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:
NCT01288443
First received: February 1, 2011
Last updated: August 21, 2015
Last verified: August 2015
  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 participants 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, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Parallel-group, Placebo-controlled, Multicenter Study Evaluating the Efficacy and Safety of Five Doses and Two Dose Regimens of SAR236553 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 From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis [ Time Frame: Baseline to Week 12 (LOCF) ] [ Designated as safety issue: No ]
    Calculated LDL-C values were obtained using the Friedewald formula. Baseline adjusted least squares (LS) means and standard errors were estimated using an analysis of covariance (ANCOVA) model including available post-baseline data on treatment from first study drug injection up to 21 days after last study drug injection (on-treatment analysis). Missing Week 12 data were imputed by last observation carried forward [LOCF] method.


Secondary Outcome Measures:
  • Absolute Change From Baseline in Calculated LDL-C (mmol/L) at Week 12 - On-Treatment Analysis [ Time Frame: Baseline to Week 12 (LOCF) ] [ Designated as safety issue: No ]
    Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.

  • Absolute Change From Baseline in Calculated LDL-C (mg/dL) at Week 12 - On-Treatment Analysis [ Time Frame: Baseline to Week 12 (LOCF) ] [ Designated as safety issue: No ]
    Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.

  • Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) and <70 mg/dL (1.81 mmol/L) at Week 12 - On-Treatment Analysis [ Time Frame: Week 12 (LOCF) ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Total Cholesterol, High-density Lipoprotein Cholesterol (HDL-C), Non-HDL-C and Apolipoprotein B (Apo-B) at Week 12 - On-Treatment Analysis [ Time Frame: Baseline to Week 12 (LOCF) ] [ Designated as safety issue: No ]
    Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.

  • Percent Change From Baseline in Fasting Triglycerides and Lipoprotein(a) at Week 12 - On-Treatment Analysis [ Time Frame: Baseline to Week 12 (LOCF) ] [ Designated as safety issue: No ]
    Since the assumptions of normal distribution and equality of variances were not verified for the lipid parameters, percent changes were expressed as median (inter-quartile range).

  • Absolute Change in the Ratio Apolipoprotein B/Apolipoprotein A-1 (ApoB/ApoA-1) From Baseline to Week 12 - On-Treatment Analysis [ Time Frame: Baseline to Week 12 (LOCF) ] [ Designated as safety issue: No ]
    Adjusted LS mean and standard errors were estimated using the same ANCOVA as for primary endpoint.


Enrollment: 183
Study Start Date: January 2011
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Q2W
Placebo (for alirocumab) every 2 weeks (Q2W) for 12-weeks in combination with atorvastatin stable dose.
Drug: Placebo (for alirocumab)
Two subcutaneous (SC) injections in the abdomen only.
Drug: Atorvastatin
Orally once daily at a stable dose of 10 mg, 20 mg, or 40 mg as background therapy.
Experimental: Alirocumab 50 mg Q2W
Alirocumab 50 mg Q2W for 12-weeks in combination with atorvastatin stable dose.
Drug: Alirocumab
Two SC injections in the abdomen only.
Other Names:
  • SAR236553
  • REGN727
Drug: Atorvastatin
Orally once daily at a stable dose of 10 mg, 20 mg, or 40 mg as background therapy.
Experimental: Alirocumab 100 mg Q2W
Alirocumab 100 mg Q2W for 12-weeks in combination with atorvastatin stable dose.
Drug: Alirocumab
Two SC injections in the abdomen only.
Other Names:
  • SAR236553
  • REGN727
Drug: Atorvastatin
Orally once daily at a stable dose of 10 mg, 20 mg, or 40 mg as background therapy.
Experimental: Alirocumab 150 mg Q2W
Alirocumab 150 mg Q2W for 12-weeks in combination with atorvastatin stable dose.
Drug: Alirocumab
Two SC injections in the abdomen only.
Other Names:
  • SAR236553
  • REGN727
Drug: Atorvastatin
Orally once daily at a stable dose of 10 mg, 20 mg, or 40 mg as background therapy.
Experimental: Alirocumab 200 mg Q4W
Alirocumab 200 mg every 4 weeks (Q4W) and alternating placebo Q2W for 12-weeks in combination with atorvastatin stable dose.
Drug: Alirocumab
Two SC injections in the abdomen only.
Other Names:
  • SAR236553
  • REGN727
Drug: Placebo (for alirocumab)
Two subcutaneous (SC) injections in the abdomen only.
Drug: Atorvastatin
Orally once daily at a stable dose of 10 mg, 20 mg, or 40 mg as background therapy.
Experimental: Alirocumab 300 mg Q4W
Alirocumab 300 mg Q4W and alternating placebo Q2W for 12-weeks in combination with atorvastatin stable dose.
Drug: Alirocumab
Two SC injections in the abdomen only.
Other Names:
  • SAR236553
  • REGN727
Drug: Placebo (for alirocumab)
Two subcutaneous (SC) injections in the abdomen only.
Drug: Atorvastatin
Orally once daily at a stable dose of 10 mg, 20 mg, or 40 mg as background therapy.

