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)

Официальное название

A Phase 2a, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Assess the Efficacy and Safety of a THRβ Agonist (ECC4703), an SSAO Inhibitor (ECC0509), and Their Combination in Adults With Presumed MASH

Обзор

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.

Вмешательства

• Препарат Placebo
  Placebo will be administered as matching oral capsules.
• Препарат ECC4703
  ECC4703 will be administered as oral capsules.
• Препарат ECC0509
  ECC0509 will be administered as oral capsules.
• Препарат ECC4703
  ECC4703 will be administered as oral capsules.

Первичные конечные точки

• Relative Change from Baseline in Liver Fat Content by MRI-PDFF, Comparing ECC4703 Monotherapy Versus Placebo [Срок оценки: Baseline and Week 12]

Вторичные конечные точки (12)

• Absolute Change from Baseline in Liver Fat Content by MRI-PDFF, Comparing ECC4703 Monotherapy Versus Placebo [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: Baseline and Week 12]

Критерии участия

Критерии включения

• 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/m\^2 to <50 kg/m\^2 (non-Asian); BMI ≥23.0 to <50.0 kg/m\^2 (Asian).
• ALT ≥60 U/L at the first screening visit and stability of ALT and AST levels during the screening period.
• Estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73m\^2 (Chronic Kidney Disease Epidemiology Collaboration, \[CKD-EPI\]).
• Stable body weight (no >5% change) for at least 6 months prior to screening.
• Willing to comply with contraception requirements (as applicable to males and females of childbearing potential).
• In the opinion of the investigator, able to participate safely and complete required MRI/biomarker assessments.

Критерии исключения

• 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.
• Type 1 diabetes, HbA1c >9.5%, or unstable type 2 diabetes requiring medication changes within 90 days.
• 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.
• Significant alcohol use within 1 year prior to screening.
• Recent cardiovascular events, including myocardial infraction (MI), stroke, unstable angina, heart failure (New York heart association \[NYHA III-IV\]), or uncontrolled arrhythmia.
• Current or recent serious psychiatric illness, including psychosis, active suicidal ideation, or suicide attempt within 5 years.
• Pregnancy, breastfeeding, or conditions that increase risk or interfere with study procedures, including MRI contraindications or other investigator-determined safety concerns.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

США · 63 центра

• Arizona Liver Health — Chandler
• Arizona Liver Health - Peoria — Peoria
• Adobe Clinical Research, LLC — Tucson
• Arizona Liver Health - Tucson — Tucson
• Arkansas Gastroenterology, P.A — Little Rock
• ARcare Center for Clinical Research — Little Rock
• Om Research — Apple Valley
• ARK Clinical Research - Fountain Valley — Fountain Valley
• … и ещё 55 центров

Идентификаторы

NCT: NCT07288138 · EC0010

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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