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Study to Evaluate the Efficacy and Safety of an Every Four Weeks Treatment Regimen of Alirocumab (REGN727/ SAR236553) in Patients With Primary Hypercholesterolemia (ODYSSEY CHOICE 1)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01926782
First Posted: August 21, 2013
Last Update Posted: March 21, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Sanofi
Information provided by (Responsible Party):
Regeneron Pharmaceuticals
  Purpose
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.

Condition Intervention Phase
Hypercholesterolemia Drug: Placebo (for alirocumab) Drug: Alirocumab Drug: Statin Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
The study was conducted in 2 separate populations concurrently: subjects receiving concomitant statin therapy and subjects not receiving concomitant statin therapy. Subjects receiving concomitant statin were to receive stable daily doses of rosuvastatin, atorvastatin, or simvastatin for at least 4 weeks. Background treatment with other lipid-modifying therapy (LMT) was allowed for all patients, provided they had been on a stable dose for at least 4 weeks (6 weeks for fenofibrate) prior to study entry.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Regeneron Pharmaceuticals:

Primary Outcome Measures:
  • Percent Change From Baseline in Calculated LDL-C in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis [ Time Frame: 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) [ Time Frame: 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.


Secondary Outcome Measures:
  • Percent Change From Baseline in Calculated LDL-C at Week 24 in Participants Not Receiving Concomitant Statin Therapy - On-Treatment Analysis [ Time Frame: From Baseline to Week 24 ]
    Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection) (on-treatment analysis). Modified ITT (mITT) population (subjects with or without concomitant statin therapy): all randomized and treated subjects who did not receive concomitant statin therapy, with one baseline and at least one post-baseline calculated LDL-C value on-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 at Week 24 in Participants Receiving Concomitant Statin Therapy - On-Treatment Analysis [ Time Frame: From Baseline to Week 24 ]
    Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection) (on-treatment analysis). Modified ITT (mITT) population (subjects with or without concomitant statin therapy): all randomized and treated subjects who did not receive concomitant statin therapy, with one baseline and at least one post-baseline calculated LDL-C value on-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 at Week 12 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis [ Time Frame: From Baseline to Week 12 ]
    Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. ITT population (subjects with or without concomitant statin therapy). 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 at Week 12 in Participants Receiving Concomitant Statin Therapy - ITT Analysis [ Time Frame: From Baseline to Week 12 ]
    Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. ITT population (subjects with or without concomitant statin therapy). 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 at Week 12 in Participants Not Receiving Concomitant Statin Therapy - On-treatment Analysis [ Time Frame: From Baseline to Week 12 ]
    Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. ITT population (subjects with or without concomitant statin therapy). 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 at Week 12 in Participants Receiving Concomitant Statin Therapy - On-treatment Analysis [ Time Frame: From Baseline to Week 12 ]
    Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. ITT population (subjects with or without concomitant statin therapy). 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 Apolipoprotein (Apo) B at Week 24 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis [ Time Frame: From Baseline to Week 24 ]
    Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. Subjects of the ITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline Apo B value on- or off-treatment (Apo B ITT population). 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 Apo B at Week 24 in Participants Receiving Concomitant Statin Therapy - ITT Analysis [ Time Frame: From Baseline to Week 24 ]
    Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. Subjects of the ITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline Apo B value on- or off-treatment (Apo B ITT population). 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 Apo B at Week 24 in Participants Not Receiving Concomitant Statin Therapy - On-Treatment Analysis [ Time Frame: From Baseline to Week 24 ]
    Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. Subjects of the ITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline Apo B value on- or off-treatment (Apo B ITT population). 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 Apo B at Week 24 in Participants Receiving Concomitant Statin Therapy - On-Treatment Analysis [ Time Frame: From Baseline to Week 24 ]
    Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. Subjects of the ITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline Apo B value on- or off-treatment (Apo B ITT population). 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 Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis [ Time Frame: From Baseline to Week 24 ]
    Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. Subjects of the ITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline non-HDL-C value on- or off-treatment (non-HDL-C ITT population). 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 Non-HDL-C at Week 24 in Participants Receiving Concomitant Statin Therapy - ITT Analysis [ Time Frame: From Baseline to Week 24 ]
    Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. Subjects of the ITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline non-HDL-C value on- or off-treatment (non-HDL-C ITT population). 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 Non-HDL-C at Week 24 in Participants Not Receiving Concomitant Statin Therapy - On-Treatment Analysis [ Time Frame: From Baseline to Week 24 ]
    Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection). Subjects of the mITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline non-HDL-C value on-treatment (non-HDL-C mITT population). 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 Non-HDL-C at Week 24 in Participants Receiving Concomitant Statin Therapy - On-Treatment Analysis [ Time Frame: From Baseline to Week 24 ]
    Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection). Subjects of the mITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline non-HDL-C value on-treatment (non-HDL-C mITT population). 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 Total Cholesterol (Total-C) at Week 24 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis [ Time Frame: From Baseline to Week 24 ]
    Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. Subjects of the ITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline Total-C value on- or off-treatment (Total-C ITT population). 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 Total-C at Week 24 in Participants Receiving Concomitant Statin Therapy - ITT Analysis [ Time Frame: From Baseline to Week 24 ]
    Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. Subjects of the ITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline Total-C value on- or off-treatment (Total-C ITT population). 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 Apo B at Week 12 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis [ Time Frame: From Baseline to Week 12 ]
    Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. Apo B ITT population (subjects with or without concomitant statin therapy). 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 Apo B at Week 12 in Participants Receiving Concomitant Statin Therapy - ITT Analysis [ Time Frame: From Baseline to Week 12 ]
    Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. Apo B ITT population (subjects with or without concomitant statin therapy). 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 Non-HDL-C at Week 12 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis [ Time Frame: From Baseline to Week 12 ]
    Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. Non-HDL-C ITT population (subjects with or without concomitant statin therapy). 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 Non-HDL-C at Week 12 in Participants Receiving Concomitant Statin Therapy - ITT Analysis [ Time Frame: From Baseline to Week 12 ]
    Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. Non-HDL-C ITT population (subjects with or without concomitant statin therapy). 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 Total-C at Week 12 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis [ Time Frame: From Baseline to Week 12 ]
    Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. Total-C ITT population (subjects with or without concomitant statin therapy). 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 Total-C at Week 12 in Participants Receiving Concomitant Statin Therapy - ITT Analysis [ Time Frame: From Baseline to Week 12 ]
    Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. Total-C ITT population (subjects with or without concomitant statin therapy). 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.

  • 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 [ Time Frame: Up to Week 24 ]
    Very high CV risk: history of documented coronary heart disease (CHD) or CHD risk equivalent. High CV risk: calculated 10-year fatal CVD risk score ≥5%, moderate chronic kidney disease, type 1/type 2 diabetes mellitus (DM) without target organ damage, or heFH not meeting definition of very high risk. Moderate CV risk: calculated 10-year fatal CVD risk score ≥1 &<5%. CHD risk equivalent: peripheral arterial disease, ischemic stroke, transient ischemic attack, abdominal aortic aneurysm, carotid artery(CA)occlusion>50%, carotid endarterectomy/CA stent procedure, renal artery stenosis/stent procedure, type 1/type 2 DM with target organ damage. Adjusted percentages at Week 24 obtained from multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment included in imputation model. ITT population (subjects with or without concomitant statin therapy).

  • 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 [ Time Frame: Up to Week 24 ]
    Very high CV risk: history of documented coronary heart disease (CHD) or CHD risk equivalent. High CV risk: calculated 10-year fatal CVD risk score ≥5%, moderate chronic kidney disease, type 1/type 2 diabetes mellitus (DM) without target organ damage, or heFH not meeting definition of very high risk. Moderate CV risk: calculated 10-year fatal CVD risk score ≥1 &<5%. CHD risk equivalent: peripheral arterial disease, ischemic stroke, transient ischemic attack, abdominal aortic aneurysm, carotid artery(CA)occlusion>50%, carotid endarterectomy/CA stent procedure, renal artery stenosis/stent procedure, type 1/type 2 DM with target organ damage. Adjusted percentages at Week 24 obtained from multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment included in imputation model. ITT population (subjects with or without concomitant statin therapy).

