Tests resmetirom in people with MASH after a liver transplant

Who can take part

• At least 12 months post-liver transplant at screening and meeting one of the following:; Cohort 1: Liver transplant for MASH cirrhosis with recurrent hepatic steatosis ≥8% by MRI-PDFF; Cohort 2: Liver transplant for non-MASH etiology with de novo hepatic steatosis ≥8% by MRI-PDFF
• Presence of at least one metabolic risk factor, including overweight/obesity, dysglycemia or type 2 diabetes, hypertension or antihypertensive treatment, hypertriglyceridemia or low HDL cholesterol, or lipid-lowering therapy
• MASH with moderate to advanced liver fibrosis (F2-F3), confirmed by noninvasive fibrosis assessment (FibroScan and/or MRE) and a liver biopsy consistent with Stage F2/F3 MASH and no evidence of other liver pathology or graft rejection
• Stable renal function with estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m² prior to and during screening
• Stable liver enzymes at screening, without clinically significant worsening compared with recent historical values
• Stable immunosuppressive regimen for at least 3 months prior to screening
• Females of childbearing potential must have a negative pregnancy test, not be breastfeeding, and agree to use effective contraception during the study and for at least 30 days after the last dose; females not of childbearing potential are eligible

Who cannot take part

• Participation in another interventional clinical trial with investigational drug exposure within 30 days (or 5 half-lives, whichever is longer) prior to screening
• Phosphatidylethanol (PEth) value of ≥20 ng/mL measured at screening or clinically significant alcohol use within 1 year prior to screening
• Steroid resistant rejection of the transplanted liver or kidney, or a history of a rejection treated with high dose steroid within 3 months of screening
• Significant post-transplant vascular or biliary complications
• Significant cardiovascular or cerebrovascular disease within 6 months prior to randomization
• Current substance abuse or drug addiction
• Use of prohibited concomitant medications that may affect liver function, steatosis, thyroid function, or study outcomes, or unstable doses of allowed metabolic therapies prior to randomization
• Use of statins above protocol-allowed doses or unstable lipid-lowering therapy prior to randomization
• Uncontrolled or clinically significant thyroid disease, including active hyperthyroidism or untreated hypothyroidism
• Evidence of active liver disease other than MASH
• History of liver transplantation for an inborn error of metabolism
• Evidence of hepatic impairment or decompensation at screening
• Chronic rejection or chronic plasma-cell hepatitis
• Uncontrolled hypertension at screening or randomization
• Known human immunodeficiency virus (HIV) infection or other clinically significant immunocompromised state
• Any serious medical condition with a life expectancy of less than 5 years
• Significant psychiatric, cognitive, or social conditions that would interfere with study participation or compliance, in the Investigator's judgment
• Known hypersensitivity to study drug or any of its excipients
• FibroScan VCTE >20 kPa, a baseline biopsy demonstrating fibrosis consistent with F4, or MRE > 5 kPa
• Current hepatocellular carcinoma
• Contraindications to MRI, including implanted devices incompatible with MRI, severe claustrophobia, or inability to undergo MRI procedures