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

Primary Purpose

Subjects With Hyperlipidemia, Dyslipidemia

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Evolocumab
Placebo
Sponsored by
Amgen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Subjects With Hyperlipidemia, Dyslipidemia focused on measuring Hyperlipidemia, Dyslipidemia, Proprotein convertase subtilisin/kexin type 9 (PCSK9) Inhibition, Arterial Wall Inflamation, Elevated lipoprotein a

Eligibility Criteria

50 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Evolocumab 420 mg QM

Arm Description

Participants received placebo to evolocumab by subcutaneous injection once a month (QM) for 12 weeks.

Participants received 420 mg evolocumab by subcutaneous injection once a month (QM) for 12 weeks.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Full Information

First Posted
March 8, 2016
Last Updated
September 9, 2022
Sponsor
Amgen
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1. Study Identification

Unique Protocol Identification Number
NCT02729025
Brief Title
Effects of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibition on Arterial Wall Inflammation in Patients With Elevated Lipoprotein(a) (Lp(a))
Acronym
ANITSCHKOW
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

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Completed
Study Start Date
April 14, 2016 (Actual)
Primary Completion Date
April 5, 2018 (Actual)
Study Completion Date
April 5, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen

4. Oversight

Data Monitoring Committee
No

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Subjects With Hyperlipidemia, Dyslipidemia
Keywords
Hyperlipidemia, Dyslipidemia, Proprotein convertase subtilisin/kexin type 9 (PCSK9) Inhibition, Arterial Wall Inflamation, Elevated lipoprotein a

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
129 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received placebo to evolocumab by subcutaneous injection once a month (QM) for 12 weeks.
Arm Title
Evolocumab 420 mg QM
Arm Type
Experimental
Arm Description
Participants received 420 mg evolocumab by subcutaneous injection once a month (QM) for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Evolocumab
Other Intervention Name(s)
Repatha, AMG 145
Intervention Description
Administered subcutaneously once a month using an autoinjector/pen.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Administered subcutaneously once a month using an autoinjector/pen.
Primary Outcome Measure Information:
Title
Percent Change From Baseline in Maximum Target-to-background Ratio in the Most Diseased Segment of the Index Vessel at Week 16
Description
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.
Time Frame
Baseline and week 16
Secondary Outcome Measure Information:
Title
Percent Change From Baseline in Lipoprotein(a) Concentration at Week 16
Time Frame
Baseline and week 16
Title
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration at Week 16
Time Frame
Baseline and week 16
Title
Percent Change From Baseline in Apolipoprotein B Concentration at Week 16
Time Frame
Baseline and week 16

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33144
Country
United States
Facility Name
Research Site
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89118
Country
United States
Facility Name
Research Site
City
Mooresville
State/Province
North Carolina
ZIP/Postal Code
28117
Country
United States
Facility Name
Research Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19141
Country
United States
Facility Name
Research Site
City
Hurst
State/Province
Texas
ZIP/Postal Code
76054
Country
United States
Facility Name
Research Site
City
Newmarket
State/Province
Ontario
ZIP/Postal Code
L3Y 5G8
Country
Canada
Facility Name
Research Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M9V 4B4
Country
Canada
Facility Name
Research Site
City
Chicoutimi
State/Province
Quebec
ZIP/Postal Code
G7H 7K9
Country
Canada
Facility Name
Research Site
City
Quebec
ZIP/Postal Code
G1V 4W2
Country
Canada
Facility Name
Research Site
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
Facility Name
Research Site
City
Apeldoorn
ZIP/Postal Code
7334 DZ
Country
Netherlands
Facility Name
Research Site
City
Nijmegen
ZIP/Postal Code
6525 GA
Country
Netherlands
Facility Name
Research Site
City
Rotterdam
ZIP/Postal Code
3015 CE
Country
Netherlands
Facility Name
Research Site
City
Venlo
ZIP/Postal Code
5912 BL
Country
Netherlands
Facility Name
Research Site
City
Waalwijk
ZIP/Postal Code
5141 BM
Country
Netherlands

12. IPD Sharing Statement

Citations:
PubMed Identifier
30561610
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.
Results Reference
background
PubMed Identifier
33078867
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.
Results Reference
derived
PubMed Identifier
32393252
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.
Results Reference
derived
PubMed Identifier
32268367
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.
Results Reference
derived
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website

Learn more about this trial

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

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