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

• Percent change in LDL-C [ Time Frame: From baseline up to week 12 ] [ Designated as safety issue: No ]
• Percent change in other lipid parameters [ Time Frame: At weeks 12 and 24 ] [ Designated as safety issue: No ]

Primary Objective:

To demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by SAR236553 (REGN727) as add-on therapy to stable maximally tolerated daily statin therapy in comparison with ezetimibe after 24 weeks of treatment in patients with hypercholesterolemia at high cardiovascular (CV) risk.

Secondary Objectives:

• To evaluate the effect of SAR236553 (REGN727) in comparison with ezetimibe on LDL-C at other time points.
• To evaluate the effect of SAR236553 (REGN727) on other lipid parameters.
• To evaluate the safety and tolerability of SAR236553 (REGN727).

The maximum study duration will be 114 weeks per patient, including a 2 week screening period, 104 week randomized treatment period and 8 week follow-up period.

• Drug: SAR236553 (REGN727)

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

  Pharmaceutical form:Solution for injection Route of administration: subcutaneous

• Drug: matching placebo SAR236553 (REGN727)
  Pharmaceutical form:Solution for injection Route of administration: subcutaneous
• Drug: Ezetimibe
  Pharmaceutical form:encapsulated tablets Route of administration: oral
• Drug: matching placebo for Ezetimibe
  Pharmaceutical form:capsules Route of administration: oral

• Experimental: SAR236553 (REGN727) / Ezetimibe placebo
  Injection through subcutaneous (SC) administration. Ezetimibe placebo is administered orally.
  Interventions:

  • Drug: SAR236553 (REGN727)
  • Drug: matching placebo for Ezetimibe
• Active Comparator: SAR236553 (REGN727) Placebo / Ezetimibe
  Injection through subcutaneous (SC) administration. Ezetimibe is administered orally.
  Interventions:

  • Drug: matching placebo SAR236553 (REGN727)
  • Drug: Ezetimibe

Inclusion criteria:

Patients with hypercholesterolemia and established coronary heart disease (CHD) or CHD risk equivalents who are 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 is greater.
• Patients without established CHD or CHD risk equivalents.
• LDL-C <70 mg/dL (<1.81 mmol/L) and patients with a history of documented cardiovascular disease.
• LDL-C <100 mg/dL (<2.59 mmol/L) and patients without a history of documented CV disease.
• Fasting serum triglycerides >400 mg/dL (>4.52 mmol/L).

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.