Study of the Safety and Efficacy of REGN727/SAR236553 in Patients With HeFH Hypercholesterolemia

August 20, 2015 updated by: Regeneron Pharmaceuticals

A Randomized, Double-Blind, Placebo-Controlled, 12-Week Study of the Safety and Efficacy of REGN727 in Patients With Heterozygous Familial Hypercholesterolemia

The purpose of this study is to assess the efficacy and safety of REGN727/SAR236553 in participants diagnosed with heterozygous familial hypercholesterolemia (heFH)

Study Overview

Status

Completed

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

77

Phase

  • 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

    • Manitoba
      • Winnipeg, Manitoba, Canada
    • Ontario
      • London, Ontario, Canada
    • Quebec
      • Chicoutimi, Quebec, Canada
      • Montreal, Quebec, Canada
      • St. Foy, Quebec, Canada
    • Alabama
      • Huntsville, Alabama, United States
    • California
      • Mission Viejo, California, United States
      • Newport Beach, California, United States
    • Connecticut
      • Bridgeport, Connecticut, United States
    • Florida
      • Jacksonville, Florida, United States
      • Miami, Florida, United States
      • Port Orange, Florida, United States
    • Illinois
      • Chicago, Illinois, United States
    • Kansas
      • Kansas City, Kansas, United States
    • Maine
      • Auburn, Maine, United States
      • Biddeford, Maine, United States
    • Missouri
      • St. Louis, Missouri, United States
    • New Hampshire
      • Concord, New Hampshire, United States
    • North Carolina
      • Durham, North Carolina, United States
    • Ohio
      • Cincinnati, Ohio, United States
    • Tennessee
      • Nashville, Tennessee, United States
    • Texas
      • Houston, Texas, 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 to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Must meet the World Health Organization criteria for heFH
  2. Participants must be on a stable statin dose, with or without ezetimibe, for at least 6 weeks before screening
  3. Serum LDL-C levels ≥ 100 mg/dL at screening
  4. Willing to follow the NCEP ATPIII TLC diet, or an equivalent diet plan, starting at screening and continuing until the last study visit
  5. A negative urine/serum pregnancy test at each screening visit and start of the study, for women of childbearing potential

Key Exclusion Criteria:

  1. Participants with homozygous FH (clinically or by previous genotyping)
  2. Use of a medication (other than a statin or EZE) to alter serum lipids within 42 days (6 weeks) before screening including, but not limited to:

    • Fibrates
    • Niacin (>500 mg/day)
    • Omega-3 fatty acids (>1000 mg/day of DHA/EPA)
    • Bile acid resins
  3. Use of nutraceuticals or OTC medications that may alter lipid levels that are not stable for at least 6 weeks before screening and are not planned to remain constant throughout the study. Examples include:

    • Omega-3 fatty acids (≤1000 mg/day of DHA/EPA)
    • Niacin (≤500 mg/day)
    • Plant stanols, such as found in Benecol, flax seed oil, psyllium
    • Red yeast rice
  4. Disorders known to influence lipid levels, such as nephrotic syndrome, significant liver disease, Cushing's disease, untreated hypothyroidism (patients on stable thyroid replacement for at least 12 weeks before the full screening visit, who are metabolically euthyroid by thyroid-stimulating hormone (TSH) testing are allowed)
  5. Use of thyroid medications (except for replacement therapy which has been stable for at least 12 weeks before the full screening visit)
  6. Fasting serum TG >350 mg/dL screening
  7. LDL apheresis within 12 months before screening

