Imaging of Coronary Plaques in Participants Treated With Evolocumab
Condition: Coronary Artery Disease (CAD)
MeSH terms: Coronary Artery Disease; Myocardial Ischemia; Coronary Disease
Intervention: Evolocumab; Placebo; Statin therapy
Intervention description: Participants will receive evolocumab (AMG 145) subcutaneous monthly.; Participants will receive matching placebo subcutaneous monthly.; 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 MeSH terms: Evolocumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking description: This is a double-blind study. Treatment assignment will be blinded to all subjects, site personnel, and Amgen
Enrollment: 164.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
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

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.
    

Eligibility 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 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.