NCT07288138招募中2 期
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
Eccogene65 个研究点 分布在 1 个国家目标入组 160 人开始时间: 2025年12月15日最近更新:
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 160
- 试验地点
- 65
- 主要终点
- Relative Change from Baseline in Liver Fat Content by MRI-PDFF, Comparing ECC4703 Monotherapy Versus Placebo
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
ECC0509 High Dose
Experimental
干预措施: ECC0509 (Drug)
ECC4703 High Dose + ECC0509 High Dose
Experimental
干预措施: ECC0509 (Drug)
ECC4703 High Dose
Experimental
干预措施: ECC4703 (Drug)
ECC4703 Low Dose
Experimental
干预措施: ECC4703 (Drug)
ECC4703 High Dose + ECC0509 High Dose
Experimental
干预措施: ECC4703 (Drug)
ECC0509 Low Dose
Experimental
干预措施: ECC0509 (Drug)
Placebo
Placebo Comparator
干预措施: Placebo (Drug)
结局指标
主要结局
Relative Change from Baseline in Liver Fat Content by MRI-PDFF, Comparing ECC4703 Monotherapy Versus Placebo
时间窗: Baseline and Week 12
次要结局
- Plasma Concentration of ECC4703 and ECC0509(Day 1, Weeks 2, 4, 6, 8, and 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 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 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 Fasting Plasma Glucose (FPG)(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 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 MASH Resolution Index, 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)
- 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 Lipoprotein(a) (Lp[a]) Profiles(Baseline to Week 12)
- Change from Baseline in Plasma Methylamine(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 Short-form Liver Disease Quality of Life (SF-LDQOL)(Baseline to 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 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 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(Baseline and 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 Chronic Liver Disease Questionnaire (CLDQ)(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 Hemoglobin A1c (HbA1c)(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)
研究者
研究点 (65)
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