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)

Phase 2RecruitingNCT07288138

Eccogene160 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

160

Conditions

Metabolic Dysfunction-associated Steatohepatitis

Interventions

PlaceboDRUG

Placebo will be administered as matching oral capsules.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Adults ≥18 years of age who can provide written informed consent and comply with study procedures. 2. Presumed MASH based on recent liver biopsy (NAFLD activity score \[NAS\] ≥4, fibrosis F1-F3) or non-invasive criteria consistent with liver fibrosis (metabolic syndrome plus FibroScan® liver stiffness 7-14 kPa). 3. Evidence of hepatic steatosis confirmed by FibroScan® CAP \>280 dB/m 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 \>1.5×upper limit of normal (ULN). 6. Estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73m\^2 (Chronic Kidney Disease Epidemiology Collaboration, \[CKD-EPI\]). 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. Exclusion Criteria: Liver-related: 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. Evidence of cirrhosis or hepatic decompensation, including prior ascites, varices, encephalopathy, or laboratory/imaging findings consistent with cirrhosis. 3. ALT or AST \>5×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 3 months. 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.

Outcomes

Primary Outcomes

Relative Change from Baseline in Liver Fat Content by MRI-PDFF, Comparing ECC4703 Monotherapy Versus Placebo

Time frame: Baseline and Week 12

Secondary Outcomes

Absolute Change from Baseline in Liver Fat Content by MRI-PDFF, Comparing ECC4703 Monotherapy Versus Placebo

Time frame: Baseline and Week 12

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

Time frame: Baseline and Week 12

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

Time frame: Baseline and Week 12

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

Time frame: Baseline and Week 12

Change From Baseline in Alanine Aminotransferase (ALT), Comparing ECC4703 and ECC0509 Monotherapy Versus Placebo, and the Combination of ECC4703 and ECC0509 Versus Each Component

Time frame: Baseline and Week 12

Percentage of Participants Achieving ≥17-unit Reduction in ALT, Comparing ECC4703 and ECC0509 Monotherapy Versus Placebo, and the Combination of ECC4703 and ECC0509 Versus Each Component

Time frame: Week 12

Percentage of Participants With 30% Reduction in MRI-PDFF, Comparing ECC4703 and ECC0509 Monotherapy Versus Placebo, and the Combination of ECC4703 and ECC0509 Versus Each Component

Time frame: Week 12

Change from Baseline in Aspartate Aminotransferase (AST), Comparing ECC4703 and ECC0509 Monotherapy Versus Placebo, and the Combination of ECC4703 and ECC0509 Versus Each Component

Time frame: Baseline and Week 12

Change from Baseline in Alkaline Phosphatase (ALP), Comparing ECC4703 and ECC0509 Monotherapy Versus Placebo, and the Combination of ECC4703 and ECC0509 Versus Each Component

Time frame: Baseline and Week 12

Change from Baseline in Gamma-glutamyl Transferase (GGT), Comparing ECC4703 and ECC0509 Monotherapy Versus Placebo, and the Combination of ECC4703 and ECC0509 Versus Each Component

Time frame: Baseline and Week 12

Change from Baseline in Fibrosis-4 Index (FIB-4), Comparing ECC4703 and ECC0509 Monotherapy Versus Placebo, and the Combination of ECC4703 and ECC0509 Versus Each Component

Time frame: Baseline and Week 12

Change from Baseline in AST to Platelet Ratio Index (APRI), Comparing ECC4703 and ECC0509 Monotherapy Versus Placebo, and the Combination of ECC4703 and ECC0509 Versus Each Component

Time frame: Baseline and Week 12

Change from Baseline in FibroScan AST Score (FAST), Comparing ECC4703 and ECC0509 Monotherapy Versus Placebo, and the Combination of ECC4703 and ECC0509 Versus Each Component

Time frame: Baseline and Week 12

Change from Baseline in Non-alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score (NFS), Comparing ECC4703 and ECC0509 Monotherapy Versus Placebo, and the Combination of ECC4703 and ECC0509 Versus Each Component

Time frame: Baseline and Week 12

Change from Baseline in Enhanced Liver Fibrosis (ELF) Score, Comparing ECC4703 and ECC0509 Monotherapy Versus Placebo, and the Combination of ECC4703 and ECC0509 Versus Each Component

Time frame: Baseline and Week 12

Change from Baseline in MASH Resolution Index, Comparing ECC4703 and ECC0509 Monotherapy Versus Placebo, and the Combination of ECC4703 and ECC0509 Versus Each Component

Time frame: Baseline and Week 12

Change from Baseline in FibroScan Liver Stiffness Measurement (LSM), Comparing ECC4703 and ECC0509 Monotherapy Versus Placebo, and the Combination of ECC4703 and ECC0509 Versus Each Component

Time frame: Baseline and Week 12

Change from Baseline in FibroScan Controlled Attenuation Parameter (CAP), Comparing ECC4703 and ECC0509 Monotherapy Versus Placebo, and the Combination of ECC4703 and ECC0509 Versus Each Component

Time frame: Baseline and Week 12

Change from Baseline in LSM as Measure by Magnetic Resonance Elastography (MRE), Comparing ECC4703 and ECC0509 Monotherapy Versus Placebo, and the Combination of ECC4703 and ECC0509 Versus Each Component

Time frame: Baseline and Week 12

Change from Baseline in Total Cholesterol (TC), Triglycerides (TG), High-density Lipoprotein (HDL), Low-density Lipoprotein (LDL) and Apoprotein B (ApoB)

Time frame: Baseline to Week 12

Change from Baseline in Lipoprotein(a) (Lp[a]) Profiles

Time frame: Baseline to Week 12

Change from Baseline in Hemoglobin A1c (HbA1c)

Time frame: Baseline to Week 12

Change from Baseline in Fasting Plasma Glucose (FPG)

Time frame: Baseline to Week 12

Change from Baseline in Fasting Insulin

Time frame: Baseline to Week 12

Change from Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Profiles

Time frame: Baseline to Week 12

Change from Baseline in Body Weight

Time frame: Baseline to Week 12

Change from Baseline Body Mass Index (BMI)

Time frame: Baseline to Week 12

Change from Baseline in Plasma Methylamine

Time frame: Baseline to Week 12

Change from Baseline in Cytokeratin-18 (CK-18)

Time frame: Baseline to Week 12

Change from Baseline in C-telopeptide of Type III Collagen (CTX-III)

Time frame: Baseline to Week 12

Change from Baseline in N-terminal Pro-peptide of Type III Collagen (Pro-C3)

Time frame: Baseline to Week 12

Change in Ratio of Pro-C3

Time frame: Week 12

Change in Ratio of CTX-III

Time frame: Week 12

Change from Baseline in Chronic Liver Disease Questionnaire (CLDQ)

Time frame: Baseline and Week 12

Change from Baseline in Short-form Liver Disease Quality of Life (SF-LDQOL)

Time frame: Baseline to Week 12

Plasma Concentration of ECC4703 and ECC0509

Time frame: Day 1, Weeks 2, 4, 6, 8, and 12

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)

Overview

Conditions

Interventions

Eligibility

Locations (2)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts