Efficacy and Safety Evaluation of Alirocumab (SAR236553/REGN727) in Patients With Primary Hypercholesterolemia on Stable Atorvastatin Therapy

August 21, 2015 updated by: Sanofi

A Randomized, Double-blind, Parallel-group, Placebo-controlled, Multicenter Study Evaluating the Efficacy and Safety of Five Doses and Two Dose Regimens of SAR236553 Over 12 Weeks in Patients With Primary Hypercholesterolemia and LDL-cholesterol ≥ 100 mg/dL (≥ 2.59 mmol/L) on Ongoing Stable Atorvastatin Therapy

Primary Objective:

  • To evaluate the effect of alirocumab (SAR236553/REGN727) on low-density lipoprotein cholesterol (LDL-C) levels after 12 weeks of treatment in comparison with placebo in participants with LDL-C ≥ 100 mg/dL (≥ 2.59 mmol/L) on ongoing stable atorvastatin therapy.

Secondary Objectives:

  • To evaluate the effects of alirocumab on other lipid levels after 12 weeks of treatment in comparison with placebo
  • To evaluate the safety and tolerability of alirocumab
  • To evaluate the development of anti-alirocumab antibodies
  • To evaluate the pharmacokinetics of alirocumab

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The duration of study participation depended on the status of the participant at screening:

  • For participants receiving atorvastatin 10 mg, 20 mg, or 40 mg at a stable dose for at least 6 weeks prior to screening, the study participation was to be approximately 21 weeks including a screening period of 1 week, a double-blind treatment period of 12 weeks and a follow-up period of 8 weeks.
  • For participants receiving a lipid-lowering treatment other than atorvastatin or not at stable dose of atorvastatin 10 mg, 20 mg, or 40 mg for at least 6 weeks prior to screening, or drug naive participants, the study participation was to be approximately 27 weeks including a screening period of 1 week, a run-in treatment period with atorvastatin 10 mg, 20 mg, or 40 mg at a stable dose of 6 weeks, a double-blind treatment period of 12 weeks, and a follow-up period of 8 weeks.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
183

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

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
    • Arizona
      • Tempe, Arizona, United States, 85282
        • Investigational Site Number 840525
    • California
      • Los Angeles, California, United States, 90057
        • Investigational Site Number 840516
      • Mission Viejo, California, United States, 92691
        • Investigational Site Number 840528
      • Newport Beach, California, United States, 92660
        • Investigational Site Number 840509
      • Palm Springs, California, United States, 92262
        • Investigational Site Number 840523
      • Westlake Village, California, United States, 91361
        • Investigational Site Number 840534
    • Colorado
      • Colorado Springs, Colorado, United States, 80903
        • Investigational Site Number 840530
    • Florida
      • Aventura, Florida, United States, 33108
        • Investigational Site Number 840504
      • Aventura, Florida, United States, 33108
        • Investigational Site Number 840519
      • Jacksonville, Florida, United States, 32216
        • Investigational Site Number 840514
      • Jupiter, Florida, United States, 33458
        • Investigational Site Number 840539
      • Miami, Florida, United States, 33143
        • Investigational Site Number 840502
      • Pembroke Pines, Florida, United States, 33026
        • Investigational Site Number 840520
      • Ponte Vedra, Florida, United States, 32081
        • Investigational Site Number 840524
      • Port Orange, Florida, United States, 32127
        • Investigational Site Number 840536
      • St. Petersburg, Florida, United States, 33609
        • Investigational Site Number 840507
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Investigational Site Number 840527
    • Indiana
      • Evansville, Indiana, United States, 47714
        • Investigational Site Number 840506
      • Indianapolis, Indiana, United States, 46260
        • Investigational Site Number 840529
    • Kansas
      • Wichita, Kansas, United States, 67203
        • Investigational Site Number 840515
    • Kentucky
      • Madisonville, Kentucky, United States, 42431
        • Investigational Site Number 840532
    • Maine
      • Auburn, Maine, United States, 04210
        • Investigational Site Number 840535
    • Massachusetts
      • Brockton, Massachusetts, United States, 02301
        • Investigational Site Number 840503
    • Nevada
      • Las Vegas, Nevada, United States, 89123
        • Investigational Site Number 840512
    • New Jersey
      • Edison, New Jersey, United States, 08817
        • Investigational Site Number 840505
    • New York
      • Rochester, New York, United States, 14609
        • Investigational Site Number 840538
    • North Carolina
      • Raleigh, North Carolina, United States, 27612
        • Investigational Site Number 840508
      • Statesville, North Carolina, United States, 28677
        • Investigational Site Number 840522
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • Investigational Site Number 840511
      • Cincinnati, Ohio, United States, 45219
        • Investigational Site Number 840526
      • Lyndhurst, Ohio, United States, 44124
        • Investigational Site Number 840510
    • Oklahoma
      • Tulsa, Oklahoma, United States, 74136
        • Investigational Site Number 840533
    • Oregon
      • Eugene, Oregon, United States, 97404
        • Investigational Site Number 840537
    • Tennessee
      • Bristol, Tennessee, United States, 37620
        • Investigational Site Number 840521
    • Utah
      • Bountiful, Utah, United States, 84010
        • Investigational Site Number 840531
    • Virginia
      • Norfolk, Virginia, United States, 23502
        • Investigational Site Number 840517
      • Richmond, Virginia, United States, 23227
        • Investigational Site Number 840518
    • Washington
      • Olympia, Washington, United States, 98502
        • Investigational Site Number 840513