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: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Placebo SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Placebo two SC injections in the abdomen only.
Experimental: Alirocumab 150 mg Q4W
Alirocumab 150 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Alirocumab two SC injections in the abdomen only.
Other Names:
  • REGN727/SAR236553
Experimental: Alirocumab 200 mg Q4W
Alirocumab 200 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Alirocumab two SC injections in the abdomen only.
Other Names:
  • REGN727/SAR236553
Experimental: Alirocumab 300 mg Q4W
Alirocumab 300 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Alirocumab two SC injections in the abdomen only.
Other Names:
  • REGN727/SAR236553
Experimental: Alirocumab 150 mg Q2W
Alirocumab 150 mg SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Alirocumab two SC injections in the abdomen only.
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 12 - On-treatment Analysis
Time Frame: From 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 investigational medicinal product (IMP) injection up to 21 days after last IMP injection (on-treatment analysis). Missing Week 12 data were imputed by last observation carried forward [LOCF] method.
From Baseline to Week 12 (LOCF)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Absolute Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis
Time Frame: From Baseline to Week 12 (LOCF)
Calculated LDL-C value was obtained from Friedewald formula. Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
From Baseline to Week 12 (LOCF)
Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 12 - On-treatment Analysis
Time Frame: Week 12 (LOCF)
Calculated LDL-C value was obtained from Friedewald formula.
Week 12 (LOCF)
Percentage of Participants Achieving LDL-C < 70 mg/dL (1.81 mmol/L) at Week 12 - On-treatment Analysis
Time Frame: Week 12 (LOCF)
Calculated LDL-C value was obtained from Friedewald formula.
Week 12 (LOCF)
Percent Change From Baseline in Total Cholesterol at Week 12 - On-treatment Analysis
Time Frame: From Baseline to Week 12 (LOCF)
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
From Baseline to Week 12 (LOCF)
Absolute Change From Baseline in Total Cholesterol at Week 12 - On-treatment Analysis
Time Frame: From Baseline to Week 12 (LOCF)
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
From Baseline to Week 12 (LOCF)
Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 12 - On-treatment Analysis
Time Frame: From Baseline to Week 12 (LOCF)
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint..
From Baseline to Week 12 (LOCF)
Absolute Change From Baseline in HDL-C at Week 12 - On-treatment Analysis
Time Frame: From Baseline to Week 12 (LOCF)
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
From Baseline to Week 12 (LOCF)
Percent Change From Baseline in Triglycerides at Week 12 - On-treatment Analysis
Time Frame: From Baseline to Week 12 (LOCF)
Since the assumptions of normal distribution and equality of variances were not verified for the lipid parameter, percent changes were expressed as median (interquartile range)
From Baseline to Week 12 (LOCF)
Absolute Change From Baseline in Triglycerides at Week at 12 - On-treatment Analysis
Time Frame: From 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 (interquartile range)
From Baseline to Week 12 (LOCF)
Percent Change From Baseline in Non-HDL-C at Week 12 - On-treatment Analysis
Time Frame: From Baseline to Week 12
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
From Baseline to Week 12
Absolute Change From Baseline in Non-HDL-C at Week 12 - On-treatment Analysis
Time Frame: From Baseline to Week 12 (LOCF)
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
From Baseline to Week 12 (LOCF)
Percent Change From Baseline in Apo Lipoprotein B (Apo-B) at Week 12 - On-treatment Analysis
Time Frame: From Baseline to Week 12 (LOCF)
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
From Baseline to Week 12 (LOCF)
Absolute Change From Baseline in Apo-B at Week 12 - On-treatment Analysis
Time Frame: From Baseline to Week 12
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
From Baseline to Week 12
Percent Change From Baseline in Apolipoprotein - A1 (Apo-A1) at Week 12 - On-treatment Analysis
Time Frame: From Baseline to Week 12 (LOCF)
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
From Baseline to Week 12 (LOCF)
Absolute Change From Baseline in Apo-A1 at Week 12 - On-treatment Analysis
Time Frame: From Baseline to Week 12 (LOCF)
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
From Baseline to Week 12 (LOCF)
Absolute Change in the Ratio ApoB/ApoA-1 From Baseline to Week 12 - On-treatment Analysis
Time Frame: From Baseline to Week 12
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
From Baseline to Week 12
Percent Change From Baseline in Lipoprotein(a) at Week 12 - On-treatment Analysis
Time Frame: From 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 (interquartile range)
From Baseline to Week 12 (LOCF)
Absolute Change From Baseline in Lipoprotein(a) at Week 12 - On-treatment Analysis
Time Frame: From Baseline to Week 12 (LOCF)
Since the assumptions of normal distribution and equality of variances were not verified for the lipid parameter, percent changes were expressed as median (interquartile range)
From Baseline to Week 12 (LOCF)

Collaborators and Investigators

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

Collaborators

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

January 1, 2011

Primary Completion (Actual)

November 1, 2011

Study Completion (Actual)

November 1, 2011

Study Registration Dates

First Submitted

December 23, 2010

First Submitted That Met QC Criteria

December 23, 2010

First Posted (Estimate)

December 24, 2010

Study Record Updates

Last Update Posted (Estimate)

September 22, 2015

Last Update Submitted That Met QC Criteria

August 20, 2015

Last Verified

August 1, 2015

More Information

Terms related to this study

Other Study ID Numbers

  • R727-CL-1003

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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