Effects of Evolocumab Versus Placebo Added to Standard Lipid-lowering Therapy on Fasting and Post Fat Load Lipids in Patients With Familial Dysbetalipoproteinemia

Exclusion Criteria

• •1. Intolerance, known allergy or hypersensitivity to evolocumab (or other PCSK-9 monoclonal antibodies), latex or any of the components of the medication.
• •2. Current or prior exposure to evolocumab or another PCSK9-inhibitor mAb in the past 12 weeks.
• •3. Unable or unwilling to drink an oral fat load.
• •4. Premenopausal women.
• •5. Uncontrolled diabetes as defined by a HbA1c \>69 mmol/mol.
• •6. BMI \>40 kg/m2.
• •7. Uncontrolled blood pressure with systolic blood pressure \>180 mmHg or diastolic blood pressure \>110 mmHg.
• •8. Increased hepatic enzymes, defined as alanine transaminase (ALAT) or aspartate transaminase (ASAT) \>3 times the ULN, or active liver disease defined as non alcoholic steatohepatitis (NASH), cirrhosis or Child Pugh B and C, or history of chronic active hepatitis B or C; subjects with documented resolution after treatment are permitted.
• •9. Impaired renal function, defined by an estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73m2, and/or need of renal placement therapy or other clinically significant renal disease.
• •10. (Sub)clinical hypothyroidism defined as TSH \>5.0 mcl/U/mL or (sub)clinical hyperthyroidism defined as TSH \< 0.35 mcl/U/ml.
• •11. Increased levels of creatinine kinase defined as \>3 times the ULN.
• •12. Increased fasting levels of triglycerides defined as \>10 mmol/L.
• •13. History of organ transplantation and/or use of immunosuppressive medication.
• •14. Use of fish oil or red yeast rice, bempedoic acid, niacin, CETP inhibitors, lomitapide, mipomersen \< 6 weeks prior to the study or the use of siRNA targeting PCSK9 inhibitors \< 36 weeks prior to the study.
• •15. Active malignancy (\<2 year prior to informed consent), except non-melanoma skin cancer or carcinoma in situ of the cervix.
• •16. Known infection with Human Immunodeficiency Virus (HIV) or AIDS.
• •17. Known celiac disease or other disorder associated with significant intestinal malabsorption.
• •18. Known galactose-intolerance, Lapp-lactase deficiency or glucose-galactose malabsorption.
• •19. Alcohol use, defined as \>14 alcoholic consumptions per week for women and \>21 alcohol consumptions per week for men. One alcohol consumption unit is defined as follows: 350 mL beer, 150 mL wine or 45 mL alcohol for mixed drinks.
• •20. Current participation or participation in a study with an investigational compound or device within 30 days of signing informed consent.
• •21. Any medical, social or physiological circumstance which interferes the study, based on judgement by the principal investigator.