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A Study of Alirocumab (REGN727/SAR236553) in Patients With ADH and GOFm of the PCSK9 Gene or LOFm of the apoB Gene

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ClinicalTrials.gov Identifier: NCT01604824
Recruitment Status : Unknown
Verified January 2015 by Regeneron Pharmaceuticals.
Recruitment status was:  Active, not recruiting
First Posted : May 24, 2012
Last Update Posted : January 30, 2015
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

Brief Summary:
The purpose of this study is to assess the pharmacodynamic (PD) effect of alirocumab on serum low-density lipoprotein cholesterol (LDL-C) in patients with autosomal dominant hypercholesterolemia (ADH) and gain-of-function mutations (GOFm) in 1 or both alleles of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene or with a loss-of-function mutation (LOFm) in 1 or more alleles of the apolipoprotein B-100 gene (apoB).

Condition or disease Intervention/treatment Phase
Hypercholesterolemia Drug: alirocumab Drug: placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2 Pilot Study With a Randomized Double-Blind Treatment Phase to Evaluate the Pharmacodynamics and Safety of Alirocumab in Patients With Autosomal Dominant Hypercholesterolemia and Gain-of-Function Mutations in 1 or Both Alleles of the PCSK9 Gene or Loss-of-Function Mutations in 1 or More Alleles of the Apolipoprotein B Gene
Study Start Date : September 2012
Actual Primary Completion Date : May 2014
Estimated Study Completion Date : September 2016


Arm Intervention/treatment
Experimental: Cohort 1
Group A: dosing regimen 1; Group B: dosing regimen 2
Drug: alirocumab
Randomized, double-blind treatment period may be followed by open-label treatment with alirocumab for all patients if certain criteria are met.
Other Names:
  • REGN727
  • SAR236553

Drug: placebo
Experimental: Cohort 2
Group C: dosing regimen 1; Group D: dosing regimen 2
Drug: alirocumab
Randomized, double-blind treatment period may be followed by open-label treatment with alirocumab for all patients if certain criteria are met.
Other Names:
  • REGN727
  • SAR236553

Drug: placebo



Primary Outcome Measures :
  1. Percent change in serum LDL-C [ Time Frame: day 1 to day 15 ]
    The primary endpoint in the study is the percent change in serum low-density lipoprotein cholesterol (LDL-C) from day 1 (baseline) to day 15.


Secondary Outcome Measures :
  1. TEAEs [ Time Frame: day 1 to day 169 ]
    The incidence and severity of TEAEs reported from the first dose of alirocumab through the last dose of alirocumab in the double-blind treatment period + 70 days.

  2. TEAEs [ Time Frame: day 1 to week 212 + 70 days ]
    The incidence and severity of TEAEs reported from the first dose of alirocumab through the last dose of alirocumab in the open-label treatment period (week 212) + 70 days (end-of-study).

  3. Percent change in ApoB100 [ Time Frame: day 1 to day 15 ]
    Percent change in ApoB100 from day 1 to day 15

  4. Percent change in non-HDL-C [ Time Frame: day 1 to day 15 ]
    Percent change in non-HDL-C (high-density lipoprotein cholesterol) from day 1 to day 15

  5. Percent change in total cholesterol [ Time Frame: day 1 to day 15 ]
    Percent change in total cholesterol from day 1 to day 15

  6. Percent change in ApoB100/ApoA1 ratio [ Time Frame: day 1 to day 15 ]
    Percent change in ApoB100/ApoA1 ratio from day 1 to day 15

  7. Trough concentrations of total alirocumab [ Time Frame: day 1 through end-of-study ]
    Trough concentrations of total alirocumab following repeat SC dosing with alirocumab throughout the study

  8. Immunogenicity of repeat SC dosing [ Time Frame: day 1 through end-of-study ]
    Immunogenicity of repeat SC dosing with alirocumab throughout the study



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Inclusion criteria include, but are not limited to the following:

  1. Between the ages of 18 and 70 years, inclusive
  2. A history of molecularly confirmed PCSK9 GOFm for cohort 1 and a history of molecularly confirmed PCSK9 GOFm or ApoB LOFm
  3. Plasma LDL-Cholesterol levels ≥70 mg/dL at the screening visit on a lipid lowering therapy (LLT) regimen stable for at least 28 days

Exclusion Criteria:

Exclusion criteria include, but are not limited to the following:

  1. Serum triglycerides >350 mg/dL at the screening visit
  2. Known to be positive for human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus
  3. Pregnant or breast-feeding women.
  4. Sexually active man or woman of childbearing potential who is unwilling to practice adequate contraception during the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01604824


Locations
United States, Utah
Salt Lake City, Utah, United States
France
Lille, Cedex, France
Nante, Cedex, France
Paris, France
Sponsors and Collaborators
Regeneron Pharmaceuticals
Sanofi
Investigators
Study Director: Clinical Trial Management Regeneron Pharmaceuticals

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01604824     History of Changes
Other Study ID Numbers: R727-CL-1018
First Posted: May 24, 2012    Key Record Dates
Last Update Posted: January 30, 2015
Last Verified: January 2015

Additional relevant MeSH terms:
Hypercholesterolemia
Hyperlipoproteinemia Type II
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Hyperlipoproteinemias
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs