A Randomized, Double-Blind, Placebo-Controlled, 12-Week Study of the Safety and Efficacy of REGN727 in Patients With Heterozygous Familial Hypercholesterolemia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 77
- 主要终点
- Percent Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis
研究概览
简要总结
The purpose of this study is to assess the efficacy and safety of REGN727/SAR236553 in participants diagnosed with heterozygous familial hypercholesterolemia (heFH)
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must meet the World Health Organization criteria for heFH
- •Participants must be on a stable statin dose, with or without ezetimibe, for at least 6 weeks before screening
- •Serum LDL-C levels ≥ 100 mg/dL at screening
- •Willing to follow the NCEP ATPIII TLC diet, or an equivalent diet plan, starting at screening and continuing until the last study visit
- •A negative urine/serum pregnancy test at each screening visit and start of the study, for women of childbearing potential
排除标准
- •Participants with homozygous FH (clinically or by previous genotyping)
- •Use of a medication (other than a statin or EZE) to alter serum lipids within 42 days (6 weeks) before screening including, but not limited to:
- •Niacin (>500 mg/day)
- •Omega-3 fatty acids (>1000 mg/day of DHA/EPA)
- •Bile acid resins
- •Use of nutraceuticals or OTC medications that may alter lipid levels that are not stable for at least 6 weeks before screening and are not planned to remain constant throughout the study. Examples include:
- •Omega-3 fatty acids (≤1000 mg/day of DHA/EPA)
- •Niacin (≤500 mg/day)
- •Plant stanols, such as found in Benecol, flax seed oil, psyllium
- •Red yeast rice
- •Disorders known to influence lipid levels, such as nephrotic syndrome, significant liver disease, Cushing's disease, untreated hypothyroidism (patients on stable thyroid replacement for at least 12 weeks before the full screening visit, who are metabolically euthyroid by thyroid-stimulating hormone (TSH) testing are allowed)
- •Use of thyroid medications (except for replacement therapy which has been stable for at least 12 weeks before the full screening visit)
- •Fasting serum TG >350 mg/dL screening
- •LDL apheresis within 12 months before screening
研究组 & 干预措施
Placebo
Placebo SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
干预措施: Placebo (Drug)
Alirocumab 150 mg Q4W
Alirocumab 150 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
干预措施: Alirocumab (Drug)
Alirocumab 200 mg Q4W
Alirocumab 200 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
干预措施: Alirocumab (Drug)
Alirocumab 300 mg Q4W
Alirocumab 300 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
干预措施: Alirocumab (Drug)
Alirocumab 150 mg Q2W
Alirocumab 150 mg SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
干预措施: Alirocumab (Drug)
结局指标
主要结局
Percent Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis
时间窗: From Baseline to Week 12 (LOCF)
Calculated LDL-C values were obtained using the Friedewald formula. Baseline adjusted least squares (LS) means and standard errors were estimated using an analysis of covariance (ANCOVA) model including available post-baseline data on treatment from first investigational medicinal product (IMP) injection up to 21 days after last IMP injection (on-treatment analysis). Missing Week 12 data were imputed by last observation carried forward \[LOCF\] method.
次要结局
- Absolute Change From Baseline in Lipoprotein(a) at Week 12 - On-treatment Analysis(From Baseline to Week 12 (LOCF))
- Percent Change From Baseline in Total Cholesterol at Week 12 - On-treatment Analysis(From Baseline to Week 12 (LOCF))
- Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 12 - On-treatment Analysis(From Baseline to Week 12 (LOCF))
- Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 12 - On-treatment Analysis(Week 12 (LOCF))
- Absolute Change From Baseline in Total Cholesterol at Week 12 - On-treatment Analysis(From Baseline to Week 12 (LOCF))
- Absolute Change From Baseline in HDL-C at Week 12 - On-treatment Analysis(From Baseline to Week 12 (LOCF))
- Percent Change From Baseline in Triglycerides at Week 12 - On-treatment Analysis(From Baseline to Week 12 (LOCF))
- Percent Change From Baseline in Non-HDL-C at Week 12 - On-treatment Analysis(From Baseline to Week 12)
- Absolute Change From Baseline in Non-HDL-C at Week 12 - On-treatment Analysis(From Baseline to Week 12 (LOCF))
- Percent Change From Baseline in Apo Lipoprotein B (Apo-B) at Week 12 - On-treatment Analysis(From Baseline to Week 12 (LOCF))
- Absolute Change From Baseline in Apo-B at Week 12 - On-treatment Analysis(From Baseline to Week 12)
- Percent Change From Baseline in Apolipoprotein - A1 (Apo-A1) at Week 12 - On-treatment Analysis(From Baseline to Week 12 (LOCF))
- Absolute Change From Baseline in Apo-A1 at Week 12 - On-treatment Analysis(From Baseline to Week 12 (LOCF))
- Percent Change From Baseline in Lipoprotein(a) at Week 12 - On-treatment Analysis(From Baseline to Week 12 (LOCF))
- Absolute Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis(From Baseline to Week 12 (LOCF))
- Percentage of Participants Achieving LDL-C < 70 mg/dL (1.81 mmol/L) at Week 12 - On-treatment Analysis(Week 12 (LOCF))
- Absolute Change From Baseline in Triglycerides at Week at 12 - On-treatment Analysis(From Baseline to Week 12 (LOCF))
- Absolute Change in the Ratio ApoB/ApoA-1 From Baseline to Week 12 - On-treatment Analysis(From Baseline to Week 12)