An 8-Week Open-Label, Sequential, Repeated Dose-Finding Study to Evaluate the Efficacy and Safety of Alirocumab in Children and Adolescents With Heterozygous Familial Hypercholesterolemia Followed by an Extension Phase
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 42
- 试验地点
- 16
- 主要终点
- Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8
研究概览
简要总结
Primary Objective:
To evaluate the effect of alirocumab on low-density lipoprotein cholesterol (LDL-C) levels after 8 weeks of treatment in heterozygous familial hypercholesterolemia (heFH) participants aged of 8 to 17 years, with LDL-C >=130 milligrams per deciliter (mg/dL) (3.37 millimoles per litre [mmol/L]) on optimal stable daily dose of statin therapy +/- other lipid modifying therapies (LMTs) or a stable dose of non-statin LMTs in case of intolerance to statins for at least 4 weeks prior to the screening period.
Secondary Objective:
- To evaluate the safety and tolerability of alirocumab.
- To evaluate the pharmacokinetics profile of alirocumab.
- To evaluate the effects of alirocumab on other lipid parameters.
详细描述
For Cohorts 1 to 3, a study duration of approximately 16-23 weeks (screening period: up to 6 (+1) weeks, open-label dose finding treatment period: 8 weeks, follow up period: 6-8 weeks).
For Cohort 4, a study duration of approximately 14-19 weeks (screening period up to 6 [+1] weeks, open-label dose finding treatment period: 12 weeks).
Optional extension period: up to a maximum of 2 years for the first participants enrolled in Cohorts 1 to 3, but a maximum of approximately 5 months for the first participants enrolled in Cohort 4.
For all participants who declined participation in the phase 3 study, their last alirocumab injection was on December 2018.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 8 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Cohort 1 - Alirocumab 30 mg Q2W: <50 kg
Period 1: Participants with body weight less than (<) 50 kilograms (kg) received subcutaneous (SC) injection of alirocumab 30 milligram(mg) administered every 2 weeks (Q2W) up to 8 weeks added to lipid modifying therapy (LMT).
Period 2: Participants with body weight < 50 kg received SC injection of alirocumab 30 mg administered Q2W from Week 16 until they started receiving dose matching to Cohort 2 dosage including dose adjustment to body weight as required. Cohort 2 dosage was: if body weight was still < 50 kg, participants received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was > = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130.
干预措施: alirocumab SAR236553 (REGN727) (Drug)
Cohort 1 - Alirocumab 30 mg Q2W: <50 kg
Period 1: Participants with body weight less than (<) 50 kilograms (kg) received subcutaneous (SC) injection of alirocumab 30 milligram(mg) administered every 2 weeks (Q2W) up to 8 weeks added to lipid modifying therapy (LMT).
Period 2: Participants with body weight < 50 kg received SC injection of alirocumab 30 mg administered Q2W from Week 16 until they started receiving dose matching to Cohort 2 dosage including dose adjustment to body weight as required. Cohort 2 dosage was: if body weight was still < 50 kg, participants received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was > = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130.
干预措施: statins (Drug)
Cohort 1 - Alirocumab 30 mg Q2W: <50 kg
Period 1: Participants with body weight less than (<) 50 kilograms (kg) received subcutaneous (SC) injection of alirocumab 30 milligram(mg) administered every 2 weeks (Q2W) up to 8 weeks added to lipid modifying therapy (LMT).
Period 2: Participants with body weight < 50 kg received SC injection of alirocumab 30 mg administered Q2W from Week 16 until they started receiving dose matching to Cohort 2 dosage including dose adjustment to body weight as required. Cohort 2 dosage was: if body weight was still < 50 kg, participants received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was > = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130.
干预措施: ezetimibe (Drug)
Cohort 1 - Alirocumab 30 mg Q2W: <50 kg
Period 1: Participants with body weight less than (<) 50 kilograms (kg) received subcutaneous (SC) injection of alirocumab 30 milligram(mg) administered every 2 weeks (Q2W) up to 8 weeks added to lipid modifying therapy (LMT).