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria:

  • Participants with primary hypercholesterolemia receiving a lipid-lowering treatment other than atorvastatin or not at stable dose of atorvastatin 10 mg, 20 mg, or 40 mg for at least 6 weeks prior to screening period or drug naive participants if they are likely to have low-density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL (≥ 2.59 mmol/L) at the end of the 6-week run-in treatment period on atorvastatin therapy

OR

  • Participants with primary hypercholesterolemia treated with atorvastatin at stable dose of 10 mg, 20 mg, or 40 mg for at least 6 weeks prior to screening period and likely to have LDL-C ≥ 100 mg/dL (≥ 2.59 mmol/L) at the screening visit

Exclusion criteria:

  1. LDL-C < 100 mg/dL (< 2.59 mmol/L):

    • After the run-in period on atorvastatin (10 mg, 20 mg, or 40 mg) for participants receiving a lipid-lowering treatment other than atorvastatin or not at stable dose of atorvastatin 10 mg, 20 mg, or 40 mg for at least 6 weeks prior to the screening, or drug naive participant

    OR

    • At the first visit for participants who were being treated with stable dose of atorvastatin (10 mg, 20 mg, or 40 mg) for at least 6 weeks prior to screening
  2. Participants not previously instructed on a cholesterol-lowering diet
  3. Participants with type 1 diabetes
  4. Participants with type 2 diabetes treated with insulin
  5. Participants with type 2 diabetes and with an glycated hemoglobin (HbA1c) ≥ 8.5% at screening visit (considered poorly controlled)

  6. Laboratory findings measured before randomization:

    • Triglycerides (TG) > 350 mg/dL (> 3.95 mmol/L) at screening visit
    • Positive serum or urine pregnancy test in females of childbearing potential
  7. Pregnant or breast-feeding women
  8. Women of childbearing potential with no effective contraceptive method

