An Open-Label Study to Evaluate the Efficacy and Safety of Alirocumab in Children and Adolescents With Homozygous Familial Hypercholesterolemia
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 18
- 试验地点
- 10
- 主要终点
- Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12: Intent-to-Treat (ITT) Analysis
研究概览
简要总结
Primary Objective:
To evaluate the efficacy of alirocumab (75 or 150 milligrams [mg] depending on body weight [BW]), administered every 2 weeks (Q2W), on low-density lipoprotein cholesterol (LDL-C) levels at Week 12 of treatment in children and adolescents with homozygous familial hypercholesterolemia (hoFH) of 8 to 17 years of age on top of background treatments.
Secondary Objectives:
- To evaluate the efficacy of alirocumab after 24 and 48 weeks of treatment on LDL-C levels.
- To evaluate the effects of alirocumab on other lipid parameters (eg, apolipoprotein B [Apo B], non-high density lipoprotein cholesterol [non-HDL-C], total cholesterol [Total-C], high density lipoprotein cholesterol [HDL-C], lipoprotein a [Lp (a)], triglycerides [TG], apolipoprotein A-1 [Apo A-1] levels) after 12, 24, and 48 weeks of treatment.
- To evaluate the safety and tolerability of alirocumab up to 48 weeks of treatment.
详细描述
The study duration was up to 62 weeks, which included (if needed) a run-in period of up to 4 weeks, a screening period of up to 2 weeks, a treatment period of up to 48 weeks, and a follow-up of 8 weeks.
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
- 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
Alirocumab
Participants with BW less than (<) 50 kilograms (kg) received subcutaneous (SC) injection of alirocumab 75 mg Q2W for 48 weeks. Alirocumab dose was up-titrated to 150 mg Q2W from Week 12 in case of increase in BW with BW greater than or equal to [>=] 50 kg.
Participants with BW >=50 kg received SC injection of alirocumab 150 mg Q2W for 48 weeks.
干预措施: Alirocumab SAR236553 (REGN727) (Drug)
Alirocumab
Participants with BW less than (<) 50 kilograms (kg) received subcutaneous (SC) injection of alirocumab 75 mg Q2W for 48 weeks. Alirocumab dose was up-titrated to 150 mg Q2W from Week 12 in case of increase in BW with BW greater than or equal to [>=] 50 kg.
Participants with BW >=50 kg received SC injection of alirocumab 150 mg Q2W for 48 weeks.
干预措施: Atorvastatin (Drug)
Alirocumab
Participants with BW less than (<) 50 kilograms (kg) received subcutaneous (SC) injection of alirocumab 75 mg Q2W for 48 weeks. Alirocumab dose was up-titrated to 150 mg Q2W from Week 12 in case of increase in BW with BW greater than or equal to [>=] 50 kg.
Participants with BW >=50 kg received SC injection of alirocumab 150 mg Q2W for 48 weeks.
干预措施: Simvastatin (Drug)
Alirocumab
Participants with BW less than (<) 50 kilograms (kg) received subcutaneous (SC) injection of alirocumab 75 mg Q2W for 48 weeks. Alirocumab dose was up-titrated to 150 mg Q2W from Week 12 in case of increase in BW with BW greater than or equal to [>=] 50 kg.
Participants with BW >=50 kg received SC injection of alirocumab 150 mg Q2W for 48 weeks.
干预措施: Fluvastatin (Drug)
Alirocumab
Participants with BW less than (<) 50 kilograms (kg) received subcutaneous (SC) injection of alirocumab 75 mg Q2W for 48 weeks. Alirocumab dose was up-titrated to 150 mg Q2W from Week 12 in case of increase in BW with BW greater than or equal to [>=] 50 kg.
Participants with BW >=50 kg received SC injection of alirocumab 150 mg Q2W for 48 weeks.
干预措施: Pravastatin (Drug)
Alirocumab
Participants with BW less than (<) 50 kilograms (kg) received subcutaneous (SC) injection of alirocumab 75 mg Q2W for 48 weeks. Alirocumab dose was up-titrated to 150 mg Q2W from Week 12 in case of increase in BW with BW greater than or equal to [>=] 50 kg.
Participants with BW >=50 kg received SC injection of alirocumab 150 mg Q2W for 48 weeks.
干预措施: Lovastatin (Drug)
Alirocumab
Participants with BW less than (<) 50 kilograms (kg) received subcutaneous (SC) injection of alirocumab 75 mg Q2W for 48 weeks. Alirocumab dose was up-titrated to 150 mg Q2W from Week 12 in case of increase in BW with BW greater than or equal to [>=] 50 kg.
