Clinical trial NCT02729025: Effects of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibition on Arterial Wall Inflammation in Patients With Elevated Lipoprotein(a) (Lp(a))
Official title: A RaNdomized Double-blInd Placebo ConTrolled Study Characterizing THe Effects of PCSK9 Inhibition On Arterial Wall Inflammation in Patients With Elevated Lp(a) (ANITSCHKOW)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Subjects With Hyperlipidemia, Dyslipidemia
Keywords: Hyperlipidemia
Dyslipidemia
Proprotein convertase subtilisin/kexin type 9 (PCSK9) Inhibition
Arterial Wall Inflamation
Elevated lipoprotein a
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2016-04-06
Enrollment: 129
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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.

Primary outcomes:
measure: Percent Change From Baseline in Maximum Target-to-background Ratio in the Most Diseased Segment of the Index Vessel at Week 16
timeFrame: Baseline and week 16
Secondary outcomes:
measure: Percent Change From Baseline in Lipoprotein(a) Concentration at Week 16
timeFrame: Baseline and week 16
measure: Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration at Week 16
timeFrame: Baseline and week 16
measure: Percent Change From Baseline in Apolipoprotein B Concentration at Week 16
timeFrame: Baseline and week 16
Other outcomes:
Locations:
city: Miami
country: United States
facility: Research Site
state: Florida
city: Las Vegas
country: United States
facility: Research Site
state: Nevada
city: Mooresville
country: United States
facility: Research Site
state: North Carolina
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Hurst
country: United States
facility: Research Site
state: Texas
city: Newmarket
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Chicoutimi
country: Canada
facility: Research Site
state: Quebec
city: Quebec
country: Canada
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Research Site
city: Apeldoorn
country: Netherlands
facility: Research Site
city: Nijmegen
country: Netherlands
facility: Research Site
city: Rotterdam
country: Netherlands
facility: Research Site
city: Venlo
country: Netherlands
facility: Research Site
city: Waalwijk
country: Netherlands
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Stiekema LCA, Stroes ESG, Verweij SL, Kassahun H, Chen L, Wasserman SM, Sabatine MS, Mani V, Fayad ZA. Persistent arterial wall inflammation in patients with elevated lipoprotein(a) despite strong low-density lipoprotein cholesterol reduction by proprotein convertase subtilisin/kexin type 9 antibody treatment. Eur Heart J. 2019 Sep 1;40(33):2775-2781. doi: 10.1093/eurheartj/ehy862.
citation: Schmidt AF, Carter JL, Pearce LS, Wilkins JT, Overington JP, Hingorani AD, Casas JP. PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2020 Oct 20;10(10):CD011748. doi: 10.1002/14651858.CD011748.pub3.
citation: Zhang X, Stiekema LCA, Stroes ESG, Groen AK. Metabolic effects of PCSK9 inhibition with Evolocumab in subjects with elevated Lp(a). Lipids Health Dis. 2020 May 11;19(1):91. doi: 10.1186/s12944-020-01280-0.
citation: Stiekema LCA, Prange KHM, Hoogeveen RM, Verweij SL, Kroon J, Schnitzler JG, Dzobo KE, Cupido AJ, Tsimikas S, Stroes ESG, de Winther MPJ, Bahjat M. Potent lipoprotein(a) lowering following apolipoprotein(a) antisense treatment reduces the pro-inflammatory activation of circulating monocytes in patients with elevated lipoprotein(a). Eur Heart J. 2020 Jun 21;41(24):2262-2271. doi: 10.1093/eurheartj/ehaa171.