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

Phase 2

Completed

• Conditions: Hypercholesterolemia
• Interventions: Drug: Alirocumab; Drug: Placebo (for alirocumab); Drug: Atorvastatin

• Registration Number: NCT01288443
• Lead Sponsor: Sanofi

Brief Summary

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

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.

Study Timeline

• Study Start: 2011-01
• Study First Submitted: 2011-02-01
• Study First Submitted QC: 2011-02-01
• Study First Posted: 2011-02-02
• Primary Completion: 2011-12
• Study Completion: 2011-12
• Disposition First Submitted: 2012-12-12
• Disposition First Submitted QC: 2012-12-12
• Disposition First Posted: 2012-12-17
• Status Verified: 2015-08
• Results First Submitted: 2015-08-21
• Results First Submitted QC: 2015-08-21
• Last Update Submitted: 2015-08-21
• Results First Posted: 2015-09-24
• Last Update Posted: 2015-09-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 183

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Alirocumab 50 mg Q2W	Alirocumab	Alirocumab 50 mg Q2W for 12-weeks in combination with atorvastatin stable dose.
Alirocumab 50 mg Q2W	Atorvastatin	Alirocumab 50 mg Q2W for 12-weeks in combination with atorvastatin stable dose.
Placebo Q2W	Placebo (for alirocumab)	Placebo (for alirocumab) every 2 weeks (Q2W) for 12-weeks in combination with atorvastatin stable dose.
Alirocumab 200 mg Q4W	Placebo (for alirocumab)	Alirocumab 200 mg every 4 weeks (Q4W) and alternating placebo Q2W for 12-weeks in combination with atorvastatin stable dose.
Alirocumab 300 mg Q4W	Placebo (for alirocumab)	Alirocumab 300 mg Q4W and alternating placebo Q2W for 12-weeks in combination with atorvastatin stable dose.
Placebo Q2W	Atorvastatin	Placebo (for alirocumab) every 2 weeks (Q2W) for 12-weeks in combination with atorvastatin stable dose.
Alirocumab 100 mg Q2W	Alirocumab	Alirocumab 100 mg Q2W for 12-weeks in combination with atorvastatin stable dose.
Alirocumab 100 mg Q2W	Atorvastatin	Alirocumab 100 mg Q2W for 12-weeks in combination with atorvastatin stable dose.
Alirocumab 150 mg Q2W	Atorvastatin	Alirocumab 150 mg Q2W for 12-weeks in combination with atorvastatin stable dose.
Alirocumab 150 mg Q2W	Alirocumab	Alirocumab 150 mg Q2W for 12-weeks in combination with atorvastatin stable dose.
Alirocumab 200 mg Q4W	Alirocumab	Alirocumab 200 mg every 4 weeks (Q4W) and alternating placebo Q2W for 12-weeks in combination with atorvastatin stable dose.
Alirocumab 200 mg Q4W	Atorvastatin	Alirocumab 200 mg every 4 weeks (Q4W) and alternating placebo Q2W for 12-weeks in combination with atorvastatin stable dose.
Alirocumab 300 mg Q4W	Alirocumab	Alirocumab 300 mg Q4W and alternating placebo Q2W for 12-weeks in combination with atorvastatin stable dose.
Alirocumab 300 mg Q4W	Atorvastatin	Alirocumab 300 mg Q4W and alternating placebo Q2W for 12-weeks in combination with atorvastatin stable dose.

Primary Outcome Measures

Name	Time	Method
Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis	Baseline to Week 12 (LOCF)	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

Name	Time	Method
Absolute Change From Baseline in Calculated LDL-C (mmol/L) at Week 12 - On-Treatment Analysis	Baseline to Week 12 (LOCF)	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	Baseline to Week 12 (LOCF)	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	Week 12 (LOCF)
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	Baseline to Week 12 (LOCF)	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	Baseline to Week 12 (LOCF)	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	Baseline to Week 12 (LOCF)	Adjusted LS mean and standard errors were estimated using the same ANCOVA as for primary endpoint.

Trial Locations

Locations (38)

Investigational Site Number 840525; 🇺🇸 Tempe, Arizona, United States

Investigational Site Number 840516; 🇺🇸 Los Angeles, California, United States

Investigational Site Number 840528; 🇺🇸 Mission Viejo, California, United States

Investigational Site Number 840509; 🇺🇸 Newport Beach, California, United States

Investigational Site Number 840523; 🇺🇸 Palm Springs, California, United States

Investigational Site Number 840534; 🇺🇸 Westlake Village, California, United States

Investigational Site Number 840530; 🇺🇸 Colorado Springs, Colorado, United States

Investigational Site Number 840504; 🇺🇸 Aventura, Florida, United States

Investigational Site Number 840519; 🇺🇸 Aventura, Florida, United States

Investigational Site Number 840514; 🇺🇸 Jacksonville, Florida, United States

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