Study to Evaluate Resmetirom in Post-Liver Transplant Patients With MASH

Korábbi kezelés

• 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.

Más betegség

• 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.

Egyéb

• 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.

• 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.