A Multicenter, Open-label Study to Assess the Long-term Safety, Tolerability, and Efficacy of Evolocumab (AMG145) on LDL-C in Subjects With Severe Familial Hypercholesterolemia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 300
- 试验地点
- 45
- 主要终点
- Number of Participants With Adverse Events
研究概览
简要总结
A study to assess the long term safety and tolerability of evolocumab (AMG 145) in adolescents and adults with severe familial hypercholesterolemia.
详细描述
This phase 2/3 open-label extension study was designed to characterize the safety and tolerability of long-term administration of evolocumab to adults and adolescents with severe FH (HoFH or non-HoFH severe FH). Participants not on lipid apheresis at enrollment or within the prior 8 weeks initiated treatment with evolocumab 420 mg once monthly (QM). Participants on lipid apheresis at enrollment initiated treatment with evolocumab 420 mg once every 2 weeks (Q2W). Dose frequency changes (420 mg QM vs 420 mg Q2W) were permitted at week 12, 24, or other visits with Sponsor approval. Participants with < 5% LDL-C reduction from baseline and serum unbound proprotein convertase subtilisin/kexin type 9 (PCSK9) < 100 ng/mL could discontinue evolocumab. If serum unbound PCSK9 was ≥ 100 ng/mL with QM dosing, the participant could switch to evolocumab 420 mg Q2W treatment. Participants on apheresis with ≥ 5% LDL-C reduction from baseline and serum unbound PCSK9 < 100 ng/mL with Q2W treatment could switch to QM dosing.
Participants were to continue to receive open-label evolocumab for up to 5 years or until evolocumab became commercially available in the relevant patient population, whichever occurred first.
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
- 12 Years 至 80 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •- Participated in Study 20110233 (NCT01588496) or another qualifying evolocumab parent protocol and have a diagnosis of familial hypercholesterolemia.
- •Have a diagnosis of familial hypercholesterolemia AND
- •Males and females ≥ 12 to ≤ 80 years of age
- •Stable low-fat diet and lipid-lowering therapies for at least 4 weeks
- •Low-density lipoprotein cholesterol (LDL-C) >= 130 mg/dl (3.4 mmol/L) for subjects without diagnosed coronary heart disease (CHD)/CHD risk equivalent OR LDL-C >= 100 mg/dl (2.6 mmol/L) for subjects with diagnosed CHD or CHD risk equivalent OR apheresis patients have no LDL-C entry requirement
- •Fasting triglycerides ≤ 400 mg/dL(4.5 mmol/L)
- •Body weight of > 40 kg or greater at screening for subjects less than 18 years of age
排除标准
- •New York Heart Failure Association (NYHA) class III or IV or last known left ventricular ejection fraction < 30%
- •Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke within 3 months of screening
- •Planned cardiac surgery or revascularization
- •Uncontrolled cardiac arrhythmia
- •Uncontrolled hypertension
结局指标
主要结局
Number of Participants With Adverse Events
时间窗: From first dose of study drug in Study 20110271 up to 30 days after the last dose or until the end of study date, whichever was earlier; median duration of treatment was 48.7 months.
The severity of each adverse event (AE) was graded according to the National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) grading scale, where grade 1 = mild AE, grade 2 = moderate AE, grade 3 = severe AE, grade 4 = life-threatening AE and grade 5 = death due to AE.
次要结局
- Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)(Baseline and weeks 4, 6, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, and 216)
- Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)(Baseline and weeks 4, 6, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, and 216)
- Percent Change From Baseline in Lipoprotein (a)(Baseline and weeks 4, 6, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, and 216)
- Percent Change From Baseline in Apolipoprotein B(Baseline and weeks 4, 6, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, and 216)
- Percent Change From Baseline in Total Cholesterol/HDL-C Ratio(Baseline and weeks 4, 6, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, and 216)
- Percentage of Participants With a 15% or Greater Reduction in LDL-C(Baseline and weeks 4, 6, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, and 216)
- Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio(Baseline and weeks 4, 6, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, and 216)