Alirocumab (SAR236553/REGN727) is a fully human monoclonal antibody that binds PCSK9 (proprotein convertase subtilisin/kexin type 9). Primary Objective of the study: To evaluate the effect of alirocumab on low-density lipoprotein cholesterol (LDL-C) levels after 24 weeks of treatment in comparison with placebo. Secondary Objectives: * To evaluate the effect of alirocumab in comparison with placebo on LDL-C at other time points * To evaluate the effects of alirocumab on other lipid parameters * To evaluate the safety and tolerability of alirocumab
The maximum study duration was planned to be 89 weeks per participant including participants who successfully completed the 78-week treatment period had the possibility to join an open-label extension study (LTS13463, NCT01954394) at the end of the treatment period.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
107
Solution for subcutaneous injection in the abdomen, thigh, or outer area of the upper arm by self-injection or by another designated person using auto-injector (also known as pre filled pen).
Solution for subcutaneous injection in the abdomen, thigh, or outer area of the upper arm by self-injection or by another designated person using auto-injector (also known as pre filled pen).
Statin (rosuvastatin, simvastatin or atorvastatin) at stable dose with or without other LMT as clinically indicated.
Investigational Site Number 840742
Bell Gardens, California, United States
Investigational Site Number 840703
Newport Beach, California, United States
Investigational Site Number 840712
Newport Beach, California, United States
Investigational Site Number 840743
Northridge, California, United States
Investigational Site Number 840734
Washington D.C., District of Columbia, United States
Percent Change From Baseline in Calculated LDL-C at Week 24 - ITT Analysis
Adjusted Least-squares (LS) means and standard errors at Week 24 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment were used in the model (ITT analysis).
Time frame: From Baseline to Week 52
Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis
Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 52 i.e. up to 21 days after last injection (on-treatment analysis).
Time frame: From Baseline to Week 52
Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Time frame: From Baseline to Week 52
Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis
Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 52 i.e. up to 21 days after last injection.
Time frame: From Baseline to Week 52
Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 24 - ITT Analysis
Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Time frame: From Baseline to Week 52
Percent Change From Baseline in Apo B at Week 24 - On-Treatment Analysis
Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 52 (i.e. up to 21 days after last injection).
Time frame: From Baseline to Week 52
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis
Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Time frame: From Baseline to Week 52
Percent Change From Baseline in Non-HDL-C at Week 24 - On-Treatment Analysis
Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 52 (i.e. up to 21 days after last injection).
Time frame: From Baseline to Week 52
Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis
Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.
Time frame: From Baseline to Week 52
Percent Change From Baseline in Apo B at Week 12 - ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Time frame: From Baseline to Week 52
Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.
Time frame: From Baseline to Week 52
Percent Change From Baseline in Total-C at Week 12 - ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.
Time frame: From Baseline to Week 52
Percent Change From Baseline in Calculated LDL-C at Week 52 - ITT Analysis
Adjusted LS means and standard errors at Week 52 from MMRM model including all available post-baseline data from week 4 to week 52 regardless of status on-or off-treatment.
Time frame: From Baseline to Week 52
Percentage of Very High Cardiovascular (CV) Risk Participants Achieving Calculated LDL-C < 70 mg/dL (<1.81 mmol/L) or High CV Risk Participants Achieving Calculated LDL-C < 100 mg/dL (<2.59 mmol/L) at Week 24 - ITT Analysis
Very high CV risk participants: Heterozygous Familial Hypercholesterolemia (heFH) participants with coronary heart disease (CHD) or CHD risk equivalents. High CV risk participants: heFH participants without CHD or CHD risk equivalents. CHD risk equivalent: peripheral arterial disease, ischemic stroke, moderate chronic kidney disease (estimated glomerular filtration rate, 30 to \<60 ml/minute/1.73 m\^2 of body-surface area), or diabetes mellitus plus 2 or more additional risk factors (hypertension; ankle-brachial index of ≤0.90; microalbuminuria, macroalbuminuria, or a urinary dipstick result of \>2+ protein; preproliferative or proliferative retinopathy or laser treatment for retinopathy; or a family history of premature CHD). Adjusted percentages at Week 24 were obtained from a multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment were included in the imputation model.
Time frame: Up to Week 52
Percentage of Very High CV Risk Participants Achieving Calculated LDL-C < 70 mg/dL (<1.81 mmol/L) or High CV Risk Participants Achieving Calculated LDL-C < 100 mg/dL (<2.59 mmol/L) at Week 24 - On-Treatment Analysis
Adjusted percentages at Week 24 from a multiple imputation approach model including available post-baseline on-treatment data from Week 4 to Week 52 i.e. up to 21 days after last injection.
Time frame: Up to Week 52
Percent Change From Baseline in Lipoprotein (a) at Week 24 - ITT Analysis
Adjusted means and standard errors at Week 24 from a multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.
Time frame: From Baseline to Week 52
Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis
Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.
Time frame: From Baseline to Week 52
Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis
Adjusted means and standard errors at Week 24 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.
Time frame: From Baseline to Week 52
Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 24 - ITT Analysis
Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.
Time frame: From Baseline to Week 52
Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis
Adjusted means and standard errors at Week 12 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.
Time frame: From Baseline to Week 52
Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.
Time frame: From Baseline to Week 52
Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis
Adjusted means and standard errors at Week 12 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.
Time frame: From Baseline to Week 52
Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.
Time frame: From Baseline to Week 52
Percentage of Participants Achieving Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis
Adjusted percentages at Week 24 from multiple imputation approach including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.
Time frame: Up to Week 52
Percentage of Participants Achieving Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis
Adjusted percentages at Week 24 from multiple imputation approach including available post-baseline on-treatment data from Week 4 to Week 52 i.e. up to 21 days after last injection.
Time frame: Up to Week 52
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Investigational Site Number 840738
Miami, Florida, United States
Investigational Site Number 840710
Ponte Vedra, Florida, United States
Investigational Site Number 840701
New York, New York, United States
Investigational Site Number 840702
Durham, North Carolina, United States
Investigational Site Number 840714
Cincinnati, Ohio, United States
...and 25 more locations