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)

October 7, 2015 updated by: Sanofi

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

316

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35209
        • Investigational Site Number 840857
      • Mobile, Alabama, United States, 36693
        • Investigational Site Number 840891
      • Montgomery, Alabama, United States, 36109
        • Investigational Site Number 840876
    • Arizona
      • Glendale, Arizona, United States, 85306
        • Investigational Site Number 840865
    • Arkansas
      • Jonesboro, Arkansas, United States, 72401
        • Investigational Site Number 840826
    • California
      • Burbank, California, United States, 91505
        • Investigational Site Number 840870
      • Los Angeles, California, United States, 90057
        • Investigational Site Number 840851
      • Los Gatos, California, United States, 95032
        • Investigational Site Number 840845
      • Sacramento, California, United States, 95823
        • Investigational Site Number 840844
      • San Jose, California, United States, 95116
        • Investigational Site Number 840801
      • Tarzana, California, United States, 91356
        • Investigational Site Number 840886
      • Torrance, California, United States, 90505
        • Investigational Site Number 840862
      • Vista, California, United States, 92083
        • Investigational Site Number 840893
    • Florida
      • Boca Raton, Florida, United States, 33432
        • Investigational Site Number 840867
      • Boynton Beach, Florida, United States, 33472
        • Investigational Site Number 840884
      • Clearwater, Florida, United States, 33761
        • Investigational Site Number 840836
      • Coral Gables, Florida, United States, 33134
        • Investigational Site Number 840866
      • Ft. Lauderdale, Florida, United States, 33308-4311
        • Investigational Site Number 840895
      • Hialeah, Florida, United States
        • Investigational Site Number 840820
      • Miami, Florida, United States, 33143
        • Investigational Site Number 840805
      • Oviedo, Florida, United States, 32765
        • Investigational Site Number 840811
      • Port Orange, Florida, United States, 32127
        • Investigational Site Number 840881
      • West Palm Beach, Florida, United States
        • Investigational Site Number 840816
    • Georgia
      • Columbus, Georgia, United States, 31904
        • Investigational Site Number 840850
    • Idaho
      • Eagle, Idaho, United States
        • Investigational Site Number 840840
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Investigational Site Number 840842
      • Evanston, Illinois, United States, 60201
        • Investigational Site Number 840898
      • Morton, Illinois, United States, 61550
        • Investigational Site Number 840847
    • Indiana
      • Indianapolis, Indiana, United States, 46260
        • Investigational Site Number 840896
      • Michigan City, Indiana, United States, 46360
        • Investigational Site Number 840894
      • Mishawaka, Indiana, United States, 46545
        • Investigational Site Number 840838
    • Kentucky
      • Paducah, Kentucky, United States, 42003
        • Investigational Site Number 840823
    • Louisiana
      • Eunice, Louisiana, United States, 70535
        • Investigational Site Number 840858
      • New Orleans, Louisiana, United States, 70119
        • Investigational Site Number 840802
    • Massachusetts
      • Salisbury, Massachusetts, United States, 01952
        • Investigational Site Number 840855
    • Michigan
      • Battle Creek, Michigan, United States, 49015
        • Investigational Site Number 840890
      • Southfield, Michigan, United States, 48034
        • Investigational Site Number 840832
    • Minnesota
      • Edina, Minnesota, United States, 55435
        • Investigational Site Number 840839
      • Minneapolis, Minnesota, United States, 55455
        • Investigational Site Number 840888
    • Mississippi
      • Port Gibson, Mississippi, United States, 39150
        • Investigational Site Number 840837
    • Missouri
      • Jefferson City, Missouri, United States, 65109
        • Investigational Site Number 840814
    • Nevada
      • Sparks, Nevada, United States
        • Investigational Site Number 840833
    • New Hampshire
      • Newington, New Hampshire, United States, 3801
        • Investigational Site Number 840817
    • New York
      • New Windsor, New York, United States, 12553
        • Investigational Site Number 840853
      • Rochester, New York, United States, 14609
        • Investigational Site Number 840822
    • North Carolina
      • Cary, North Carolina, United States
        • Investigational Site Number 840824
      • Smithfield, North Carolina, United States
        • Investigational Site Number 840880
      • Winston-Salem, North Carolina, United States, 27103
        • Investigational Site Number 840502
      • Winston-Salem, North Carolina, United States, 27103
        • Investigational Site Number 840852
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • Investigational Site Number 840846
      • Cincinnati, Ohio, United States, 45245
        • Investigational Site Number 840899
      • Columbus, Ohio, United States, 43231
        • Investigational Site Number 840831
      • Kettering, Ohio, United States, 45429
        • Investigational Site Number 840860
      • Willoughby Hills, Ohio, United States, 44094
        • Investigational Site Number 840809
    • Oklahoma
      • Norman, Oklahoma, United States, 73069
        • Investigational Site Number 840818
    • Oregon
      • Eugene, Oregon, United States, 97404
        • Investigational Site Number 840812
    • Pennsylvania
      • Downington, Pennsylvania, United States, 19335
        • Investigational Site Number 840803
      • Philadelphia, Pennsylvania, United States, 19146
        • Investigational Site Number 840869
      • Pittsburgh, Pennsylvania, United States, 15206
        • Investigational Site Number 840825
    • South Carolina
      • Anderson, South Carolina, United States, 29621
        • Investigational Site Number 840872
      • Charleston, South Carolina, United States, 29407
        • Investigational Site Number 840885
      • Greer, South Carolina, United States, 29651
        • Investigational Site Number 840813
      • Mt. Pleasant, South Carolina, United States, 29464
        • Investigational Site Number 840827
    • Texas
      • Corpus Christi, Texas, United States, 78404
        • Investigational Site Number 840868
      • Houston, Texas, United States, 77070
        • Investigational Site Number 840877
      • Houston, Texas, United States, 77072
        • Investigational Site Number 840841
      • San Antonio, Texas, United States, 78224
        • Investigational Site Number 840830
      • San Antonio, Texas, United States, 78229
        • Investigational Site Number 840854
      • San Antonio, Texas, United States, 78258
        • Investigational Site Number 840883
      • Tomball, Texas, United States, 77375
        • Investigational Site Number 840889
    • Utah
      • Bountiful, Utah, United States, 84010
        • Investigational Site Number 840878
      • Orem, Utah, United States, 84058
        • Investigational Site Number 840819
      • Salt Lake City, Utah, United States, 84102
        • Investigational Site Number 840863
    • Virginia
      • Manassas, Virginia, United States, 20110
        • Investigational Site Number 840804
      • Norfolk, Virginia, United States, 23507
        • Investigational Site Number 840882
      • Weber City, Virginia, United States, 24290
        • Investigational Site Number 840810

