A Study to Evaluate the Effect of Resmetirom on Clinical Outcomes in Patients With Well-compensated NASH Cirrhosis
Study Details
Study Description
Brief Summary
This study will determine the effect of oral 80 mg resmetirom administered once daily on participants with well-compensated non-alcoholic steatohepatitis (NASH) cirrhosis by measuring the time to experiencing a Composite Clinical Outcome event.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Detailed Description
This is a multi-national, multicenter, double-blind, randomized, placebo-controlled study in participants with well-compensated NASH cirrhosis. Participants will be randomized 3:1 in a blinded manner to receive 80 mg resmetirom or matching placebo given orally once daily in the morning for the duration of the study and until the required number of Composite Clinical Outcome events are achieved. Composite Clinical Outcome events are defined as any of the following: all-cause mortality, liver transplant, and significant hepatic events, including potential hepatic decompensation events (ascites, hepatic encephalopathy, or gastroesophageal variceal hemorrhage), and confirmed increase of Model for End-stage Liver Disease (MELD) score from <12 to ≥15. The study comprises an up to 60-day screening period and an approximately 3-year treatment period.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Resmetirom
|
Drug: Resmetirom
Randomized 80 mg resmetirom or matching placebo
|
| Placebo Comparator: Placebo
|
Drug: Resmetirom
Randomized 80 mg resmetirom or matching placebo
|
Outcome Measures
Primary Outcome Measures
- Incidence Of adjudicated Composite Clinical Outcome event [Baseline up to Month 36]
Any event of all-cause mortality, liver transplant, ascites, hepatic encephalopathy, gastroesophageal variceal hemorrhage, and confirmed increase of MELD score from ,12 to .>/= 15 due to liver disease
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Definitive (by histologic documentation) or probable NASH as causative agent for cirrhosis, following a modified version of the NASH Cirrhosis: Liver Forum Consensus Definitions for Clinical Trials.
-
NASH cirrhosis on most recent biopsy (within last 5 years) which is estimated to be approximately 70% of the study population
-
historical biopsy shows NASH with significant fibrosis, now with progression to cirrhosis based on clinical diagnosis, which is estimated to be approximately 20% of the study population
-
historical biopsy shows NASH with steatosis, now with progression to cirrhosis based on clinical diagnosis, which is estimated to be approximately 10% of the study population
-
Well-compensated NASH cirrhosis at screening and baseline with Child-Pugh A (score of 5-6) (no history of hepatic decompensation event).
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At least 3 metabolic risk factors
-
Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) that is obtained during the Screening period or a historic MRI-PDFF at ≤8 weeks old at the time of randomization with no weight change ≥5% weight change in that interval.
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MRE ≥4.2 where MRE is available.
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Enhanced liver function (ELF) ≥9.8, only if MRE is unavailable or contraindicated.
Exclusion Criteria:
-
Participants with a chronic liver diseases other than NASH cirrhosis, such as primary biliary cholangitis, primary sclerosing cholangitis, Hepatitis B positive, Hepatitis C, history or evidence of current active autoimmune hepatitis, history or evidence of Wilson's disease, history or evidence of alpha-1-antitrypsin deficiency, history or evidence of genetic hemochromatosis (hereditary, primary), evidence of drug-induced liver disease, as defined on the basis of typical exposure and history, known bile duct obstruction, or suspected or confirmed liver cancer, are excluded.
-
Participants with MELD score ≥12 due to liver disease are excluded.
-
Participants with a history of hepatic decompensation or impairment are excluded.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Arkansas Gastroenterology | North Little Rock | Arkansas | United States | 72117 |
Sponsors and Collaborators
- Madrigal Pharmaceuticals, Inc.
Investigators
- Study Director: Thomas Hare, VP, Clinical Research
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- MGL-3196-19