Efficacy and Safety Evaluation of Alirocumab SAR236553 (REGN727) in Patients With Primary Hypercholesterolemia on Stable Atorvastatin Therapy

This study has been completed.
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01812707
First received: March 14, 2013
Last updated: January 30, 2014
Last verified: January 2014
  Purpose

Primary Objective:

To evaluate the effect of alirocumab SAR236553 (REGN727) on low-density lipoprotein cholesterol (LDL-C) levels after 12 weeks of treatment in comparison with placebo in patients with LDL-C ≥100 mg/dL (≥2.59 mmol/L) on ongoing stable atorvastatin therapy.

Secondary Objectives:

To evaluate the effects of alirocumab SAR236553 (REGN727) on other lipid levels after 12 weeks of treatment in comparison with placebo.

To evaluate the safety and tolerability of alirocumab SAR236553 (REGN727).

To evaluate the development of anti-alirocumab SAR236553 (REGN727) antibodies.

To evaluate the pharmacokinetics of alirocumab SAR236553 (REGN727).


Condition Intervention Phase
Hypercholesterolemia
Drug: alirocumab SAR236553 (REGN727)
Drug: placebo
Drug: atorvastatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled Study Evaluating the Efficacy and Safety of Three Doses of SAR236553 (REGN727) Over 12 Weeks in Patients With Primary Hypercholesterolemia and LDL-cholesterol ≥100 mg/dL (≥2.59 mmol/L) on Ongoing Stable Atorvastatin Therapy

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Percent change in calculated low-density lipoprotein cholesterol (LDL-C) [ Time Frame: From baseline to Week 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Absolute change in calculated low-density lipoprotein cholesterol (LDL-C) [ Time Frame: From baseline to Week 12 ] [ Designated as safety issue: No ]
  • Percent and absolute changes in other lipid parameters [ Time Frame: At Week 12 ] [ Designated as safety issue: No ]

Enrollment: 100
Study Start Date: March 2013
Study Completion Date: January 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: alirocumab SAR236553 (REGN727) Dose 1

Injection of 1 mL alirocumab SAR236553 (REGN727) Dose 1 every 2 weeks through subcutaneous administration in the abdomen.

alirocumab SAR236553 (REGN727) is a fully human monoclonal antibody that binds PCSK9 (proprotein convertase subtilisin/kexin type 9).

Atorvastatin will be administered once daily in the evening at a stable dose as background therapy.

Drug: alirocumab SAR236553 (REGN727)
Pharmaceutical form:solution for injection Route of administration: subcutaneous
Drug: atorvastatin
Pharmaceutical form:tablet Route of administration: oral
Experimental: alirocumab SAR236553 (REGN727) Dose 2

Injection of 1 mL alirocumab SAR236553 (REGN727) Dose 2 every 2 weeks through subcutaneous administration in the abdomen.

Atorvastatin will be administered once daily in the evening at a stable dose as background therapy.

Drug: alirocumab SAR236553 (REGN727)
Pharmaceutical form:solution for injection Route of administration: subcutaneous
Drug: atorvastatin
Pharmaceutical form:tablet Route of administration: oral
Experimental: alirocumab SAR236553 (REGN727) Dose 3

Injection of 1 mL alirocumab SAR236553 (REGN727) Dose 3 every 2 weeks through subcutaneous administration in the abdomen.

Atorvastatin will be administered once daily in the evening at a stable dose as background therapy.

Drug: alirocumab SAR236553 (REGN727)
Pharmaceutical form:solution for injection Route of administration: subcutaneous
Drug: atorvastatin
Pharmaceutical form:tablet Route of administration: oral
Placebo Comparator: Placebo

Injection of 1 mL alirocumab SAR236553 (REGN727) matching placebo every 2 weeks through subcutaneous administration in the abdomen.

Atorvastatin will be administered once daily in the evening at a stable dose as background therapy.

Drug: placebo
Pharmaceutical form:solution for injection Route of administration: subcutaneous
Drug: atorvastatin
Pharmaceutical form:tablet Route of administration: oral

Detailed Description:

The duration of study participation will depend on the status of the patient at screening: 21 to 27 weeks including a screening period of 1 to 7 weeks, a double-blind treatment period of 12 weeks, followed by an 8 week follow-up period.

  Eligibility

Ages Eligible for Study:   20 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria :

Patients with primary hypercholesterolemia treated with atorvastatin at stable dose of 5-20 mg for at least 6 weeks prior to screening and likely to have LDL-C ≥100 mg/dL (≥2.59 mmol/L) at the screening visit.

OR Patients with primary hypercholesterolemia who are receiving a lipid-lowering treatment other than atorvastatin, or who are not at stable dose of atorvastatin 5-20 mg for at least 6 weeks prior to screening and who are likely to have LDL-C ≥100 mg/dL (≥2.59 mmol/L) after the run-in period on atorvastatin therapy.

Exclusion criteria:

  1. LDL-C <100 mg/dL (<2.59 mmol/L) at Week -1 (V1): At the first visit for patients who are being treated with stable dose of atorvastatin 5-20 mg for at least 6 weeks prior to screening period.

    OR After the run-in period on atorvastatin (5-20 mg) for patients receiving a lipid lowering treatment other than atorvastatin, or not at stable dose of atorvastatin 5-20 mg for at least 6 weeks prior to screening period.

  2. Patients with type 1 diabetes
  3. Patients with type 2 diabetes treated with insulin, or without, and considered poorly controlled at screening.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01812707

Locations
Japan
Investigational Site Number 392002
Koganei-Shi, Japan
Investigational Site Number 392001
Shinjuku-Ku, Japan
Investigational Site Number 392003
Suita-Shi, Japan
Investigational Site Number 392004
Suita-Shi, Japan
Sponsors and Collaborators
Sanofi
Regeneron Pharmaceuticals
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01812707     History of Changes
Other Study ID Numbers: DFI12361, U1111-1134-4749
Study First Received: March 14, 2013
Last Updated: January 30, 2014
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Additional relevant MeSH terms:
Hypercholesterolemia
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Atorvastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on October 01, 2014