Study of Alirocumab (REGN727/SAR236553) in Patients With Primary Hypercholesterolemia and Moderate, High, or Very High Cardiovascular (CV) Risk, Who Are Intolerant to Statins (ODYSSEY ALTERNATIVE)

June 10, 2020 updated by: Regeneron Pharmaceuticals

A Randomized, Double-Blind, Double-Dummy, Active-Controlled Study to Evaluate the Efficacy and Safety of REGN727/SAR236553 in Patients With Primary Hypercholesterolemia Who Are Intolerant to Statins

This is a randomized, double-blind, double-dummy, active-controlled, parallel-group, multi-national, multi-center study to compare alirocumab (REGN727/SAR236553) versus ezetimibe in participants with primary hypercholesterolemia and moderate, high, or very high CV risk, who are intolerant to statins. An atorvastatin arm is added to determine that the population selected in the study is a truly statin intolerant population by assessing skeletal muscle-related adverse events.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

314

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

  • Austria
      • Feldkirch, Austria
      • Graz, Austria
      • Innsbruck, Austria
  • Canada
    • Quebec
      • Chicoutimi, Quebec, Canada
      • Montreal (2 locations), Quebec, Canada
      • Sainte-Foy, Quebec, Canada
  • France
      • Bron, France
      • Dijon, France
      • Lille, France
      • Paris, France
      • Saint-Herblain, France
      • Venissieux, France
  • Israel
      • Holon, Israel
      • Jerusalem, Israel
      • Ofakim, Israel
      • Safed, Israel
      • Tel-Hashomer, Israel
  • Italy
      • Cinisello Balsamo, Italy
      • Napoli, Italy
      • Palermo, Italy
      • Roma, Italy
  • Norway
      • Oslo (2 Locations), Norway
  • United Kingdom
      • Burton-on-Trent, United Kingdom
      • Chesterfield, United Kingdom
      • Isle Of White, United Kingdom
      • Londonderry/N. Ireland, United Kingdom
      • Peterborough, United Kingdom
      • Salford, United Kingdom
      • Stevenage, United Kingdom
  • United States
    • California
      • Anaheim, California, United States
      • Beverly Hills, California, United States
      • Mission Viejo, California, United States
      • Newport Beach, California, United States
      • Northridge, California, United States
      • Thousand Oaks, California, United States
    • Connecticut
      • Hartford, Connecticut, United States
    • Florida
      • Boynton Beach, Florida, United States
      • Jacksonville, Florida, United States
      • Lakeland, Florida, United States
      • Pembroke Pines, Florida, United States
      • Sarasota, Florida, United States
      • Tampa, Florida, United States
      • Trinity, Florida, United States
    • Illinois
      • Addison, Illinois, United States
      • Chicago, Illinois, United States
    • Indiana
      • Indianapolis, Indiana, United States
    • Kansas
      • Kansas City, Kansas, United States
    • Maine
      • Auburn, Maine, United States
    • Massachusetts
      • Boston, Massachusetts, United States
    • Minnesota
      • Minneapolis, Minnesota, United States
      • Rochester, Minnesota, United States
    • Missouri
      • Saint Louis, Missouri, United States
    • New Jersey
      • Clifton, New Jersey, United States
    • New York
      • New York, New York, United States
      • Poughkeepsie, New York, United States
    • North Carolina
      • Durham, North Carolina, United States
    • Ohio
      • Cincinnati, Ohio, United States
      • Marion, Ohio, United States
    • Pennsylvania
      • Danville, Pennsylvania, United States
      • Philadelphia, Pennsylvania, United States
      • Port Matilda, Pennsylvania, United States
      • Scranton, Pennsylvania, United States
      • Wilkes-Barre, Pennsylvania, United States
    • South Carolina
      • Summerville, South Carolina, United States
    • Tennessee
      • Kingsport, Tennessee, United States
      • Nashville, Tennessee, United States
    • Texas
      • Dallas, Texas, United States
      • Fort Worth, Texas, United States
    • Utah
      • Salt Lake City, Utah, United States
    • Virginia
      • Richmond, Virginia, United States

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:

  1. Patients with primary hypercholesterolemia [Heterozygous Familial Hypercholesterolemia (heFH) or non-FH] with moderate, high or very high CV risk and a history of statin intolerance
  2. Provide signed informed consent

Exclusion:

  1. Calculated serum LDL-C <70 mg/dL (1.81 mmol/L) and very high CV risk at the screening visit
  2. Calculated serum LDL-C <100 mg/dL (2.59 mmol/L) and high or moderate CV risk at the screening visit
  3. A 10-year fatal cardiovascular disease risk score <1% at the screening visit

(The inclusion/ exclusion criteria provided above is not intended to contain all considerations relevant to a patient's potential participation in this 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
Other: Atorvastatin (statin rechallenge arm)
Atorvastatin 20 mg over-encapsulated tablets orally once daily (QD) for 24 weeks and placebo (for alirocumab) subcutaneous (SC) injection every two weeks (Q2W) for 24 weeks added to stable lipid-modifying therapy (LMT).
Drug: Atorvastatin
Atorvastatin over-encapsulated tablets.
Drug: Placebo
Placebo for alirocumab, ezitimibe and atorvastatin.
Active Comparator: Ezetimibe
Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.
Drug: Placebo
Placebo for alirocumab, ezitimibe and atorvastatin.
Drug: Ezetimibe
Ezetimibe over-encapsulated tablet.
Other Names:
  • Zetia
Experimental: Alirocumab 75 mg/ up to 150 mg
Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
Drug: Placebo
Placebo for alirocumab, ezitimibe and atorvastatin.
Drug: Alirocumab
Alirocumab SC injection of 1 mL into the abdomen, thigh, or outer area of the upper arm.
Other Names:
  • REGN727/SAR236553

