A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Alirocumab in Patients With Heterozygous Familial Hypercholesterolemia Undergoing Lipid Apheresis Therapy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 62
- 主要终点
- Change in Standardized Rate of Apheresis Treatments From Week 7 to Week 18
研究概览
简要总结
The primary objective of the study is to evaluate the effect of alirocumab 150 mg every 2 weeks (Q2W) in comparison with placebo on the frequency of low-density lipoprotein (LDL) apheresis treatments in participants with heterozygous familial hypercholesterolemia (HeFH) undergoing weekly or bi-weekly LDL apheresis therapy.
详细描述
LDL apheresis removes low-density lipoproteins (LDL) that transport cholesterol in the plasma portion of the blood. This treatment is mainly used for familial hypercholesterolemia, but can be used in other rare diseases. Familial hypercholesterolemia (HeFH) is an inherited genetic condition that causes accumulation of cholesterol in the blood, which can lead to atherosclerosis and heart disease. This treatment is recommended for patients who do not respond to dietary and/or medication control of LDL cholesterol.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women ≥18 years of age at the time of the screening visit
- •Diagnosis of HeFH (Heterozygous familial hypercholesterolemia)
- •Currently undergoing LDL (low-density lipoprotein) apheresis therapy QW (weekly) or Q2W (every 2 weeks) or at least 8 weeks prior to the screening visit
排除标准
- •Homozygous FH (familial hypercholesterolemia)
- •Background medical LMT (lipid-modifying therapy) (if applicable) that has not been stable for at least 8 weeks prior to the screening visit
- •LDL apheresis schedule/ apheresis settings that have not been stable for at least 8 weeks prior to the screening visit
- •An LDL apheresis schedule other than QW to Q2W
- •Initiation of a new exercise program or exercise that has not remained stable within 8 weeks prior to the screening visit (week -2)
- •Initiation of a new diet or a diet that has not been stable within 8 weeks prior to the screening visit (week -2)
- •Use of nutraceuticals or over-the-counter therapies known to affect lipids, at a dose/amount that has not been stable for at least 8 weeks prior to the screening visit (week -2), or between the screening and randomization visit
- •Presence of any clinically significant uncontrolled endocrine disease known to influence serum lipids or lipoproteins
- •Known history of a positive test for human immunodeficiency virus
- •Use of any active investigational drugs within 1 month or 5 half-lives of screening, whichever is longer
- •Patients who have been treated with at least 1 dose of alirocumab or any other anti-PCSK9 monoclonal antibody in any other clinical studies
- •Pregnant or breastfeeding women
研究组 & 干预措施
Placebo Q2W (Double Blind Period)
Placebo (for alirocumab) subcutaneous (SC) injection Q2W up to Week 16.
干预措施: Placebo (Drug)
Alirocumab 150 mg Q2W (Double Blind Period)
Alirocumab 150 mg SC injection Q2W up to Week 16.
干预措施: Alirocumab (Drug)
Alirocumab 150 Q2W (Open Label Treatment Period)
Alirocumab 150 mg SC injection Q2W starting from Week 18 up to Week 76.
干预措施: Alirocumab (Drug)
结局指标
主要结局
Change in Standardized Rate of Apheresis Treatments From Week 7 to Week 18
时间窗: Week 7 to Week 18 (before start of open-label treatment)
Rate of apheresis treatments were normalized by the number of planned apheresis treatments according to each participant's established schedule at screening, week -10 to week -2. The normalized rate of apheresis was defined for each participant as the number of actual apheresis treatments received from week 7 to week 18 divided by the number of planned apheresis treatments per randomization strata at baseline (6 for Q2W and 12 for QW).
次要结局
- Percent Change From Baseline in Calculated LDL-C (Pre-apheresis) at Week 6(Baseline and at Week 6)
- Change in Standardized Rate of Apheresis Treatments From Week 15 to Week 18(Week 15 up to Week 18 (before the start of open-label treatment dose))
- Percent Change From Baseline in Apolipoprotein B (Apo B) (Pre-apheresis) to Week 6(From Baseline to Week 6)
- Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) (Pre-apheresis) to Week 6(From Baseline to Week 6)
- Percent Change From Baseline in Total Cholesterol (Pre-apheresis) to Week 6(From Baseline to Week 6)
- Percent Change From Baseline in Apolipoprotein A (Apo A1) (Pre-apheresis) to Week 6(From Baseline to Week 6)
- Percentage of Participants With At Least (>=) 30% Reduction in Calculated LDL-C (Pre-apheresis) at Week 6(From Baseline to Week 6)
- Percentage of Participants With At Least (>=) 50% Reduction in Calculated LDL-C (Pre-apheresis) at Week 6(From Baseline to Week 6)
- Percent Change From Baseline in Calculated LDL-C (Pre-Apheresis) to Week 18(From Baseline to Week 18)
- Percent Change From Baseline in Apolipoprotein B (Apo B) (Pre-apheresis) to Week 18(From Baseline to Week 18)
- Percent Change From Baseline in Non-HDL-C (Pre-apheresis) to Week 18(From Baseline to Week 18)
- Percent Change From Baseline in Total Cholesterol (Pre-apheresis) to Week 18(From Baseline to Week 18)
- Percent Change From Baseline in Apo A1 (Pre-apheresis) to Week 18(From Baseline to Week 18)
- Percentage of Participants With At Least (>=) 30% Reduction in Calculated LDL-C (Pre-apheresis) at Week 18(From Baseline to Week 18)
- Percentage of Participants With At Least (>=) 50% Reduction in Calculated LDL-C (Pre-apheresis) at Week 18(From Baseline to Week 18)
- Change From Baseline in W-BQ22 (Well-being Questionnaire) Index Score at Week 18(From Baseline to Week 18)
- Percent Change From Baseline in Lipoprotein (a) (Lp [a]) (Pre-apheresis) to Week 6(From Baseline to Week 6)
- Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) (Pre-apheresis) to Week 6(From Baseline to Week 6)
- Percent Change From Baseline in Triglyceride (TG) Levels (Pre-apheresis) to Week 6(From Baseline to Week 6)
- Percent Change From Baseline in Lp (a) (Pre-apheresis) to Week 18(From Baseline to Week 18)
- Percent Change From Baseline in HDL-C (Pre-apheresis) to Week 18(From Baseline to Week 18)
- Percent Change From Baseline in TG Levels (Pre-apheresis) to Week 18(From Baseline to Week 18)