Low-Dose IL-2 For The Reduction Of Vascular Inflammation In ACS -Clinical Outcomes & Follow-up Study (IVORY-FINALE)

The Low-Dose Interleukin-2 For The Reduction Of Vascular Inflammation In Acute Coronary Syndromes -Clinical Outcomes And Follow-up Study

The preceding IVORY trial (NCT04241601) has completed. As atherosclerosis and its complications are driven by inflammation the investigators hypothesise that treatment with low-dose IL2 may reduce adverse cardiovascular outcomes compared to placebo.

In this follow-up study, the investigators aim to collect cardiovascular clinical outcome data for patients who completed the IVORY clinical trial and will look at major adverse cardiovascular events (MACE), defined as cardiovascular death, non-fatal myocardial infarction, resuscitated cardiac arrest, ischaemic stroke, or unplanned coronary revascularization. In addition, data on adverse events such as all cause death, haemorrhagic stroke, new atrial fibrillation, ventricular arrhythmias, hospitalisation due to cardiovascular causes (e.g. stable and unstable angina, TIAs, heart failure), amputations and revascularisation due to peripheral vascular disease.

Study Overview

• Status: Recruiting
• Conditions: Acute Coronary Syndromes
• Intervention / Treatment: Drug: Aldesleukin; Drug: Dextrose 5% in water

Detailed Description

A heart attack occurs when there is reduced blood flow to heart muscle cells which results from narrowings or blockages in walls of blood vessels supplying the heart, due to fatty deposits and inflammatory cells that build up over time. This build-up leads to heart muscle damage called a heart attack.

The immune system plays an important role in both the development of the narrowings and the damage to the heart muscle during a heart attack. Studies have shown that there is a lower level of protective immune cells called regulatory T-cells (Tregs) in heart attack patients. Increasing the number of circulating Tregs may have a direct effect in reducing the inflammation in arteries, preventing further narrowings in blood vessels and improving heart muscle function. Aldesleukin, also known as interleukin-2 (IL2), is a medicine that stimulates the production of Treg cells when given at low doses. The effectiveness of IL2 in influencing the immune system was tested in a phase 2 trial, IVORY.

Participants were recruited to the IVORY trial following a sudden narrowing/blockages in walls of blood vessels to the heart resulting in a heart attack (Acute Coronary Syndrome (ACS)). Participants were randomised to receive either low dose IL2 or placebo, researchers and participants were blinded to the treatment allocation. Participants underwent two PET/CT (Positron emission tomography-computed tomography) scans to observe change of inflammation in the blood vessels from baseline between the two trial groups.

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

Study Locations

• United Kingdom
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB20QQ
      • Recruiting
      • Addenbrooke's Hospital
      • Principal Investigator: Joseph Cheriyan, MBChB, FRCP
      • Contact: Joseph Cheriyan, MBChB,FRCP; Phone Number: 0044 1223 256653; Email: jc403@medschl.cam.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Participants of the IVORY trial (NCT04241601) and who consented to be contacted for future research received all scheduled doses of either placebo or IL2 and are alive at the time of data collection will be approached.

Description

Inclusion Criteria:

• Participants who completed the full per-protocol treatment regime of low-dose IL2 or placebo having attended the final dosing visit in the IVORY trial. IVORY patients who previously consented to have their medical records inspected in the IVORY trial and who have already passed away at the commencement of IVORY-FINALE will also be included in analyses

Exclusion Criteria:

• Patients who decline participation
• Patients who did not consent to being contacted about future research
• Patients who were withdrawn from the IVORY trial for any reason

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Aldesleukin; Aldesleukin loading dose 1.5 x 10^6 IU followed by maintenance dose of 1.5 x 10^6 IU	Drug: Aldesleukin; IL2 antagonist; Other Names: Proleukin
Placebo; Dextrose 5%	Drug: Dextrose 5% in water; matched placebo to active; Other Names: Dextrose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major adverse cardiovascular outcomes	Number of major adverse cardiovascular outcomes	1 year from when initially dosed in preceding IVORY trial
Major adverse cardiovascular outcomes	Number of major adverse cardiovascular outcomes	2 years from when initially dosed in preceding IVORY trial
Major adverse cardiovascular outcomes	Number of major adverse cardiovascular outcomes	5 years from when initially dosed in preceding IVORY trial

