Effects of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibition on Arterial Wall Inflammation in Patients With Elevated Lipoprotein(a) (Lp(a))

Recruitment & Eligibility

Inclusion Criteria

Fasting lipoprotein(a) (Lp(a)) 50 mg/dL or more at screening 1
Fasting Low-density lipoprotein-cholesterol (LDL-C) 100 mg/dL or more at screening 1
Lipid lowering therapy including statin dose unchanged for at least 8 weeks prior to screening
Target-to-background ratio (TBR) maximum higher than 1.6 (either right, left carotid or thoracic aorta) on fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT).

Exclusion Criteria

Currently receiving, or less than 4 weeks since receiving, treatment in another investigational device or drug study(ies), or participating in other investigational procedures
Known diagnosis of diabetes mellitus or screening fasting serum glucose ≥ 126 mg/dL or hemoglobin A1C (HbA1C) ≥ 6.5%
Subject with a history of homozygous familial hypercholesterolemia
History of a Cardiovascular event
Subject currently undergoing lipid apheresis
Known contraindications or limitations to FDG-PET/ CT (scanner weight limit, devices that can cause image artifacts, or carotid/aortic stents/grafts
Subject has had exposure to investigational drugs targeting Lp(a) within the last 12 months, prior to Screening
Other Exclusion Criteria May Apply.

Study & Design

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants received placebo to evolocumab by subcutaneous injection once a month (QM) for 12 weeks.
Evolocumab 420 mg QM	Evolocumab	Participants received 420 mg evolocumab by subcutaneous injection once a month (QM) for 12 weeks.

Primary Outcome Measures

Name	Time	Method
Percent Change From Baseline in Maximum Target-to-background Ratio in the Most Diseased Segment of the Index Vessel at Week 16	Baseline and week 16	Arterial inflammation was assessed using 18F-fluoro-deoxyglucose positron-emission tomography/computed tomography (18F-FDG PET/CT). Arterial 18F-FDG uptake is correlated with arterial macrophage content and predicts cardiovascular events. Images were analyzed by an experienced radiologist blinded to all patient characteristics. The maximum standardized uptake value was calculated as a time- and dose- corrected tissue radioactivity divided by body weight in the index and the target-to-background ratio (TBR) was calculated from the ratio of the standardized uptake value of the artery compared to mean background venous activity. The average maximum TBR for the most diseased segment (MDS) was calculated from a group of 3 contiguous slices (approximately 1.5 cm), centered on the slice with the highest maximum TBR in the index vessel. The index vessel was defined as the vessel (either the right or left carotid or aorta) with the highest mean TBR at baseline.

Secondary Outcome Measures

Name	Time	Method
Percent Change From Baseline in Lipoprotein(a) Concentration at Week 16	Baseline and week 16
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration at Week 16	Baseline and week 16
Percent Change From Baseline in Apolipoprotein B Concentration at Week 16	Baseline and week 16

Recruitment & Eligibility