Period 2: Participants with body weight < 50 kg received SC injection of alirocumab 30 mg administered Q2W from Week 16 until they started receiving dose matching to Cohort 2 dosage including dose adjustment to body weight as required. Cohort 2 dosage was: if body weight was still < 50 kg, participants received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was > = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130.
干预措施: cholestyramine (Drug)
Cohort 1 - Alirocumab 30 mg Q2W: <50 kg
Period 1: Participants with body weight less than (<) 50 kilograms (kg) received subcutaneous (SC) injection of alirocumab 30 milligram(mg) administered every 2 weeks (Q2W) up to 8 weeks added to lipid modifying therapy (LMT).
Period 2: Participants with body weight < 50 kg received SC injection of alirocumab 30 mg administered Q2W from Week 16 until they started receiving dose matching to Cohort 2 dosage including dose adjustment to body weight as required. Cohort 2 dosage was: if body weight was still < 50 kg, participants received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was > = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130.
干预措施: fenofibrate (Drug)
Cohort 1 - Alirocumab 30 mg Q2W: <50 kg
Period 1: Participants with body weight less than (<) 50 kilograms (kg) received subcutaneous (SC) injection of alirocumab 30 milligram(mg) administered every 2 weeks (Q2W) up to 8 weeks added to lipid modifying therapy (LMT).
Period 2: Participants with body weight < 50 kg received SC injection of alirocumab 30 mg administered Q2W from Week 16 until they started receiving dose matching to Cohort 2 dosage including dose adjustment to body weight as required. Cohort 2 dosage was: if body weight was still < 50 kg, participants received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was > = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130.
干预措施: omega-3 fatty acids (Drug)
Cohort 1 - Alirocumab 30 mg Q2W: <50 kg
Period 1: Participants with body weight less than (<) 50 kilograms (kg) received subcutaneous (SC) injection of alirocumab 30 milligram(mg) administered every 2 weeks (Q2W) up to 8 weeks added to lipid modifying therapy (LMT).
Period 2: Participants with body weight < 50 kg received SC injection of alirocumab 30 mg administered Q2W from Week 16 until they started receiving dose matching to Cohort 2 dosage including dose adjustment to body weight as required. Cohort 2 dosage was: if body weight was still < 50 kg, participants received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was > = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130.
干预措施: nicotinic acid (Drug)
Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg
Period 1: Participants with body weight greater than or equal to (>=) 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT.
Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 50 mg administered Q2W from Week 16 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130.
干预措施: alirocumab SAR236553 (REGN727) (Drug)
Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg
Period 1: Participants with body weight greater than or equal to (>=) 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT.
Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 50 mg administered Q2W from Week 16 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130.
干预措施: statins (Drug)
Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg
Period 1: Participants with body weight greater than or equal to (>=) 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT.
Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 50 mg administered Q2W from Week 16 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130.
干预措施: ezetimibe (Drug)
Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg
Period 1: Participants with body weight greater than or equal to (>=) 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT.
Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 50 mg administered Q2W from Week 16 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130.
干预措施: cholestyramine (Drug)
Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg
Period 1: Participants with body weight greater than or equal to (>=) 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT.
Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 50 mg administered Q2W from Week 16 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130.
干预措施: fenofibrate (Drug)
Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg
Period 1: Participants with body weight greater than or equal to (>=) 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT.
Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 50 mg administered Q2W from Week 16 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130.
干预措施: omega-3 fatty acids (Drug)
Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg
Period 1: Participants with body weight greater than or equal to (>=) 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT.
Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 50 mg administered Q2W from Week 16 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130.
干预措施: nicotinic acid (Drug)
Cohort 2 - Alirocumab 40 mg Q2W: <50 kg
Period 1: Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT.
Period 2: Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W from Week 16 until switch of dosage in Cohorts 1 and 3. If body weight was still < 50 kg, participants continued to receive SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was > = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130.
干预措施: alirocumab SAR236553 (REGN727) (Drug)
Cohort 2 - Alirocumab 40 mg Q2W: <50 kg
Period 1: Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT.
Period 2: Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W from Week 16 until switch of dosage in Cohorts 1 and 3. If body weight was still < 50 kg, participants continued to receive SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was > = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130.