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death due to cardiovascular causes	Number of deaths due to cardiovascular causes comparing IL2 to placebo	1 year from when initially dosed in preceding IVORY trial
Deaths due to cardiovascular causes comparing IL2 to placebo	Number of deaths due to cardiovascular causes comparing IL2 to placebo	2 years from when initially dosed in preceding IVORY trial
Deaths due to cardiovascular causes comparing IL2 to placebo	Number of deaths due to cardiovascular causes comparing IL2 to placebo	5 years from when initially dosed in preceding IVORY trial
Resuscitated cardiac arrests comparing IL2 to placebo	Numbers of resuscitated cardiac arrests comparing IL2 to placebo	1 year from when initially dosed in preceding IVORY trial
Resuscitated cardiac arrests comparing IL2 to placebo	Numbers of resuscitated cardiac arrests comparing IL2 to placebo	2 years from when initially dosed in preceding IVORY trial
Resuscitated cardiac arrests comparing IL2 to placebo	Numbers of resuscitated cardiac arrests comparing IL2 to placebo	5 years from when initially dosed in preceding IVORY trial
Non-fatal MI (including NSTEMI and STEMI) comparing IL2 to placebo	Number of non-fatal MI (including NSTEMI and STEMI) comparing IL2 to placebo	1 year from when initially dosed in preceding IVORY trial
Non-fatal MI (including NSTEMI and STEMI) comparing IL2 to placebo	Number of non-fatal MI (including NSTEMI and STEMI) comparing IL2 to placebo	2 years from when initially dosed in preceding IVORY trial
Non-fatal MI (including NSTEMI and STEMI) comparing IL2 to placebo	Number of non-fatal MI (including NSTEMI and STEMI) comparing IL2 to placebo	5 years from when initially dosed in preceding IVORY trial
Ischaemic strokes comparing IL2 to placebo	Number of ischaemic strokes comparing IL2 to placebo	1 year from when initially dosed in preceding IVORY trial
Ischaemic strokes comparing IL2 to placebo	Number of ischaemic strokes comparing IL2 to placebo	2 years from when initially dosed in preceding IVORY trial
Ischaemic strokes comparing IL2 to placebo	Number of ischaemic strokes comparing IL2 to placebo	5 years from when initially dosed in preceding IVORY trial
Unplanned coronary vascularisations comparing IL2 to placebo	Number of unplanned coronary vascularisations comparing IL2 to placebo	1 year from when initially dosed in preceding IVORY trial
Unplanned coronary vascularisations comparing IL2 to placebo	Number of unplanned coronary vascularisations comparing IL2 to placebo	2 years from when initially dosed in preceding IVORY trial
Unplanned coronary vascularisations comparing IL2 to placebo	Number of unplanned coronary vascularisations comparing IL2 to placebo	5 years from when initially dosed in preceding IVORY trial
Hospitalisations due to cardiovascular causes comparing IL2 to placebo	Number of hospitalisations due to cardiovascular causes comparing IL2 to placebo	1 year from when initially dosed in preceding IVORY trial
Hospitalisations due to cardiovascular causes comparing IL2 to placebo	Number of hospitalisations due to cardiovascular causes comparing IL2 to placebo	2 years from when initially dosed in preceding IVORY trial
Hospitalisations due to cardiovascular causes comparing IL2 to placebo	Number of hospitalisations due to cardiovascular causes comparing IL2 to placebo	5 years from when initially dosed in preceding IVORY trial
All-cause deaths comparing IL2 to placebo	Number of all-cause deaths comparing IL2 to placebo	1 year from when initially dosed in preceding IVORY trial
All-cause death comparing IL2 to placebo	Number of all-cause deaths comparing IL2 to placebo	2 years from when initially dosed in preceding IVORY trial
All-cause death comparing IL2 to placebo	Number of all-cause deaths comparing IL2 to placebo	5 years from when initially dosed in preceding IVORY trial
Hospitalisations due to symptoms from heart failure (incl admission due to pulmonary oedema and congestive heart failure) comparing IL2 to placebo	Number of hospitalisations due to symptoms from heart failure (incl admission due to pulmonary oedema and congestive heart failure) comparing IL2 to placebo	1 year from when initially dosed in preceding IVORY trial
Hospitalisations due to symptoms from heart failure (incl admission due to pulmonary oedema and congestive heart failure) comparing IL2 to placebo	Number of hospitalisations due to symptoms from heart failure (incl admission due to pulmonary oedema and congestive heart failure)comparing IL2 to placebo	2 years from when initially dosed in preceding IVORY trial
