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 22, 2015
Last verified: January 2015
  Purpose

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

Primary Objective of the study:

To evaluate the effect of alirocumab 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 on other lipid levels after 12 weeks of treatment in comparison with placebo.
  • To evaluate the safety and tolerability of alirocumab.
  • To evaluate the development of anti-alirocumab antibodies.
  • To evaluate the pharmacokinetics of alirocumab.

Condition Intervention Phase
Hypercholesterolemia
Drug: Alirocumab
Drug: Placebo (for alirocumab)
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) at Week 12 [ Time Frame: From baseline (randomization) to Week 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Absolute change in calculated low-density lipoprotein cholesterol (LDL-C) at Week 12 [ Time Frame: From baseline (randomization) to Week 12 ] [ Designated as safety issue: No ]
  • Percent and absolute changes in other lipid parameters at Week 12 [ Time Frame: From baseline (randomization) to 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 dose 1
Alirocumab dose 1 every 2 weeks through subcutaneous injection (SC) + atorvastatin stable dose orally once daily (background therapy)
Drug: Alirocumab

Pharmaceutical form: solution for injection

Route of administration: subcutaneous injection (1 mL) in the abdomen

Other Names:
  • SAR236553
  • RGEN727
Drug: Atorvastatin

Pharmaceutical form: tablet

Route of administration: oral administration in the evening

Experimental: Alirocumab dose 2
Alirocumab dose 2 every 2 weeks through subcutaneous injection (SC) + atorvastatin stable dose orally once daily (background therapy)
Drug: Alirocumab

Pharmaceutical form: solution for injection

Route of administration: subcutaneous injection (1 mL) in the abdomen

Other Names:
  • SAR236553
  • RGEN727
Drug: Atorvastatin

Pharmaceutical form: tablet

Route of administration: oral administration in the evening

Experimental: Alirocumab dose 3
Alirocumab dose 3 every 2 weeks through subcutaneous injection (SC) + atorvastatin stable dose orally once daily (background therapy)
Drug: Alirocumab

Pharmaceutical form: solution for injection

Route of administration: subcutaneous injection (1 mL) in the abdomen

Other Names:
  • SAR236553
  • RGEN727
Drug: Atorvastatin

Pharmaceutical form: tablet

Route of administration: oral administration in the evening

Placebo Comparator: Placebo
Placebo (for alirocumab) every 2 weeks through subcutaneous injection (SC) + atorvastatin stable dose orally once daily (background therapy)
Drug: Placebo (for alirocumab)

Pharmaceutical form: solution for injection

Route of administration: subcutaneous injection (1 mL) in the abdomen

Drug: Atorvastatin

Pharmaceutical form: tablet

Route of administration: oral administration in the evening


Detailed Description:

The duration of study participation will depend on the status of the patient at screening: 21 to 27 weeks including a screening/run-in 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 if they are likely to have LDL-C ≥100 mg/dL (≥2.59 mmol/L) after a 6-week run-in treatment period on atorvastatin therapy.

Exclusion criteria:

  1. LDL-C <100 mg/dL (<2.59 mmol/L)

    • at screening visit for patients who are being treated with stable dose of atorvastatin 5-20 mg for at least 6 weeks prior to screening OR
    • at the end of the 6-week run-in period on atorvastatin 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.
  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 22, 2015
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

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

ClinicalTrials.gov processed this record on July 05, 2015