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Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Ezetimibe in Patients With Hypercholesterolemia (ODYSSEY MONO)

This study has been completed.
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01644474
First received: July 17, 2012
Last updated: October 7, 2015
Last verified: October 2015
  Purpose

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

Primary Objective of the study:

To demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by alirocumab in comparison with ezetimibe after 24 weeks of treatment in participants with hypercholesterolemia.

Secondary Objectives:

  • To evaluate the effect of alirocumab in comparison with ezetimibe 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

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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Active-Controlled, Parallel-Group Study to Evaluate the Efficacy And Safety of SAR236553/REGN727 Over 24 Weeks in Patients With Hypercholesterolemia

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis [ Time Frame: From Baseline to Week 24 ] [ 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 24 regardless of status on- or off-treatment were used in the model (ITT analysis).


Secondary Outcome Measures:
  • Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis [ Time Frame: From Baseline to Week 24 ] [ Designated as safety issue: No ]
    Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

  • Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 24 - ITT Analysis [ Time Frame: From Baseline to Week 24 ] [ 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 24 regardless of status on- or off-treatment.

  • Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis [ Time Frame: From Baseline to Week 24 ] [ 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 24 regardless of status on- or off-treatment.

  • Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis [ Time Frame: From Baseline to Week 24 ] [ 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 24 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 24 ] [ 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 24 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 24 ] [ 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 24 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 24 ] [ 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 24 regardless of status on- or off-treatment.

  • Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - ITT Analysis [ Time Frame: Up to Week 24 ] [ 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 24 regardless of status on- or off-treatment were included in the imputation model.

  • Percentage of Participants Achieving Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis [ Time Frame: Up to Week 24 ] [ Designated as safety issue: No ]
    Adjusted percentages at Week 24 from multiple imputation approach model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

  • Percent Change From Baseline in Lipoprotein (a) at Week 24 - ITT Analysis [ Time Frame: From Baseline to Week 24 ] [ Designated as safety issue: No ]
    Adjusted means and standard errors at Week 24 from a multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

  • Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis [ Time Frame: From Baseline to Week 24 ] [ 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 24 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 24 ] [ 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 24 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 24 ] [ 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 24 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 24 ] [ Designated as safety issue: No ]
    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.

  • Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis [ Time Frame: From Baseline to Week 24 ] [ 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 24 regardless of status on- or off-treatment.

  • Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 24 - ITT Analysis [ Time Frame: From Baseline to Week 24 ] [ 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 24 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 24 ] [ 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 24 regardless of status on- or off-treatment.


Enrollment: 103
Study Start Date: July 2012
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Ezetimibe 10 mg
Oral ezetimibe 10 mg capsule daily and subcutaneous (SC) placebo injection for alirocumab every 2 weeks (Q2W) for 24 weeks.
Drug: Ezetimibe
One over-encapsulated tablet orally once daily at approximately the same time of the day with or without food.
Drug: Placebo (for Alirocumab)
1 mL subcutaneous injection in the abdomen, thigh, or outer area of the upper arm by self--injection or by another designated person using the autoinjector.
Experimental: Alirocumab 75/Up to 150 mg Q2W
SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 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: Alirocumab
1 mL subcutaneous injection in the abdomen, thigh, or outer area of the upper arm by self-injection or by another designated person using the autoinjector.
Other Names:
  • SAR236553
  • REGN727
Drug: Placebo (for Ezetimibe)
One capsule orally once daily at approximately the same time of the day with or without food..

Detailed Description:
The maximum study duration was 34 weeks per participant, including a 24-week randomized treatment period.
  Eligibility

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

Inclusion criteria:

  • Participants with hypercholesterolemia

Exclusion criteria:

  • Age < 18 or legal age of adulthood, whichever was greater
  • LDL-C < 100 mg/dL (< 2.59 mmol/L) or > 190 mg/dL (> 4.9 mmol/L)
  • Fasting serum triglycerides (TG) > 400 mg/dL (> 4.52 mmol/L)
  • Known history of homozygous or heterozygous familial hypercholesterolemia

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

  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01644474

Locations
United States, Kansas
Investigational Site Number 840603
Overland Park, Kansas, United States, 66212
United States, Ohio
Investigational Site Number 840601
Cincinnati, Ohio, United States, 45219
United States, Virginia
Investigational Site Number 840602
Richmond, Virginia, United States, 23227
Belgium
Investigational Site Number 056601
Antwerpen, Belgium, 2060
Finland
Investigational Site Number 246601
Helsinki, Finland, 00290
Netherlands
Investigational Site Number 528602
Groningen, Netherlands, 9711 SG
Investigational Site Number 528601
Rotterdam, Netherlands, 3021 HC
Investigational Site Number 528603
Velp, Netherlands, 6883 ES
Sponsors and Collaborators
Sanofi
Regeneron Pharmaceuticals
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

Publications:
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01644474     History of Changes
Other Study ID Numbers: EFC11716  U1111-1124-1167  2011-001424-38 
Study First Received: July 17, 2012
Results First Received: August 20, 2015
Last Updated: October 7, 2015
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on December 02, 2016