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo Q2W
Placebo (for alirocumab) every 2 weeks (Q2W) added to stable Lipid-Modifying Therapy (LMT) for 52 weeks.
Drug: Lipid-Modifying Therapy (LMT)
Statin (rosuvastatin, simvastatin or atorvastatin) at stable dose with or without other LMT as clinically indicated.
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).
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.
Drug: Lipid-Modifying Therapy (LMT)
Statin (rosuvastatin, simvastatin or atorvastatin) at stable dose with or without other LMT as clinically indicated.
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis
Time Frame: From 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).
From Baseline to Week 52

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis
Time Frame: From 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.
From Baseline to Week 52
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
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.
From Baseline to Week 52
Percent Change From Baseline in Apo B at Week 12 - ITT Analysis
Time Frame: From 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.
From Baseline to Week 52
Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis
Time Frame: From Baseline to Week 52
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).
From Baseline to Week 52
Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis
Time Frame: From 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.
From Baseline to Week 52
Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis
Time Frame: From 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.
From Baseline to Week 52
Percent Change From Baseline in Total-C at Week 12 - ITT Analysis
Time Frame: From 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.
From Baseline to Week 52
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
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.
Up to Week 52
Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis
Time Frame: From 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.
From Baseline to Week 52
Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis
Time Frame: From 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.
From Baseline to Week 52
Percent Change From Baseline in Calculated LDL-C at Week 52 - ITT Analysis
Time Frame: From 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.
From Baseline to Week 52
Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis
Time Frame: From 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).
From Baseline to Week 52
Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis
Time Frame: From 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.
From baseline to Week 52
Percent Change From Baseline in Apo B at Week 24 - On-treatment Analysis
Time Frame: From 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).
From Baseline to Week 52
Percent Change From Baseline in Non-HDL-C at Week 24 - On-treatment Analysis
Time Frame: From 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).
From Baseline to Week 52
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
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.
Up to Week 52
Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis
Time Frame: From baseline to Week 52
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.
From baseline to Week 52
Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis
Time Frame: From Baseline to Week 52
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.
From Baseline to Week 52
Percent Change From Baseline in Apolipoprotein A-1 at Week 24 - ITT Analysis
Time Frame: From 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.
From Baseline to Week 52
Percent Change From Baseline in Lipoprotein(a) at Week 12- ITT Analysis
Time Frame: From 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.
From Baseline to Week 52
Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis
Time Frame: From Baseline to Week 52
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.
From Baseline to Week 52
Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis
Time Frame: From 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.
From Baseline to Week 52

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sanofi

Collaborators

Regeneron Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2012

Primary Completion (Actual)

April 1, 2014

Study Completion (Actual)

April 1, 2014

Study Registration Dates

First Submitted

July 16, 2012

First Submitted That Met QC Criteria

July 16, 2012

First Posted (Estimate)

July 18, 2012

Study Record Updates

Last Update Posted (Estimate)

November 6, 2015

Last Update Submitted That Met QC Criteria

October 7, 2015

Last Verified

October 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EFC11568
  • U1111-1121-4356 (Other Identifier: UTN)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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