A 12-week, Open-label, Dose-escalating, Phase 2 Study to Evaluate the Effects of MBX-8025 in Patients With Homozygous Familial Hypercholesterolemia (HoFH)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 13
- 试验地点
- 5
- 主要终点
- LDL-C
研究概览
简要总结
A 12-week, open-label, dose-escalating, phase 2 study to evaluate the effects of MBX-8025 in patients with Homozygous Familial Hypercholesterolemia (HoFH).
详细描述
Open-label, single arm, non-controlled, dose ascending (50 mg/day, 100 mg/day and 200 mg/day) with three consecutive dose escalation periods.
After signing an informed consent subject will enter a screening period and a run-in stabilization period. At the end of run-in period patients will enter treatment phase. MBX-8025 in ascending doses (50 mg, 100 mg, and 200 mg) will be given within three consecutive 4 weeks periods, for a total of 12 weeks. At the end of treatment, subjects will enter a follow-up period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must have given written informed consent (signed and dated) and any authorizations required by local law and be able to comply with all study requirements.
- •Male or female with HoFH confirmed by genotype (two mutant alleles at the LDL-Receptor (LDL-R) gene locus or double heterozygotes LDL-R/Apo-B).
- •18 years of age or older.
- •Existing lipid lowering therapies (statins, cholesterol absorption inhibitors, bile acid sequestrants, nicotinic acid and their combinations, low-density lipoprotein (LDL) LDL-C apheresis) on a stable regimen for at least four weeks before screening visit.
- •Stable lipid lowering diet compatible with a Step I diet of the American Heart Association (AHA).
- •Fasting LDL-C ≥ 4.8 mmol/L (≥ 185.6 mg/dL) during screening.
- •For females or males of reproductive potential, use of at least one barrier contraceptive and a second effective birth control method during the study and for at least two weeks after the last dose.
排除标准
- •Treatment with lomitapide or mipomersen within two months of screening.
- •Heart Failure (HF) with New York Heart Association (NYHA) class III and class IV or a Left ventricular ejection fraction (LVEF) of less than 30%.
- •Uncontrolled cardiac arrhythmia during the past three months of screening.
- •Myocardial infarction, unstable angina, percutaneous coronary intervention, coronary artery bypass graft or stroke during the past three months of screening.
- •Planned cardiac surgery, or planned revascularization, in the next four months.
- •Uncontrolled hypertension.
- •Aspartate transaminase (AST) or Alanine transaminase (ALT) ≥ 3 times the Upper Limit of Normal (ULN).
- •Unexplained creatine kinase (CK) ≥ 5 times the upper limit of normal (ULN).
- •For females, pregnancy or breast-feeding.
- •Any other condition(s) that would compromise the safety of the patient or compromise the quality of the clinical study as judged by the Investigator and/or Medical Monitor.
研究组 & 干预措施
placebo, MBX-8025 50 mg, 100 mg or 200 mg capsules
干预措施: MBX-8025 50 mg (Dose Escalation Period 1) (Drug)
placebo, MBX-8025 50 mg, 100 mg or 200 mg capsules
干预措施: MBX-8025 50 mg or 100 mg (Dose Escalation Period 2) (Drug)
placebo, MBX-8025 50 mg, 100 mg or 200 mg capsules
干预措施: MBX-8025 50 mg, 100 mg or 200 mg (Dose Escalation Period 3) (Drug)
结局指标
主要结局
LDL-C
时间窗: 12-Weeks
Absolute and percentage (%) reduction in serum LDL-C at any point from baseline through Week 16.
次要结局
- Total Cholesterol (TC)(12-Weeks)
- High-density lipoprotein (HDL) cholesterol [HDL-C](12-Weeks)
- Remnant-like Particle (RLP-C)(12-Weeks)
- Apolipoprotein B (Apo B)(12-Weeks)
- Lipoprotein(12-Weeks)
- Very Low-Density Lipoprotein (VLDL)(12-Weeks)
- Non HDL-C(12-Weeks)
- Apolipoprotein C-III (Apo CIII)(12-Weeks)
- Apolipoprotein A-I (Apo A-I)(12-Weeks)
- Serum Triglyceride (TG)(12-Weeks)