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

Inclusion criteria: 1. Patients diagnosed with Familial Dysbetalipoproteinemia; * ε2ε2 genotype or dominant APOE mutation genotype (confirmed by genotyping or isoelectric focusing) with any lipid-lowering treatment at a stable dose for at least three months and non-HDL-C \>1.6 mmol/L or; * Patients with ε2ε2 genotype or dominant APOE mutation (confirmed by genotyping or isoelectric focusing) without lipid-lowering treatment and with an ApoB/TC ratio \< 0.15. 2. \>18 years old (on the day of signing informed consent). 3. Women are postmenopausal and not receiving hormone therapy (including cyclic and non-cyclical hormone replacement therapy or any estrogen antagonist/agonist). Postmenopausal status is defined as: * no menses for ≥3 years or; * no menses for ≥1 year but \<3 years and confirmed by FSH levels elevated into the postmenopausal range (15-150 IU/L). 4. Willingness to maintain a stable diet for the duration of the study. 5. Understanding of the study procedures, alternative treatments available, and risks involved with the study and voluntarily agreement to participate by giving written informed consent. 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.