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Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Placebo on Top of Lipid-Modifying Therapy in Patients With Heterozygous Familial Hypercholesterolemia Not Adequately Controlled With Their Lipid-Modifying Therapy

Phase 3
Completed
Conditions
Hypercholesterolemia
Interventions
Drug: Placebo (for alirocumab)
Drug: Lipid Modifying Therapy (LMT)
Registration Number
NCT01623115
Lead Sponsor
Sanofi
Brief Summary

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

Detailed Description

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
486
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlacebo (for alirocumab)Placebo for alirocumab every 2 weeks (Q2W) on top of stable lipid-modifying therapy (LMT) for 78 weeks.
PlaceboLipid Modifying Therapy (LMT)Placebo for alirocumab every 2 weeks (Q2W) on top of stable lipid-modifying therapy (LMT) for 78 weeks.
Alirocumab 75 mg/Up to 150 mg Q2WAlirocumabAlirocumab 75 mg Q2W on top of stable LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when low-density lipoprotein cholesterol (LDL-C) levels ≥ 70 mg/dL (1.81 mmol/L) at Week 8.
Alirocumab 75 mg/Up to 150 mg Q2WLipid Modifying Therapy (LMT)Alirocumab 75 mg Q2W on top of stable LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when low-density lipoprotein cholesterol (LDL-C) levels ≥ 70 mg/dL (1.81 mmol/L) at Week 8.
Primary Outcome Measures
NameTimeMethod
Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) AnalysisFrom Baseline to Week 52

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).

Secondary Outcome Measures
NameTimeMethod
Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment AnalysisFrom Baseline to Week 52

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).

Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 24 - ITT AnalysisFrom Baseline to Week 52

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.

Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT AnalysisFrom Baseline to Week 52

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.

Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT AnalysisFrom Baseline to Week 52

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.

Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment AnalysisFrom Baseline to Week 52

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).

Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT AnalysisFrom Baseline to Week 52

Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.

Percent Change From Baseline in Non-HDL-C at Week 24 - On-Treatment AnalysisFrom Baseline to Week 52

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).

Percent Change From Baseline in Apo B at Week 12 - ITT AnalysisFrom Baseline to Week 52

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.

Percent Change From Baseline in Non-HDL-C at Week 12 - ITT AnalysisFrom Baseline to Week 52

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.

Percent Change From Baseline in Apo B at Week 24 - On-Treatment AnalysisFrom Baseline to Week 52

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).

Percent Change From Baseline in Total-C at Week 12 - ITT AnalysisFrom Baseline to Week 52

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.

Percent Change From Baseline in Calculated LDL-C at Week 52 - ITT AnalysisFrom Baseline to Week 52

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.

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 AnalysisUp to Week 52

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 multiple imputation approach 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.

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 AnalysisUp to Week 52

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.

Percentage of Participants Achieving Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT AnalysisUp to Week 52

Adjusted percentages at Week 24 from multiple imputation approach model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.

Percentage of Participants Achieving Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment AnalysisUp to Week 52

Adjusted percentages at Week 24 from 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.

Percent Change From Baseline in Lipoprotein (a) at Week 24 - ITT AnalysisFrom Baseline to Week 52

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.

Percent Change From Baseline in HDL-C at Week 24 - ITT AnalysisFrom Baseline to Week 52

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.

Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT AnalysisFrom Baseline to Week 52

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.

Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 24 - ITT AnalysisFrom Baseline to Week 52

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.

Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT AnalysisFrom Baseline to Week 52

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.

Percent Change From Baseline in HDL-C at Week 12 - ITT AnalysisFrom Baseline to Week 52

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.

Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT AnalysisFrom Baseline to Week 52

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.

Percent Change From Baseline in Apo A-1 at Week 12 - ITT AnalysisFrom Baseline to Week 52

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.

Trial Locations

Locations (91)

Investigational Site Number 840417

🇺🇸

Bell Gardens, California, United States

Investigational Site Number 840429

🇺🇸

Long Beach, California, United States

Investigational Site Number 840419

🇺🇸

Los Angeles, California, United States

Investigational Site Number 840421

🇺🇸

Mission Viejo, California, United States

Investigational Site Number 840412

🇺🇸

Newport Beach, California, United States

Investigational Site Number 840428

🇺🇸

Newport Beach, California, United States

Investigational Site Number 840461

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Northridge, California, United States

Investigational Site Number 840452

🇺🇸

Washington, District of Columbia, United States

Investigational Site Number 840456

🇺🇸

Miami, Florida, United States

Investigational Site Number 840418

🇺🇸

Ponte Vedra, Florida, United States

Scroll for more (81 remaining)
Investigational Site Number 840417
🇺🇸Bell Gardens, California, United States

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