Safety, Tolerability, and Effect of Alirocumab in High Cardiovascular Risk Patients With Severe Hypercholesterolemia Not Adequately Controlled With Conventional Lipid-modifying Therapies (ODYSSEY APPRISE)
Safety, Tolerability, and Effect of Alirocumab in High Cardiovascular Risk Patients With Severe Hypercholesterolemia Not Adequately Controlled With Conventional Lipid-modifying Therapies (ODYSSEY APPRISE)
Primary Objective:

 To provide participants with severe hypercholesterolemia at risk for subsequent
 cardiovascular (CV) events and not adequately controlled with currently available
 lipid-modifying therapy (LMT) access to alirocumab ahead of commercial availability and to
 document the overall safety and tolerability of alirocumab in this participant population.

 Secondary Objectives:

 To document the effect of alirocumab on low-density lipoprotein cholesterol (LDL-C) levels as
 well as non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (total-C),
 high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels after 12 weeks of
 treatment.

 To document participant's acceptability of self-injection (Self Injection Assessment
 Questionnaire, SIAQ).
The study duration included a screening period of up to 3 weeks, a treatment period of a
 minimum of 12 weeks and up to a maximum of 120 weeks (30 months), and at least 2 weeks after
 the last study treatment injection.
Inclusion criteria:

 Either A, B, C, D, or E below and not adequately controlled with a maximally tolerated dose
 of statin with or without other LMTs, all at stable doses for at least 4 weeks prior to the
 screening visit (Week-3):

 A. Participants suffering from heterozygous familial hypercholesterolemia (heFH) with LDL-C
 concentrations greater than or equal to (>=)160 mg/dL (4.14 millimoles per liter [mmol/L])
 despite treatment.

 B. Participants suffering from heFH with LDL-C concentrations >=130 mg/dL (3.36 mmol/L)
 despite treatment and two or more CV risk factors among this list:

 -  LDL-C greater than (>) 250 milligrams per deciliter (mg/dL) (6.46 mmol/L) at the time
 of the familial hypercholesterolemia (FH) diagnosis (before treatment).

 -  Family history of premature-onset coronary heart disease (CHD; first-degree male
 relative with onset before age 55 years; first-degree female relative with onset
 before age 65 years).

 -  Metabolic syndrome.

 -  HDL-C less than (<) 40 mg/dL (1.03 mmol/L).

 -  Hypertension (blood pressure >140/90 mmHg or drug treatment).

 -  Lipoprotein a (Lp[a]) >=50 mg/dL (1.78 µmol/L).

 -  Tendon xanthoma.

 C. Participants suffering from heFH with LDL-C concentrations >=130 mg/dL (3.36 mmol/L)
 despite treatment and one of the following characteristics:

 -  Established CHD or other cardiovascular disease (CVD; history of acute myocardial
 infarction, ischemic stroke, peripheral arterial disease, coronary or peripheral
 arterial revascularization, stable or unstable angina, transient ischemic attack,
 carotid artery stenosis >=50 percent (%), or aortic abdominal aneurysm).

 -  Drug-treated type 2 diabetes mellitus or type 1 with target organ damage.

 -  Family history of first- or second-degree relative with very premature onset CHD
 (first- or second-degree male relative with onset before age 45; first- or
 second-degree female relative with onset before age 55).

 D. Non-FH participants suffering from established CHD or other CVD (history of acute
 myocardial infarction (MI), ischemic stroke, peripheral arterial disease, coronary or
 peripheral arterial revascularization, stable or unstable angina, transient ischemic
 attack, carotid artery stenosis >=50%, or aortic abdominal aneurysm) and with LDL-C
 concentrations >=130 mg/dL (3.36 mmol/L).

 E. Participants suffering from progressive CVD (coronary artery disease, or peripheral
 arterial occlusive disease or cerebrovascular disease as documented clinically or by
 imaging techniques, with a subsequent CV event [acute MI, ischemic stroke, ischemia-driven
 revascularization, unstable angina, transient ischemic attack] occurring despite stable
 doses of maximally tolerated LMT) with LDL-C concentrations >=100 mg/dL (2.59 mmol/L).

 Exclusion criteria:

 Not on a stable dose of LMT (including statin) for at least 4 weeks prior to the screening
 visit (Week -3) and from screening to enrollment.

 Use of a fibrate other than fenofibrate within 4 weeks of the screening visit (Week-3) or
 between screening and enrollment.

 Daily doses above atorvastatin 80 mg, rosuvastatin 40 mg, or simvastatin 40 mg (except for
 participants on simvastatin 80 mg for more than one year, who were eligible).

 Use of statin other than simvastatin, atorvastatin, or rosuvastatin prior to the screening
 visit (Week-3) or between screening and enrollment, except when there was a documented
 reason for intolerance to the above mentioned potent statins (in which case the use of a
 different statin was allowed).

 Fasting serum TG >400 mg/dL (>4.52 mmol/L) at the screening visit (Week -3). Uncontrolled
 hypertension (>180 mmHg systolic and/or >110 mmHg diastolic at randomization visit).

 New York Heart Association Class III or IV congestive heart failure persisting despite
 treatment.

 History of hemorrhagic stroke. Liver transaminases >3 times the upper limit of normal.
 Laboratory evidence of current hepatitis B or C infection. Creatine kinase >3 times the
 upper limit of normal. Estimated glomerular filtration rate <30 mL/min/1.73 m^2. Pregnant
 or breastfeeding woman or with childbearing potential without appropriate contraception.

 Male participant with a female partner of childbearing potential not protected by a
 highly-effective method(s) of birth control.

 Participants eligible for enrollment into an ongoing clinical study of alirocumab conducted
 at the same investigational site.

 Hypersensitivity to alirocumab or any of the excipients.

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