Back to resultsStudy of the Safety and Efficacy of REGN727/SAR236553 in Patients With HeFH Hypercholesterolemia
Primary Purpose
Hypercholesterolemia
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Alirocumab
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Hypercholesterolemia
Eligibility Criteria
Inclusion Criteria:
- Must meet the World Health Organization criteria for heFH
- Participants must be on a stable statin dose, with or without ezetimibe, for at least 6 weeks before screening
- Serum LDL-C levels ≥ 100 mg/dL at screening
- Willing to follow the NCEP ATPIII TLC diet, or an equivalent diet plan, starting at screening and continuing until the last study visit
- A negative urine/serum pregnancy test at each screening visit and start of the study, for women of childbearing potential
Key Exclusion Criteria:
- Participants with homozygous FH (clinically or by previous genotyping)
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
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
- 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)
- Use of thyroid medications (except for replacement therapy which has been stable for at least 12 weeks before the full screening visit)
- Fasting serum TG >350 mg/dL screening
- LDL apheresis within 12 months before screening
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Placebo Comparator
Experimental
Experimental
Experimental
Experimental
Arm Label
Placebo
Alirocumab 150 mg Q4W
Alirocumab 200 mg Q4W
Alirocumab 300 mg Q4W
Alirocumab 150 mg Q2W
Arm Description
Placebo SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Alirocumab 150 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Alirocumab 200 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Alirocumab 300 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Alirocumab 150 mg SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Outcomes
Primary Outcome Measures
Percent Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis
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
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
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
Calculated LDL-C value was obtained from Friedewald formula.
Percent Change From Baseline in Total Cholesterol at Week 12 - On-treatment Analysis
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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)
Full Information
NCT ID
NCT01266876
First Posted
December 23, 2010
Last Updated
August 20, 2015
Sponsor
Regeneron Pharmaceuticals
Collaborators
Sanofi
1. Study Identification
Unique Protocol Identification Number
NCT01266876
Brief Title
Study of the Safety and Efficacy of REGN727/SAR236553 in Patients With HeFH Hypercholesterolemia
Official Title
A Randomized, Double-Blind, Placebo-Controlled, 12-Week Study of the Safety and Efficacy of REGN727 in Patients With Heterozygous Familial Hypercholesterolemia
Study Type
Interventional
2. Study Status
Record Verification Date
August 2015
Overall Recruitment Status
Completed
Study Start Date
January 2011 (undefined)
Primary Completion Date
November 2011 (Actual)
Study Completion Date
November 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Regeneron Pharmaceuticals
Collaborators
Sanofi
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to assess the efficacy and safety of REGN727/SAR236553 in participants diagnosed with heterozygous familial hypercholesterolemia (heFH)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypercholesterolemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
77 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Arm Title
Alirocumab 150 mg Q4W
Arm Type
Experimental
Arm Description
Alirocumab 150 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Arm Title
Alirocumab 200 mg Q4W
Arm Type
Experimental
Arm Description
Alirocumab 200 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Arm Title
Alirocumab 300 mg Q4W
Arm Type
Experimental
Arm Description
Alirocumab 300 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Arm Title
Alirocumab 150 mg Q2W
Arm Type
Experimental
Arm Description
Alirocumab 150 mg SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Alirocumab
Other Intervention Name(s)
REGN727/SAR236553
Intervention Description
Alirocumab two SC injections in the abdomen only.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo two SC injections in the abdomen only.
Primary Outcome Measure Information:
Title
Percent Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis
Description
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.
Time Frame
From Baseline to Week 12 (LOCF)
Secondary Outcome Measure Information:
Title
Absolute Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis
Description
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.
Time Frame
From Baseline to Week 12 (LOCF)
Title
Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 12 - On-treatment Analysis
Description
Calculated LDL-C value was obtained from Friedewald formula.
Time Frame
Week 12 (LOCF)
Title
Percentage of Participants Achieving LDL-C < 70 mg/dL (1.81 mmol/L) at Week 12 - On-treatment Analysis
Description
Calculated LDL-C value was obtained from Friedewald formula.
Time Frame
Week 12 (LOCF)
Title
Percent Change From Baseline in Total Cholesterol at Week 12 - On-treatment Analysis
Description
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Time Frame
From Baseline to Week 12 (LOCF)
Title
Absolute Change From Baseline in Total Cholesterol at Week 12 - On-treatment Analysis
Description
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Time Frame
From Baseline to Week 12 (LOCF)
Title
Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 12 - On-treatment Analysis
Description
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint..
