Homozygous familial hypercholesterolemia MedDRA version: 20.1 Level: LLT Classification code 10020604 Term: Hypercholesterolemia System Organ Class: 100000004861
Conditions
Sponsors
Regeneron Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female patients =12 years of age with HoFH. Patients aged =12 years old will be enrolled only in countries where permitted by the Regulatory Agency and Institutional Review Board (IRB) or Ethics Committee (EC). 2. Diagnosis of functional HoFH by at least 1 of the following genetic or clinical criteria: a. Documented functional mutation or mutations in both LDLR alleles Note: patients who have null receptor mutations on both LDLR alleles, ie, double null, are eligible b. Presence of homozygous or compound heterozygous mutations in Apo B or PCSK9 Note: patients who are double heterozygous, ie, mutations on different genes (eg, LDLR/PCSK9) and patients with homozygous LDLRAP1 mutations are eligible c. Untreated TC >500 mg/dL (12.93 mmol/L) and TG 250 mg/dL (6.47 mmol) OR cutaneous or tendinous xanthoma before the age of 10 years 3. For patients who have participated in a previous evinacumab or alirocumab study: completion of the study in which they participated. 4. Willing and able to comply with clinic visits and study-related procedures. 5. Provide signed informed consent. Are the trial subjects under 18? yes Number of subjects for this age range: 6 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 94 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Exclusion Criteria for Evinacumab-Naïve Patients 1. Concomitant medications and procedures that have not been stable prior to the baseline visit 2. Any new condition or worsening of an existing condition, which in the opinion of the investigator would make the patient unsuitable for enrollment, or could interfere with the patient participating in or completing the study. 3. History of a MI, unstable angina leading to hospitalization, coronary artery bypass graft surgery, percutaneous coronary intervention, uncontrolled cardiac arrhythmia, carotid surgery or stenting, stroke, transient ischemic attack, valve replacement surgery, carotid revascularization, endovascular procedure or surgical intervention for peripheral vascular disease within 3 months prior to the baseline visit 4. Presence of any clinically significant uncontrolled endocrine disease known to influence serum lipids or lipoproteins 5. Newly diagnosed (within 3 months prior to screening visit diabetes mellitus or poorly controlled (HbA1c >9%) diabetes 6. Use of systemic corticosteroids, unless used as replacement therapy for pituitary/adrenal disease with a stable regimen for at least 6 weeks prior to screening visit 7. Use of estrogen or testosterone therapy unless the regimen has been stable 6 weeks prior to the screening visit and no plans to change the regimen during the study 8. Systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg at the screening visit 9. 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 10. History of New York Heart Association (NYHA) Class IV heart failure within 12 months before screening 11. Laboratory findings during the screening period (applies to patients undergoing Screening): • Alanine aminotransferase or aspartate aminotransferase >3 x upper limit of normal (ULN)(1 repeat lab is allowed) • CPK >3 x ULN (1 repeat lab is allowed) • Positive serum beta-human chorionic gonadotropin or urine pregnancy test in WOCBP • TSH >1.5 x ULN of the central laboratory (1 repeat lab is allowed) for patients not on thyroid replacement therapy • Positive test for hepatitis B surface antigen and/or hepatitis C antibody (associated with a positive HCV RNA polymerase chain reaction) • eGFR <30 mL/min/1.73 m2 (calculated by central lab) • Postmenopausal status will be confirmed by measurement of follicle-stimulating hormone (FSH) 12. Member of the clinical site study team and/or his/her immediate family. 13. Pregnant of breastfeeding women 14. Women of child bearing potential (see protocol for more information) 15. Sexually active men unwilling to use forms of medically acceptable methods of birth control (see protocol for more information) 16. LDL-C level <40 mg/dL at screening visit 17. Use of any active investigational drugs (except alirocumab) within 1 month or 5 half lives prior to the screening visit, whichever is longer. 18. Age <12 years at the screening visit 19. Tanner stage <2
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to evaluate the long-term safety and tolerability of evinacumab in patients with HoFH.;Primary end point(s): The primary endpoint is the incidence and severity of treatment-emergent adverse events (TEAEs) and other safety variables during the open-label treatment period.;Timepoint(s) of evaluation of this end point: Overall safety will be assessed by monitoring/evaluation of TEAEs, physical examinations, electrocardiograms (ECG), and clinical safety laboratory tests at pre-specified time points. The potential emergence of anti-evinacumab antibodies will also be evaluated.; Secondary Objective: The secondary objectives of the study are: - To evaluate the effect of evinacumab on lipid parameters (ie, LDL-C, Apo B, non-HDL-C, total cholesterol [TC], and TG) in patients with HoFH - To evaluate the potential development of anti-evinacumab antibodies | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary efficacy endpoints are: - The percent and absolute change in LDL-C over time - The percent and absolute change in Apo B over time - The percent and absolute change in non-HDL-C over time - The percent and absolute change in TC over time - The percent and absolute change in TGs over time ;Timepoint(s) of evaluation of this end point: Efficacy will be assessed by clinical laboratory evaluation of lipid levels at pre-specified time points throughout the study. | — |
Countries
Australia, Austria, Canada, Czech Republic, France, Germany, Greece, Italy, Japan, Netherlands, Norway, South Africa, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical Trial Information
Regeneron Pharmaceuticals, Inc.
Outcome results
None listed