Effects of the PCSK9 Antibody AliroCuMab on Coronary Atherosclerosis in PatieNts with Acute Myocardial Infarction. A Serial, Multivessel, Intravascular Ultrasound, Near-Infrared Spectroscopy And Optical Coherence Tomography Imaging Study

Phase 3

Completed

Conditions: Coronary Atherosclerosis
Cardiovascular disease
10011082

Registration Number: NL-OMON50428

Lead Sponsor: Insel Gruppe AG - Inselspital

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 50

Inclusion Criteria

- Male or female, age *18 years at screening
- Acute myocardial infarction: acute ST-segment elevation myocardial infarction
(STEMI) with pain onset within *24h, or non-ST segment elevation myocardial
infarction (NSTEMI), with at least one coronary segment (culprit lesion)
requiring PCI
- LDL-C *70 mg/dL (*1.8 mmol/L) assessed prior to, or during PCI in patients
who have been receiving any stable statin regimen within * 4 weeks prior to
enrollment; OR LDL-C *125 mg/dL (*3.2 mmol/L) in patients who are statin-naïve
or have not been on stable statin regimen for * 4 weeks prior to enrollment
- At least two major native coronary arteries (*target vessels*) each meeting
the following criteria for intracoronary imaging immediately following the
qualifying PCI procedure:
- Angiographic evidence of <50% reduction in lumen diameter by angiographic
visual estimation
- Target vessel deemed to be accessible to imaging catheters and suitable for
intracoronary imaging in the proximal (50mm) segment (*target segment*)
- Target vessel may not be a bypass (saphenous vein or arterial) graft or a
bypassed native vessel
- Target vessel must not have undergone previous PCI within the target segment
- Target vessel is not candidate for intervention at the time of qualifying PCI
or over the following 6 months in the judgment of the Investigator
- Hemodynamic stability allowing the repetitive administration of nitroglycerine
- Ability to understand the requirements of the study and to provide informed
consent
- Willingness to undergo follow-up intracoronary imaging

Exclusion Criteria

- Left-main disease, defined as *50% reduction in lumen diameter of the left
main coronary artery by angiographic visual estimation
- Three-vessel disease, defined as *70% reduction in lumen diameter of three
major epicardial coronary arteries by angiographic visual estimation or in
major branches of one or more of these arteries, irrespective of the
localization (proximal 50mm or more distal localization) of the obstructive
lesions
- History of coronary artery bypass surgery
- TIMI flow <2 of the infarct-related artery after PCI
- Unstable clinical status (hemodynamic or electrical instability)
- Significant coronary calcification or tortuosity deemed to preclude IVUS,
NIRS and OCT evaluation
- Uncontrolled cardiac arrhythmia, defined as recurrent and symptomatic
ventricular tachycardia or atrial fibrillation with rapid ventricular response
not controlled by medications in the past 3 months prior to screening
- Severe renal dysfunction, defined by estimated glomerular filtration rate <30
ml/min/1.73m2
- Active liver disease or hepatic dysfunction;
- Known intolerance to rosuvastatin OR
Known statin intolerance defined by the following criteria: inability to
tolerate at least 2 different statins (one statin at the lowest starting
average daily dose and the other statin at any dose); intolerance associated
with confirmed, intolerable statin-related adverse effect(s) or significant
biomarker abnormalities; symptom or biomarker changes resolution or significant
improvement upon dose decrease or discontinuation; and symptoms or biomarker
changes not attributable to established predispositions such as drug-drug
interactions and recognized conditions increasing the risk of statin intolerance
- Known allergy to contrast medium, heparin, aspirin, ticagrelor or prasugrel
- Known sensitivity to any substances to be administered, including known
statin intolerance
- Patients who previously received alirocumab or other PCSK9 inhibitor
- Patient who received cholesterol ester transfer protein inhibitors in the
past 12 months prior to screening
- Treatment with systemic steroids or systemic cyclosporine in the past 3 months
- Known active infection or major hematologic, metabolic, or endocrine
dysfunction in the judgment of the Investigator
- Planned surgery within 12 months
- Patients who will not be available for study-required visits in the judgment
of the Investigator
- Current enrollment in another investigational device or drug study
- History of cancer within the past 5 years, except for adequately treated
basal cell skin cancer, squamous cell skin cancer, or in situ cervical cancer
- Estimated life expectancy less than 1 year
- Female of childbearing potential (age <50 years and last menstruation within
the last 12 months), who did not undergo tubal ligation, ovariectomy or
hysterectomy

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>- Change in percent atheroma volume (PAV)</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- Change in lipid core burden index (defined by NIRS), macrophage accumulation,<br /><br>and fibrous cap thickness of coronary plaques (defined by OCT)<br /><br><br /><br>- Change in lipid levels (cholesterol, LDL-C, HDL-C, Lp(a), triglycerides,<br /><br>non-HDL-C, Apo B, Apo A-1, ratio Apo B/Apo A-1, Apo C-III), inflammatory<br /><br>biomarkers (hs-CRP, TNFa, IL-1b, IL-6, MPO, cystatine, SIRT1, SIRT6) and other<br /><br>selected biomarkers (hs-troponin T, NT-pro-BNP)<br /><br><br /><br>Safety objective<br /><br>- Amount of adverse events </p><br>