Time Frame
From Baseline to Week 12 (LOCF)
Title
Absolute Change From Baseline in HDL-C at Week 12 - On-treatment Analysis
Description
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Time Frame
From Baseline to Week 12 (LOCF)
Title
Percent Change From Baseline in Triglycerides at Week 12 - On-treatment Analysis
Description
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)
Time Frame
From Baseline to Week 12 (LOCF)
Title
Absolute Change From Baseline in Triglycerides at Week at 12 - On-treatment Analysis
Description
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)
Time Frame
From Baseline to Week 12 (LOCF)
Title
Percent Change From Baseline in Non-HDL-C at Week 12 - On-treatment Analysis
Description
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Time Frame
From Baseline to Week 12
Title
Absolute Change From Baseline in Non-HDL-C at Week 12 - On-treatment Analysis
Description
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Time Frame
From Baseline to Week 12 (LOCF)
Title
Percent Change From Baseline in Apo Lipoprotein B (Apo-B) at Week 12 - On-treatment Analysis
Description
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Time Frame
From Baseline to Week 12 (LOCF)
Title
Absolute Change From Baseline in Apo-B at Week 12 - On-treatment Analysis
Description
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Time Frame
From Baseline to Week 12
Title
Percent Change From Baseline in Apolipoprotein - A1 (Apo-A1) at Week 12 - On-treatment Analysis
Description
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Time Frame
From Baseline to Week 12 (LOCF)
Title
Absolute Change From Baseline in Apo-A1 at Week 12 - On-treatment Analysis
Description
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Time Frame
From Baseline to Week 12 (LOCF)
Title
Absolute Change in the Ratio ApoB/ApoA-1 From Baseline to Week 12 - On-treatment Analysis
Description
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Time Frame
From Baseline to Week 12
Title
Percent Change From Baseline in Lipoprotein(a) at Week 12 - On-treatment Analysis
Description
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)
Time Frame
From Baseline to Week 12 (LOCF)
Title
Absolute Change From Baseline in Lipoprotein(a) at Week 12 - On-treatment Analysis
Description
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)
Time Frame
From Baseline to Week 12 (LOCF)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Must meet the World Health Organization criteria for heFH
Participants must be on a stable statin dose, with or without ezetimibe, for at least 6 weeks before screening
Serum LDL-C levels ≥ 100 mg/dL at screening
Willing to follow the NCEP ATPIII TLC diet, or an equivalent diet plan, starting at screening and continuing until the last study visit
A negative urine/serum pregnancy test at each screening visit and start of the study, for women of childbearing potential
Key Exclusion Criteria:
Participants with homozygous FH (clinically or by previous genotyping)
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
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
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)
Use of thyroid medications (except for replacement therapy which has been stable for at least 12 weeks before the full screening visit)
Fasting serum TG >350 mg/dL screening
LDL apheresis within 12 months before screening
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trial Management
Organizational Affiliation
Regeneron Pharmaceuticals
Official's Role
Study Director
Facility Information:
City
Huntsville
State/Province
Alabama
Country
United States
City
Mission Viejo
State/Province
California
Country
United States
City
Newport Beach
State/Province
California
Country
United States
City
Bridgeport
State/Province
Connecticut
Country
United States
City
Jacksonville
State/Province
Florida
Country
United States
City
Miami
State/Province
Florida
Country
United States
City
Port Orange
State/Province
Florida
Country
United States
City
Chicago
State/Province
Illinois
Country
United States
City
Kansas City
State/Province
Kansas
Country
United States
City
Auburn
State/Province
Maine
Country
United States
City
Biddeford
State/Province
Maine
Country
United States
City
St. Louis
State/Province
Missouri
Country
United States
City
Concord
State/Province
New Hampshire
Country
United States
City
Durham
State/Province
North Carolina
Country
United States
City
Cincinnati
State/Province
Ohio
Country
United States
City
Nashville
State/Province
Tennessee
Country
United States
City
Houston
State/Province
Texas
Country
United States
City
Winnipeg
State/Province
Manitoba
Country
Canada
City
London
State/Province
Ontario
Country
Canada
City
Chicoutimi
State/Province
Quebec
Country
Canada
City
Montreal
State/Province
Quebec
Country
Canada
City
St. Foy
State/Province
Quebec
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
30183102
Citation
Leiter LA, Tinahones FJ, Karalis DG, Bujas-Bobanovic M, Letierce A, Mandel J, Samuel R, Jones PH. Alirocumab safety in people with and without diabetes mellitus: pooled data from 14 ODYSSEY trials. Diabet Med. 2018 Dec;35(12):1742-1751. doi: 10.1111/dme.13817. Epub 2018 Oct 9.
Results Reference
derived
PubMed Identifier
28964736
Citation
Defesche JC, Stefanutti C, Langslet G, Hopkins PN, Seiz W, Baccara-Dinet MT, Hamon SC, Banerjee P, Kastelein JJP. Efficacy of alirocumab in 1191 patients with a wide spectrum of mutations in genes causative for familial hypercholesterolemia. J Clin Lipidol. 2017 Nov-Dec;11(6):1338-1346.e7. doi: 10.1016/j.jacl.2017.08.016. Epub 2017 Sep 4. Erratum In: J Clin Lipidol. 2020 Sep - Oct;14(5):742.
Results Reference
derived
PubMed Identifier
26872608
Citation
Toth PP, Hamon SC, Jones SR, Martin SS, Joshi PH, Kulkarni KR, Banerjee P, Hanotin C, Roth EM, McKenney JM. Effect of alirocumab on specific lipoprotein non-high-density lipoprotein cholesterol and subfractions as measured by the vertical auto profile method: analysis of 3 randomized trials versus placebo. Lipids Health Dis. 2016 Feb 13;15:28. doi: 10.1186/s12944-016-0197-4.
Results Reference
derived
PubMed Identifier
22633824
Citation
Stein EA, Gipe D, Bergeron J, Gaudet D, Weiss R, Dufour R, Wu R, Pordy R. Effect of a monoclonal antibody to PCSK9, REGN727/SAR236553, to reduce low-density lipoprotein cholesterol in patients with heterozygous familial hypercholesterolaemia on stable statin dose with or without ezetimibe therapy: a phase 2 randomised controlled trial. Lancet. 2012 Jul 7;380(9836):29-36. doi: 10.1016/S0140-6736(12)60771-5. Epub 2012 May 26.
Results Reference
derived
Learn more about this trial
Study of the Safety and Efficacy of REGN727/SAR236553 in Patients With HeFH Hypercholesterolemia
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