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

This study has been completed.
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01266876
First received: December 23, 2010
Last updated: August 20, 2015
Last verified: August 2015
  Purpose
The purpose of this study is to assess the efficacy and safety of REGN727/SAR236553 in participants diagnosed with heterozygous familial hypercholesterolemia (heFH)

Condition Intervention Phase
Hypercholesterolemia
Drug: Alirocumab
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, 12-Week Study of the Safety and Efficacy of REGN727 in Patients With Heterozygous Familial Hypercholesterolemia

Resource links provided by NLM:


Further study details as provided by Regeneron Pharmaceuticals:

Primary Outcome Measures:
  • Percent Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis [ Time Frame: From Baseline to Week 12 (LOCF) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Absolute Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis [ Time Frame: From Baseline to Week 12 (LOCF) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    Calculated LDL-C value was obtained from Friedewald formula.

  • Percentage of Participants Achieving LDL-C < 70 mg/dL (1.81 mmol/L) at Week 12 - On-treatment Analysis [ Time Frame: Week 12 (LOCF) ] [ Designated as safety issue: No ]
    Calculated LDL-C value was obtained from Friedewald formula.

  • Percent Change From Baseline in Total Cholesterol at Week 12 - On-treatment Analysis [ Time Frame: From Baseline to Week 12 (LOCF) ] [ Designated as safety issue: No ]
    Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.

  • Absolute Change From Baseline in Total Cholesterol at Week 12 - On-treatment Analysis [ Time Frame: From Baseline to Week 12 (LOCF) ] [ Designated as safety issue: No ]
    Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.

  • 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) ] [ Designated as safety issue: No ]
    Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint..

  • Absolute Change From Baseline in HDL-C at Week 12 - On-treatment Analysis [ Time Frame: From Baseline to Week 12 (LOCF) ] [ Designated as safety issue: No ]
    Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.

  • Percent Change From Baseline in Triglycerides at Week 12 - On-treatment Analysis [ Time Frame: From Baseline to Week 12 (LOCF) ] [ Designated as safety issue: No ]
    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)

  • Absolute Change From Baseline in Triglycerides at Week at 12 - On-treatment Analysis [ Time Frame: From Baseline to Week 12 (LOCF) ] [ Designated as safety issue: No ]
    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)

  • Percent Change From Baseline in Non-HDL-C at Week 12 - On-treatment Analysis [ Time Frame: From Baseline to Week 12 ] [ Designated as safety issue: No ]
    Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.

  • Absolute Change From Baseline in Non-HDL-C at Week 12 - On-treatment Analysis [ Time Frame: From Baseline to Week 12 (LOCF) ] [ Designated as safety issue: No ]
    Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.

  • Percent Change From Baseline in Apo Lipoprotein B (Apo-B) at Week 12 - On-treatment Analysis [ Time Frame: From Baseline to Week 12 (LOCF) ] [ Designated as safety issue: No ]
    Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.

  • Absolute Change From Baseline in Apo-B at Week 12 - On-treatment Analysis [ Time Frame: From Baseline to Week 12 ] [ Designated as safety issue: No ]
    Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.

  • Percent Change From Baseline in Apolipoprotein - A1 (Apo-A1) at Week 12 - On-treatment Analysis [ Time Frame: From Baseline to Week 12 (LOCF) ] [ Designated as safety issue: No ]
    Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.

  • Absolute Change From Baseline in Apo-A1 at Week 12 - On-treatment Analysis [ Time Frame: From Baseline to Week 12 (LOCF) ] [ Designated as safety issue: No ]
    Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.

  • Absolute Change in the Ratio ApoB/ApoA-1 From Baseline to Week 12 - On-treatment Analysis [ Time Frame: From Baseline to Week 12 ] [ Designated as safety issue: No ]
    Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.

  • Percent Change From Baseline in Lipoprotein(a) at Week 12 - On-treatment Analysis [ Time Frame: From Baseline to Week 12 (LOCF) ] [ Designated as safety issue: No ]
    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)

  • Absolute Change From Baseline in Lipoprotein(a) at Week 12 - On-treatment Analysis [ Time Frame: From Baseline to Week 12 (LOCF) ] [ Designated as safety issue: No ]
    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)


Enrollment: 77
Study Start Date: January 2011
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Placebo SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Drug: Placebo
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.
Drug: Alirocumab
Alirocumab two SC injections in the abdomen only.
Other Name: 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.
Drug: Alirocumab
Alirocumab two SC injections in the abdomen only.
Other Name: 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.
Drug: Alirocumab
Alirocumab two SC injections in the abdomen only.
Other Name: 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.
Drug: Alirocumab
Alirocumab two SC injections in the abdomen only.
Other Name: REGN727/SAR236553

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01266876

  Show 22 Study Locations
Sponsors and Collaborators
Regeneron Pharmaceuticals
Sanofi
Investigators
Study Director: Clinical Trial Management Regeneron Pharmaceuticals
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01266876     History of Changes
Other Study ID Numbers: R727-CL-1003 
Study First Received: December 23, 2010
Results First Received: August 20, 2015
Last Updated: August 20, 2015
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Additional relevant MeSH terms:
Hypercholesterolemia
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 28, 2016