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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01604824
First received: May 22, 2012
Last updated: February 14, 2014
Last verified: February 2014
  Purpose

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 Intervention Phase
Hypercholesterolemia
Drug: alirocumab
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Regeneron Pharmaceuticals:

Primary Outcome Measures:
  • Percent change in serum LDL-C [ Time Frame: day 1 to day 15 ] [ Designated as safety issue: No ]
    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:
  • TEAEs [ Time Frame: day 1 to day 169 ] [ Designated as safety issue: Yes ]
    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.

  • TEAEs [ Time Frame: day 1 to week 212 + 70 days ] [ Designated as safety issue: Yes ]
    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).

  • Percent change in ApoB100 [ Time Frame: day 1 to day 15 ] [ Designated as safety issue: No ]
    Percent change in ApoB100 from day 1 to day 15

  • Percent change in non-HDL-C [ Time Frame: day 1 to day 15 ] [ Designated as safety issue: No ]
    Percent change in non-HDL-C (high-density lipoprotein cholesterol) from day 1 to day 15

  • Percent change in total cholesterol [ Time Frame: day 1 to day 15 ] [ Designated as safety issue: No ]
    Percent change in total cholesterol from day 1 to day 15

  • Percent change in ApoB100/ApoA1 ratio [ Time Frame: day 1 to day 15 ] [ Designated as safety issue: No ]
    Percent change in ApoB100/ApoA1 ratio from day 1 to day 15

  • Trough concentrations of total alirocumab [ Time Frame: day 1 through end-of-study ] [ Designated as safety issue: No ]
    Trough concentrations of total alirocumab following repeat SC dosing with alirocumab throughout the study

  • Immunogenicity of repeat SC dosing [ Time Frame: day 1 through end-of-study ] [ Designated as safety issue: No ]
    Immunogenicity of repeat SC dosing with alirocumab throughout the study


Enrollment: 23
Study Start Date: September 2012
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: 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
  More Information

No publications provided

Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01604824     History of Changes
Other Study ID Numbers: R727-CL-1018
Study First Received: May 22, 2012
Last Updated: February 14, 2014
Health Authority: United States: Food and Drug Administration
France: Ministry of Health

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

ClinicalTrials.gov processed this record on April 14, 2014