Metabolic Dysfunction-associated Steatohepatitis
Conditions
Keywords
Liver Disease, Nonalcoholic Steatohepatitis, ECC0509, ECC4703
Brief summary
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.
Interventions
Sponsors
Eccogene
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
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. 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
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Relative Change from Baseline in Liver Fat Content by MRI-PDFF, Comparing ECC4703 Monotherapy Versus Placebo | Baseline and Week 12 |
Secondary
| Measure | Time frame |
|---|---|
| Change from Baseline in Lipoprotein(a) (Lp[a]) Profiles | Baseline to Week 12 |
| Change from Baseline in Hemoglobin A1c (HbA1c) | Baseline to Week 12 |
| Change from Baseline in Fasting Plasma Glucose (FPG) | Baseline to Week 12 |
| Change from Baseline in Fasting Insulin | Baseline to Week 12 |
| Change from Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Profiles | Baseline to Week 12 |
| Change from Baseline in Body Weight | Baseline to Week 12 |
| Change from Baseline Body Mass Index (BMI) | Baseline to Week 12 |
| Change from Baseline in Plasma Methylamine | Baseline to Week 12 |
| Change from Baseline in Cytokeratin-18 (CK-18) | Baseline to Week 12 |
| Change from Baseline in C-telopeptide of Type III Collagen (CTX-III) | Baseline to Week 12 |
| Change from Baseline in N-terminal Pro-peptide of Type III Collagen (Pro-C3) | Baseline to Week 12 |
| Change in Ratio of Pro-C3 | Week 12 |
| Change in Ratio of CTX-III | Week 12 |
| Change from Baseline in Chronic Liver Disease Questionnaire (CLDQ) | Baseline and Week 12 |
| Change from Baseline in Short-form Liver Disease Quality of Life (SF-LDQOL) | Baseline to Week 12 |
| Plasma Concentration of ECC4703 and ECC0509 | Day 1, Weeks 2, 4, 6, 8, and 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 | 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 | Baseline and Week 12 |
| Absolute Change from Baseline in Liver Fat Content by MRI-PDFF, Comparing ECC4703 Monotherapy Versus Placebo | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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) | Baseline to 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 | Baseline and Week 12 |
Countries
United States
Contacts
CONTACTEccogene Clinical Trials
STUDY_DIRECTOREccogene Clinical Trials
Eccogene
Outcome results
None listed