Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Ezetimibe on Top of Statin in High Cardiovascular Risk Patients With Hypercholesterolemia (ODYSSEY COMBO II)

Sanofi

Status and phase: Completed; Phase 3

Conditions: Hypercholesterolemia

Treatments: Drug: Lipid Modifying Therapy (LMT); Drug: Placebo (for alirocumab); Drug: Ezetimibe; Drug: Alirocumab; Drug: Placebo (for ezetimibe)

Study type: Interventional

Funder types: Industry

Identifiers

NCT01644188

U1111-1121-4315 (Other Identifier)

2011-004130-34 (EudraCT Number)

EFC11569

Details and patient eligibility

About

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

Primary Objective of the study:

To demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by alirocumab as add-on therapy to stable maximally tolerated daily statin therapy in comparison with ezetimibe after 24 weeks of treatment in participants with hypercholesterolemia at high cardiovascular (CV) risk.

Secondary Objectives:

• To evaluate the effect of alirocumab in comparison with ezetimibe on LDL-C at other time points
• To evaluate the effect of alirocumab on other lipid parameters
• To evaluate the safety and tolerability of alirocumab

Full description

The maximum study duration was 115 weeks per participant, including a 3-week screening period, 104-week randomized treatment period and 8-week follow-up period.

Enrollment: 720 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Participants with hypercholesterolemia and established coronary heart disease (CHD) or CHD risk equivalents who were not adequately controlled with a maximally tolerated daily dose of statin at stable dose for at least 4 weeks prior to the screening visit (Week -2).

Exclusion criteria

• Age < 18 or legal age of adulthood, whichever was greater
• Participants without established CHD or CHD risk equivalents
• LDL-C <70 mg/dL (<1.81 mmol/L) and participants with a history of documented cardiovascular disease
• LDL-C <100 mg/dL (<2.59 mmol/L) and participants without a history of documented CV disease
• Fasting serum triglycerides >400 mg/dL (>4.52 mmol/L)

The above information was 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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720 participants in 2 patient groups

Alirocumab 75 /up to 150 mg Q2W

Experimental group

Description:

Alirocumab 75 mg every 2 weeks (Q2W) and oral placebo capsule for ezetimibe daily added to stable Lipid Modifying Therapy (LMT) for 104 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C level ≥70 mg/dL (1.81 mmol/L) at Week 8.

Treatment:

Drug: Placebo (for ezetimibe)

Drug: Alirocumab

Drug: Lipid Modifying Therapy (LMT)

Ezetimibe 10 mg

Active Comparator group

Description:

Ezetimibe 10 mg capsule daily and subcutaneous placebo for alirocumab Q2W added to stable LMT for 104 weeks.

Treatment:

Drug: Lipid Modifying Therapy (LMT)

Drug: Placebo (for alirocumab)

Drug: Ezetimibe