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

Sanofi

Status and phase: Completed; Phase 2

Conditions: Hypercholesterolemia

Treatments: Drug: Alirocumab; Drug: Placebo (for alirocumab); Drug: Atorvastatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT01812707

U1111-1134-4749 (Other Identifier)

DFI12361

Details and patient eligibility

About

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

Full 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.

Enrollment: 100 patients

Sex: All

Ages: 20 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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100 participants in 4 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Placebo (for alirocumab) every 2 weeks (Q2W) for 12-weeks in combination with atorvastatin stable dose.

Treatment:

Drug: Atorvastatin

Drug: Placebo (for alirocumab)

Alirocumab 50 mg Q2W

Experimental group

Description:

Alirocumab 50 mg Q2W for 12-weeks in combination with atorvastatin stable dose.

Treatment:

Drug: Atorvastatin

Drug: Alirocumab

Alirocumab 75 mg Q2W

Experimental group

Description:

Alirocumab 75 mg Q2W for 12-weeks in combination with atorvastatin stable dose.

Treatment:

Drug: Atorvastatin

Drug: Alirocumab

Alirocumab 150 mg Q2W

Placebo Comparator group

Description:

Alirocumab 150 mg Q2W for 12-weeks in combination with atorvastatin stable dose.

Treatment:

Drug: Atorvastatin

Drug: Alirocumab