A Phase 2A Study to Evaluate MET409 Alone or in Combination With Empagliflozin in Patients With Type 2 Diabetes Mellitus (T2DM) and Nonalcoholic Steatohepatitis (NASH)
试验速览
- 阶段
- 2 期
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Safety and tolerability of MET409 with or without empagliflozin (incidence of adverse events)
研究概览
简要总结
A randomized, multi-center study evaluating MET409 (50 mg) alone or in combination with empagliflozin (10 mg) for 12 weeks. Assignment to MET409 will be double-blind and placebo-controlled. Empagliflozin will be incorporated into two of the treatment arms in an open-label manner.
详细描述
Subjects assigned to receive empagliflozin will be dosed at 10 mg per day for the duration of the study.
Approximately 30 subjects will be enrolled per treatment arm.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Males and females 18 through 75 years of age.
- •Diagnosis of NASH based on NAFLD Activity Score (NAS) ≥ 4 with at least 1 point in each of steatosis, inflammation, and ballooning; Magnetic Resonance Elastography (MRE) showing kPa ≥ 2.61 or a multiparametric MRI (ie, LiverMultiScan) showing iron-corrected T1(cT1) > 830 ms within 6 months of enrollment; or Transient elastography (TE, FibroScan) with liver stiffness ≥ 8.5 kPa and controlled attenuation parameter (CAP) > 300 dB/m obtained within 3 months of enrollment.
- •Liver fat content ≥ 8% measured by magnetic resonance imaging-proton density fat fraction (MRI-PDFF) during screening.
- •Diagnosis of T2DM for ≤ 10 years, with hemoglobin A1c ≤ 10.0% during screening, stable and controlled with diet or treatment for at least 3 months.
排除标准
- •History of significant liver disease (eg, alcoholic liver disease, viral hepatitis, etc.) or liver transplant.
- •Presence of cirrhosis on any prior liver biopsy (stage 4 fibrosis).
- •Excessive consumption of alcohol.
- •Use of any insulin (injectable or inhaled), SGLT-2 inhibitor or glucagon-like peptide 1 (GLP-1, injectable or oral) products for > 7 days within 3 months of screening.
- •Weight loss > 10% in the 6 months prior to screening or > 5% during screening.
- •Use of drugs historically associated with causing NAFLD for more than 4 consecutive weeks within 12 months prior to screening.
- •Concomitant use of drugs that are strong or moderate CYP3A4 inhibitors.
- •Concomitant consumption of grapefruit juice with the study drug.
- •History of diabetic ketoacidosis (DKA) within 1 month prior to the Screening Visit, or more than 2 episodes within 6 months prior to the Screening Visit.
- •History of > 2 episodes of urosepsis or pyelonephritis within 5 years of screening.
研究组 & 干预措施
MET409P +Open-Label Empagliflozin
MET409 Placebo (50mg) + Empagliflozin (10mg)
干预措施: MET409 Placebo (Drug)
MET409 A
MET409 Active (50mg)
干预措施: MET409 Active (Drug)
MET409 P
MET409 Placebo (50mg)
干预措施: MET409 Placebo (Drug)
MET409A +Open-Label Empagliflozin
MET409 Active (50mg) + Empagliflozin (10mg)
干预措施: MET409 Active (Drug)
MET409A +Open-Label Empagliflozin
MET409 Active (50mg) + Empagliflozin (10mg)
干预措施: Empagliflozin (Drug)
MET409P +Open-Label Empagliflozin
MET409 Placebo (50mg) + Empagliflozin (10mg)
干预措施: Empagliflozin (Drug)
结局指标
主要结局
Safety and tolerability of MET409 with or without empagliflozin (incidence of adverse events)
时间窗: Up to 28 days after last dose
Incidence of Treatment-emergent adverse events, incidence of clinically significant changes in vital signs, abnormal laboratory safety tests, and abnormal ECGs.
次要结局
- Pharmacological activity of MET409 alone or in combination with empagliflozin(16 weeks)
- Pharmacodynamic profile of MET409 alone or in combination with empagliflozin(16 weeks)
- Pharmacokinetic profile of MET409 alone or in combination with empagliflozin(12 weeks)