  • 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 [ Time Frame: Up to Week 24 ]
    Adjusted percentages at Week 24 were from multiple imputation approach model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection). mITT population (subjects with or without concomitant statin therapy). 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.

  • 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 [ Time Frame: Up to Week 24 ]
    Adjusted percentages at Week 24 were from multiple imputation approach model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection). mITT population (subjects with or without concomitant statin therapy). 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.

  • Percentage of Participants (Without Concomitant Statin Therapy) Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis [ Time Frame: Up to Week 24 ]
    Adjusted percentages at Week 24 were obtained from multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were included in the imputation model. ITT population (subjects with or without concomitant statin therapy). 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.

  • Percentage of Participants (With Concomitant Statin Therapy) Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis [ Time Frame: Up to Week 24 ]
    Adjusted percentages at Week 24 were obtained from multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were included in the imputation model. ITT population (subjects with or without concomitant statin therapy). 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.

  • Percentage of Participants (Without Concomitant Statin Therapy) Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis [ Time Frame: Up to Week 24 ]
    Adjusted percentages at Week 24 from multiple imputation approach model including available post-baseline data from Week 4 to Week 24 (i.e. up to 21 days after last injection). mITT population (subjects with or without concomitant statin therapy). 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.

  • Percentage of Participants (With Concomitant Statin Therapy) Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis [ Time Frame: Up to Week 24 ]
    Adjusted percentages at Week 24 from multiple imputation approach model including available post-baseline data from Week 4 to Week 24 (i.e. up to 21 days after last injection). mITT population (subjects with or without concomitant statin therapy). 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 Lipoprotein (a) in Participants Not Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis [ Time Frame: From Baseline to Week 24 ]
    Adjusted means and standard errors at Week 24 from a multiple imputation approach followed by robust regression model for handling of missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment were included in the imputation model. ITT population (subjects with or without concomitant statin therapy). 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 Lipoprotein (a) in Participants Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis [ Time Frame: From Baseline to Week 24 ]
    Adjusted means and standard errors at Week 24 from a multiple imputation approach followed by robust regression model for handling of missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment were included in the imputation model. ITT population (subjects with or without concomitant statin therapy). 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 Lipoprotein (a) in Participants Not Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis [ Time Frame: From Baseline to Week 12 ]
    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 24 regardless of status on-or off-treatment. ITT population (subjects with or without concomitant statin therapy). 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 Lipoprotein (a) in Participants Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis [ Time Frame: From Baseline to Week 12 ]
    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 24 regardless of status on-or off-treatment. ITT population (subjects with or without concomitant statin therapy). 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 HDL-C in Participants Not Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis [ Time Frame: From Baseline to Week 24 ]
    Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. Subjects of the ITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline HDL-C value on- or off-treatment (HDL-C ITT population). 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 HDL-C in Participants Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis [ Time Frame: From Baseline to Week 24 ]
    Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. Subjects of the ITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline HDL-C value on- or off-treatment (HDL-C ITT population). 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 HDL-C in Participants Not Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis [ Time Frame: From Baseline to Week 12 ]
    Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. HDL-C ITT population (subjects with or without concomitant statin therapy). 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 HDL-C in Participants Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis [ Time Frame: From Baseline to Week 12 ]
    Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. HDL-C ITT population (subjects with or without concomitant statin therapy). 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 Fasting Triglycerides in Participants Not Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis [ Time Frame: From Baseline to Week 24 ]
    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 24 regardless of status on-or off-treatment. ITT population (subjects with or without concomitant statin therapy). 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 Fasting Triglycerides in Participants Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis [ Time Frame: From Baseline to Week 24 ]
    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 24 regardless of status on-or off-treatment. ITT population (subjects with or without concomitant statin therapy). 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 Fasting Triglycerides in Participants Not Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis [ Time Frame: From Baseline to Week 12 ]
    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 24 regardless of status on-or off-treatment. ITT population (subjects with or without concomitant statin therapy). 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 Fasting Triglycerides in Participants Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis [ Time Frame: From Baseline to Week 12 ]
    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 24 regardless of status on-or off-treatment. ITT population (subjects with or without concomitant statin therapy). 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 Apo A1 in Participants Not Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis [ Time Frame: From Baseline to Week 24 ]
    Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. Subjects of the ITT population (subjects with or without concomitant statin therapy) with one baseline and at least one post-baseline Apo A1 value on- or off-treatment (Apo A1 ITT population). 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 Apo A1 in Participants Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis [ Time Frame: From Baseline to Week 24 ]
    Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. Subjects of the ITT population (subjects with or without concomitant statin therapy) with one baseline and at least one post-baseline Apo A1 value on- or off-treatment (Apo A1 ITT population). 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 Apo A1 in Participants Not Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis [ Time Frame: From Baseline to Week 12 ]
    Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. Apo A1 ITT population (subjects with or without concomitant statin therapy). 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 Apo A1 in Participants Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis [ Time Frame: From Baseline to Week 12 ]
    Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. Apo A1 ITT population (subjects with or without concomitant statin therapy). 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.


