Heterozygous Familial Hypercholesterolemia MedDRA version: 18.1 Level: LLT Classification code 10057079 Term: Heterozygous familial hypercholesterolemia System Organ Class: 100000004850
Conditions
Interventions
Product Name: Alirocumab
Product Code: SAR236553/REGN727
Pharmaceutical Form: Solution for injection in pre-filled pen
INN or Proposed INN: Alirocumab
CAS Number: 1245916-14-6
Current Sponsor code: Al
Sponsors
Regeneron Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A patient must meet the following criteria to be eligible for inclusion in the study: 1. Men and women =18 years of age at the time of the screening visit 2. Diagnosis of HeFH 3. Currently undergoing LDL apheresis therapy QW for at least 4 weeks, or Q2W for at least 8 weeks prior to the screening visit (week -2) and have initiated apheresis treatment for at least 5 months prior to that Note: A stable apheresis schedule is considered as 4 apheresis procedures performed during a 4-week period, approximately 1 week apart, or 4 apheresis procedures performed during an 8-week period, approximately 2 weeks apart. 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 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 33
Exclusion criteria
Exclusion criteria: A patient who meets any of the following criteria will be excluded from the study: 1. Homozygous FH 2. Background medical LMT (if applicable) that has not been stable for at least 8 weeks prior to the screening visit (week -2) 3. LDL apheresis schedule/apheresis settings that have not been stable for at least 4 weeks prior to the screening visit (week -2) for patients undergoing apheresis weekly and at least 8 weeks prior to the screening visit (week -2) for patients undergoing apheresis bi weekly 4. An LDL apheresis schedule other than QW to Q2W 5. Initiation of a new exercise program or exercise that has not remained stable within 8 weeks prior to the screening visit (week -2) 6. Initiation of a new diet or a diet that has not been stable within 8 weeks prior to the screening visit (week -2) 7. Use of nutraceuticals or over-the-counter therapies known to affect lipids, at a dose/amount that has not been stable for at least 8 weeks prior to the screening visit (week -2), or between the screening and randomization visit 8. Presence of any clinically significant uncontrolled endocrine disease known to influence serum lipids or lipoproteins 9. Signs and symptoms of hypothyroidism (thyroid replacement therapy is permitted) 10. History of bariatric surgery within 12 months prior to the screening visit (week -2) 11. Unstable weight (variation >5 kg) within 2 months prior to the screening visit (week -2) 12. Newly diagnosed (within 3 months prior to randomization visit [day 1]) diabetes mellitus or poorly controlled (hemoglobin A1c [HbA1c] >9%) diabetes 13. 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; topical, intra-articular, nasal, inhaled and ophthalmic steroid therapies are not considered as ‘systemic’ and are allowed 14. Use of estrogen or testosterone therapy, unless the regimen has been stable in the past 6 weeks prior to the screening visit (week -2) and no plans to change the regimen during the study 15. Systolic blood pressure >160 mm Hg or diastolic blood pressure >100 mm Hg at the screening visit (week -2) or time of randomization (day 1) Note: Blood pressure assessment for study eligibility may be obtained at a visit occurring between these 2 visits in the event that the patient had not taken, or plans not to take, prescribed hypertensive medications at the screening or randomization visit due to apheresis schedule. 16. History of a myocardial infarction (MI), unstable angina leading to hospitalization, coronary artery bypass graft surgery (CABG), percutaneous coronary intervention (PCI), uncontrolled cardiac arrhythmia, carotid surgery or stenting, stroke, transient ischemic attack or carotid revascularization within 3 months prior to the screening visit (week -2), or endovascular procedure or surgical intervention for peripheral vascular disease within 1 month prior to the screening visit (week -2) 17. History of New York Heart Association Class III or IV heart failure within 12 months prior to the screening visit 18. Known history of a hemorrhagic stroke 19. 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 20. Known history of a positive test for human immunodeficiency virus 21. Use of any active investigational drugs within 1 month or 5 half-lives of screening, whichever is longer 22. Patients who have be
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to evaluate the effect of alirocumab 150 mg every 2 weeks (Q2W) in comparison with placebo on the frequency of low-density lipoprotein (LDL) apheresis treatments in patients with heterozygous familial hypercholesterolemia (HeFH) undergoing weekly or bi-weekly LDL apheresis therapy.;Secondary Objective: The secondary objectives are: • To evaluate the effect of alirocumab 150 mg Q2W on LDL-C levels in patients with HeFH undergoing LDL apheresis therapy • To evaluate the effect of alirocumab 150 mg Q2W on the following lipid parameters: ApoB, non-HDL-C, total cholesterol, Lp(a), HDL-C, TGs, and ApoA-1 in patients with HeFH undergoing LDL apheresis therapy during the study • To evaluate the safety and tolerability of alirocumab 150 mg Q2W in patients with HeFH undergoing LDL apheresis therapy • To assess the PK of alirocumab 150 mg Q2W in patients with HeFH undergoing LDL apheresis therapy (QW versus Q2W) • To evaluate the development of anti-alirocumab antibodies • To evaluate PCSK9 levels in response to alirocumab therapy as well as pre and post-apheresis • To evaluate QOL in patients;Primary end point(s): The primary efficacy endpoint is the rate of apheresis treatments during the 12-week period from week 7 to week 18, normalized by the number of planned apheresis treatments according to each patient’s established schedule at screening, week -10 to week -2.;Timepoint(s) of evaluation of this end point: Throughout the duration of the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The key secondary endpoints are: • Percent change from baseline in LDL-C (pre-apheresis) to week 6, regardless of adherence to treatment • The standardized rate of apheresis treatments during the 4-week period from week 15 to week 18, defined similarly as for the primary efficacy endpoint • Percent change from baseline in (pre-apheresis): ApoB, non-HDL-C, total cholesterol and ApoA-1to week 6, regardless of adherence to treatment • Proportion of patients with =30% and =50% reduction in LDL-C (pre-apheresis) at week 6, regardless of adherence to treatment • Percent change from baseline in (pre-apheresis): LDL-C, ApoB, non-HDL-C, total cholesterol, in ApoA-1 to week 18, regardless of adherence to treatment • Proportion of patients with =30% and =50% reduction in LDL-C (pre-apheresis) at week 18, regardless of adherence to treatment • Change of W-BQ22 index score from baseline to week 18, regardless of adherence to treatment • Percent change from baseline in (pre-apheresis): Lp(a), HDL-C and TG levels to week 6, regardless of adherence to treatment • Percent change from baseline in (pre-apheresis): Lp(a), HDL-C and TG levels to week 18, regardless of adherence to treatment;Timepoint(s) of evaluation of this end point: Throughout the duration of the study | — |
Countries
Germany, United States
Contacts
Public ContactGaren Manvelian
Regeneron Pharmaceuticals, Inc.
Outcome results
None listed