干预措施: statins (Drug)
Cohort 2 - Alirocumab 40 mg Q2W: <50 kg
Period 1: Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT.
Period 2: Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W from Week 16 until switch of dosage in Cohorts 1 and 3. If body weight was still < 50 kg, participants continued to receive SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was > = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130.
干预措施: ezetimibe (Drug)
Cohort 2 - Alirocumab 40 mg Q2W: <50 kg
Period 1: Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT.
Period 2: Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W from Week 16 until switch of dosage in Cohorts 1 and 3. If body weight was still < 50 kg, participants continued to receive SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was > = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130.
干预措施: cholestyramine (Drug)
Cohort 2 - Alirocumab 40 mg Q2W: <50 kg
Period 1: Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT.
Period 2: Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W from Week 16 until switch of dosage in Cohorts 1 and 3. If body weight was still < 50 kg, participants continued to receive SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was > = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130.
干预措施: fenofibrate (Drug)
Cohort 2 - Alirocumab 40 mg Q2W: <50 kg
Period 1: Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT.
Period 2: Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W from Week 16 until switch of dosage in Cohorts 1 and 3. If body weight was still < 50 kg, participants continued to receive SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was > = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130.
干预措施: omega-3 fatty acids (Drug)
Cohort 2 - Alirocumab 40 mg Q2W: <50 kg
Period 1: Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT.
Period 2: Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W from Week 16 until switch of dosage in Cohorts 1 and 3. If body weight was still < 50 kg, participants continued to receive SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was > = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130.
干预措施: nicotinic acid (Drug)
Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg
Period 1: Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT.
Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W from Week 16 until Week 130.
干预措施: alirocumab SAR236553 (REGN727) (Drug)
Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg
Period 1: Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT.
Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W from Week 16 until Week 130.
干预措施: statins (Drug)
Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg
Period 1: Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT.
Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W from Week 16 until Week 130.
干预措施: ezetimibe (Drug)
Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg
Period 1: Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT.
Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W from Week 16 until Week 130.
干预措施: cholestyramine (Drug)
Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg
Period 1: Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT.
Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W from Week 16 until Week 130.
干预措施: fenofibrate (Drug)
Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg
Period 1: Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT.
Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W from Week 16 until Week 130.
干预措施: omega-3 fatty acids (Drug)
Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg
Period 1: Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT.
Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W from Week 16 until Week 130.
干预措施: nicotinic acid (Drug)
Cohort 3 - Alirocumab 75 mg Q4W: <50 kg
Period 1: Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered every 4 weeks (Q4W) up to 8 weeks added to LMT.
Period 2: Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered Q4W from Week 14 until switch to Cohort 2 dosage including dose adjustment to body weight as required, then Cohort 2 dosage: if body weight was still < 50 kg, participants received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was > = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130.
干预措施: alirocumab SAR236553 (REGN727) (Drug)
Cohort 3 - Alirocumab 75 mg Q4W: <50 kg
Period 1: Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered every 4 weeks (Q4W) up to 8 weeks added to LMT.
Period 2: Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered Q4W from Week 14 until switch to Cohort 2 dosage including dose adjustment to body weight as required, then Cohort 2 dosage: if body weight was still < 50 kg, participants received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was > = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130.
干预措施: statins (Drug)
Cohort 3 - Alirocumab 75 mg Q4W: <50 kg
Period 1: Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered every 4 weeks (Q4W) up to 8 weeks added to LMT.
Period 2: Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered Q4W from Week 14 until switch to Cohort 2 dosage including dose adjustment to body weight as required, then Cohort 2 dosage: if body weight was still < 50 kg, participants received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was > = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130.
干预措施: ezetimibe (Drug)
Cohort 3 - Alirocumab 75 mg Q4W: <50 kg
Period 1: Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered every 4 weeks (Q4W) up to 8 weeks added to LMT.
Period 2: Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered Q4W from Week 14 until switch to Cohort 2 dosage including dose adjustment to body weight as required, then Cohort 2 dosage: if body weight was still < 50 kg, participants received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was > = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130.
干预措施: cholestyramine (Drug)
Cohort 3 - Alirocumab 75 mg Q4W: <50 kg
Period 1: Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered every 4 weeks (Q4W) up to 8 weeks added to LMT.
