PASSIvation of Vulnerable Plaque With AZD5718 in AcuTe Coronary syndromE

NCT ID: NCT04601467

Last Updated: 2025-04-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 243 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-12
• Study Completion Date: 2024-08-14

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.

Detailed Description

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 60 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.

Conditions

Acute Coronary Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

AZD5718

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

Group Type: EXPERIMENTAL

AZD5718

Intervention Type: DRUG

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

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

AZD5718

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

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

University of Otago

OTHER

Sponsor Role: collaborator

National University Heart Centre, Singapore

OTHER

Sponsor Role: lead

Responsible Party

Mark Chan

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mark Chan

Role: PRINCIPAL_INVESTIGATOR

National University Heart Centre, Singapore

Derek Hausenloy

Role: PRINCIPAL_INVESTIGATOR

National Heart Centre Singapore

A. Mark Richards

Role: STUDY_CHAIR

National University Heart Centre, Singapore

Locations

North Shore Hospital

Auckland, , New Zealand

Christchurch Heart Institute (CHI)

Christchurch, , New Zealand

Changi General Hospital (CGH)

Singapore, , Singapore

Khoo Teck Puat Hospital (KTPH)

Singapore, , Singapore

National Heart Centre Singapore (NHCS)

Singapore, , Singapore

National University Heart Centre, Singapore (NUHCS)

Singapore, , Singapore

Ng Teng Fong General Hospital (NTFGH)

Singapore, , Singapore

Tan Tock Seng Hospital (TTSH)

Singapore, , Singapore

Countries

New Zealand; Singapore

References

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.

Reference Type: BACKGROUND

PMID: 29517132 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 30869888 (View on PubMed)

Other Identifiers

2020/

Identifier Type: -

Identifier Source: org_study_id