## Protocol Section
### Identification Module
**NCT ID:** NCT06427694

**Acronym:** IVORY-FINALE

**Brief Title:** Low-Dose IL-2 For The Reduction Of Vascular Inflammation In ACS -Clinical Outcomes & Follow-up Study

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

#### Organization Study ID Info
**ID:** IVORY-FINALE (A096877)
#### Organization
**Class:** OTHER
**Full Name:** Cambridge University Hospitals NHS Foundation Trust
#### Secondary ID Infos
**Domain:** IRAS
**ID:** 339102
**Type:** OTHER
### Status Module
#### Completion Date
**Date:** 2030-02-11

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-24

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-20

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2027-04-30

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-06-01

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-24
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-20
**Study First Submit QC Date:** 2024-05-20
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Cambridge University Hospitals NHS Foundation Trust

#### Responsible Party

**Investigator Affiliation:** Cambridge University Hospitals NHS Foundation Trust

**Investigator Full Name:** Joseph Cheriyan, MBChB, MA, FRCP, FESC, FACC

**Investigator Title:** Dr Joseph Cheriyan, Consultant Clinical Pharmacologist/Affilitated Associate Professor

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

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

In this follow-up study, we 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.

**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.

### Conditions Module

**Conditions:**

- Acute Coronary Syndromes

**Keywords:**

- Acute Coronary Syndromes

### Design Module

#### Design Info

**Observational Model:** COHORT

**Time Perspective:** PROSPECTIVE

#### Enrollment Info

**Count:** 60

**Type:** ESTIMATED

**Study Type:** OBSERVATIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Aldesleukin loading dose 1.5 x 10\^6 IU followed by maintenance dose of 1.5 x 10\^6 IU

**Intervention Names:**

- Drug: Aldesleukin

**Label:** Aldesleukin

#### Arm Group 2

**Description:** Dextrose 5%

**Intervention Names:**

- Drug: Dextrose 5% in water

**Label:** Placebo

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Aldesleukin

**Description:** IL2 antagonist

**Name:** Aldesleukin

**Other Names:**

- Proleukin

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Placebo

**Description:** matched placebo to active

**Name:** Dextrose 5% in water

**Other Names:**

- Dextrose

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Number of major adverse cardiovascular outcomes

