A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of an Every Four Weeks Treatment Regimen of Alirocumab in Patients With Primary Hypercholesterolemia
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 803
- 主要终点
- Percent Change From Baseline in Calculated LDL-C in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis
研究概览
简要总结
To determine the efficacy, long-term safety, and tolerability of alirocumab 300 mg every 4 weeks (Q4W), in comparison with placebo, as well as its potential as a starting regimen. The dose regimen of 75 mg every 2 weeks (Q2W), as used in other studies, was added as a calibrator.
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 > age 18 or legal age of majority with elevated LDL-C
- •Patients not having adequate control of their hypercholesterolemia based on their individual level of CVD risk
- •Willing and able to comply with clinic visits and study-related procedures
- •Provided signed informed consent
排除标准
- •Recent (within 3 months prior to the screening visit) myocardial infarction, unstable angina leading to hospitalization, percutaneous coronary intervention (PCI), coronary artery bypass graft surgery (CABG), uncontrolled cardiac arrhythmia, stroke, transient ischemic attack, carotid revascularization, endovascular procedure or surgical intervention for peripheral vascular disease
- •Known history of positive test for human immunodeficiency virus (HIV)
- •Any clinically significant abnormality identified at the time of screening that in the judgment of the investigator or any sub-investigator would preclude safe completion of the study or constrain assessment of endpoints, such as major systemic diseases or participants with short life expectancy.
- •Participants considered by the investigator or any sub-investigator to be inappropriate for this study (e.g, geographic or social), actual or anticipated, that the investigator felt would restrict or limit the participant's participation for the duration of the study.
- •Certain laboratory findings obtained during the screening period
- •The information listed above is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial and not all inclusion/ exclusion criteria are listed.
研究组 & 干预措施
Placebo Q2W
Two subcutaneous (SC) injections of placebo (for alirocumab) Q2W with or without stable statin therapy for 48 weeks.
干预措施: Placebo (for alirocumab) (Drug)
Placebo Q2W
Two subcutaneous (SC) injections of placebo (for alirocumab) Q2W with or without stable statin therapy for 48 weeks.
干预措施: Statin (Drug)
Alirocumab 75 mg/ Up 150 mg Q2W
One SC injection of each Alirocumab 75 mg and placebo Q2W with or without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk participants) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk participants) at Week 8.
干预措施: Placebo (for alirocumab) (Drug)
Alirocumab 75 mg/ Up 150 mg Q2W
One SC injection of each Alirocumab 75 mg and placebo Q2W with or without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk participants) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk participants) at Week 8.
干预措施: Alirocumab (Drug)
Alirocumab 75 mg/ Up 150 mg Q2W
One SC injection of each Alirocumab 75 mg and placebo Q2W with or without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk participants) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk participants) at Week 8.
干预措施: Statin (Drug)
Alirocumab 300 mg/ Up 150 mg Q4W
Two SC injections of Alirocumab 150 mg Q4W alternating with two SC injections of placebo Q4W with or without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk participants) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk participants) at Week 8.
干预措施: Placebo (for alirocumab) (Drug)
Alirocumab 300 mg/ Up 150 mg Q4W
Two SC injections of Alirocumab 150 mg Q4W alternating with two SC injections of placebo Q4W with or without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk participants) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk participants) at Week 8.
干预措施: Alirocumab (Drug)
Alirocumab 300 mg/ Up 150 mg Q4W
Two SC injections of Alirocumab 150 mg Q4W alternating with two SC injections of placebo Q4W with or without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk participants) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk participants) at Week 8.
干预措施: Statin (Drug)
结局指标
主要结局
Percent Change From Baseline in Calculated LDL-C in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis
时间窗: From Baseline to Week 24
Adjusted LS means and standard errors at Week 24 and at averaged Week 21 to 24 from MMRM including available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. ITT population (subjects without concomitant statin therapy): all randomized subjects who did not receive concomitant statin therapy, with one baseline and at least one post-baseline calculated LDL-C value on- or off-treatment. Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Percent Change From Baseline in Calculated LDL-C in Participants Receiving Concomitant Statin Therapy - Intent-to-Treat (ITT Analysis)
时间窗: From Baseline to Week 24
Adjusted least squares (LS) means and standard errors at Week 24 and at averaged Week 21 to 24 were obtained from a mixed effect model with repeated measures (MMRM) model to account for missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were used in this model (ITT analysis). ITT population (subjects with concomitant statin therapy): all randomized subjects who received concomitant statin therapy, with one baseline and at least one post-baseline calculated LDL-C value on- or off-treatment. Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
次要结局
- Percent Change From Baseline in Calculated LDL-C at Week 24 in Participants Not Receiving Concomitant Statin Therapy - On-Treatment Analysis(From Baseline to Week 24)
- Percent Change From Baseline in Calculated LDL-C at Week 24 in Participants Receiving Concomitant Statin Therapy - On-Treatment Analysis(From Baseline to Week 24)
- Percent Change From Baseline in Calculated LDL-C at Week 12 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis(From Baseline to Week 12)
- Percent Change From Baseline in Calculated LDL-C at Week 12 in Participants Receiving Concomitant Statin Therapy - ITT Analysis(From Baseline to Week 12)