Detailed Description:

The duration of study participation depended on the status of the participant at screening:

  • For participants receiving atorvastatin 10 mg, 20 mg, or 40 mg at a stable dose for at least 6 weeks prior to screening, the study participation was to be approximately 21 weeks including a screening period of 1 week, a double-blind treatment period of 12 weeks and a follow-up period of 8 weeks.
  • For participants receiving a lipid-lowering treatment other than atorvastatin or not at stable dose of atorvastatin 10 mg, 20 mg, or 40 mg for at least 6 weeks prior to screening, or drug naive participants, the study participation was to be approximately 27 weeks including a screening period of 1 week, a run-in treatment period with atorvastatin 10 mg, 20 mg, or 40 mg at a stable dose of 6 weeks, a double-blind treatment period of 12 weeks, and a follow-up period of 8 weeks.
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Participants with primary hypercholesterolemia receiving a lipid-lowering treatment other than atorvastatin or not at stable dose of atorvastatin 10 mg, 20 mg, or 40 mg for at least 6 weeks prior to screening period or drug naive participants if they are likely to have low-density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL (≥ 2.59 mmol/L) at the end of the 6-week run-in treatment period on atorvastatin therapy

OR

  • Participants with primary hypercholesterolemia treated with atorvastatin at stable dose of 10 mg, 20 mg, or 40 mg for at least 6 weeks prior to screening period and likely to have LDL-C ≥ 100 mg/dL (≥ 2.59 mmol/L) at the screening visit

Exclusion criteria:

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

    • After the run-in period on atorvastatin (10 mg, 20 mg, or 40 mg) for participants receiving a lipid-lowering treatment other than atorvastatin or not at stable dose of atorvastatin 10 mg, 20 mg, or 40 mg for at least 6 weeks prior to the screening, or drug naive participant

    OR

    • At the first visit for participants who were being treated with stable dose of atorvastatin (10 mg, 20 mg, or 40 mg) for at least 6 weeks prior to screening
  2. Participants not previously instructed on a cholesterol-lowering diet
  3. Participants with type 1 diabetes
  4. Participants with type 2 diabetes treated with insulin
  5. Participants with type 2 diabetes and with an glycated hemoglobin (HbA1c) ≥ 8.5% at screening visit (considered poorly controlled)
  6. Laboratory findings measured before randomization:

    • Triglycerides (TG) > 350 mg/dL (> 3.95 mmol/L) at screening visit
    • Positive serum or urine pregnancy test in females of childbearing potential
  7. Pregnant or breast-feeding women
  8. Women of childbearing potential with no effective contraceptive method

The above information is not intended to contain all considerations relevant to a participant'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: NCT01288443

  Show 38 Study Locations
Sponsors and Collaborators
Sanofi
Regeneron Pharmaceuticals
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01288443     History of Changes
Other Study ID Numbers: DFI11565  U1111-1116-5252 
Study First Received: February 1, 2011
Results First Received: August 21, 2015
Last Updated: August 21, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hypercholesterolemia
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Atorvastatin Calcium
Antibodies, Monoclonal
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 25, 2016