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

Study Overview
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Brief Summary
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A study to assess the effects of proprotein convertase subtilisin/ kexin type 9 (PCSK9) inhibition on the arterial wall inflammation in patients with elevated lipoprotein(a).

Official Title
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A RaNdomized Double-blInd Placebo ConTrolled Study Characterizing THe Effects of PCSK9 Inhibition On Arterial Wall Inflammation in Patients With Elevated Lp(a) (ANITSCHKOW)

Conditions
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Subjects With Hyperlipidemia, Dyslipidemia

Intervention / Treatment
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* Drug: Evolocumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants received placebo to evolocumab by subcutaneous injection once a month (QM) for 12 weeks. | Drug: Placebo<br>* Administered subcutaneously once a month using an autoinjector/pen.<br>|
| Experimental: Evolocumab 420 mg QM<br>Participants received 420 mg evolocumab by subcutaneous injection once a month (QM) for 12 weeks. | Drug: Evolocumab<br>* Administered subcutaneously once a month using an autoinjector/pen.<br>* Other names: AMG 145;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Maximum Target-to-background Ratio in the Most Diseased Segment of the Index Vessel at 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. | Baseline and week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hyperlipidemia, Dyslipidemia, Proprotein convertase subtilisin/kexin type 9 (PCSK9) Inhibition, Arterial Wall Inflamation, Elevated lipoprotein a