Impact of Triglyceride-Lowering on Inflammatory Activity in Patients with Hypertriglyceridemia

INTERVENTION: Pharmaceutical Form: CONDITION: ‐ Hypertriglyceridemia ‐ Inflammation ‐ Lipoproteins Therapeutic area: Diseases [C] ‐ Cardiovascular Diseases [C14] PRIMARY OUTCOME: Main Objective: To study the impact of AKCEA‐APOCIII‐LRx on lipid and inflammatory measurements in the fasting and postprandial phase. Primary end point(s): ‐ The mean percentage change in fasting apoC‐III and triglyceride reduction between the treatment and placebo group, at the primary analysis time point, compared to baseline.; ‐ Postprandial TG (AUC) change at the primary analysis time point from baseline as compared to placebo.; Secondary Objective: Study the impact of AKCEA‐APOCIII‐LRx on 15 expression markers on monocyte phenotyping using mass cytometry. Timepoint(s) of evaluation of this end point: The primary analysis time point is at 7 weeks. SECONDARY OUTCOME: Secondary end point(s): The secondary outcome is:; • Mass cytometry: whole‐blood with 15 marker panel for monocyte phenotyping; expression markers such as CD14 and CD16; ; Exploratory study parameters/endpoints; • The mean percentage change of the following parameters between the treatment and placebo group, at the primary analysis time point, compared to baseline:; o Lipid parameters: LDL‐C, HDL‐C, VLDL‐C, TC, (non‐HDL‐C), apoA‐I, apoB, apoB48, Lp(a), remnant cholesterol (RC) (by a deika‐senken assay); o Inflammatory parameters: hsCRP, IL‐6, Il‐1beta, IL‐10, IL‐18, E‐selectin, P‐selectin, soluble ICAM, soluble VCAM, von Willebrand factor; • CD14‐bead isolation of monocytes for:; o Lipid droplets, lipid size with Nile Red Quantifier (NRQ); • Kinetic monocyte transendothelial migration (TEM) assay in the fasting and postprandial phase, comparing the treatment with the placebo group; • Extracellular vesicle count and composition Timepoint(s) of evaluation of this end point: The primary analysis time point is at 7 weeks. INCLUSION CRITERIA: ‐ Adults above 18 years old ‐ Triglyceride levels > 4mmol/l (350 mg/dl) 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 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10