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)
Purpose
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.
Condition
- Metabolic Dysfunction-associated Steatohepatitis
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- 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.
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Placebo Comparator Placebo |
|
|
|
Experimental ECC4703 Low Dose |
|
|
|
Experimental ECC4703 High Dose |
|
|
|
Experimental ECC4703 High Dose + ECC0509 High Dose |
|
|
|
Experimental ECC0509 Low Dose |
|
|
|
Experimental ECC0509 High Dose |
|
Recruiting Locations
Chandler 5289282, Arizona 5551752 85224
Peoria 5308480, Arizona 5551752 85381
Little Rock 4119403, Arkansas 4099753 71913
Little Rock 4119403, Arkansas 4099753 77205
Fountain Valley 5350207, California 5332921 92708
Long Beach 5367929, California 5332921 90815
Miami Lakes 4164186, Florida 4155751 33016
Port Orange 4169156, Florida 4155751 32127
Marietta 4207783, Georgia 4197000 30060
South Bend 4926563, Indiana 4921868 46635
Greenbelt 4356847, Maryland 4361885 20770
Akron 5145476, Ohio 5165418 44333
San Antonio 4726206, Texas 4736286 78209
More Details
- Status
- Recruiting
- Sponsor
- Eccogene