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CompletedNCT02729025ANITSCHKOWUpdated Sep 23, 2022Results posted

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

A Phase 3 interventional study of Evolocumab and Placebo in Subjects With Hyperlipidemia, Dyslipidemia, sponsored by Amgen. Completed at 15 sites in 3 countries. Open to participants aged 50 Years to 80 Years. Per ClinicalTrials.gov, last updated 2022-09-23.

Sponsored by Amgen · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
129
Allocation
Randomized
Ages
50 Years to 80 Years
Sex
All
01

Study 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).

02

Conditions studied

  • Subjects With Hyperlipidemia, Dyslipidemia

Keywords

  • Hyperlipidemia
  • Dyslipidemia
  • Proprotein convertase subtilisin/kexin type 9 (PCSK9) Inhibition
  • Arterial Wall Inflamation
  • Elevated lipoprotein a
03

In context

Dyslipidemias

1,073 studies on the registry are indexed under Dyslipidemias; 158 are open to participants now.

This study's enrollment of 129 is above the median of 99 across 842 interventional studies indexed under Dyslipidemias.

Browse Dyslipidemias studies →

Lead sponsor

Amgen is the lead sponsor of 1,015 studies on the registry; 49 are open to participants now.

Of its 245 completed or terminated interventional studies of FDA-regulated products, 159 (65%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
50 Years to 80 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
129 participants (actual)

Study arms

  • Placebo comparator
    Placebo

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

    Drug: Placebo

  • Experimental
    Evolocumab 420 mg QM

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

    Drug: Evolocumab

Interventions

  • DrugEvolocumab

    Administered subcutaneously once a month using an autoinjector/pen.

    Also known as: Repatha, AMG 145

  • DrugPlacebo

    Administered subcutaneously once a month using an autoinjector/pen.

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Baseline and week 16

Secondary outcomes

  1. Percent Change From Baseline in Lipoprotein(a) Concentration at Week 16

    Time frame: Baseline and week 16

  2. Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration at Week 16

    Time frame: Baseline and week 16

  3. Percent Change From Baseline in Apolipoprotein B Concentration at Week 16

    Time frame: Baseline and week 16

07

Results

Posted Apr 23, 2019

Participant flow

This study was conducted at 14 centers in Canada, the Netherlands, and the United States. Participants were enrolled from 14 April 2016 to 07 December 2017.

Participant flow — Overall Study
MilestonePlaceboEvolocumab 420 mg QM
Started6465
Completed6464
Not completed01
Withdrew: Sponsor decision01

Outcome measures

PrimaryPercent 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.

Time frame:
Baseline and week 16
Reported as:
Least squares mean · percent change
Percent Change From Baseline in Maximum Target-to-background Ratio in the Most Diseased Segment of the Index Vessel at Week 16
percent changePlaceboEvolocumab 420 mg QM
Percent Change From Baseline in Maximum Target-to-background Ratio in the Most Diseased Segment of the Index Vessel at Week 16-5.31 ± 1.67-8.31 ± 1.67
Statistical analysis
  • Placebo vs Evolocumab 420 mg QM · Multivariate regression model · p = 0.18 · Ls mean treatment difference: -3.00 · 95% CI -7.40 to 1.39Treatment difference used placebo as the reference
SecondaryPercent Change From Baseline in Lipoprotein(a) Concentration at Week 16
Time frame:
Baseline and week 16
Reported as:
Least squares mean · percent change
Percent Change From Baseline in Lipoprotein(a) Concentration at Week 16
percent changePlaceboEvolocumab 420 mg QM
Percent Change From Baseline in Lipoprotein(a) Concentration at Week 161.06 ± 1.94-12.83 ± 1.92
Statistical analysis
  • Placebo vs Evolocumab 420 mg QM · Repeated measures linear effects model · p = <0.0001 · Ls mean treatment difference: -13.89 · 95% CI -19.29 to -8.49Treatment difference used placebo as the reference
SecondaryPercent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration at Week 16
Time frame:
Baseline and week 16
Reported as:
Least squares mean · percent change
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration at Week 16
percent changePlaceboEvolocumab 420 mg QM
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration at Week 161.64 ± 1.86-59.02 ± 1.82
Statistical analysis
  • Placebo vs Evolocumab 420 mg QM · Repeated measures linear effects model · p = <0.0001 · Ls mean treatment difference: -60.66 · 95% CI -65.81 to -55.51Treatment difference used placebo as the reference
SecondaryPercent Change From Baseline in Apolipoprotein B Concentration at Week 16
Time frame:
Baseline and week 16
Reported as:
Least squares mean · percent change
Percent Change From Baseline in Apolipoprotein B Concentration at Week 16
percent changePlaceboEvolocumab 420 mg QM
Percent Change From Baseline in Apolipoprotein B Concentration at Week 163.29 ± 1.53-48.30 ± 1.51
Statistical analysis
  • Placebo vs Evolocumab 420 mg QM · Repeated measures linear effects model · p = <0.0001 · Ls mean treatment difference: -51.29 · 95% CI -55.85 to -47.33Treatment difference used placebo as the reference

