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

Sanofi

Status and phase: Completed; Phase 2

Conditions: Hypercholesterolemia

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT01288443

DFI11565

U1111-1116-5252 (Other Identifier)

Details and patient eligibility

About

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

Full 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.

Enrollment: 183 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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183 participants in 6 patient groups, including a placebo group

Placebo Q2W

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo (for alirocumab)

Drug: Atorvastatin

Alirocumab 50 mg Q2W

Experimental group

Description:

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

Treatment:

Drug: Alirocumab

Drug: Atorvastatin

Alirocumab 100 mg Q2W

Experimental group

Description:

Alirocumab 100 mg Q2W for 12-weeks in combination with atorvastatin stable dose.

Treatment:

Drug: Alirocumab

Drug: Atorvastatin

Alirocumab 150 mg Q2W

Experimental group

Description:

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

Treatment:

Drug: Alirocumab

Drug: Atorvastatin

Alirocumab 200 mg Q4W

Experimental group

Description:

Alirocumab 200 mg every 4 weeks (Q4W) and alternating placebo Q2W for 12-weeks in combination with atorvastatin stable dose.

Treatment:

Drug: Alirocumab

Drug: Placebo (for alirocumab)

Drug: Atorvastatin

Alirocumab 300 mg Q4W

Experimental group

Description:

Alirocumab 300 mg Q4W and alternating placebo Q2W for 12-weeks in combination with atorvastatin stable dose.

Treatment:

Drug: Alirocumab

Drug: Placebo (for alirocumab)

Drug: Atorvastatin