Participants with BW >=50 kg received SC injection of alirocumab 150 mg Q2W for 48 weeks.
干预措施: Rosuvastatin (Drug)
Alirocumab
Participants with BW less than (<) 50 kilograms (kg) received subcutaneous (SC) injection of alirocumab 75 mg Q2W for 48 weeks. Alirocumab dose was up-titrated to 150 mg Q2W from Week 12 in case of increase in BW with BW greater than or equal to [>=] 50 kg.
Participants with BW >=50 kg received SC injection of alirocumab 150 mg Q2W for 48 weeks.
干预措施: Ezetimibe (Drug)
Alirocumab
Participants with BW less than (<) 50 kilograms (kg) received subcutaneous (SC) injection of alirocumab 75 mg Q2W for 48 weeks. Alirocumab dose was up-titrated to 150 mg Q2W from Week 12 in case of increase in BW with BW greater than or equal to [>=] 50 kg.
Participants with BW >=50 kg received SC injection of alirocumab 150 mg Q2W for 48 weeks.
干预措施: Cholestyramine (Drug)
Alirocumab
Participants with BW less than (<) 50 kilograms (kg) received subcutaneous (SC) injection of alirocumab 75 mg Q2W for 48 weeks. Alirocumab dose was up-titrated to 150 mg Q2W from Week 12 in case of increase in BW with BW greater than or equal to [>=] 50 kg.
Participants with BW >=50 kg received SC injection of alirocumab 150 mg Q2W for 48 weeks.
干预措施: Nicotinic acid (Drug)
Alirocumab
Participants with BW less than (<) 50 kilograms (kg) received subcutaneous (SC) injection of alirocumab 75 mg Q2W for 48 weeks. Alirocumab dose was up-titrated to 150 mg Q2W from Week 12 in case of increase in BW with BW greater than or equal to [>=] 50 kg.
Participants with BW >=50 kg received SC injection of alirocumab 150 mg Q2W for 48 weeks.
干预措施: Fenofibrate (Drug)
Alirocumab
Participants with BW less than (<) 50 kilograms (kg) received subcutaneous (SC) injection of alirocumab 75 mg Q2W for 48 weeks. Alirocumab dose was up-titrated to 150 mg Q2W from Week 12 in case of increase in BW with BW greater than or equal to [>=] 50 kg.
Participants with BW >=50 kg received SC injection of alirocumab 150 mg Q2W for 48 weeks.
干预措施: Omega-3 fatty acids (Drug)
结局指标
主要结局
Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12: Intent-to-Treat (ITT) Analysis
时间窗: Baseline to Week 12
Adjusted least square (LS) means and standard errors were obtained from the mixed model analysis with repeated measures (MMRM) to account for missing data using all available post-baseline data from Week 4 to Week 48 regardless of status on- or off-treatment used in the model (ITT analysis).
次要结局
- Percent Change From Baseline in Apolipoprotein A1 (Apo A1) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis(Baseline to Weeks 12, 24 and 48)
- Number of Participants With Tanner Staging at Baseline, Weeks 12, 24 and 48(Baseline, Weeks 12, 24 and 48)
- Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Weeks 12, 24 and 48 - ITT Analysis/On-treatment Analysis(Baseline to Weeks 12, 24 and 48)
- Percent Change From Baseline in Total Cholesterol (Total-C) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis(Baseline to Weeks 12, 24 and 48)
- Percent Change From Baseline in Lipoprotein a (Lp) (a) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis(Baseline to Weeks 12, 24 and 48)
- Percentage of Participants Reporting >=15 Percent (%) Reduction in LDL-C Level at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis(Baseline to Weeks 12, 24 and 48)
- Percent Change From Baseline in Low-Density Lipoprotein Cholesterol at Week 12: On-treatment Analysis(Baseline to Week 12)
- Percent Change From Baseline in Low-Density Lipoprotein Cholesterol at Weeks 24 and 48: ITT Analysis/On-treatment Analysis(Baseline to Weeks 24 and 48)
- Percent Change From Baseline in Apolipoprotein (Apo) B at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis(Baseline to Weeks 12, 24 and 48)
- Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis(Baseline to Weeks 12, 24 and 48)
- Percent Change From Baseline in Fasting Triglycerides (TG) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis(Baseline to Weeks 12, 24 and 48)
- Absolute Change From Baseline in LDL-C Level at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis(Baseline to Weeks 12, 24 and 48)