Adverse events

Collected over From the first dose of study drug up to 30 days after the last dose or until the end of study date, whichever was earlier; the maximum duration of treatment was 3.9 months.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo QM0/64 (0%)0/64 (0%)47/64 (73.4%)
Evolocumab 420 mg QM0/65 (0%)2/65 (3.1%)49/65 (75.4%)
Most frequent serious events
Most frequent serious events
EventPlacebo QMEvolocumab 420 mg QM
Diffuse large B-cell lymphomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/641/65
NephrolithiasisRenal and urinary disorders0/641/65
Most frequent other events
Showing 10 of 114
Most frequent other events
EventPlacebo QMEvolocumab 420 mg QM
NasopharyngitisInfections and infestations13/646/65
HeadacheNervous system disorders7/644/65
InfluenzaInfections and infestations3/647/65
DiarrhoeaGastrointestinal disorders5/641/65
NauseaGastrointestinal disorders5/641/65
MyalgiaMusculoskeletal and connective tissue disorders1/645/65
Influenza like illnessGeneral disorders4/644/65
InsomniaPsychiatric disorders0/644/65
Chest painGeneral disorders3/640/65
Urinary tract infectionInfections and infestations3/641/65

Baseline characteristics

Age, Continuous
Age, Continuous(years)PlaceboEvolocumab 420 mg QMTotal
Mean60.7 ± 7.660.0 ± 6.860.3 ± 7.2
Age, Customized
Age, Customized(Participants)PlaceboEvolocumab 420 mg QMTotal
18 - 64 years414889
≥ 65 years231740
Sex: Female, Male
Sex: Female, Male(Participants)PlaceboEvolocumab 420 mg QMTotal
Female303969
Male342660
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)PlaceboEvolocumab 420 mg QMTotal
Hispanic or Latino011
Not Hispanic or Latino6464128
Unknown or Not Reported000
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)PlaceboEvolocumab 420 mg QMTotal
American Indian or Alaska Native000
Asian325
Black or African American246
Native Hawaiian or Other Pacific Islander101
White5858116
Other011
Location of the Index Vessel Used for Calculation of Maximum Target-to-background Ratio
Location of the Index Vessel Used for Calculation of Maximum Target-to-background Ratio(Participants)PlaceboEvolocumab 420 mg QMTotal
Ascending thoracic aorta5449103
Left common carotid134
Right common carotid81119
Missing123
Maximum Target-to-background Ratio (TBR) in the Most Diseased Section of the Index Vessel
Maximum Target-to-background Ratio (TBR) in the Most Diseased Section of the Index Vessel(ratio)PlaceboEvolocumab 420 mg QMTotal
Mean2.28765 ± 0.412842.29667 ± 0.460632.29216 ± 0.43566
Stratification Factor: Baseline Statin Therapy
Stratification Factor: Baseline Statin Therapy(Participants)PlaceboEvolocumab 420 mg QMTotal
Yes333467
No313162

4 further baseline measures are reported on the registry.

08

Study locations

15 sites
  • Research Site
    Miami, Florida 33144, United States
  • Research Site
    Las Vegas, Nevada 89118, United States
  • Research Site
    Mooresville, North Carolina 28117, United States
  • Research Site
    Philadelphia, Pennsylvania 19141, United States
  • Research Site
    Hurst, Texas 76054, United States
  • Research Site
    Newmarket, Ontario L3Y 5G8, Canada
  • Research Site
    Toronto, Ontario M9V 4B4, Canada
  • Research Site
    Chicoutimi, Quebec G7H 7K9, Canada
  • Research Site
    Quebec, G1V 4W2, Canada
  • Research Site
    Amsterdam, 1105 AZ, Netherlands
  • Research Site
    Apeldoorn, 7334 DZ, Netherlands
  • Research Site
    Nijmegen, 6525 GA, Netherlands
  • Research Site
    Rotterdam, 3015 CE, Netherlands
  • Research Site
    Venlo, 5912 BL, Netherlands
  • Research Site
    Waalwijk, 5141 BM, Netherlands
09

References and documents

Publications

  • 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. PubMed 30561610 ↗
  • 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. PubMed 33078867 ↗
  • 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. PubMed 32393252 ↗
  • 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. PubMed 32268367 ↗

Study documents

  • Study protocol · Feb 8, 2017
  • Statistical analysis plan · Feb 26, 2018

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 23, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02729025
Lead sponsor
Amgen
Responsible party
Sponsor
First posted
Apr 6, 2016
Start date
Apr 14, 2016
Primary completion
Apr 5, 2018
Completion
Apr 5, 2018
Results posted
Apr 23, 2019
Last update
Sep 23, 2022

Study contacts

MD
study director · Amgen

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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