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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03570697




Registration number
NCT03570697
Ethics application status
Date submitted
18/06/2018
Date registered
27/06/2018
Date last updated
2/01/2020

Titles & IDs
Public title
Imaging of Coronary Plaques in Subjects Treated With Evolocumab
Scientific title
High-Resolution Assessment of Coronary Plaques in a Global Evolocumab Randomized Study (HUYGENS)
Secondary ID [1] 0 0
2017-003236-37
Secondary ID [2] 0 0
20160184
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Coronary Artery Disease (CAD) 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Coronary heart disease
Cardiovascular 0 0 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Evolocumab
Other interventions - Placebo

Experimental: Evolucumab - Participants receive Evolocumab subcutaneous injection once every month (QM=every 4 weeks + 3 days) for 48 weeks. As prescribed and provided by the investigator, participants will be treated with maximally tolerated statin therapy and not expected to change for the duration of the study participation.

Placebo Comparator: Placebo - Participants receive placebo subcutaneous injection once every month (QM=every 4 weeks + 3 days) for 48 weeks. As prescribed and provided by the Investigator, participants will be treated with maximally tolerated statin therapy and not expected to change for the duration of the study participation.


Other interventions: Evolocumab
Subjects will receive Evolocumab (AMG 145) subcutaneous monthly.

Other interventions: Placebo
Subjects will receive Evolocumab (AMG 145) matching placebo subcutaneous monthly.

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Absolute change in minimum fiberous cap thickness (FCT) - Absolute change in minimum fiberous cap thickness (FCT) in a matched segment of artery as determined by optical coherence tomography (OCT) from baseline to week 50
Timepoint [1] 0 0
week 50
Secondary outcome [1] 0 0
Percent change in minimum FCT in a matched segment of artery - Coronary artery segment based: Percent change in minimum FCT in a matched segment of artery as determined by OCT from baseline to week 50.
Timepoint [1] 0 0
week 50
Secondary outcome [2] 0 0
Absolute change in minimum FCT, maximum lipid arc, and lipid core length in lipid rich plaques - Plaque-based: Absolute change in minimum FCT, maximum lipid arc, and lipid core length in lipid rich plaques defined as minimum FCT less than 120 µm and lipid arc greater than 90° in at least 3 consecutive images as determined by OCT from baseline to week 50
Timepoint [2] 0 0
week 50.
Secondary outcome [3] 0 0
Absolute change in mean mínimum FCT for all images assessed - Coronary artery segment-based: Absolute change in mean mínimum FCT for all images assessed in an individual subject as determined by OCT from baseline to week 50.
Timepoint [3] 0 0
week 50
Secondary outcome [4] 0 0
Absolute change in the maximum lipid arc in a matched segment of artery - Coronary artery segment-based: Absolute change in the maximum lipid arc in a matched segment of artery as determined by OCT from baseline to week 50.
Timepoint [4] 0 0
week 50

Eligibility
Key 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 non-ST-segment
elevation acute coronary syndrome (NSTE-ACS) with interventional treatment of culprit
plaque

- An eligible 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 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 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- ST-segment elevation myocardial infarction (STEMI) or left bundle branch block (LBBB).

- 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/1.73m2 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 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Research Site - Camperdown
Recruitment hospital [2] 0 0
Research Site - St Leonards
Recruitment hospital [3] 0 0
Research Site - Adelaide
Recruitment hospital [4] 0 0
Research Site - Clayton
Recruitment hospital [5] 0 0
Research Site - Epping
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2065 - St Leonards
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
3168 - Clayton
Recruitment postcode(s) [5] 0 0
3076 - Epping
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
District of Columbia
Country [3] 0 0
United States of America
State/province [3] 0 0
Indiana
Country [4] 0 0
United States of America
State/province [4] 0 0
Missouri
Country [5] 0 0
United States of America
State/province [5] 0 0
Ohio
Country [6] 0 0
Czechia
State/province [6] 0 0
Brno
Country [7] 0 0
Czechia
State/province [7] 0 0
Hradec Kralove
Country [8] 0 0
Germany
State/province [8] 0 0
Berlin
Country [9] 0 0
Germany
State/province [9] 0 0
Hamburg
Country [10] 0 0
Germany
State/province [10] 0 0
München
Country [11] 0 0
Hungary
State/province [11] 0 0
Balatonfured
Country [12] 0 0
Hungary
State/province [12] 0 0
Budapest
Country [13] 0 0
Hungary
State/province [13] 0 0
Pecs
Country [14] 0 0
Italy
State/province [14] 0 0
Bergamo
Country [15] 0 0
Italy
State/province [15] 0 0
Cuneo
Country [16] 0 0
Italy
State/province [16] 0 0
Firenze
Country [17] 0 0
Italy
State/province [17] 0 0
Milano
Country [18] 0 0
Italy
State/province [18] 0 0
Napoli
Country [19] 0 0
Italy
State/province [19] 0 0
Roma
Country [20] 0 0
Italy
State/province [20] 0 0
Rozzano MI
Country [21] 0 0
Netherlands
State/province [21] 0 0
Alkmaar
Country [22] 0 0
Netherlands
State/province [22] 0 0
Amsterdam
Country [23] 0 0
Netherlands
State/province [23] 0 0
Nijmegen
Country [24] 0 0
Netherlands
State/province [24] 0 0
Tilburg
Country [25] 0 0
Netherlands
State/province [25] 0 0
Zwolle

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
To evaluate the effect of evolocumab on fibrous cap thickness (FCT) in subjects with
non-ST-elevation acute coronary syndrome (NSTE-ACS) who are taking maximally tolerated statin
therapy.
Trial website
https://clinicaltrials.gov/show/NCT03570697
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications