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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03570697
Ethics application status
Date submitted
18/06/2018
Date registered
27/06/2018

Titles & IDs
Public title
Imaging of Coronary Plaques in Participants 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
Treatment: Drugs - Evolocumab
Treatment: Drugs - Placebo
Treatment: Drugs - Statin therapy

Experimental: 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.

Placebo comparator: 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.


Treatment: Drugs: Evolocumab
Participants will receive evolocumab (AMG 145) subcutaneous monthly.

Treatment: Drugs: Placebo
Participants will receive matching placebo subcutaneous monthly.

Treatment: Drugs: 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 code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Absolute Change From Baseline in Minimum FCT
Timepoint [1] 0 0
Baseline, week 50
Secondary outcome [1] 0 0
Percent Change From Baseline in Minimum FCT
Timepoint [1] 0 0
Baseline, week 50
Secondary outcome [2] 0 0
Absolute Change From Baseline in Mean Minimum FCT
Timepoint [2] 0 0
Baseline, week 50
Secondary outcome [3] 0 0
Absolute Change From Baseline in the Maximum Lipid Arc
Timepoint [3] 0 0
Baseline, week 50
Secondary outcome [4] 0 0
Absolute Change From Baseline in Minimum FCT in Lipid Rich Plaques
Timepoint [4] 0 0
Baseline, week 50
Secondary outcome [5] 0 0
Absolute Change From Baseline in Maximum Lipid Arc in Lipid Rich Plaques
Timepoint [5] 0 0
Baseline, week 50
Secondary outcome [6] 0 0
Absolute Change From Baseline in Lipid Core Length in Lipid Rich Plaques
Timepoint [6] 0 0
Baseline, 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 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
19/11/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
21/01/2021
Sample size
Target
Accrual to date
Final
164
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [3] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [4] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [5] 0 0
The Northern Hospital - 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
Trial website
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
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.
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.amgen.com/datasharing


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT03570697