Imaging of Coronary Plaques in Participants Treated With Evolocumab

NCT ID: NCT03570697

Last Updated: 2022-05-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 164 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-19
• Study Completion Date: 2021-01-21

Brief Summary

To evaluate the effect of evolocumab on fibrous cap thickness (FCT) in participants with non-ST-elevation acute coronary syndrome (NSTE-ACS) who are taking maximally tolerated statin therapy.

Detailed Description

This study seeks to identify morphologic changes, such as increase in FCT in atherosclerotic plaques associated with treatment with evolocumab and maximally tolerated statin therapy with or without additional lipid-modifying medication in patients presenting with NSTE-ACS using optical coherence tomography (OCT; primary, secondary, and exploratory endpoints).

Conditions

Coronary Artery Disease (CAD)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Evolocumab

Participants receive evolocumab subcutaneous injection once every month (QM) for 48 weeks. As prescribed and provided by the investigator, participants will be treated with maximally tolerated statin therapy, not expected to change for the duration of the study participation.

Group Type: EXPERIMENTAL

Evolocumab

Intervention Type: DRUG

Participants will receive evolocumab (AMG 145) subcutaneous monthly.

Statin therapy

Intervention Type: DRUG

high-intensity statin treatment with atorvastatin ≥ 40 mg daily or equivalent as background therapy

Investigators will up-titrate statin therapy to the maximally tolerated dose, in accordance with local guidelines, prior to randomization.

Placebo

Participants receive placebo subcutaneous injection QM for 48 weeks. As prescribed and provided by the Investigator, participants will be treated with maximally tolerated statin therapy, not expected to change for the duration of the study participation.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Participants will receive matching placebo subcutaneous monthly.

Statin therapy

Intervention Type: DRUG

high-intensity statin treatment with atorvastatin ≥ 40 mg daily or equivalent as background therapy

Investigators will up-titrate statin therapy to the maximally tolerated dose, in accordance with local guidelines, prior to randomization.

Interventions

Evolocumab

Participants will receive evolocumab (AMG 145) subcutaneous monthly.

Intervention Type: DRUG

Placebo

Participants will receive matching placebo subcutaneous monthly.

Intervention Type: DRUG

Statin therapy

high-intensity statin treatment with atorvastatin ≥ 40 mg daily or equivalent as background therapy

Investigators will up-titrate statin therapy to the maximally tolerated dose, in accordance with local guidelines, prior to randomization.

Intervention Type: DRUG

Other Intervention Names

Repatha, AMG 145, EvoMab

Eligibility Criteria

Inclusion Criteria

• Provided informed consent prior to initiation of any study-specific activities/procedures.
• Age greater than or equal to 18 years at screening
• Clinical indication for coronary angiography during admission due to NSTE-ACS with interventional treatment of culprit plaque
• An eligible low-density lipoprotein cholesterol (LDL-C) level via local lab assessment based on statin use at screening

No statin use: greater than or equal to 130 mg/dL Low- or moderate-intensity statin use greater than or equal to 80 mg/dL High-intensity statin use greater than or equal to 60 mg/dL

• On maximally tolerated statin therapy in accordance with standard of care per local guidelines prior to randomization.
• Tolerates placebo run-in injection at screening
• Meets all the following criteria at the qualifying coronary angiogram:

Angiographic evidence of coronary artery disease (CAD) with greater than or equal to 20% reduction of lumen diameter by angiographic visual estimation, in addition to the culprit plaque.

Left main coronary artery must not have a greater than 50% reduction in lumen diameter by visual angiographic estimation.

Targeted vessel:

May not be the culprit vessel for the current or a previous myocardial infarction (MI).

Has not undergone prior percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), and may not be a bypass graft.

May not be a candidate for PCI or CABG currently or over the next 12 months, in the opinion of the investigator.

Must be accessible by the optical coherence tomography (OCT) catheter.

Targeted segment:

Must have up to 50% but not greater than 50% reduction in lumen diameter by visual angiographic estimation and must be at least 40 mm in length.

Must contain at least 1 image with a fibrous cap thickness (FCT) of less than or equal to 120 μm and at least 1 image with a lipid arc of greater than 90° as determined by the imaging core laboratory Distal plaques of up to 50% stenosis by visual angiographic estimation are permitted, provided that such stenosis is not a target for PCI or CABG.

Exclusion Criteria

• ST-segment elevation myocardial infarction (STEMI) or left bundle branch block (LBBB).
• Acute coronary syndromes (ACS) likely to be caused by a non-atherosclerotic process, in the opinion of the investigator (ie, type 2 myocardial infarction, which is characterized by an imbalance between myocardial oxygen demand and supply).
• Clinically significant heart disease which in the opinion of the investigator is likely to require coronary bypass surgery, PCI (does not apply to PCI of non-STEMI (NSTEMI) during initial screening angiogram), surgical or percutaneous valve repair and/or replacement during the course of the study.
• Any cardiac surgery within 6 weeks prior to screening.
• Triglycerides greater than or equal to 400 mg/dL (4.5 mmol/L) at screening.
• Moderate to severe renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73m^2 at screening.
• Malignancy except non-melanoma skin cancers, cervical, or breast ductal carcinoma in situ within the last 5 years.
• Intolerant to statins as determined by principal investigator.
• Previously received or receiving evolocumab or any other therapy to inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9).
• Previously received a cholesterol ester transfer protein (CETP) inhibitor (ie, anacetrapib, dalcetrapib, evacetrapib), mipomersen, lomitapide, or has undergone LDL-apheresis in the last 12 months prior to LDL-C screening.
• Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded.
• Baseline OCT does not meet OCT imaging criteria as determined by the imagine core laboratory technical standards.
• Female subject is pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 15 weeks after the last dose of investigational product. (Females of childbearing potential should only be included in the study after a confirmed menstrual period and a negative highly sensitive urine or serum pregnancy test.)
• Female subjects of childbearing potential unwilling to use 1 acceptable method of effective contraception during treatment and for an additional 15 weeks after the last dose of investigational product.
• Female subject who has not used an acceptable method(s) of birth control for at least 1 month prior to screening, unless the female subject is sterilized or postmenopausal.
• Known sensitivity to any of the products or components (eg, carboxymethylcellulose) to be administered during dosing.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Locations

