A Randomized Double-Blind Placebo-Controlled Parallel-Group Study to Evaluate the Effect of Alirocumab (SAR236553/REGN727) on the Occurrence of Cardiovascular Events in Patients Who Have Recently Experienced an Acute Coronary Syndrome
Brief Description Of Study
This is a double-blind, randomized, placebo-controlled, parallel-group study, multi-national, multicenter study to compare the effect of alirocumab with placebo on the occurrence of cardiovascular events (composite endpoint of coronary heart disease (CHD) death, non-fatal myocardial infarction (MI), fatal and non-fatal ischemic stroke, unstable angina requiring hospitalization) in adult patients age 40 or older who have experienced an acute coronary syndrome (ACS) event 4 to 52 weeks prior to randomization and are treated with an Lipid Modifying Treatment (LMT) regimen that is statin-intensive (defined as atorvastatin 40 or 80 mg, or rosuvastatin 20 or 40 mg) or at maximally tolerated dose of these given statins and optimized for long-term chronic use with other non-statin LMT(s) at investigators discretion. During the double-blind treatment period, the dosing of alirocumab is intended to achieve LDL-C levels of 30-50 mg/dL which is considered as the physiologic ideal level and to avoid levels of LDL-C that are clearly below the physiologic range (ie, less than15 mg/dL). To achieve this goal the following up-titration or down-titration scheme (including discontinuation if needed) will be applied: At randomization Visit (V3), the starting dose of alirocumab will be 75 mg every 2 weeks (Q2W) by Subcutaneous (SC) injection in the abdomen, thigh or outer area of upper arm. At Month 2 (V5), patients randomized to alirocumab will, in a blinded manner, either: - Continue alirocumab 75 mg Q2W, if the Month 1 (V4) LDL-C is less than 50 mg/dL OR - Be titrated-up to alirocumab 150 mg Q2W, if the Month 1 (V4) LDL-C is equal to or greater than 50 mg/dL At subsequent visits, for patients on alirocumab, the following adjustments may be applied depending on the dose received: - For patients receiving 150 mg Q2W: if LDL-C less than 25 mg/dL (including LDL-C less than15 mg/dL) on 2 consecutive measurements, down-titration to 75 mg Q2W will be done in a blinded manner at the next visit. Additional monitoring will be implemented until the down-titration is done. - For patients receiving 75 mg Q2W: o If LDL-C less than 25 mg/dL but equal to or greater than 15 mg/dL on 2 consecutive measurements: alirocumab will be continued but additional monitoring will be implemented, to further confirm the safety of low LDL-C levels. o If LDL-C less than15 mg/dL on 2 consecutive measurements: alirocumab treatment will be discontinued at the next visit. In order to maintain the blind there will be blinded substitution to placebo injections for the remaining duration of the study. Additional monitoring will be implemented until the study treatment discontinuation is done. As lipid values will not be communicated to investigators after randomization to maintain the blind, the continuation of the 75 mg dose, the up-titration to the 150 mg dose, the down-titration from 150 to 75 mg, or discontinuation will occur automatically, without site or patient awareness.