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

NCT02729025 | Completed Phase 3 Results

• 2 other identifiers: 201302932015-003731-35
• Study Type: interventional
• Target: 129
• Locations: 3 countries
• Sites: 15

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).

Conditions

Subjects With Hyperlipidemia, Dyslipidemia

Keywords

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

Outcome Measures

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.

  Baseline and week 16

Secondary Outcomes (3)

• 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

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Evolocumab 420 mg QM

EXPERIMENTAL

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

Drug: Evolocumab

Interventions

Evolocumab DRUG

Administered subcutaneously once a month using an autoinjector/pen.

Also known as: Repatha, AMG 145

Evolocumab 420 mg QM

Placebo DRUG

Administered subcutaneously once a month using an autoinjector/pen.

Placebo

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Study Sites (15)

Research Site

Miami, Florida, 33144, United States

Location

Research Site

Las Vegas, Nevada, 89118, United States

Location

Research Site

Mooresville, North Carolina, 28117, United States

Location

Research Site

Philadelphia, Pennsylvania, 19141, United States

Location

Research Site

Hurst, Texas, 76054, United States

Location

Research Site

Newmarket, Ontario, L3Y 5G8, Canada

Location

Research Site

Toronto, Ontario, M9V 4B4, Canada

Location

Research Site

Chicoutimi, Quebec, G7H 7K9, Canada

Location

Research Site

Québec, Quebec, G1V 4W2, Canada

Location

Research Site

Amsterdam, 1105 AZ, Netherlands

Location

Research Site

Apeldoorn, 7334 DZ, Netherlands

Location

Research Site

Nijmegen, 6525 GA, Netherlands

Location

Research Site

Rotterdam, 3015 CE, Netherlands

Location

Research Site

Venlo, 5912 BL, Netherlands

Location

Research Site

Waalwijk, 5141 BM, Netherlands

Location

Related Publications (4)

• 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.

  PMID: 30561610 BACKGROUND

• 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.

  PMID: 33078867 DERIVED

• 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.

  PMID: 32393252 DERIVED

• 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.

  PMID: 32268367 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Dyslipidemias; Hyperlipidemias; Hypercholesterolemia, Autosomal Dominant, 3; Inhibition, Psychological

Interventions

evolocumab

Condition Hierarchy (Ancestors)

Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Behavior

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2016
• First Posted: April 6, 2016
• Study Start: April 14, 2016
• Primary Completion: April 5, 2018
• Study Completion: April 5, 2018
• Last Updated: September 23, 2022
• Results First Posted: April 23, 2019

Record last verified: 2022-09

Locations

CA (4); US (5); NL (6)