NCT03156621已完成3 期
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Alirocumab in Patients With Homozygous Familial Hypercholesterolemia
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 69
- 试验地点
- 2
- 主要终点
- Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 12 (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) with alirocumab subcutaneous (SC) every 2 weeks (Q2W) in comparison to placebo after 12 weeks of treatment.
The secondary objectives of the study are:
- To evaluate the effect of alirocumab Q2W on other lipid parameters (ie, apolipoprotein [Apo] A-1 and B, non-high-density lipoprotein cholesterol [non-HDL-C], total-cholesterol [TC], proportion of participants with 15%, 30%, and 50% LDL-C reductions, Lp(a), HDL-C, triglycerides [TG]) in participants with HoFH
- To evaluate the safety and tolerability of alirocumab SC Q2W in participants with HoFH
- To assess the pharmacokinetics of alirocumab SC Q2W in participants with HoFH
- To assess the potential development of anti-drug (alirocumab) 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
- Triple (Participant, Investigator, Outcomes Assessor)
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
- 未提供
排除标准
- •Documented evidence of a null mutation in both LDLR alleles
- •Use of a PCSK9 inhibitor within 10 weeks from screening visit
- •Background medical lipid modifying therapy (LMT) that has not been stable for at least 4 weeks (6 weeks for fibrates, 24 weeks for mipomersen, 12 weeks for maximum tolerated dose of lomitapide) before the screening visit.
- •LDL apheresis schedule/apheresis settings that have not been stable for at least 8 weeks before the screening visit or an apheresis schedule/settings that is not anticipated to be stable over the next 24 weeks.
- •Use of nutraceuticals or over-the-counter (OTC) therapies known to affect lipids, at a dose/amount that has not been stable for at least 4 weeks prior to the screening visit or between the screening and randomization visits.
- •Chronic use of systemic corticosteroids, unless on a stable regimen of 10 mg daily prednisone equivalent or less for at least 6 weeks prior to randomization. Note: topical, intra-articular, nasal, inhaled and ophthalmic steroid therapies are not considered as 'systemic' and are allowed
- •Systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg at the screening visit (1 repeat measurement is allowed).
- •LDL-C level <70 mg/dL (1.81 mmol/L) at the screening visit
- •History of a myocardial infarction (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.
研究组 & 干预措施
Alirocumab SC Q2W
Experimental
Alirocumab SC every 2 weeks (Q2W) from baseline (day 1) through week 10 during the double-blind treatment period
Starting at week 12, and continuing through week 22, participants will receive open-label alirocumab SC Q2W
干预措施: Alirocumab (Drug)
Placebo SC Q2W
Experimental
Matching placebo SC Q2W from baseline through week 10 during the double-blind treatment period
Starting at week 12, and continuing through week 22, participants will receive open-label alirocumab SC Q2W
干预措施: Alirocumab (Drug)
Placebo SC Q2W
Experimental
Matching placebo SC Q2W from baseline through week 10 during the double-blind treatment period
Starting at week 12, and continuing through week 22, participants will receive open-label alirocumab SC Q2W
干预措施: Placebo (Drug)
结局指标
主要结局
Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 12 (Intent-to-Treat [ITT] Estimand)
时间窗: Baseline to Week 12
The percent change in LDL-C from baseline to week 12 is defined as: 100x (LDL-C value at week 12 - LDL-C value at baseline) / LDL-C value at baseline.
次要结局
- Percentage of Participants With ≥50% Reduction in LDL-C at Week 12(At Week 12)
- Percent Change in Non-HDL-C From Baseline to Week 12 (On-treatment Estimand)(Baseline to Week 12)
- Percent Change in Apo A-1 From Baseline to Week 12 -- ITT Analysis(Baseline to Week 12)
- Percent Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 12(Baseline to Week 12)
- Percent Change in Lipoprotein(a) [Lp(a)] From Baseline to Week 12(Baseline to Week 12)
- Percent Change in HDL-C From Baseline to Week 12 - ITT Analysis(Baseline to Week 12)
- Percent Change in Apo B From Baseline to Week 12 (On-treatment Estimand)(Baseline to Week 12)
- Percent Change in Lp(a) From Baseline to Week 12 (On-treatment Estimand)(Baseline to Week 12)
- Percent Change in Total Cholesterol (TC) From Baseline to Week 12(Baseline to Week 12)
- Percentage of Participants With ≥15% Reduction in LDL-C at Week 12(At Week 12)
- Percent Change in TC From Baseline to Week 12 (On-treatment Estimand)(Baseline to Week 12)
- Percent Change in Apo A-1 From Baseline to Week 12 (On-treatment Estimand)(Baseline to Week 12)
- Percent Change in Apolipoprotein (Apo) B From Baseline to Week 12 (ITT Estimand)(Baseline to Week 12)
- Percentage of Participants With ≥30% Reduction in LDL-C at Week 12(At Week 12)
- Percent Change in Fasting Triglycerides (TG) From Baseline to Week 12(Baseline to Week 12)
- Percent Change in LDL-C From Baseline to Week 12 (On-treatment Estimand)(Baseline to Week 12)
- Percent Change in HDL-C From Baseline to Week 12 (On-treatment Estimand)(Baseline to Week 12)
- Percent Change in Fasting TG From Baseline to Week 12 (On-treatment Estimand)(Baseline to Week 12)
- Percentage of Participants With ≥15% Reduction, ≥30% Reduction, and ≥50% Reduction in LDL-C at Week 12 (On-treatment Estimand)(At Week 12)
- Number of Participants With Adverse Events (AEs)(Baseline to week 32 (End of Study))
- Absolute Change in the Ratio of Apo B/Apo A-1 From Baseline to Week 12 (ITT Estimand)(Baseline to Week 12)
- Number of Participants With Anti-Drug Antibodies (ADA) to REGN727 Over Time(26 weeks)
研究者
研究点 (2)
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