- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01266876
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
Conditions
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
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Manitoba
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Winnipeg, Manitoba, Canada
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Ontario
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London, Ontario, Canada
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Quebec
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Chicoutimi, Quebec, Canada
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Montreal, Quebec, Canada
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St. Foy, Quebec, Canada
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Alabama
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Huntsville, Alabama, United States
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California
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Mission Viejo, California, United States
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Newport Beach, California, United States
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Connecticut
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Bridgeport, Connecticut, United States
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Florida
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Jacksonville, Florida, United States
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Miami, Florida, United States
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Port Orange, Florida, United States
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Illinois
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Chicago, Illinois, United States
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Kansas
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Kansas City, Kansas, United States
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Maine
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Auburn, Maine, United States
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Biddeford, Maine, United States
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Missouri
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St. Louis, Missouri, United States
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New Hampshire
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Concord, New Hampshire, United States
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North Carolina
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Durham, North Carolina, United States
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Ohio
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Cincinnati, Ohio, United States
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Tennessee
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Nashville, Tennessee, United States
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Texas
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Houston, Texas, United States
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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:
- 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
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 |
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Placebo Comparator: Placebo
Placebo SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
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Placebo two SC injections in the abdomen only.
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Experimental: Alirocumab 150 mg Q4W
Alirocumab 150 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
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Alirocumab two SC injections in the abdomen only.
Other Names:
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Experimental: Alirocumab 200 mg Q4W
Alirocumab 200 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.
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Alirocumab two SC injections in the abdomen only.
Other Names:
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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:
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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:
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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)
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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.
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From Baseline to Week 12 (LOCF)
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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)
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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.
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From Baseline to Week 12 (LOCF)
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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)
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Calculated LDL-C value was obtained from Friedewald formula.
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Week 12 (LOCF)
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Percentage of Participants Achieving LDL-C < 70 mg/dL (1.81 mmol/L) at Week 12 - On-treatment Analysis
Time Frame: Week 12 (LOCF)
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Calculated LDL-C value was obtained from Friedewald formula.
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Week 12 (LOCF)
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Percent Change From Baseline in Total Cholesterol at Week 12 - On-treatment Analysis
Time Frame: From Baseline to Week 12 (LOCF)
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Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
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From Baseline to Week 12 (LOCF)
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Absolute Change From Baseline in Total Cholesterol at Week 12 - On-treatment Analysis
Time Frame: From Baseline to Week 12 (LOCF)
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Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
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From Baseline to Week 12 (LOCF)
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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)
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Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint..
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From Baseline to Week 12 (LOCF)
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Absolute Change From Baseline in HDL-C at Week 12 - On-treatment Analysis
Time Frame: From Baseline to Week 12 (LOCF)
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Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
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From Baseline to Week 12 (LOCF)
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Percent Change From Baseline in Triglycerides at Week 12 - On-treatment Analysis
Time Frame: From Baseline to Week 12 (LOCF)
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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)
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From Baseline to Week 12 (LOCF)
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Absolute Change From Baseline in Triglycerides at Week at 12 - On-treatment Analysis
Time Frame: From Baseline to Week 12 (LOCF)
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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)
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From Baseline to Week 12 (LOCF)
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Percent Change From Baseline in Non-HDL-C at Week 12 - On-treatment Analysis
Time Frame: From Baseline to Week 12
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Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
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From Baseline to Week 12
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Absolute Change From Baseline in Non-HDL-C at Week 12 - On-treatment Analysis
Time Frame: From Baseline to Week 12 (LOCF)
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Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
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From Baseline to Week 12 (LOCF)
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Percent Change From Baseline in Apo Lipoprotein B (Apo-B) at Week 12 - On-treatment Analysis
Time Frame: From Baseline to Week 12 (LOCF)
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Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
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From Baseline to Week 12 (LOCF)
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Absolute Change From Baseline in Apo-B at Week 12 - On-treatment Analysis
Time Frame: From Baseline to Week 12
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Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
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From Baseline to Week 12
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Percent Change From Baseline in Apolipoprotein - A1 (Apo-A1) at Week 12 - On-treatment Analysis
Time Frame: From Baseline to Week 12 (LOCF)
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Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
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From Baseline to Week 12 (LOCF)
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Absolute Change From Baseline in Apo-A1 at Week 12 - On-treatment Analysis
Time Frame: From Baseline to Week 12 (LOCF)
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Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
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From Baseline to Week 12 (LOCF)
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Absolute Change in the Ratio ApoB/ApoA-1 From Baseline to Week 12 - On-treatment Analysis
Time Frame: From Baseline to Week 12
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Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
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From Baseline to Week 12
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Percent Change From Baseline in Lipoprotein(a) at Week 12 - On-treatment Analysis
Time Frame: From Baseline to Week 12 (LOCF)
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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)
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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)
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From Baseline to Week 12 (LOCF)
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
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
- 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.
- 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.
- 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.
- 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.
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
Additional Relevant MeSH Terms
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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