Enrollment: 803
Study Start Date: September 2013
Study Completion Date: April 2015
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Q2W
Two subcutaneous (SC) injections of placebo (for alirocumab) Q2W with or without stable statin therapy for 48 weeks.
Drug: Placebo (for alirocumab)
Solution for injection, subcutaneous injections in the abdomen, thigh, or outer area of upper arm with an auto-injector.
Drug: Statin
Atorvastatin, rosuvastatin and simvastatin at stable dose in participants with stable statin therapy
Experimental: 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.
Drug: Placebo (for alirocumab)
Solution for injection, subcutaneous injections in the abdomen, thigh, or outer area of upper arm with an auto-injector.
Drug: Alirocumab
Solution for injection, subcutaneous injection in the abdomen, thigh, or outer area of upper arm with an auto-injector.
Other Names:
  • SAR236553
  • REGN727
  • Praluent
Drug: Statin
Atorvastatin, rosuvastatin and simvastatin at stable dose in participants with stable statin therapy
Experimental: 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.
Drug: Placebo (for alirocumab)
Solution for injection, subcutaneous injections in the abdomen, thigh, or outer area of upper arm with an auto-injector.
Drug: Alirocumab
Solution for injection, subcutaneous injection in the abdomen, thigh, or outer area of upper arm with an auto-injector.
Other Names:
  • SAR236553
  • REGN727
  • Praluent
Drug: Statin
Atorvastatin, rosuvastatin and simvastatin at stable dose in participants with stable statin therapy

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Men and women > age 18 or legal age of majority with elevated LDL-C
  2. Patients not having adequate control of their hypercholesterolemia based on their individual level of CVD risk
  3. Willing and able to comply with clinic visits and study-related procedures
  4. Provided signed informed consent

Exclusion Criteria:

  1. 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
  2. Known history of positive test for human immunodeficiency virus (HIV)
  3. 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.
  4. 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.
  5. 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.

  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01926782


  Show 83 Study Locations
Sponsors and Collaborators
Regeneron Pharmaceuticals
Sanofi
Investigators
Study Director: Clinical Trial Management Regeneron Pharmaceuticals
  More Information

Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01926782     History of Changes
Other Study ID Numbers: R727-CL-1308
First Submitted: August 19, 2013
First Posted: August 21, 2013
Results First Submitted: January 30, 2017
Results First Posted: March 21, 2017
Last Update Posted: March 21, 2017
Last Verified: January 2017

Additional relevant MeSH terms:
Hypercholesterolemia
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Antibodies, Monoclonal
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Lipid Regulating Agents
Immunologic Factors
Physiological Effects of Drugs