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Imaging of Coronary Plaques in Subjects Treated With Evolocumab

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03570697
Recruitment Status : Recruiting
First Posted : June 27, 2018
Last Update Posted : October 3, 2019
Sponsor:
Information provided by (Responsible Party):
Amgen

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.

Condition or disease Intervention/treatment Phase
Coronary Artery Disease (CAD) Biological: Evolocumab Other: Placebo Phase 3

Detailed Description:
This study seeks to identify morphologic changes, such as increase in fibrous cap thickness (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 non-ST-segment elevation (NSTE)-ACS using optical coherence tomography (OCT;primary, secondary, and exploratory endpoints) and intravascular ultrasound (IVUS; exploratory endpoints only)

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: High-Resolution Assessment of Coronary Plaques in a Global Evolocumab Randomized Study (HUYGENS)
Actual Study Start Date : November 19, 2018
Estimated Primary Completion Date : December 11, 2020
Estimated Study Completion Date : December 11, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Evolocumab

Arm Intervention/treatment
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.
Biological: Evolocumab
Subjects will receive Evolocumab (AMG 145) subcutaneous monthly.
Other Name: Repatha, AMG 145

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: Placebo
Subjects will receive Evolocumab (AMG 145) matching placebo subcutaneous monthly.
Other Name: Placebo to Evolocumab or Matching Placebo




Primary Outcome Measures :
  1. Absolute change in minimum fiberous cap thickness (FCT) [ Time Frame: week 50 ]
    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


Secondary Outcome Measures :
  1. Percent change in minimum FCT in a matched segment of artery [ Time Frame: week 50 ]
    Coronary artery segment based: Percent change in minimum FCT in a matched segment of artery as determined by OCT from baseline to week 50.

  2. Absolute change in minimum FCT, maximum lipid arc, and lipid core length in lipid rich plaques [ Time Frame: week 50. ]
    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

  3. Absolute change in mean mínimum FCT for all images assessed [ Time Frame: week 50 ]
    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.

  4. Absolute change in the maximum lipid arc in a matched segment of artery [ Time Frame: week 50 ]
    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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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.

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03570697


Contacts
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Contact: Amgen Call Center 866-572-6436 medinfo@amgen.com

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Sponsors and Collaborators
Amgen
Investigators
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Study Director: MD Amgen

Additional Information:
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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT03570697     History of Changes
Other Study ID Numbers: 20160184
2017-003236-37 ( EudraCT Number )
First Posted: June 27, 2018    Key Record Dates
Last Update Posted: October 3, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (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 link below.
URL: https://www.amgen.com/datasharing

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Amgen:
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
Additional relevant MeSH terms:
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Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Evolocumab
Antibodies, Monoclonal
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Lipid Regulating Agents
Immunologic Factors
Physiological Effects of Drugs