PASSIvation of Vulnerable Plaque With AZD5718 in AcuTe Coronary syndromE

Study Overview
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Brief Summary
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This is a multi-center study conducted at 13 sites in 3 countries (Singapore, New Zealand, and the Australia). Approximately 260 patients with an acute myocardial infarction (AMI) will be randomized in a ratio of 1:1 ratio to receive AZD5718 125 mg or placebo for 12 months.

Detailed Description
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PASSIVATE is a randomized, double-blind, placebo-controlled Phase IIa trial that investigates how 12 months of treatment with AZD5718 modifies coronary plaque volume. Patients with recent STEMI or NSTEMI will receive an additional oral dose of AZD5718 (or placebo) once daily to standard clinical care for 12 months. The primary hypothesis being tested in PASSIVATE is that 12 months of treatment with AZD5718 attenuates the progression of non-calcified plaque (NCP) volume on serial computed tomography coronary angiography (CTCA) studies. Patients who gave consent (within 30 days after their index event) will undergo a CTCA scan and start treatment (AZD5718 or Placebo). The treatment duration will be 12 months. During the treatment period, patients will come to the clinic for follow-ups. At 12 months (end treatment), the patients will undergo their 2nd CTCA scan. A follow-up visit will be performed 4 weeks after the last dose in order to ensure the safety and well-being of the patients.

Official Title
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PASSIvation of Vulnerable Plaque With AZD5718 in AcuTe Coronary syndromE

Conditions
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Acute Coronary Syndrome

Intervention / Treatment
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* Drug: AZD5718
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: hospitalised for STEMI or non-STEMI, as defined by the 4th universal definition of MI underwent coronary angiography during the index hospitalisation showing at least one epicardial coronary artery with ≥50% stenosis and a 2nd epicardial coronary artery with ≥20% stenosis on the coronary angiogram Body Mass Index (BMI) ≥18 to ≤40 kg/m2 White Blood Cell count ≥ 7.0 X 103/uL during admission Exclusion Criteria: Prior coronary artery bypass grafting (CABG) CABG planned within 12 months of admission Known history of drug or alcohol abuse within 5 years of screening History of QT prolongation associated with other medications that required discontinuation of that medication Congenital long QT syndrome Systolic blood pressure persistently <90 mm Hg or HR<40 beats per minute at time of enrolment ALT >2 x ULN, cirrhosis, recent hepatitis, or positive screening test for hepatitis B (hepatitis B surface antigen) or other viral hepatitis Uncontrolled Type 1 or Type 2 DM defined as HbA1c >10% or 74.9 mmol/mol (by IFCC) Any planned coronary revascularisation, valve surgery, or cardiac resynchronisation within 7 months after randomisation Any concomitant medications known to be associated with Torsades de Pointes or potent inducers of cytochrome P450 3A4 (CYP3A4) Planned treatment with zileuton, leukotriene receptor antagonists (e.g., montelukast) during trial Participated in another interventional clinical study with an investigational pharmaceutical product during the last 3 months Known hypersensitivity to drugs with a similar chemical structure or class of study drugs or any of the excipients of the product Known conditions that either increase the risk of performing the CT or make the procedure technically impractical No severe asthma attack that require emergency treatment or hospitalisation in the past 6 months Had severe course of COVID-19 (extracorporeal membrane oxygenation, mechanically ventilated), and/or had a confirmed case of COVID-19 within 4 weeks of Screening Visit

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD5718<br>Patients will receive once daily oral dose of AZD5718 for 12 months | Drug: AZD5718<br>* Oral dose of AZD5718 (tablet) once daily for 12 months<br>|
| Placebo Comparator: Placebo<br>Patients will receive once daily oral dose of placebo matched to AZD5718 for 12 months | Drug: Placebo<br>* Oral dose of matching placebo (tablet) once daily for 12 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in noncalcified coronary artery plaque volume (NCPV) | Percent change in NCPV (in mm3), as assessed by CT coronary angiography, from baseline (before treatment) to after 12-month of treatment | Baseline (before treatment) and after 12 months of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in CT pericoronary adipose tissue (PCAT) | To assess whether AZD5718 reduces coronary inflammation | Baseline (before treatment) and after 12 months of treatment | 
| Change in total plaque volume (mm3) | Percent change in total plaque volume (in mm3), as assessed by CT coronary angiography, from baseline (before treatment) to after 12-month of treatment | Baseline (before treatment) and after 12 months of treatment | 
| Echocardiographic assessment: Change in left ventricular ejection fraction (LVEF) | Percent change in LVEF (%), as assessed by 2D echocardiography, from baseline (before treatment) to after 12-month of treatment | Baseline (before treatment) and after 12 months of treatment | 
| Plasma concentrations of AZD5718 | To assess the PK of AZD5718 after repeated oral dosing for 12 months | 12 month | 
| Change in levels of urinary LTE4 (u-LTE4) | To assess the pharmacodynamics (PD) effect of AZD5718 by assessment of u-LTE4 in AMI patients | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Myocardial Infarction, Computed Tomography Coronary Angiography