Imaging of Coronary Plaques in Participants Treated With Evolocumab

Coronary Artery Disease (CAD) Clinical Trial

Official title:

High-Resolution Assessment of Coronary Plaques in a Global Evolocumab Randomized Study (HUYGENS)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03570697
• Other study ID #: 20160184
• Secondary ID: 2017-003236-37
• Status: Completed
• Phase: Phase 3
• Start date: November 19, 2018
• Est. completion date: January 21, 2021

Study information

• Verified date: April 2022
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 164
• Est. completion date: January 21, 2021
• Est. primary completion date: December 18, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Artery Disease (CAD)
• Coronary Disease
• Myocardial Ischemia

Intervention

Drug:
• Evolocumab
Participants will receive evolocumab (AMG 145) subcutaneous monthly.
• Placebo
Participants will receive matching placebo subcutaneous monthly.
• 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.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Monash Medical Centre	Clayton	Victoria
Australia	The Northern Hospital	Epping	Victoria
Australia	Royal North Shore Hospital	St Leonards	New South Wales
Czechia	Fakultni nemocnice Brno	Brno
Czechia	Fakultni nemocnice Hradec Kralove	Hradec Kralove
Germany	Charite Universitätsmedizin Berlin Campus Benjamin Franklin	Berlin
Germany	Universitäres Herzzentrum Hamburg GmbH	Hamburg
Germany	Deutsches Herzzentrum München des Freistaates Bayern	München
Hungary	Allami Szivkorhaz Balatonfured	Balatonfured
Hungary	Magyar Honvedseg Egeszsegugyi Kozpont	Budapest
Hungary	Semmelweis Egyetem	Budapest
Hungary	Pecsi Tudomanyegyetem Klinikai Kozpont	Pecs
Italy	Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII	Bergamo
Italy	Azienda Ospedaliera Santa Croce e Carle	Cuneo
Italy	Azienda Ospedaliera Universitaria Careggi	Firenze
Italy	IRCCS Centro Cardiologico Monzino	Milano
Italy	Azienda Ospedaliera Universitaria Federico II	Napoli
Italy	Azienda Ospedaliera San Giovanni Addolorata	Roma
Italy	IRCCS Istituto Clinico Humanitas	Rozzano MI
Netherlands	Noordwest Ziekenhuisgroep	Alkmaar
Netherlands	Onze Lieve Vrouwe Gasthuis	Amsterdam
Netherlands	Vrjie Universiteit Medisch Centrum	Amsterdam
Netherlands	Canisius-Wilhelmina Ziekenhuis	Nijmegen
Netherlands	Radboud Universitair Medisch Centrum	Nijmegen
Netherlands	Elisabeth-TweeSteden Ziekenhuis	Tilburg
Netherlands	Isala Klinieken	Zwolle
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Midwest Cardiovascular Research And Education Foundation	Elkhart	Indiana
United States	University of California at Los Angeles	Los Angeles	California
United States	Saint Louis University Hospital	Saint Louis	Missouri
United States	Medstar Heart and Vascular Institute	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

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

References & Publications (2)

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. — View Citation

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/ — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Percent Change From Baseline in Minimum FCT	Percent 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	Absolute Change From Baseline in Mean Minimum FCT	Absolute change from baseline in mean minimum FCT for all images assessed in an individual participant 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	Absolute Change From Baseline in the Maximum Lipid Arc	Absolute change from baseline in the maximum lipid arc in a matched segment of artery as determined by OCT. Lower value of lipid arc indicates a better situation.	Baseline, week 50
Secondary	Absolute Change From Baseline in Minimum FCT in Lipid Rich Plaques	Absolute change from baseline in minimum FCT in lipid rich plaques as determined by OCT. Lipid rich plaques are defined as minimum FCT less than 120 µm and lipid arc greater than 90° in at least 3 consecutive images as determined by OCT. Higher value of FCT indicates a better situation	Baseline, week 50
Secondary	Absolute Change From Baseline in Maximum Lipid Arc in Lipid Rich Plaques	Absolute change from baseline in maximum lipid arc in lipid rich plaques. Lipid rich plaques are defined as minimum FCT less than 120 µm and lipid arc greater than 90° in at least 3 consecutive images as determined by OCT. Lower value of lipid arc indicates a better situation.	Baseline, week 50
Secondary	Absolute Change From Baseline in Lipid Core Length in Lipid Rich Plaques	Absolute change from baseline in lipid core length in lipid rich plaques. Lipid rich plaques are defined as minimum FCT less than 120 µm and lipid arc greater than 90° in at least 3 consecutive images as determined by OCT. Lower value of lipid core length indicates a better situation.	Baseline, week 50

External Links

•   AmgenTrials clinical trials website