Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Placebo on Top of Lipid-Modifying Therapy in Patients With High Cardiovascular Risk and Hypercholesterolemia (ODYSSEY COMBO I)

This study has been completed.
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01644175
First received: July 16, 2012
Last updated: October 7, 2015
Last verified: October 2015

July 16, 2012
October 7, 2015
July 2012
April 2014   (final data collection date for primary outcome measure)
Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis [ Time Frame: From Baseline to Week 52 ] [ Designated as safety issue: No ]
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).
Percent change in LDL-C [ Time Frame: From baseline to week 24 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01644175 on ClinicalTrials.gov Archive Site
  • Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis [ Time Frame: From Baseline to Week 52 ] [ Designated as safety issue: No ]
    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 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 Analysis [ Time Frame: From Baseline to Week 52 ] [ Designated as safety issue: No ]
    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 12 - On-Treatment Analysis [ Time Frame: From Baseline to Week 52 ] [ Designated as safety issue: No ]
    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 (Apo) B at Week 24 - ITT Analysis [ Time Frame: From baseline to Week 52 ] [ Designated as safety issue: No ]
    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 Apo B at Week 24 - On-treatment Analysis [ Time Frame: From Baseline to Week 52 ] [ Designated as safety issue: No ]
    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 Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis [ Time Frame: From Baseline to Week 52 ] [ Designated as safety issue: No ]
    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-HDL-C at Week 24 - On-treatment Analysis [ Time Frame: From Baseline to Week 52 ] [ Designated as safety issue: No ]
    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 Cholesterol (Total-C) at Week 24 - ITT Analysis [ Time Frame: From Baseline to Week 52 ] [ Designated as safety issue: No ]
    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 Apo B at Week 12 - ITT Analysis [ Time Frame: From Baseline to Week 52 ] [ Designated as safety issue: No ]
    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 Analysis [ Time Frame: From Baseline to Week 52 ] [ Designated as safety issue: No ]
    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 Total-C at Week 12 - ITT Analysis [ Time Frame: From Baseline to Week 52 ] [ Designated as safety issue: No ]
    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 Analysis [ Time Frame: From Baseline to Week 52 ] [ Designated as safety issue: No ]
    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 Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis [ Time Frame: Up to Week 52 ] [ Designated as safety issue: No ]
    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 52 regardless of status on- or off-treatment were included in the imputation model.
  • Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-treatment Analysis [ Time Frame: Up to Week 52 ] [ Designated as safety issue: No ]
    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 Analysis [ Time Frame: From baseline to Week 52 ] [ Designated as safety issue: No ]
    Adjusted means and standard errors at Week 24 were obtained from multiple imputation approach followed by robust regression 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.
  • Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis [ Time Frame: From Baseline to Week 52 ] [ Designated as safety issue: No ]
    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 Analysis [ Time Frame: From Baseline to Week 52 ] [ Designated as safety issue: No ]
    Adjusted means and standard errors at Week 24 from multiple imputation approach followed be 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 at Week 24 - ITT Analysis [ Time Frame: From Baseline to Week 52 ] [ Designated as safety issue: No ]
    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 Analysis [ Time Frame: From Baseline to Week 52 ] [ Designated as safety issue: No ]
    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 Analysis [ Time Frame: From Baseline to Week 52 ] [ Designated as safety issue: No ]
    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 Analysis [ Time Frame: From Baseline to Week 52 ] [ Designated as safety issue: No ]
    Adjusted means and standard errors at Week 12 from multiple imputation approach followed by a 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 Analysis [ Time Frame: From Baseline to Week 52 ] [ Designated as safety issue: No ]
    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 in LDL-C [ Time Frame: From baseline to weeks 12 and 52 ] [ Designated as safety issue: No ]
  • Percent change in other lipid parameters [ Time Frame: From baseline to weeks 12, 24 and 52 ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Placebo on Top of Lipid-Modifying Therapy in Patients With High Cardiovascular Risk and Hypercholesterolemia (ODYSSEY COMBO I)
A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of SAR236553/REGN727 in High Cardiovascular Risk Patients With Hypercholesterolemia Not Adequately Controlled With Their Lipid-Modifying Therapy

Alirocumab (SAR236553/REGN727) is a fully human monoclonal antibody that binds proprotein convertase subtilisin/kexin type 9 (PCSK9).

Primary Objective of the study:

  • To demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by alirocumab as add-on therapy to stable maximally tolerated daily statin therapy with or without other lipid-modifying therapy (LMT) in comparison with placebo after 24 weeks of treatment in high cardiovascular (CV) risk participants with hypercholesterolemia

Secondary Objectives:

  • To evaluate the effect of alirocumab in comparison with placebo on LDL-C at other time points
  • To evaluate the effect of alirocumab on other lipid parameters
  • To evaluate the safety and tolerability of alirocumab
The maximum study duration was 62 weeks per participant, including a 2-week screening period, 52-week randomized treatment period, and 8-week follow-up period.
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Hypercholesterolemia
  • Drug: Placebo (for alirocumab)
    Solution for injection, one subcutaneous injection in the abdomen, thigh, or outer area of upper arm with a disposable auto-injector (also known as pre-filled pen).
  • Drug: Alirocumab
    Solution for injection, one subcutaneous injection in the abdomen, thigh, or outer area of upper arm with a disposable auto-injector (also known as pre-filled pen).
    Other Names:
    • SAR236553
    • REGN727
  • Drug: Lipid-Modifying Therapy (LMT)
    Statin (rosuvastatin, simvastatin or atorvastatin) at stable dose with or without other LMT as clinically indicated.
  • Placebo Comparator: Placebo Q2W
    Placebo (for alirocumab) every 2 weeks (Q2W) added to stable Lipid-Modifying Therapy (LMT) for 52 weeks.
    Interventions:
    • Drug: Placebo (for alirocumab)
    • Drug: Lipid-Modifying Therapy (LMT)
  • Experimental: Alirocumab
    Alirocumab 75 mg Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
    Interventions:
    • Drug: Alirocumab
    • Drug: Lipid-Modifying Therapy (LMT)

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
316
April 2014
April 2014   (final data collection date for primary outcome measure)

Inclusion criteria:

  • Participants with hypercholesterolemia and established coronary heart disease (CHD) or CHD risk equivalents who were not adequately controlled with a maximally tolerated daily dose of statin with or without other LMT, both at stable dose for at least 4 weeks to 6 weeks prior to screening (Week -2)

Exclusion criteria:

  • Age <18 or legal age of adulthood, whichever was greater
  • Participants without established CHD or CHD risk equivalent
  • LDL-C <70 mg/dL (<1.81 mmol/L) and participants with a history of documented cardiovascular disease
  • LDL-C <100 mg/dL (<2.59 mmol/L) and participants without a history of documented cardiovascular disease
  • Not on a stable dose of LMT (including statin) for at least 4 weeks and/or fenofibrate for at least 6 weeks, as applicable, prior to the screening visit (Week -2) and from screening to randomization
  • Fasting serum triglycerides > 400 mg/dL (>4.52 mmol/L)

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01644175
EFC11568, U1111-1121-4356
Yes
Not Provided
Not Provided
Sanofi
Sanofi
Regeneron Pharmaceuticals
Study Director: Clinical Sciences & Operations Sanofi
Sanofi
October 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP