A Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Evinacumab in Patients With Homozygous Familial Hypercholesterolemia
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 65
- 试验地点
- 4
- 主要终点
- Percent Change in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 24 (Intent-to-Treat [ITT] Estimand)
研究概览
简要总结
The primary objective of the study is to demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by evinacumab intravenously (IV) in comparison to placebo after 24 weeks in patients with homozygous familial hypercholesterolemia (HoFH). The secondary objectives of the study are to evaluate the effect of evinacumab IV on other lipid parameters, evaluate the effect of evinacumab on LDL-C goal attainment, assess the effect of evinacumab on eligibility for apheresis (using German and US apheresis criteria), evaluate the safety and tolerability of evinacumab in patients with HoFH, assess the pharmacokinetics (PK) of evinacumab in patients with HoFH and evaluate the potential development of anti-evinacumab antibodies.
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
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of functional HoFH
- •If undergoing LDL apheresis, must have initiated LDL apheresis at least 3 months prior to screening and must have been on a stable weekly or every other week schedule and/or stable settings for at least 8 weeks
- •Willing to consistently maintain his/her usual low fat or heart-healthy diet for the duration of the study
排除标准
- •LDL-C level <70 mg/dL (1.81 mmol/L) at the screening visit
- •Background medical Lipid Modifying Therapy (LMT) (if applicable) that has not been stable before the screening visit
- •Lipid-apheresis schedule /apheresis settings (if applicable) that have not been stable for at least 8 weeks before the screening visit
- •Use of nutraceuticals or over-the-counter therapies known to affect lipids, at a dose/amount that has not been stable for at least 4 weeks prior to the screening visit
- •Presence of any clinically significant uncontrolled endocrine disease known to influence serum lipids or lipoproteins
- •Newly diagnosed (within 3 months prior to randomization visit) diabetes mellitus or poorly controlled (HbA1c >9%) diabetes
- •History of a MI, unstable angina leading to hospitalization, coronary artery bypass graft surgery, percutaneous coronary intervention, uncontrolled cardiac arrhythmia, carotid surgery or stenting, stroke, transient ischemic attack, valve replacement surgery, carotid revascularization, endovascular procedure or surgical intervention for peripheral vascular disease within 3 months prior to the screening visit
- •Pregnant or breastfeeding women
- •Sexually active women of child bearing potential (WOCBP), who are unwilling to practice a highly effective birth control method prior to the initial dose, during the study, and for 24 weeks after the last dose of study drug
- •Men who are sexually active with women of child bearing potential (WOCBP) and are unwilling to consistently use condoms during the study drug treatment period and for 24 weeks after the last dose of study drug regardless of vasectomy status
- •Note: Other protocol defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
evinacumab
干预措施: evinacumab (Drug)
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Percent Change in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 24 (Intent-to-Treat [ITT] Estimand)
时间窗: Week 24
Percent change was calculated as 100x(calculated LDL-C value at Week 24 - calculated LDL-C value at baseline)/calculated LDL-C value at baseline. The baseline LDL-C value was the last calculated LDL-C value obtained before the first dose of double-blind-study drug. The calculated LDL-C at week 24 was the LDL-C value obtained within the week 24 efficacy analysis window, regardless of adherence to treatment and subsequent therapies (intent-to-treat \[ITT\] estimand). The ITT population included all randomized participants who received at least one dose or part of a dose of double-blind study drug. Participants in the ITT population were analyzed according to the treatment group allocated by randomization (i.e., as randomized participant group).
次要结局
- Percent Change in Total Cholesterol (TC) From Baseline to Week 24 (ITT Estimand)(Week 24)
- Percentage of Participants With ≥30% Reduction in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24 (ITT Estimand)(At Week 24)
- Percentage of Participants With ≥50% Reduction in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24 (ITT Estimand)(At Week 24)
- Absolute Change in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 24 (ITT Estimand)(Week 24)
- Percent Change in Apolipoprotein B (Apo B) From Baseline to Week 24 (ITT Estimand)(Week 24)
- Percent Change in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 24 (ITT Estimand)(Week 24)
- Percentage of Participants With Low-Density Lipoprotein Cholesterol (LDL-C) <100 Milligrams Per Deciliter (mg/dL) (2.59 Millimoles Per Liter [mmol/L]) at Week 24 (ITT Estimand)(At Week 24)
- Percentage of Participants Who Met United States (US) Apheresis Eligibility Criteria at Week 24 (ITT Estimand)(At Week 24)
- Percentage of Participants Who Met European Union (EU) Apheresis Eligibility Criteria at Week 24 (ITT Estimand)(At Week 24)
- Percentage of Participants With Calculated Low-Density Lipoprotein Cholesterol (LDL-C) <70 mg/dL (1.81 mmol/L) at Week 24 (ITT Estimand)(At Week 24)
- Percent Change in Fasting Triglycerides (TG) From Baseline to Week 24 (ITT Estimand)(Week 24)
- Percent Change in Lipoprotein A (Lp[a]) From Baseline to Week 24 (ITT Estimand)(Week 24)
- Absolute Change in Apolipoprotein B (Apo B) From Baseline to Week 24 (ITT Estimand)(Week 24)
- Absolute Change in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 24 (ITT Estimand)(Week 24)
- Absolute Change in Total Cholesterol (TC) From Baseline to Week 24 (ITT Estimand)(Week 24)
- Percent Change in Apolipoprotein CIII (Apo CIII) From Baseline to Week 24 (ITT Estimand)(Week 24)