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

December 23, 2010
August 20, 2015
January 2011
November 2011   (final data collection date for primary outcome measure)
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.
Percent change of low-density lipoprotein cholesterol (LDL-C) from baseline to week 12 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01266876 on ClinicalTrials.gov Archive Site
  • 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)
  • Percent change in LDL-C from baseline to each visit [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Immunogenicity of repeated SC doses of REGN727 throughout the course of the study [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Pharmacokinetic (PK) profile of multiple doses of REGN727. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Safety and tolerability of multiple doses of REGN727 [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Study of the Safety and Efficacy of REGN727/SAR236553 in Patients With HeFH Hypercholesterolemia
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)
Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Hypercholesterolemia
  • Drug: Alirocumab
    Alirocumab two SC injections in the abdomen only.
    Other Name: REGN727/SAR236553
  • Drug: Placebo
    Placebo two SC injections in the abdomen only.
  • Placebo Comparator: Placebo
    Placebo SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
    Intervention: Drug: Placebo
  • Experimental: Alirocumab 150 mg Q4W
    Alirocumab 150 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
    Intervention: Drug: Alirocumab
  • Experimental: Alirocumab 200 mg Q4W
    Alirocumab 200 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
    Intervention: Drug: Alirocumab
  • Experimental: Alirocumab 300 mg Q4W
    Alirocumab 300 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
    Intervention: Drug: Alirocumab
  • Experimental: Alirocumab 150 mg Q2W
    Alirocumab 150 mg SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
    Intervention: Drug: Alirocumab

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
77
November 2011
November 2011   (final data collection date for primary outcome measure)

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
Both
18 Years to 75 Years   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
Netherlands
 
NCT01266876
R727-CL-1003
Yes
Not Provided
Not Provided
Regeneron Pharmaceuticals
Regeneron Pharmaceuticals
Sanofi
Study Director: Clinical Trial Management Regeneron Pharmaceuticals
Regeneron Pharmaceuticals
August 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP