PASSIvation of Vulnerable Plaque With AZD5718 in AcuTe Coronary syndromE

NCT04601467 | Terminated Phase 2 DMC

• 1 other identifier: 2020/
• Study Type: interventional
• Target: 243
• Locations: 2 countries
• Sites: 8

Brief Summary

This is a multi-center study conducted at 8 sites in 2 countries (Singapore, New Zealand). Patients with an acute myocardial infarction (AMI) were randomized in a ratio of 1:1 ratio to receive AZD5718 (Atuliflapon) 125 mg or placebo for 12 months to assess the efficacy of AZD5718 to prevent coronary plaque progression as measured on serial computer tomographic coronary angiography.

Conditions

Acute Coronary Syndrome

Keywords

Acute Myocardial Infarction; Computed Tomography Coronary Angiography

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Change in CT peri vascular (coronary) adipose tissue (PVAT)

  Baseline (before treatment) and after 12 months of treatment

• Change in total plaque volume (mm3)

  Baseline (before treatment) and after 12 months of treatment

• Echocardiographic assessment: Change in left ventricular ejection fraction (LVEF)

  Baseline (before treatment) and after 12 months of treatment

• Change in levels of urinary LTE4 (u-LTE4)

  12 months

Other Outcomes (5)

• Change in low attenuation plaque burden

  Baseline (before treatment) and after 12 months of treatment

• Change in plasma hs-CRP concentration

  Baseline (before treatment) and after 12 months of treatment

• Echocardiographic assessment: Change in LV global longitudinal strain

  Baseline (before treatment) and after 12 months of treatment

Study Arms (2)

AZD5718

EXPERIMENTAL

Patients will receive once daily oral dose of AZD5718 for 12 months

Drug: AZD5718

Placebo

PLACEBO COMPARATOR

Patients will receive once daily oral dose of placebo matched to AZD5718 for 12 months

Drug: Placebo

Interventions

AZD5718 DRUG

Oral dose of AZD5718 (tablet) once daily for 12 months

AZD5718

Placebo DRUG

Oral dose of matching placebo (tablet) once daily for 12 months

Placebo

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National University Heart Centre, Singapore: lead
• AstraZeneca: collaborator
• University of Otago: collaborator

Study Sites (8)

North Shore Hospital

Auckland, New Zealand

Location

Christchurch Heart Institute (CHI)

Christchurch, New Zealand

Location

Changi General Hospital (CGH)

Singapore, Singapore

Location

Khoo Teck Puat Hospital (KTPH)

Singapore, Singapore

Location

National Heart Centre Singapore (NHCS)

Singapore, Singapore

Location

National University Heart Centre, Singapore (NUHCS)

Singapore, Singapore

Location

Ng Teng Fong General Hospital (NTFGH)

Singapore, Singapore

Location

Tan Tock Seng Hospital (TTSH)

Singapore, Singapore

Location

Related Publications (2)

• Ericsson H, Nelander K, Lagerstrom-Fermer M, Balendran C, Bhat M, Chialda L, Gan LM, Heijer M, Kjaer M, Lambert J, Lindstedt EL, Forsberg GB, Whatling C, Skrtic S. Initial Clinical Experience with AZD5718, a Novel Once Daily Oral 5-Lipoxygenase Activating Protein Inhibitor. Clin Transl Sci. 2018 May;11(3):330-338. doi: 10.1111/cts.12546. Epub 2018 Mar 8.

  PMID: 29517132 BACKGROUND

• Pettersen D, Broddefalk J, Emtenas H, Hayes MA, Lemurell M, Swanson M, Ulander J, Whatling C, Amilon C, Ericsson H, Westin Eriksson A, Granberg K, Plowright AT, Shamovsky I, Dellsen A, Sundqvist M, Nagard M, Lindstedt EL. Discovery and Early Clinical Development of an Inhibitor of 5-Lipoxygenase Activating Protein (AZD5718) for Treatment of Coronary Artery Disease. J Med Chem. 2019 May 9;62(9):4312-4324. doi: 10.1021/acs.jmedchem.8b02004. Epub 2019 Mar 26.

  PMID: 30869888 BACKGROUND

MeSH Terms

Conditions

Acute Coronary Syndrome

Interventions

AZD5718

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Study Officials

• Mark Chan

  National University Heart Centre, Singapore

  PRINCIPAL INVESTIGATOR

• Derek Hausenloy

  National Heart Centre Singapore

  PRINCIPAL INVESTIGATOR

• A. Mark Richards

  National University Heart Centre, Singapore

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: CT coronary angiogram core laboratory
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: September 11, 2020
• First Posted: October 23, 2020
• Study Start: July 12, 2021
• Primary Completion: May 27, 2024
• Study Completion: August 14, 2024
• Last Updated: April 27, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Start date and end date will be specified upon publication of the primary trial results
• Access Criteria: Only investigators employed by universities or healthcare organisations upon reasonable request to the study PIs.

Locations

NZ (2); SG (6)