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

Phase 2

Completed

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

• Registration Number: NCT01812707
• Lead Sponsor: Sanofi

Brief Summary

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

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.

Study Timeline

• Study Start: 2013-03
• Study First Submitted: 2013-03-14
• Study First Submitted QC: 2013-03-14
• Study First Posted: 2013-03-18
• Primary Completion: 2014-01
• Study Completion: 2014-01
• Disposition First Submitted: 2015-01-22
• Disposition First Submitted QC: 2015-01-22
• Disposition First Posted: 2015-01-30
• Status Verified: 2015-08
• Results First Submitted: 2015-08-21
• Results First Submitted QC: 2015-08-21
• Results First Posted: 2015-09-24
• Last Update Submitted: 2016-09-27
• Last Update Posted: 2016-10-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo (for alirocumab)	Placebo (for alirocumab) every 2 weeks (Q2W) for 12-weeks in combination with atorvastatin stable dose.
Placebo	Atorvastatin	Placebo (for alirocumab) every 2 weeks (Q2W) for 12-weeks in combination with atorvastatin stable dose.
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.
Alirocumab 75 mg Q2W	Alirocumab	Alirocumab 75 mg Q2W for 12-weeks in combination with atorvastatin stable dose.
Alirocumab 75 mg Q2W	Atorvastatin	Alirocumab 75 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 150 mg Q2W	Atorvastatin	Alirocumab 150 mg 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 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

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.
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 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.
Absolute Change From Baseline in Apolipoprotein B/Apolipoprotein A-1 (ApoB/ApoA-1) Ratio at Week 12 - On-Treatment Analysis	From Baseline to Week 12 (LOCF)	Adjusted LS mean and standard errors were estimated using the same ANCOVA as for primary endpoint.

Trial Locations

Locations (4)

Investigational Site Number 392001; 🇯🇵 Shinjuku-Ku, Japan

Investigational Site Number 392003; 🇯🇵 Suita-Shi, Japan

Investigational Site Number 392002; 🇯🇵 Koganei-Shi, Japan

Investigational Site Number 392004; 🇯🇵 Suita-Shi, Japan