Primary Hypercholesterolemia MedDRA version: 17.0 Level: LLT Classification code 10020604 Term: Hypercholesterolemia System Organ Class: 100000004861
Conditions
Interventions
Product Name: Alirocumab
Product Code: REGN727/SAR236553
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Alirocumab
CAS Number: 1245916-14-6
Current Sponsor code: REGN727
Other descri
Sponsors
Regeneron Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Men and women > age 18 or legal age of majority with elevated LDL-C. 2. Patients not having adequate control of their hypercholesterolemia, defined as follows: for moderate and high CVD risk, LDL-C =100 mg/dL, and for very high CVD risk, LDL-C = 70 mg/dL. Patients who are not on statin therapy must be at moderate CVD risk and must have LDL-C =65 years) yes F.1.3.1 Number of subjects for this age range 175
Exclusion criteria
Exclusion criteria: 1. Patient with homozygous FH (clinically or by previous genotyping) 2. Currently taking a statin that is not atorvastatin, rosuvastatin, or simvastatin 3. Use of fibrates other than fenofibrate within 6 weeks of the screening visit 4. Use of allowed LMTs (eg, omega-3 fatty acids, cholesterol absorption inhibitors [eg, ezetimibe], bile acid resins, niacin, and plant stanols/sterols [such as those found in Benecol®, flax seed oil, or psyllium]) that have not been at a stable dose/regimen for at least 4 weeks prior to the screening visit 5. Use of nutraceutical products or over-the-counter therapies that may affect lipids and that have not been at a stable dose/amount for at least 4 weeks prior to the screening visit 6. Use of red yeast rice products within 4 weeks of the screening visit or between screening and randomization visits 7. Uncontrolled hypothyroidism 8. Uncontrolled blood pressure (systolic blood pressure >160 mm Hg or diastolic blood pressure >100 mm Hg) at the screening visit 9. Patient who has received plasmapheresis treatment within 2 months prior to the screening visit, or has plans to receive it during the study 10. Recent (within 3 months prior to the screening visit) myocardial infarction, unstable angina leading to hospitalization, percutaneous coronary intervention (PCI), coronary artery bypass graft surgery (CABG), uncontrolled cardiac arrhythmia, stroke, transient ischemic attack, carotid revascularization, endovascular procedure or surgical intervention for peripheral vascular disease 11. Planning to undergo scheduled PCI, CABG, or carotid or peripheral revascularization during the study 12. Known history of a hemorrhagic stroke 13. History of New York Heart Association Class III or IV heart failure within 12 months prior to the screening visit. 14. Newly diagnosed diabetes (within 3 months prior to the screening visit) or poorly controlled diabetes (hemoglobin A1c [HbA1c] >9% at the screening visit) 15. History of bariatric surgery within 12 months prior to the screening visit 16. Unstable weight, defined by a variation >5 kg within 2 months prior to the screening visit 17. Known history of loss of function of PCSK9 (ie, genetic mutation or sequence variation) 18. Use of systemic corticosteroids, unless used as replacement therapy for pituitary/adrenal disease with a stable regimen for at least 6 weeks prior to randomization 19. Use of continuous estrogen or testosterone hormone replacement therapy, unless the regimen has been stable for 6 weeks prior to the screening visit and there are no plans to change the regimen during the study 20. History of cancer within the past 5 years, except for adequately treated basal cell skin cancer, squamous cell skin cancer, or in situ cervical cancer 21. Known history of positive test for human immunodeficiency virus (HIV) 22. Has been previously treated with at least 1 dose of alirocumab or any other anti-PCSK9 monoclonal antibody in other clinical studies 23. Has taken any active investigational drugs within 1 month or 5 half-lives, whichever is longer; however, patients who have taken anti-PCSK9 therapy at any time are excluded 24. Conditions/situations such as: ? Any clinically significant abnormality identified at the time of screening that in the judgment of the investigator or any sub-investigator would preclude safe completion of the study or constrain assessment of endpoints, such as major systemic diseases or patients with short life expecta
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: *To determine the efficacy, long-term safety, and tolerability of a dosing regimen of 300 mg alirocumab q4w and its potential as a starting regimen. ;Secondary Objective: * To investigate the pharmacokinetic (PK)/pharmacodynamic (PD) profile of alirocumab from weekly data at steady state and evaluate patients for the development of anti-alirocumab antibodies.;Primary end point(s): *The percent change in calculated LDL-C from baseline to week 24 in the intent-to-treat(ITT) population, using all LDL-C values regardless of adherence to treatment (ITT estimand). *The percent change in calculated LDL-C from baseline to averaged weeks 21 to 24 in the ITT population, using all LDL-C values regardless of adherence to treatment (ITT estimand).;Timepoint(s) of evaluation of this end point: From baseline to week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: * At week 24 * From baseline to week 12 *From baseline to week 24;Secondary end point(s): *The percent change in calculated LDL-C from baseline to week 24 in the mITT population, using all LDL-C values during the efficacy treatment period (on-treatment estimand). *The percent change in calculated LDL-C from baseline to week 12 (ITT estimand). *The percent change in calculated LDL-C from baseline to week 12 (ontreatment estimand). *The percent change in ApoB from baseline to week 24 (ITT estimand). *The percent change in ApoB from baseline to week 24 (on-treatment estimand). *The percent change in non-HDL-C from baseline to week 24 (ITT estimand). *The percent change in non-HDL-C from baseline to week 24 (on-treatment estimand). *The percent change in total-C from baseline to week 24 (ITT estimand). *The percent change in ApoB from baseline to week 12 (ITT estimand). *The percent change in non-HDL-C from baseline to week 12 (ITT estimand). *The percent change in total-C from baseline to week 12 (ITT estimand). *The proportion of very high CV risk patients reaching calculated LDL-C <70 mg/dL (1.81 mmol/L), or moderate or high CV risk patients reaching calculated LDL-C <100 mg/dL (2.59 mmol/L) at week 24 (ITT estimand). *The proportion of very high CV risk patients reaching calculated LDL-C <70 mg/dL (1.81 mmol/L), or moderate or high CV risk patients reaching calculated LDL-C <100 mg/dL (2.59 mmol/L) at week 24 (ontreatment estimand). *The proportion of patients reaching calculated LDL-C <70 mg/dL at week 24 (ITT estimand). *The proportion of patients reaching calculated LDL-C <70 mg/dL at week 24 (on-treatment estimand). *The percent change in Lp(a) from baseline to week 24 (ITT estimand). *The percent change in Lp(a) from baseline to week 12 (ITT estimand). *The percent change in HDL-C from baseline to week 24 (ITT estimand). *The percent change in HDL-C from baseline to week 12 (I | — |
Countries
Bulgaria, Canada, Hungary, Israel, Norway, Poland, Slovakia, South Africa, United Kingdom, United States
Contacts
Public ContactMedical Monitor
Regeneron Pharmaceuticals, Inc.
Outcome results
None listed