Imaging of Coronary Plaques in Participants Treated With Evolocumab

NCT03570697 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: 201601842017-003236-37
• Study Type: interventional
• Target: 164
• Locations: 7 countries
• Sites: 33

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.

Conditions

Coronary Artery Disease (CAD)

Keywords

Optical coherence tomography (OCT); Intravascular ultrasound (IVUS); Coronary angiography; Coronary artery disease; Cardiovascular events; Coronary atherosclerotic plaques; Lipid-lowering therapy; Statin; Maximally tolerated statin therapy

Outcome Measures

Primary Outcomes (1)

• Absolute Change From Baseline in Minimum FCT

  Absolute change from baseline in minimum FCT in a matched segment of artery as determined by OCT. Minimum FCT for a participant is defined as the minimum of all minimum FCT measurements within each individual frame across all frames of that participant. Higher value of FCT indicates a better situation.

  Baseline, week 50

Secondary Outcomes (6)

• Percent Change From Baseline in Minimum FCT

  Baseline, week 50

• Absolute Change From Baseline in Mean Minimum FCT

  Baseline, week 50

• Absolute Change From Baseline in the Maximum Lipid Arc

  Baseline, week 50

• Absolute Change From Baseline in Minimum FCT in Lipid Rich Plaques

  Baseline, week 50

• Absolute Change From Baseline in Maximum Lipid Arc in Lipid Rich Plaques

  Baseline, week 50

Study Arms (2)

Evolocumab

EXPERIMENTAL

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.

Drug: Evolocumab; Drug: Statin therapy

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo; Drug: Statin therapy

Interventions

Evolocumab DRUG

Participants will receive evolocumab (AMG 145) subcutaneous monthly.

Also known as: Repatha, AMG 145, EvoMab

Evolocumab

Placebo DRUG

Participants will receive matching placebo subcutaneous monthly.

Placebo

Statin therapy 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.

Evolocumab; Placebo

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amgen: lead

Study Sites (33)

University of California at Los Angeles

Los Angeles, California, 90095, United States

Location

Medstar Heart and Vascular Institute

Washington D.C., District of Columbia, 20010, United States

Location

Midwest Cardiovascular Research And Education Foundation

Elkhart, Indiana, 46514, United States

Location

Saint Louis University Hospital

St Louis, Missouri, 63110, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

Royal North Shore Hospital

St Leonards, New South Wales, 2065, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

The Northern Hospital

Epping, Victoria, 3076, Australia

Location

Fakultni nemocnice Brno

Brno, 625 00, Czechia

Location

Fakultni nemocnice Hradec Kralove

Hradec Králové, 500 05, Czechia

Location

Charite Universitätsmedizin Berlin Campus Benjamin Franklin

Berlin, 12203, Germany

Location

Universitäres Herzzentrum Hamburg GmbH

Hamburg, 20246, Germany

Location

Deutsches Herzzentrum München des Freistaates Bayern

München, 80636, Germany

Location

Allami Szivkorhaz Balatonfured

Balatonfüred, 8230, Hungary

Location

Semmelweis Egyetem

Budapest, 1122, Hungary

Location

Magyar Honvedseg Egeszsegugyi Kozpont

Budapest, 1134, Hungary

Location

Pecsi Tudomanyegyetem Klinikai Kozpont

Pécs, 7624, Hungary

Location

Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII

Bergamo, 24127, Italy

Location

Azienda Ospedaliera Santa Croce e Carle

Cuneo, 12100, Italy

Location

Azienda Ospedaliera Universitaria Careggi

Florence, 50134, Italy

Location

IRCCS Centro Cardiologico Monzino

Milan, 20138, Italy

Location

Azienda Ospedaliera Universitaria Federico II

Napoli, 80131, Italy

Location

Azienda Ospedaliera San Giovanni Addolorata

Roma, 00184, Italy

Location

IRCCS Istituto Clinico Humanitas

Rozzano MI, 20089, Italy

Location

Noordwest Ziekenhuisgroep

Alkmaar, 1815 JD, Netherlands

Location

Vrjie Universiteit Medisch Centrum

Amsterdam, 1081 HV, Netherlands

Location

Onze Lieve Vrouwe Gasthuis

Amsterdam, 1091 AC, Netherlands

Location

Radboud Universitair Medisch Centrum

Nijmegen, 6525 GA, Netherlands

Location

Canisius-Wilhelmina Ziekenhuis

Nijmegen, 6532 SZ, Netherlands

Location

Elisabeth-TweeSteden Ziekenhuis

Tilburg, 5042 AD, Netherlands

Location

Isala Klinieken

Zwolle, 8025 AB, Netherlands

Location

Related Publications (5)

• 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.

  PMID: 33708484 BACKGROUND

• 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/

  PMID: 33355725 BACKGROUND

• 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.

  PMID: 40424182 DERIVED

• 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.

  PMID: 40020597 DERIVED

• 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.

  PMID: 35431172 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

evolocumab

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

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
• Masking Details: This is a double-blind study. Treatment assignment will be blinded to all subjects, site personnel, and Amgen
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2018
• First Posted: June 27, 2018
• Study Start: November 19, 2018
• Primary Completion: December 18, 2020
• Study Completion: January 21, 2021
• Last Updated: May 3, 2022
• Results First Posted: November 24, 2021

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.

Locations

NL (7); US (5); CZ (2); AU (5); HU (4); IT (7); DE (3)