A Study of a Thyroid Hormone Receptor Beta Isoform (THRβ) Agonist and an Semicarbazide Sensitive Amine Oxidase (SSAO) Inhibitor, Alone and in Combination, in Adults With Presumed Metabolic Dysfunction-associated Steatohepatitis (MASH)

Korábbi kezelés

• Use of medications that affect liver fat or fibrosis (e.g., Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RAs) not on a stable dose, pioglitazone, obeticholic acid, high-dose vitamin E, hepatotoxic drugs) within protocol-specified washout periods.
• Significant alcohol use within 1 year prior to screening.

Más betegség

• Chronic liver disease other than metabolic dysfunction-associated steatotic liver disease (MASLD)/MASH, including alcoholic liver disease, autoimmune hepatitis, cholestatic disease, genetic liver diseases, or drug-induced liver injury.
• Presence of cirrhosis on liver histology according to the assessment of the central reader, and/or cross-sectional imaging evidence consistent with cirrhosis and/or portal hypertension (e.g, nodular liver contour; portosystemic collaterals, ascites, splenomegaly; known presence or history of esophageal varices; and/or elastography evidence consistent with cirrhosis).
• Clinically significant thyroid or adrenal dysfunction, including uncontrolled hypothyroidism, hyperthyroidism, or adrenal disorders.
• Recent cardiovascular events, including myocardial infraction (MI), stroke, unstable angina, heart failure (New York heart association \[NYHA III-IV\]), or uncontrolled arrhythmia.
• Current or recent serious psychiatric illness, including psychosis, active suicidal ideation, or suicide attempt within 5 years.
• Pregnancy, breastfeeding, or conditions that increase risk or interfere with study procedures, including MRI contraindications or other investigator-determined safety concerns.

Laborértékek

• ALT and/or AST \>5× Upper Limit of Normal (ULN) or ALP \>2×ULN at screening.
• Type 1 diabetes, HbA1c \>9.5%, or unstable type 2 diabetes requiring medication changes within 90 days.

• Adults between 18 and 75 years of age, inclusive, who can provide written informed consent and comply with study procedures.
• Diagnosis of presumed MASH based on: liver biopsy within 180 days prior to screening showing an NAFLD activity score (NAS) of ≥3 and a fibrosis score (F) of F1-3 OR FibroScan® CAP \>280 dB/m at screening with presence of metabolic risk factors.
• Evidence of hepatic steatosis confirmed by FibroScan® LSM \> 7 kPa and \< 20 kPa and MRI-PDFF \>8% at screening.
• BMI \>25 kg/m\^2 to \<50 kg/m\^2 (non-Asian); BMI ≥23.0 to \<50.0 kg/m\^2 (Asian).
• ALT ≥60 U/L at the first screening visit and stability of ALT and AST levels during the screening period.
• Estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73m\^2 (Chronic Kidney Disease Epidemiology Collaboration, \[CKD-EPI\]).
• Stable body weight (no \>5% change) for at least 6 months prior to screening.
• Willing to comply with contraception requirements (as applicable to males and females of childbearing potential).
• In the opinion of the investigator, able to participate safely and complete required MRI/biomarker assessments.