- Percent Change From Baseline in Calculated LDL-C at Week 12 in Participants Not Receiving Concomitant Statin Therapy - On-treatment Analysis(From Baseline to Week 12)
- Percent Change From Baseline in Calculated LDL-C at Week 12 in Participants Receiving Concomitant Statin Therapy - On-treatment Analysis(From Baseline to Week 12)
- Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis(From Baseline to Week 24)
- Percent Change From Baseline in Apo B at Week 24 in Participants Receiving Concomitant Statin Therapy - ITT Analysis(From Baseline to Week 24)
- Percent Change From Baseline in Apo B at Week 24 in Participants Not Receiving Concomitant Statin Therapy - On-Treatment Analysis(From Baseline to Week 24)
- Percent Change From Baseline in Apo B at Week 24 in Participants Receiving Concomitant Statin Therapy - On-Treatment Analysis(From Baseline to Week 24)
- Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis(From Baseline to Week 24)
- Percent Change From Baseline in Non-HDL-C at Week 24 in Participants Receiving Concomitant Statin Therapy - ITT Analysis(From Baseline to Week 24)
- Percent Change From Baseline in Non-HDL-C at Week 24 in Participants Not Receiving Concomitant Statin Therapy - On-Treatment Analysis(From Baseline to Week 24)
- Percent Change From Baseline in Non-HDL-C at Week 24 in Participants Receiving Concomitant Statin Therapy - On-Treatment Analysis(From Baseline to Week 24)
- Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis(From Baseline to Week 24)
- Percent Change From Baseline in Total-C at Week 24 in Participants Receiving Concomitant Statin Therapy - ITT Analysis(From Baseline to Week 24)
- Percent Change From Baseline in Apo B at Week 12 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis(From Baseline to Week 12)
- Percent Change From Baseline in Apo B at Week 12 in Participants Receiving Concomitant Statin Therapy - ITT Analysis(From Baseline to Week 12)
- Percent Change From Baseline in Non-HDL-C at Week 12 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis(From Baseline to Week 12)
- Percent Change From Baseline in Non-HDL-C at Week 12 in Participants Receiving Concomitant Statin Therapy - ITT Analysis(From Baseline to Week 12)
- Percent Change From Baseline in Total-C at Week 12 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis(From Baseline to Week 12)
- Percent Change From Baseline in Total-C at Week 12 in Participants Receiving Concomitant Statin Therapy - ITT Analysis(From Baseline to Week 12)
- Percentage of Very High CV Risk Participants Reaching Calculated LDL-C<70 mg/dL or Moderate or High CV Risk Participants Reaching Calculated LDL-C<100 mg/dL (Without Concomitant Statin Therapy) at Week 24 - ITT Analysis(Up to Week 24)
- Percentage of Very High Cardiovascular (CV) Risk Participants Reaching Calculated LDL-C <70 mg/dL or Moderate or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (With Concomitant Statin Therapy) at Week 24 - ITT Analysis(Up to Week 24)
- Percentage of Very High CV Risk Participants Reaching Calculated LDL-C<70 mg/dL (1.81 mmol/L) or Moderate or High CV Risk Participants Reaching Calculated LDL-C<100 mg/dL(2.59 mmol/L) (Without Concomitant Statin Therapy) at Week 24 - On-Treatment Analysis(Up to Week 24)
- Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL(1.81 mmol/L) or Moderate or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL(2.59 mmol/L) (With Concomitant Statin Therapy) at Week 24 - On-Treatment Analysis(Up to Week 24)
- Percentage of Participants (Without Concomitant Statin Therapy) Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis(Up to Week 24)
- Percentage of Participants (With Concomitant Statin Therapy) Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis(Up to Week 24)
- Percentage of Participants (Without Concomitant Statin Therapy) Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis(Up to Week 24)
- Percentage of Participants (With Concomitant Statin Therapy) Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis(Up to Week 24)
- Percent Change From Baseline in Lipoprotein (a) in Participants Not Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis(From Baseline to Week 24)
- Percent Change From Baseline in Lipoprotein (a) in Participants Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis(From Baseline to Week 24)
- Percent Change From Baseline in Lipoprotein (a) in Participants Not Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis(From Baseline to Week 12)
- Percent Change From Baseline in Lipoprotein (a) in Participants Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis(From Baseline to Week 12)
- Percent Change From Baseline in HDL-C in Participants Not Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis(From Baseline to Week 24)
- Percent Change From Baseline in HDL-C in Participants Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis(From Baseline to Week 24)
- Percent Change From Baseline in HDL-C in Participants Not Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis(From Baseline to Week 12)
- Percent Change From Baseline in HDL-C in Participants Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis(From Baseline to Week 12)
- Percent Change From Baseline in Fasting Triglycerides in Participants Not Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis(From Baseline to Week 24)
- Percent Change From Baseline in Fasting Triglycerides in Participants Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis(From Baseline to Week 24)
- Percent Change From Baseline in Fasting Triglycerides in Participants Not Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis(From Baseline to Week 12)
- Percent Change From Baseline in Fasting Triglycerides in Participants Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis(From Baseline to Week 12)
- Percent Change From Baseline in Apo A1 in Participants Not Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis(From Baseline to Week 24)
- Percent Change From Baseline in Apo A1 in Participants Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis(From Baseline to Week 24)
- Percent Change From Baseline in Apo A1 in Participants Not Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis(From Baseline to Week 12)
- Percent Change From Baseline in Apo A1 in Participants Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis(From Baseline to Week 12)