 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 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 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 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 after 52 weeks on FibroScan controlled attenuation parameter (CAP) 52 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)
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 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 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 hepatic fat fraction as determined by MRI-PDFF from baseline to Week 16.
The change from baseline to Week 52 in FibroScan vibration controlled transient elastography (kPa) 52 weeks 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)
Trial Locations
- Locations (77)
Northwestern Memorial Physicians Group
🇺🇸Chicago, Illinois, United States
Floridian Clinical Research
🇺🇸Hialeah, Florida, United States
Dallas Research Center
🇺🇸Dallas, Texas, United States
Gastrointestinal Specialists of Georgia
🇺🇸Marietta, Georgia, United States
Clarity Clinical Research
🇺🇸East Syracuse, New York, United States
The Liver Institute At Methodist Dallas
🇺🇸Dallas, Texas, United States
East Valley Family Physicians
🇺🇸Chandler, Arizona, United States
Arizona Liver Health - Chandler
🇺🇸Chandler, Arizona, United States
Arizona - Desert Clinical Research
🇺🇸Mesa, Arizona, United States
Chicago Research Center
🇺🇸Chicago, Illinois, United States
Tandem Clinical Research - New Orleans Area Site
🇺🇸Marrero, Louisiana, United States
Miami Dade Medical Research Institute
🇺🇸Miami, Florida, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Liver Associates of Texas
🇺🇸Houston, Texas, United States
Pinnacle Clinical Research - San Antonio
🇺🇸San Antonio, Texas, United States
San Antonio Research Center
🇺🇸San Antonio, Texas, United States
Liver Institute Northwest
🇺🇸Seattle, Washington, United States
South Denver Gastroenterology - Swedish Medical Center Office
🇺🇸Englewood, Colorado, United States
Kansas Medical Clinic - Gastroenterology
🇺🇸Topeka, Kansas, United States
Central Research Associates
🇺🇸Birmingham, Alabama, United States
The Institute For Liver Health - Glendale
🇺🇸Glendale, Arizona, United States
Arkansas Gastroenterology
🇺🇸North Little Rock, Arkansas, United States
The Institute For Liver Health - Tucson
🇺🇸Tucson, Arizona, United States
Fresno Clinical Research Center
🇺🇸Fresno, California, United States
Ruane Clinical Research Group
🇺🇸Los Angeles, California, United States
National Research Institute - Huntington Park
🇺🇸Huntington Park, California, United States
National Research Institute - Los Angeles
🇺🇸Los Angeles, California, United States
Catalina Research Institute
🇺🇸Montclair, California, United States
National Research Institute - Panorama City
🇺🇸Panorama City, California, United States
Alliance Clinical Research
🇺🇸Poway, California, United States
San Fernando Valley Health Institute
🇺🇸West Hills, California, United States
Excel Medical Clinical Trials
🇺🇸Boca Raton, Florida, United States
Velocity Clinical Research, Hallandale Beach (MD Clinical)
🇺🇸Hallandale Beach, Florida, United States
Jacksonville Center for Clinical Research
🇺🇸Jacksonville, Florida, United States
Nature Coast Clinical Research - Inverness
🇺🇸Inverness, Florida, United States
Progressive Medical Research
🇺🇸Port Orange, Florida, United States
Florida Research Institute
🇺🇸Lakewood Ranch, Florida, United States
Covenant Research
🇺🇸Sarasota, Florida, United States
The Villages Research Center
🇺🇸The Villages, Florida, United States
Iowa Diabetes Research
🇺🇸West Des Moines, Iowa, United States
Huron Gastroenterology
🇺🇸Ypsilanti, Michigan, United States
Clinical Trials of America
🇺🇸West Monroe, Louisiana, United States
Southern Therapy and Advanced Research
🇺🇸Jackson, Mississippi, United States
Gastrointestinal Associates & Endoscopy Center - Flowood
🇺🇸Flowood, Mississippi, United States
Henderson Research Center
🇺🇸Henderson, Nevada, United States
Mount Sinai Health System
🇺🇸New York, New York, United States
Cumberland Research Associates
🇺🇸Fayetteville, North Carolina, United States
Diabetes and Endocrinology Consultants
🇺🇸Morehead City, North Carolina, United States
TMA - Wilmington Gastroenterology Accociates
🇺🇸Wilmington, North Carolina, United States
Platinum - Sterling Research Group - Springdale
🇺🇸Cincinnati, Ohio, United States
Awasty Research Network
🇺🇸Marion, Ohio, United States
Northeast Clinical Research Center
🇺🇸Bethlehem, Pennsylvania, United States
Aventiv Research Columbus
🇺🇸Columbus, Ohio, United States
Premier Medical Group - Clarksville - Dunlop Lane
🇺🇸Clarksville, Tennessee, United States
Gastro One - Germantown Office - Wolf Park Drive
🇺🇸Germantown, Tennessee, United States
South Texas Research Institute
🇺🇸Edinburg, 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
Doctor's Hospital at Renaissance
🇺🇸McAllen, Texas, United States
Plano Research Center
🇺🇸Plano, 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
Texas Digestive Disease Consultants - Bay Area Houston Endoscopy Center
🇺🇸Webster, Texas, United States
Wasatch Peak Family Practice
🇺🇸Layton, Utah, United States
Salt Lake City Research Center
🇺🇸Murray, Utah, United States
Fundacion de Investigacion de Diego
🇵🇷San Juan, Puerto Rico
Texas Digestive Disease Consultants - Forth Worth - Downtown
🇺🇸Fort Worth, Texas, United States
Digestive Health Center of Louisiana
🇺🇸Baton Rouge, Louisiana, United States
Orlando Research Center
🇺🇸Orlando, Florida, United States
East-West Medical Research Institute
🇺🇸Honolulu, Hawaii, United States
Kansas City Research Institute
🇺🇸Kansas City, Missouri, United States
Pinnacle Clinical Research - Austin
🇺🇸Austin, Texas, United States
National Clinical Research - Richmond
🇺🇸Richmond, Virginia, United States
Virginia Commonwealth University School of Medicine
🇺🇸Richmond, Virginia, United States
L-MARC Research Center
🇺🇸Louisville, Kentucky, United States
Bon Secours Liver Institute of Richmond
🇺🇸Richmond, Virginia, United States
Adobe Gastroenterology
🇺🇸Tucson, Arizona, United States