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)

Eccogene

Status and phase: Enrolling; Phase 2

Conditions: Metabolic Dysfunction-associated Steatohepatitis

Treatments: Drug: Placebo; Drug: ECC4703; Drug: ECC0509

Study type: Interventional

Funder types: Industry

Identifiers

NCT07288138

EC0010

Details and patient eligibility

About

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.

Enrollment: 160 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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160 participants in 6 patient groups, including a placebo group

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo

ECC4703 Low Dose

Experimental group

Treatment:

Drug: ECC4703

Drug: ECC4703

ECC4703 High Dose

Experimental group

Treatment:

Drug: ECC4703

Drug: ECC4703

ECC4703 High Dose + ECC0509 High Dose

Experimental group

Treatment:

Drug: ECC4703

Drug: ECC0509

Drug: ECC4703

ECC0509 Low Dose

Experimental group

Treatment:

Drug: ECC0509

ECC0509 High Dose

Experimental group

Treatment:

Drug: ECC0509