Status:
UNKNOWN
Effects of Evolocumab Versus Placebo Added to Standard Lipid-lowering Therapy on Fasting and Post Fat Load Lipids in Patients With Familial Dysbetalipoproteinemia
Lead Sponsor:
UMC Utrecht
Collaborating Sponsors:
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Erasmus Medical Center
Conditions:
Familial Dysbetalipoproteinemia
Hyperlipoproteinemia Type III
Eligibility:
All Genders
18+ years
Phase:
PHASE4
Brief Summary
Patients with familial dysbetalipoproteinemia (FD) have increased triglycerides, non-high-density lipoprotein cholesterol (non-HDL-C), beta VLDL, premature atherosclerosis and cardiovascular disease. ...
Detailed Description
See brief summary
Eligibility Criteria
Inclusion
- Inclusion criteria:
- 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.
- \>18 years old (on the day of signing informed consent).
- 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).
- Willingness to maintain a stable diet for the duration of the study.
- 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:
- Intolerance, known allergy or hypersensitivity to evolocumab (or other PCSK-9 monoclonal antibodies), latex or any of the components of the medication.
- Current or prior exposure to evolocumab or another PCSK9-inhibitor mAb in the past 12 weeks.
- Unable or unwilling to drink an oral fat load.
- Premenopausal women.
- Uncontrolled diabetes as defined by a HbA1c \>69 mmol/mol.
- BMI \>40 kg/m2.
- Uncontrolled blood pressure with systolic blood pressure \>180 mmHg or diastolic blood pressure \>110 mmHg.
- 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.
- 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.
- (Sub)clinical hypothyroidism defined as TSH \>5.0 mcl/U/mL or (sub)clinical hyperthyroidism defined as TSH \< 0.35 mcl/U/ml.
- Increased levels of creatinine kinase defined as \>3 times the ULN.
- Increased fasting levels of triglycerides defined as \>10 mmol/L.
- History of organ transplantation and/or use of immunosuppressive medication.
- 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.
- Active malignancy (\<2 year prior to informed consent), except non-melanoma skin cancer or carcinoma in situ of the cervix.
- Known infection with Human Immunodeficiency Virus (HIV) or AIDS.
- Known celiac disease or other disorder associated with significant intestinal malabsorption.
- Known galactose-intolerance, Lapp-lactase deficiency or glucose-galactose malabsorption.
- 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.
- Current participation or participation in a study with an investigational compound or device within 30 days of signing informed consent.
- Any medical, social or physiological circumstance which interferes the study, based on judgement by the principal investigator.
Exclusion
Key Trial Info
Start Date :
August 1 2019
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
March 1 2021
Estimated Enrollment :
30 Patients enrolled
Trial Details
Trial ID
NCT03811223
Start Date
August 1 2019
End Date
March 1 2021
Last Update
January 22 2019
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