Hospitalisations due to symptoms from heart failure (incl admission due to pulmonary oedema and congestive heart failure) comparing IL2 to placebo	Number of hospitalisation due to symptoms from heart failure (incl admission due to pulmonary oedema and congestive heart failure) comparing IL2 to placebo	5 years from when initially dosed in preceding IVORY trial
Revascularisations for peripheral vascular disease comparing IL2 to placebo	Number of revascularisations for peripheral vascular disease comparing IL2 to placebo	1 year from when initially dosed in preceding IVORY trial
Revascularisations for peripheral vascular disease comparing IL2 to placebo	Number of revascularisations for peripheral vascular diseasecomparing IL2 to placebo	2 years from when initially dosed in preceding IVORY trial
Revascularisations for peripheral vascular disease comparing IL2 to placebo	Number of revascularisations for peripheral vascular disease comparing IL2 to placebo	5 years from when initially dosed in preceding IVORY trial
Amputations due to peripheral vascular disease comparing IL2 to placebo	Number of amputations due to peripheral vascular disease comparing IL2 to placebo	1 year from when initially dosed in preceding IVORY trial
Amputations due to peripheral vascular disease comparing IL2 to placebo	Number of amputations due to peripheral vascular disease comparing IL2 to placebo	2 years from when initially dosed in preceding IVORY trial
Amputations due to peripheral vascular disease comparing IL2 to placebo	Number of amputations due to peripheral vascular disease comparing IL2 to placebo	5 years from when initially dosed in preceding IVORY trial
Haemorrhagic strokes comparing IL2 to placebo	Number of haemorrhagic strokes comparing IL2 to placebo	1 year from when initially dosed in preceding IVORY trial
Haemorrhagic strokes comparing IL2 to placebo	Number of haemorrhagic strokes comparing IL2 to placebo	2 years from when initially dosed in preceding IVORY trial
Haemorrhagic strokes comparing IL2 to placebo	Number of haemorrhagic strokes comparing IL2 to placebo	5 years from when initially dosed in preceding IVORY trial
New atrial fibrillation diagnosis comparing IL2 to placebo	Number of new atrial fibrillation diagnoses comparing IL2 to placebo	1 year from when initially dosed in preceding IVORY trial
New atrial fibrillation diagnosis comparing IL2 to placebo	Number of new atrial fibrillation diagnoses comparing IL2 to placebo	2 years from when initially dosed in preceding IVORY trial
New atrial fibrillation diagnosis comparing IL2 to placebo	Number of new atrial fibrillation diagnoses comparing IL2 to placebo	5 years from when initially dosed in preceding IVORY trial
Ventricular arrhythmia (sustained ventricular tachycardia and ventricular fibrillation) comparing IL2 to placebo	Number of ventricular arrhythmia episodes (sustained ventricular tachycardia and ventricular fibrillation) comparing IL2 to placebo	1 year from when initially dosed in preceding IVORY trial
Ventricular arrhythmia (sustained ventricular tachycardia and ventricular fibrillation) comparing IL2 to placebo	Number of ventricular arrhythmia episodes (sustained ventricular tachycardia and ventricular fibrillation) comparing IL2 to placebo	2 years from when initially dosed in preceding IVORY trial
Ventricular arrhythmia (sustained ventricular tachycardia and ventricular fibrillation) comparing IL2 to placebo	Number of ventricular arrhythmia episodes (sustained ventricular tachycardia and ventricular fibrillation) comparing IL2 to placebo	5 years from when initially dosed in preceding IVORY trial

Collaborators and Investigators

• Sponsor: Cambridge University Hospitals NHS Foundation Trust
• Investigators: Principal Investigator: Joseph Cheriyan, MBChB, FRCP, Cambridge University Hospitals NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2024
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): February 11, 2030

Study Registration Dates

• First Submitted: May 20, 2024
• First Submitted That Met QC Criteria: May 20, 2024
• First Posted (Actual): May 24, 2024

Study Record Updates

• Last Update Posted (Actual): June 10, 2024
• Last Update Submitted That Met QC Criteria: June 7, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Acute Coronary Syndromes
• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Disease; Syndrome; Inflammation; Acute Coronary Syndrome; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Antineoplastic Agents; Aldesleukin
• Other Study ID Numbers: IVORY-FINALE (A096877); 339102 (Other Identifier: IRAS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: On completion of the study the data will be analysed and tabulated and a Final Study Report prepared. Data will be published in an open access journal.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No