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
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
PLACEBO_COMPARATOR: Placebo Q2W
Placebo (for alirocumab) every 2 weeks (Q2W) for 12-weeks in combination with atorvastatin stable dose.
Drug: Placebo (for alirocumab)
Two subcutaneous (SC) injections in the abdomen only.
Drug: Atorvastatin
Orally once daily at a stable dose of 10 mg, 20 mg, or 40 mg as background therapy.
EXPERIMENTAL: Alirocumab 50 mg Q2W
Alirocumab 50 mg Q2W for 12-weeks in combination with atorvastatin stable dose.
Drug: Atorvastatin
Orally once daily at a stable dose of 10 mg, 20 mg, or 40 mg as background therapy.
Drug: Alirocumab
Two SC injections in the abdomen only.
Other Names:
  • SAR236553
  • REGN727
EXPERIMENTAL: Alirocumab 100 mg Q2W
Alirocumab 100 mg Q2W for 12-weeks in combination with atorvastatin stable dose.
Drug: Atorvastatin
Orally once daily at a stable dose of 10 mg, 20 mg, or 40 mg as background therapy.
Drug: Alirocumab
Two SC injections in the abdomen only.
Other Names:
  • SAR236553
  • REGN727
EXPERIMENTAL: Alirocumab 150 mg Q2W
Alirocumab 150 mg Q2W for 12-weeks in combination with atorvastatin stable dose.
Drug: Atorvastatin
Orally once daily at a stable dose of 10 mg, 20 mg, or 40 mg as background therapy.
Drug: Alirocumab
Two SC injections in the abdomen only.
Other Names:
  • SAR236553
  • REGN727
EXPERIMENTAL: Alirocumab 200 mg Q4W
Alirocumab 200 mg every 4 weeks (Q4W) and alternating placebo Q2W for 12-weeks in combination with atorvastatin stable dose.
Drug: Placebo (for alirocumab)
Two subcutaneous (SC) injections in the abdomen only.
Drug: Atorvastatin
Orally once daily at a stable dose of 10 mg, 20 mg, or 40 mg as background therapy.
Drug: Alirocumab
Two SC injections in the abdomen only.
Other Names:
  • SAR236553
  • REGN727
EXPERIMENTAL: Alirocumab 300 mg Q4W
Alirocumab 300 mg Q4W and alternating placebo Q2W for 12-weeks in combination with atorvastatin stable dose.
Drug: Placebo (for alirocumab)
Two subcutaneous (SC) injections in the abdomen only.
Drug: Atorvastatin
Orally once daily at a stable dose of 10 mg, 20 mg, or 40 mg as background therapy.
Drug: Alirocumab
Two SC injections in the abdomen only.
Other Names:
  • SAR236553
  • REGN727

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis
Time Frame: Baseline to Week 12 (LOCF)
Calculated LDL-C values were obtained using the Friedewald formula. Baseline adjusted least squares (LS) means and standard errors were estimated using an analysis of covariance (ANCOVA) model including available post-baseline data on treatment from first study drug injection up to 21 days after last study drug injection (on-treatment analysis). Missing Week 12 data were imputed by last observation carried forward [LOCF] method.
Baseline to Week 12 (LOCF)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Absolute Change From Baseline in Calculated LDL-C (mmol/L) at Week 12 - On-Treatment Analysis
Time Frame: Baseline to Week 12 (LOCF)
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Baseline to Week 12 (LOCF)
Absolute Change From Baseline in Calculated LDL-C (mg/dL) at Week 12 - On-Treatment Analysis
Time Frame: Baseline to Week 12 (LOCF)
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Baseline to Week 12 (LOCF)
Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) and <70 mg/dL (1.81 mmol/L) at Week 12 - On-Treatment Analysis
Time Frame: Week 12 (LOCF)
Week 12 (LOCF)
Percent Change From Baseline in Total Cholesterol, High-density Lipoprotein Cholesterol (HDL-C), Non-HDL-C and Apolipoprotein B (Apo-B) at Week 12 - On-Treatment Analysis
Time Frame: Baseline to Week 12 (LOCF)
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Baseline to Week 12 (LOCF)
Percent Change From Baseline in Fasting Triglycerides and Lipoprotein(a) at Week 12 - On-Treatment Analysis
Time Frame: Baseline to Week 12 (LOCF)
Since the assumptions of normal distribution and equality of variances were not verified for the lipid parameters, percent changes were expressed as median (inter-quartile range).
Baseline to Week 12 (LOCF)
Absolute Change in the Ratio Apolipoprotein B/Apolipoprotein A-1 (ApoB/ApoA-1) From Baseline to Week 12 - On-Treatment Analysis
Time Frame: Baseline to Week 12 (LOCF)
Adjusted LS mean and standard errors were estimated using the same ANCOVA as for primary endpoint.
Baseline to Week 12 (LOCF)

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Sanofi

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2011

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2011

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2011

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 1, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 1, 2011

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 2, 2011

Study Record Updates

Last Update Posted (ESTIMATE)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 24, 2015

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 21, 2015

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • DFI11565
  • U1111-1116-5252 (OTHER: 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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