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

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: August 21, 2015
Last verified: August 2015
  Purpose

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

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 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, 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 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 investigational product (IP) injection up to 21 days after last IP 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 From Baseline in Apolipoprotein B/Apolipoprotein A-1 (ApoB/ApoA-1) Ratio at Week 12 - On-Treatment Analysis [ Time Frame: From 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: 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
Placebo Comparator: Placebo
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

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

Drug: Atorvastatin

Orally once daily at a stable dose of 5 to 20 mg as background therapy

Route of administration: oral administration in the evening

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
  • RGEN727
Drug: Atorvastatin

Orally once daily at a stable dose of 5 to 20 mg as background therapy

Route of administration: oral administration in the evening

Experimental: Alirocumab 75 mg Q2W
Alirocumab 75 mg Q2W for 12-weeks in combination with atorvastatin stable dose.
Drug: Alirocumab
Two SC injections in the abdomen only
Other Names:
  • SAR236553
  • RGEN727
Drug: Atorvastatin

Orally once daily at a stable dose of 5 to 20 mg as background therapy

Route of administration: oral administration in the evening

Placebo Comparator: 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
  • RGEN727
Drug: Atorvastatin

Orally once daily at a stable dose of 5 to 20 mg as background therapy

Route of administration: oral administration in the evening


Detailed Description:
The duration of study participation depended on the status of the participant 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 :

- Participants 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

- Participants with primary hypercholesterolemia who were receiving a lipid-lowering treatment other than atorvastatin, or who were not at stable dose of atorvastatin 5-20 mg for at least 6 weeks prior to screening if they were 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 participants who were 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 participants 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. Participants with type 1 diabetes
  3. Participants 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 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: 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
Results First Received: August 21, 2015
Last Updated: August 21, 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 February 10, 2016