Clareo Health | 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)
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)
1. Adults between 18 and 75 years of age, inclusive, who can provide written informed consent and comply with study procedures.
2. 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.
3. Evidence of hepatic steatosis confirmed by FibroScan® LSM \> 7 kPa and \< 20 kPa and MRI-PDFF \>8% at screening.
4. BMI \>25 kg/m\^2 to \<50 kg/m\^2 (non-Asian); BMI ≥23.0 to \<50.0 kg/m\^2 (Asian).
5. ALT ≥60 U/L at the first screening visit and stability of ALT and AST levels during the screening period.
7. Stable body weight (no \>5% change) for at least 6 months prior to screening.
8. Willing to comply with contraception requirements (as applicable to males and females of childbearing potential).
9. In the opinion of the investigator, able to participate safely and complete required MRI/biomarker assessments.
You may not be if
1. 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.
2. 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).
3. ALT and/or AST \>5× Upper Limit of Normal (ULN) or ALP \>2×ULN at screening.
4. Clinically significant thyroid or adrenal dysfunction, including uncontrolled hypothyroidism, hyperthyroidism, or adrenal disorders.
5. Type 1 diabetes, HbA1c \>9.5%, or unstable type 2 diabetes requiring medication changes within 90 days.
6. 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.
7. Significant alcohol use within 1 year prior to screening.
8. Recent cardiovascular events, including myocardial infraction (MI), stroke, unstable angina, heart failure (New York heart association \[NYHA III-IV\]), or uncontrolled arrhythmia.
9. Current or recent serious psychiatric illness, including psychosis, active suicidal ideation, or suicide attempt within 5 years.
10. Pregnancy, breastfeeding, or conditions that increase risk or interfere with study procedures, including MRI contraindications or other investigator-determined safety concerns.
