Clinical trial NCT01266876: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypercholesterolemia
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2010-12-24
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)


Eligibility 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

Primary outcomes:
measure: Percent Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis
timeFrame: From Baseline to Week 12 (LOCF)
Secondary outcomes:
measure: Absolute Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis
timeFrame: From Baseline to Week 12 (LOCF)
measure: Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 12 - On-treatment Analysis
timeFrame: Week 12 (LOCF)
measure: Percentage of Participants Achieving LDL-C < 70 mg/dL (1.81 mmol/L) at Week 12 - On-treatment Analysis
timeFrame: Week 12 (LOCF)
measure: Percent Change From Baseline in Total Cholesterol at Week 12 - On-treatment Analysis
timeFrame: From Baseline to Week 12 (LOCF)
measure: Absolute Change From Baseline in Total Cholesterol at Week 12 - On-treatment Analysis
timeFrame: From Baseline to Week 12 (LOCF)
measure: Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 12 - On-treatment Analysis
timeFrame: From Baseline to Week 12 (LOCF)
measure: Absolute Change From Baseline in HDL-C at Week 12 - On-treatment Analysis
timeFrame: From Baseline to Week 12 (LOCF)
measure: Percent Change From Baseline in Triglycerides at Week 12 - On-treatment Analysis
timeFrame: From Baseline to Week 12 (LOCF)
measure: Absolute Change From Baseline in Triglycerides at Week at 12 - On-treatment Analysis
timeFrame: From Baseline to Week 12 (LOCF)
measure: Percent Change From Baseline in Non-HDL-C at Week 12 - On-treatment Analysis
timeFrame: From Baseline to Week 12
measure: Absolute Change From Baseline in Non-HDL-C at Week 12 - On-treatment Analysis
timeFrame: From Baseline to Week 12 (LOCF)
measure: Percent Change From Baseline in Apo Lipoprotein B (Apo-B) at Week 12 - On-treatment Analysis
timeFrame: From Baseline to Week 12 (LOCF)
measure: Absolute Change From Baseline in Apo-B at Week 12 - On-treatment Analysis
timeFrame: From Baseline to Week 12
measure: Percent Change From Baseline in Apolipoprotein - A1 (Apo-A1) at Week 12 - On-treatment Analysis
timeFrame: From Baseline to Week 12 (LOCF)
measure: Absolute Change From Baseline in Apo-A1 at Week 12 - On-treatment Analysis
timeFrame: From Baseline to Week 12 (LOCF)
measure: Absolute Change in the Ratio ApoB/ApoA-1 From Baseline to Week 12 - On-treatment Analysis
timeFrame: From Baseline to Week 12
measure: Percent Change From Baseline in Lipoprotein(a) at Week 12 - On-treatment Analysis
timeFrame: From Baseline to Week 12 (LOCF)
measure: Absolute Change From Baseline in Lipoprotein(a) at Week 12 - On-treatment Analysis
timeFrame: From Baseline to Week 12 (LOCF)
Other outcomes:
Locations:
city: Huntsville
country: United States
state: Alabama
city: Mission Viejo
country: United States
state: California
city: Newport Beach
country: United States
state: California
city: Bridgeport
country: United States
state: Connecticut
city: Jacksonville
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Port Orange
country: United States
state: Florida
city: Chicago
country: United States
state: Illinois
city: Kansas City
country: United States
state: Kansas
city: Auburn
country: United States
state: Maine
city: Biddeford
country: United States
state: Maine
city: St. Louis
country: United States
state: Missouri
city: Concord
country: United States
state: New Hampshire
city: Durham
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Nashville
country: United States
state: Tennessee
city: Houston
country: United States
state: Texas
city: Winnipeg
country: Canada
state: Manitoba
city: London
country: Canada
state: Ontario
city: Chicoutimi
country: Canada
state: Quebec
city: Montreal
country: Canada
state: Quebec
city: St. Foy
country: Canada
state: Quebec
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References:
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.
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.
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.
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.