Period 2: Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered Q4W from Week 14 until switch to Cohort 2 dosage including dose adjustment to body weight as required, then Cohort 2 dosage: if body weight was still < 50 kg, participants received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was > = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130.
干预措施: fenofibrate (Drug)
Cohort 3 - Alirocumab 75 mg Q4W: <50 kg
Period 1: Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered every 4 weeks (Q4W) up to 8 weeks added to LMT.
Period 2: Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered Q4W from Week 14 until switch to Cohort 2 dosage including dose adjustment to body weight as required, then Cohort 2 dosage: if body weight was still < 50 kg, participants received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was > = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130.
干预措施: omega-3 fatty acids (Drug)
Cohort 3 - Alirocumab 75 mg Q4W: <50 kg
Period 1: Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered every 4 weeks (Q4W) up to 8 weeks added to LMT.
Period 2: Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered Q4W from Week 14 until switch to Cohort 2 dosage including dose adjustment to body weight as required, then Cohort 2 dosage: if body weight was still < 50 kg, participants received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was > = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130.
干预措施: nicotinic acid (Drug)
Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg
Period 1: Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT.
Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W from Week 14 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130.
干预措施: alirocumab SAR236553 (REGN727) (Drug)
Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg
Period 1: Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT.
Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W from Week 14 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130.
干预措施: statins (Drug)
Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg
Period 1: Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT.
Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W from Week 14 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130.
干预措施: ezetimibe (Drug)
Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg
Period 1: Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT.
Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W from Week 14 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130.
干预措施: cholestyramine (Drug)
Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg
Period 1: Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT.
Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W from Week 14 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130.
干预措施: fenofibrate (Drug)
Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg
Period 1: Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT.
Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W from Week 14 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130.
干预措施: omega-3 fatty acids (Drug)
Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg
Period 1: Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT.
Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W from Week 14 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130.
干预措施: nicotinic acid (Drug)
Cohort 4 - Alirocumab 150 mg Q4W: <50 kg
Period 1: Participants with body weight < 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT.
Period 2: Participants with body weight < 50 kg received SC injection of Alirocumab 150 mg administered Q4W from Week 12 until Week 48.
干预措施: alirocumab SAR236553 (REGN727) (Drug)
Cohort 4 - Alirocumab 150 mg Q4W: <50 kg
Period 1: Participants with body weight < 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT.
Period 2: Participants with body weight < 50 kg received SC injection of Alirocumab 150 mg administered Q4W from Week 12 until Week 48.
干预措施: statins (Drug)
Cohort 4 - Alirocumab 150 mg Q4W: <50 kg
Period 1: Participants with body weight < 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT.
Period 2: Participants with body weight < 50 kg received SC injection of Alirocumab 150 mg administered Q4W from Week 12 until Week 48.
干预措施: ezetimibe (Drug)
Cohort 4 - Alirocumab 150 mg Q4W: <50 kg
Period 1: Participants with body weight < 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT.
Period 2: Participants with body weight < 50 kg received SC injection of Alirocumab 150 mg administered Q4W from Week 12 until Week 48.
干预措施: cholestyramine (Drug)
Cohort 4 - Alirocumab 150 mg Q4W: <50 kg
Period 1: Participants with body weight < 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT.
Period 2: Participants with body weight < 50 kg received SC injection of Alirocumab 150 mg administered Q4W from Week 12 until Week 48.
干预措施: fenofibrate (Drug)
Cohort 4 - Alirocumab 150 mg Q4W: <50 kg
Period 1: Participants with body weight < 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT.
Period 2: Participants with body weight < 50 kg received SC injection of Alirocumab 150 mg administered Q4W from Week 12 until Week 48.
干预措施: omega-3 fatty acids (Drug)
Cohort 4 - Alirocumab 150 mg Q4W: <50 kg
Period 1: Participants with body weight < 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT.
Period 2: Participants with body weight < 50 kg received SC injection of Alirocumab 150 mg administered Q4W from Week 12 until Week 48.
干预措施: nicotinic acid (Drug)
Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg
Period 1: Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT.
Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W from Week 12 until Week 48.
干预措施: alirocumab SAR236553 (REGN727) (Drug)
Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg
Period 1: Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT.
Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W from Week 12 until Week 48.
干预措施: statins (Drug)
Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg
Period 1: Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT.
Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W from Week 12 until Week 48.
干预措施: ezetimibe (Drug)
Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg
Period 1: Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT.
Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W from Week 12 until Week 48.
干预措施: cholestyramine (Drug)
Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg
Period 1: Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT.
Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W from Week 12 until Week 48.
干预措施: fenofibrate (Drug)
Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg
Period 1: Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT.
Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W from Week 12 until Week 48.
干预措施: omega-3 fatty acids (Drug)
Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg
Period 1: Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT.
Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W from Week 12 until Week 48.
干预措施: nicotinic acid (Drug)
结局指标
主要结局
Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8
时间窗: Baseline, Week 8
Percent change in calculated LDL-C was defined as 100\*(calculated LDL-C value at Week 8 - calculated LDL-C value at baseline)/calculated LDL-C value at baseline. All available baseline and post-baseline calculated LDL-C value during the OLDFI efficacy treatment period \& within one of the analysis windows up to Week 8 were used in the model. OLDFI efficacy treatment period was defined as the period from first investigational medicinal product (IMP) injection to last OLDFI IMP injection + 21 days(for Cohorts 1 \& 2) or +35 days (for Cohorts 3 \& 4). Adjusted Least-squares (LS) mean \& standard error (SE) at Week 8 were obtained from mixed-effect model with repeated measures (MMRM) analysis, with fixed categorical effects of alirocumab dose/dose regimen (30 mg Q2W \[\<50 kg\], 40 mg Q2W \[\<50 kg\], 50 mg Q2W \[\>=50 kg\], 75 mg Q2W \[\>=50 kg\], 75 mg Q4W \[\<50 kg\],150 mg Q4W \[\>=50 kg\], 150 mg Q4W \[\<50 kg\] and 300 mg Q4W (\[\>=50 kg\] dose), time point \& dose/dose regimen-by-time point interaction.
次要结局
- Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 8(Baseline, Week 8)
- Percent Change From Baseline in Apolipoprotein A-1 at Week 8(Baseline, Week 8)
- Absolute Change From Baseline in Apolipoprotein B at Week 8(Baseline, Week 8)
- Absolute Change From Baseline in HDL-C at Week 8(Baseline, Week 8)
- Absolute Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8(Baseline, Week 8)
- Percentage of Participants Achieving Calculated Low Density Lipoprotein Cholesterol (LDL-C) <130 mg/dL (3.37 mmol/L) at Week 8(At Week 8)
- Percentage of Participants Achieving Calculated LDL-C <110 mg/dL (2.84 mmol/L) at Week 8(At Week 8)
- Percent Change From Baseline in Calculated LDL-C at Week 12: Cohort 4(Baseline, Week 12)
- Absolute Change From Baseline in Total Cholesterol (Total-C) at Week 8(Baseline, Week 8)
- Percent Change From Baseline in Apolipoprotein (Apo) B at Week 8(Baseline, Week 8)
- Percent Change From Baseline in Non-High Density Lipoprotein (HDL-C) at Week 8(Baseline, Week 8)
- Percent Change From Baseline in Total Cholesterol (Total-C) at Week 8(Baseline, Week 8)
- Percent Change From Baseline in Lipoprotein(a) at Week 8(Baseline, Week 8)
- Percent Change From Baseline in Fasting Triglyceride at Week 8(Baseline, Week 8)
- Absolute Change From Baseline in Non-High-Density Lipoprotein (Non-HDL-C) at Week 8(Baseline, Week 8)
- Absolute Change From Baseline in Lipoprotein(a) at Week 8(Baseline, Week 8)
- Absolute Change From Baseline in Fasting Triglyceride at Week 8(Baseline, Week 8)
- Absolute Change From Baseline in Apolipoprotein A-1 at Week 8(Baseline, Week 8)
- Absolute Change From Baseline in Ratio Apolipoprotein B/Apolipoprotein A-1 at Week 8(Baseline, Week 8)