The primary objective of this trial is to evaluate the dose-dependent and comparative effects of ECC4703 (low and high dose), ECC0509 (low and high dose), and their combination on hepatic fat reduction as assessed by change in magnetic resonance imaging proton density fat fraction (MRI-PDFF) at Week 12.
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/m² to <50 kg/m² (non-Asian); BMI ≥23.0 to <50.0 kg/m² (Asian).
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).
ALT and/or AST >5× Upper Limit of Normal (ULN) or ALP >2×ULN at screening.
Clinically significant thyroid or adrenal dysfunction, including uncontrolled hypothyroidism, hyperthyroidism, or adrenal disorders.
Parallel
Placebo
DrugPlacebo will be administered as matching oral capsules.
ECC4703
DrugECC4703 will be administered as oral capsules.
ECC0509
DrugECC0509 will be administered as oral capsules.
ECC4703
DrugECC4703 will be administered as oral capsules.
6
Treatment groupsSee each treatment group below.
Relative Change from Baseline in Liver Fat Content by MRI-PDFF, Comparing ECC4703 Monotherapy Versus Placebo
Absolute Change from Baseline in Liver Fat Content by MRI-PDFF, Comparing ECC4703 Monotherapy Versus Placebo
Relative Change from Baseline in Liver Fat Content by MRI-PDFF, Comparing ECC0509 Monotherapy Versus Placebo, and the Combination of ECC4703 and ECC0509 Versus Each Component
Absolute Change From Baseline in Liver Fat Content by MRI-PDFF, Comparing ECC0509 Monotherapy Versus Placebo, and the Combination of ECC4703 and ECC0509 Versus Each Component
Percentage of Participants With ≥30%, ≥50%, and ≥70% Relative Reduction and Normalization (<5%) in Liver Fat Content by MRI-PDFF, Comparing ECC4703 and ECC0509 Monotherapy Versus Placebo, and the Combination of ECC4703 and ECC0509 Versus Each Component