University of California at Los Angeles

Los Angeles, California, United States

Medstar Heart and Vascular Institute

Washington D.C., District of Columbia, United States

Midwest Cardiovascular Research And Education Foundation

Elkhart, Indiana, United States

Saint Louis University Hospital

St Louis, Missouri, United States

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

Royal North Shore Hospital

St Leonards, New South Wales, Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Monash Medical Centre

Clayton, Victoria, Australia

The Northern Hospital

Epping, Victoria, Australia

Fakultni nemocnice Brno

Brno, , Czechia

Fakultni nemocnice Hradec Kralove

Hradec Králové, , Czechia

Charite Universitätsmedizin Berlin Campus Benjamin Franklin

Berlin, , Germany

Universitäres Herzzentrum Hamburg GmbH

Hamburg, , Germany

Deutsches Herzzentrum München des Freistaates Bayern

München, , Germany

Allami Szivkorhaz Balatonfured

Balatonfüred, , Hungary

Semmelweis Egyetem

Budapest, , Hungary

Magyar Honvedseg Egeszsegugyi Kozpont

Budapest, , Hungary

Pecsi Tudomanyegyetem Klinikai Kozpont

Pécs, , Hungary

Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII

Bergamo, , Italy

Azienda Ospedaliera Santa Croce e Carle

Cuneo, , Italy

Azienda Ospedaliera Universitaria Careggi

Florence, , Italy

IRCCS Centro Cardiologico Monzino

Milan, , Italy

Azienda Ospedaliera Universitaria Federico II

Napoli, , Italy

Azienda Ospedaliera San Giovanni Addolorata

Roma, , Italy

IRCCS Istituto Clinico Humanitas

Rozzano MI, , Italy

Noordwest Ziekenhuisgroep

Alkmaar, , Netherlands

Vrjie Universiteit Medisch Centrum

Amsterdam, , Netherlands

Onze Lieve Vrouwe Gasthuis

Amsterdam, , Netherlands

Radboud Universitair Medisch Centrum

Nijmegen, , Netherlands

Canisius-Wilhelmina Ziekenhuis

Nijmegen, , Netherlands

Elisabeth-TweeSteden Ziekenhuis

Tilburg, , Netherlands

Isala Klinieken

Zwolle, , Netherlands

Countries

United States; Australia; Czechia; Germany; Hungary; Italy; Netherlands

References

Nicholls SJ, Nissen SE, Prati F, Windecker S, Kataoka Y, Puri R, Hucko T, Kassahun H, Liao J, Somaratne R, Butters J, Di Giovanni G, Jones S, Psaltis PJ. Assessing the impact of PCSK9 inhibition on coronary plaque phenotype with optical coherence tomography: rationale and design of the randomized, placebo-controlled HUYGENS study. Cardiovasc Diagn Ther. 2021 Feb;11(1):120-129. doi: 10.21037/cdt-20-684.

Reference Type: BACKGROUND

PMID: 33708484 (View on PubMed)

Pharmacoeconomic Review Report: Icosapent Ethyl (Vascepa): (HLS Therapeutics Inc.): Indication: Prevention of cardiovascular events in statin-treated patients [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2020 Aug. Available from http://www.ncbi.nlm.nih.gov/books/NBK566010/

Reference Type: BACKGROUND

PMID: 33355725 (View on PubMed)

Di Giovanni G, Fujino M, Kataoka Y, Butters J, Hucko T, Puri R, Nissen SE, Nelson AJ, Psaltis PJ, Nicholls SJ. Impact of evolocumab on plaque phenotypic changes in patients with acute coronary syndrome and elevated lipoprotein(a) levels: a HUYGENS secondary analysis. Eur J Prev Cardiol. 2025 Apr 8:zwaf211. doi: 10.1093/eurjpc/zwaf211. Online ahead of print.

Reference Type: DERIVED

PMID: 40424182 (View on PubMed)

Fujino M, Di Giovanni G, Butters Bhsc J, Kataoka Y, Hucko T, Nelson AJ, Nissen SE, Psaltis PJ, Nicholls SJ. Achieved levels of apolipoprotein B and plaque composition after acute coronary syndromes: Insights from HUYGENS. Atherosclerosis. 2025 Apr;403:119145. doi: 10.1016/j.atherosclerosis.2025.119145. Epub 2025 Feb 20.

Reference Type: DERIVED

PMID: 40020597 (View on PubMed)

Nicholls SJ, Kataoka Y, Nissen SE, Prati F, Windecker S, Puri R, Hucko T, Aradi D, Herrman JR, Hermanides RS, Wang B, Wang H, Butters J, Di Giovanni G, Jones S, Pompili G, Psaltis PJ. Effect of Evolocumab on Coronary Plaque Phenotype and Burden in Statin-Treated Patients Following Myocardial Infarction. JACC Cardiovasc Imaging. 2022 Jul;15(7):1308-1321. doi: 10.1016/j.jcmg.2022.03.002. Epub 2022 Mar 16.

Reference Type: DERIVED

PMID: 35431172 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

2017-003236-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

20160184

Identifier Type: -

Identifier Source: org_study_id