Hypercholesterolemia MedDRA version: 18.0 Level: PT Classification code 10020603 Term: Hypercholesterolaemia System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Product Name: Alirocumab
Product Code: SAR236553 (REGN727)
Pharmaceutical Form: Solution for injection in pre-filled pen
INN or Proposed INN: Alirocumab
Sponsors
sanofi-aventis groupe
Eligibility
Sex/Gender
All
Inclusion criteria
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. Patients suffering from heterozygous familial hypercholesterolemia (heFH) with LDL-C concentrations =160 mg/dL (4.14 mmol/L) despite treatment. B. Patients 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 >250 mg/dL (6.46 mmol/L) at the time of the 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 140/90 mmHg or drug treatment). - Lipoprotein a (Lp[a]) =50 mg/dL (1.78 µmol/L). - Tendon xanthoma. C. Patients 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%, 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 patients suffering from established CHD or other 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%, or aortic abdominal aneurysm) and with LDL-C concentrations =130 mg/dL (3.36 mmol/L). E. Patients 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 LLT) with LDL-C concentrations =100 mg/dL (2.59 mmol/L). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 650 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 450
Exclusion criteria
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 patients on simvastatin 80 mg for more than one year, who are 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 is a documented reason for intolerance to the abovementioned potent statins (in which case the use of a different statin is 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. Patients eligible for enrollment into an ongoing clinical study of alirocumab conducted at the same investigational site. Hypersensitivity to alirocumab or any of the excipients.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To provide patients 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 patient population.; Secondary Objective: 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 patient’s acceptability of self-injection (Self Injection Assessment Questionnaire, SIAQ). ; Primary end point(s): a) Proportion of patients with adverse events b) Change from baseline in laboratory data (hematology and biochemistry) c) Change from baseline in vital signs ;Timepoint(s) of evaluation of this end point: a), b), c) : up to 30 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): a) Assessment of patient’s acceptability of self-injection using Self Injection Assessment Questionnaire (SIAQ) b) Percent change from baseline in calculated LDL-C levels c) Percent change from baseline in total-C levels d) Percent change from baseline in HDL-C levels e) Percent change from baseline in TG levels ; Timepoint(s) of evaluation of this end point: a) : Up to 30 months b), c), d), e): Baseline to week 12 | — |
Countries
Austria, Belgium, Canada, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Italy, Poland, Slovakia, Slovenia, Spain, Sweden, Switzerland
Contacts
Public ContactContact Point
Sanofi S.p.A.
Outcome results
None listed