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 24
Calculated LDL-C values were obtained from Friedewald formula. 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).
From Baseline to Week 24

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent Change From Baseline in HDL-C 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.
From Baseline to Week 24
Percent Change From Baseline in Non-HDL-C 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.
From Baseline to Week 12
Percent Change From Baseline in Total-C 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.
From Baseline to Week 12
Percent Change From Baseline in Apo A-1 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.
From Baseline to Week 24
Percent Change From Baseline in Calculated LDL-C at Week 24 - On--Treatment Analysis
Time Frame: From Baseline to Week 24
Calculated LDL-C values were obtained from Friedewald formula. 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 or 3 days after the last capsule, whichever came first) (on-treatment analysis).
From Baseline to Week 24
Percent Change From Baseline in Calculated LDL--C at Week 12 -- ITT Analysis
Time Frame: From Baseline to Week 12
Calculated LDL-C values were obtained from Friedewald formula. 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.
From Baseline to Week 12
Percent Change From Baseline in Calculated LDL-C at Week 12 - On--Treatment Analysis
Time Frame: From Baseline to Week 12
Calculated LDL-C values were obtained from Friedewald formula. Adjusted LS means and standard errors at Week 12 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 or 3 days after the last capsule, whichever came first) (on-treatment analysis).
From Baseline to Week 12
Percent Change From Baseline in Apolipoprotein (Apo) B 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.
From Baseline to Week 24
Percent Change From Baseline in Apo B at Week 24 -- 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 or 3 days after the last capsule, whichever came first).
From Baseline to Week 24
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
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.
From Baseline to Week 24
Percent Change From Baseline in Non--HDL-C at Week 24 -- 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 or 3 days after the last capsule, whichever came first).
From Baseline to Week 24
Percent Change From Baseline in Total Cholesterol (Total--C) 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.
From Baseline to Week 24
Percent Change From Baseline in Apo B 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.
From Baseline to Week 12
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) at Week 24 - ITT Analysis
Time Frame: Up to Week 24
Adjusted percentages at Week 24 were obtained from a 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 analysis).
Up to Week 24
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) at Week 24 - On-Treatment Analysis
Time Frame: Up to Week 24
Adjusted percentages at Week 24 were obtained from a 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 or 3 days after the last capsule, whichever came first (on-treatment analysis).
Up to Week 24
Percentage of Participants 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 a 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 analysis).
Up to Week 24
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 24
Adjusted percentages at Week 24 were obtained from a 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 or 3 days after the last capsule, whichever came first (on-treatment analysis).
Up to Week 24
Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis
Time Frame: From Baseline to Week 24
Combined Estimate for Adjusted Mean (Standard Error) at Week 24 from multiple imputation followed by robust regression including all available post-baseline data from Week 4 to Week 24 regardless of status on or off-treatment.
From Baseline to Week 24
Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis
Time Frame: From Baseline to Week 24
Combined Estimate for Adjusted Mean (Standard Error) at Week 24 from multiple imputation followed by robust regression including all available post-baseline data from Week 4 to Week 24 regardless of status on or off-treatment.
From Baseline to Week 24
Percent Change From Baseline in Lipoprotein(a) at Week 12 -- ITT Analysis
Time Frame: From Baseline to Week 12
Combined Estimate for Adjusted Mean (Standard Error) at Week 24 from multiple imputation followed by robust regression including all available post-baseline data from Week 4 to Week 24 regardless of status on or off-treatment.
From Baseline to Week 12
Percent Change in HDL-C From Baseline to Week 12 -- ITT Analysis
Time Frame: From Baseline to Week 12
Least-squares (LS) means and standard errors (SE) taken from MMRM (mixed-effect model with repeated measures) analysis
From Baseline to Week 12
Percent Change in Fasting Triglycerides From Baseline to Week 12 -- ITT Analysis
Time Frame: From Baseline to Week 12
Combined Estimate for Adjusted Mean (Standard Error) at Week 24 from multiple imputation followed by robust regression including all available post-baseline data from Week 4 to Week 24 regardless of status on or off-treatment.
From Baseline to Week 12
Percent Change From Baseline in Apo A--1 at Week 12 -- ITT Analysis
Time Frame: From Baseline to Week 12
Least squares (LS) means and standard errors (SE) taken from MMRM (mixed effect model with repeated measures) analysis.
From Baseline to Week 12

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants Who Experienced Skeletal Muscle-related Adverse Event (AE)
Time Frame: From Baseline up to Week 24
Skeletal muscle-related adverse events were a predefined category including myalgia, muscle spasms, muscular weakness, musculoskeletal stiffness and muscle fatigue. Events that developed during treatment emergent adverse events period (the time from the first double-blindstudy treatment [injection or capsules, whichever came first] up to the day of the last double-blind injection + 70 days ) are reported.
From Baseline up to Week 24
Percent Change From Baseline in Calculated LDL-C at Week 24 Versus Atorvastatin - Raw Data Description - Intent-To-Treat (ITT) Analysis
Time Frame: From Baseline up to Week 24
From Baseline up to Week 24

Collaborators and Investigators

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

Sponsor

Regeneron Pharmaceuticals

Collaborators

Sanofi

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 (Actual)

September 30, 2012

Primary Completion (Actual)

May 31, 2014

Study Completion (Actual)

May 31, 2017

Study Registration Dates

First Submitted

October 8, 2012

First Submitted That Met QC Criteria

October 16, 2012

First Posted (Estimate)

October 18, 2012

Study Record Updates

Last Update Posted (Actual)

June 23, 2020

Last Update Submitted That Met QC Criteria

June 10, 2020

Last Verified

June 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • R727-CL-1119

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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