Imaging of Coronary Plaques in Subjects Treated With Evolocumab

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)

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.