**Measure:** Major adverse cardiovascular outcomes

**Time Frame:** 1 year from when initially dosed in preceding IVORY trial

**Description:** Number of major adverse cardiovascular outcomes

**Measure:** Major adverse cardiovascular outcomes

**Time Frame:** 2 years from when initially dosed in preceding IVORY trial

**Description:** Number of major adverse cardiovascular outcomes

**Measure:** Major adverse cardiovascular outcomes

**Time Frame:** 5 years from when initially dosed in preceding IVORY trial

#### Secondary Outcomes

**Description:** Number of deaths due to cardiovascular causes comparing IL2 to placebo

**Measure:** Death due to cardiovascular causes

**Time Frame:** 1 year from when initially dosed in preceding IVORY trial

**Description:** Number of deaths due to cardiovascular causes comparing IL2 to placebo

**Measure:** Deaths due to cardiovascular causes comparing IL2 to placebo

**Time Frame:** 2 years from when initially dosed in preceding IVORY trial

**Description:** Number of deaths due to cardiovascular causes comparing IL2 to placebo

**Measure:** Deaths due to cardiovascular causes comparing IL2 to placebo

**Time Frame:** 5 years from when initially dosed in preceding IVORY trial

**Description:** Numbers of resuscitated cardiac arrests comparing IL2 to placebo

**Measure:** Resuscitated cardiac arrests comparing IL2 to placebo

**Time Frame:** 1 year from when initially dosed in preceding IVORY trial

**Description:** Numbers of resuscitated cardiac arrests comparing IL2 to placebo

**Measure:** Resuscitated cardiac arrests comparing IL2 to placebo

**Time Frame:** 2 years from when initially dosed in preceding IVORY trial

**Description:** Numbers of resuscitated cardiac arrests comparing IL2 to placebo

**Measure:** Resuscitated cardiac arrests comparing IL2 to placebo

**Time Frame:** 5 years from when initially dosed in preceding IVORY trial

**Description:** Number of non-fatal MI (including NSTEMI and STEMI) comparing IL2 to placebo

**Measure:** Non-fatal MI (including NSTEMI and STEMI) comparing IL2 to placebo

**Time Frame:** 1 year from when initially dosed in preceding IVORY trial

**Description:** Number of non-fatal MI (including NSTEMI and STEMI) comparing IL2 to placebo

**Measure:** Non-fatal MI (including NSTEMI and STEMI) comparing IL2 to placebo

**Time Frame:** 2 years from when initially dosed in preceding IVORY trial

**Description:** Number of non-fatal MI (including NSTEMI and STEMI) comparing IL2 to placebo

**Measure:** Non-fatal MI (including NSTEMI and STEMI) comparing IL2 to placebo

**Time Frame:** 5 years from when initially dosed in preceding IVORY trial

**Description:** Number of ischaemic strokes comparing IL2 to placebo

**Measure:** Ischaemic strokes comparing IL2 to placebo

**Time Frame:** 1 year from when initially dosed in preceding IVORY trial

**Description:** Number of ischaemic strokes comparing IL2 to placebo

**Measure:** Ischaemic strokes comparing IL2 to placebo

**Time Frame:** 2 years from when initially dosed in preceding IVORY trial

**Description:** Number of ischaemic strokes comparing IL2 to placebo

**Measure:** Ischaemic strokes comparing IL2 to placebo

**Time Frame:** 5 years from when initially dosed in preceding IVORY trial

**Description:** Number of unplanned coronary vascularisations comparing IL2 to placebo

**Measure:** Unplanned coronary vascularisations comparing IL2 to placebo

**Time Frame:** 1 year from when initially dosed in preceding IVORY trial

**Description:** Number of unplanned coronary vascularisations comparing IL2 to placebo

**Measure:** Unplanned coronary vascularisations comparing IL2 to placebo

**Time Frame:** 2 years from when initially dosed in preceding IVORY trial

**Description:** Number of unplanned coronary vascularisations comparing IL2 to placebo

**Measure:** Unplanned coronary vascularisations comparing IL2 to placebo

**Time Frame:** 5 years from when initially dosed in preceding IVORY trial

**Description:** Number of hospitalisations due to cardiovascular causes comparing IL2 to placebo

**Measure:** Hospitalisations due to cardiovascular causes comparing IL2 to placebo

**Time Frame:** 1 year from when initially dosed in preceding IVORY trial

**Description:** Number of hospitalisations due to cardiovascular causes comparing IL2 to placebo

**Measure:** Hospitalisations due to cardiovascular causes comparing IL2 to placebo

**Time Frame:** 2 years from when initially dosed in preceding IVORY trial

**Description:** Number of hospitalisations due to cardiovascular causes comparing IL2 to placebo

**Measure:** Hospitalisations due to cardiovascular causes comparing IL2 to placebo

**Time Frame:** 5 years from when initially dosed in preceding IVORY trial

**Description:** Number of all-cause deaths comparing IL2 to placebo

**Measure:** All-cause deaths comparing IL2 to placebo

**Time Frame:** 1 year from when initially dosed in preceding IVORY trial

**Description:** Number of all-cause deaths comparing IL2 to placebo

**Measure:** All-cause death comparing IL2 to placebo

**Time Frame:** 2 years from when initially dosed in preceding IVORY trial

**Description:** Number of all-cause deaths comparing IL2 to placebo

**Measure:** All-cause death comparing IL2 to placebo

**Time Frame:** 5 years from when initially dosed in preceding IVORY trial

**Description:** Number of hospitalisations due to symptoms from heart failure (incl admission due to pulmonary oedema and congestive heart failure) comparing IL2 to placebo

**Measure:** Hospitalisations due to symptoms from heart failure (incl admission due to pulmonary oedema and congestive heart failure) comparing IL2 to placebo

**Time Frame:** 1 year from when initially dosed in preceding IVORY trial

**Description:** Number of hospitalisations due to symptoms from heart failure (incl admission due to pulmonary oedema and congestive heart failure)comparing IL2 to placebo

**Measure:** Hospitalisations due to symptoms from heart failure (incl admission due to pulmonary oedema and congestive heart failure) comparing IL2 to placebo

**Time Frame:** 2 years from when initially dosed in preceding IVORY trial

**Description:** Number of hospitalisation due to symptoms from heart failure (incl admission due to pulmonary oedema and congestive heart failure) comparing IL2 to placebo

**Measure:** Hospitalisations due to symptoms from heart failure (incl admission due to pulmonary oedema and congestive heart failure) comparing IL2 to placebo

**Time Frame:** 5 years from when initially dosed in preceding IVORY trial

**Description:** Number of revascularisations for peripheral vascular disease comparing IL2 to placebo

**Measure:** Revascularisations for peripheral vascular disease comparing IL2 to placebo

**Time Frame:** 1 year from when initially dosed in preceding IVORY trial

**Description:** Number of revascularisations for peripheral vascular diseasecomparing IL2 to placebo

**Measure:** Revascularisations for peripheral vascular disease comparing IL2 to placebo

**Time Frame:** 2 years from when initially dosed in preceding IVORY trial

**Description:** Number of revascularisations for peripheral vascular disease comparing IL2 to placebo

**Measure:** Revascularisations for peripheral vascular disease comparing IL2 to placebo

**Time Frame:** 5 years from when initially dosed in preceding IVORY trial

**Description:** Number of amputations due to peripheral vascular disease comparing IL2 to placebo

**Measure:** Amputations due to peripheral vascular disease comparing IL2 to placebo

**Time Frame:** 1 year from when initially dosed in preceding IVORY trial

**Description:** Number of amputations due to peripheral vascular disease comparing IL2 to placebo

**Measure:** Amputations due to peripheral vascular disease comparing IL2 to placebo

**Time Frame:** 2 years from when initially dosed in preceding IVORY trial

**Description:** Number of amputations due to peripheral vascular disease comparing IL2 to placebo

**Measure:** Amputations due to peripheral vascular disease comparing IL2 to placebo

**Time Frame:** 5 years from when initially dosed in preceding IVORY trial

**Description:** Number of haemorrhagic strokes comparing IL2 to placebo

**Measure:** Haemorrhagic strokes comparing IL2 to placebo

**Time Frame:** 1 year from when initially dosed in preceding IVORY trial

**Description:** Number of haemorrhagic strokes comparing IL2 to placebo

**Measure:** Haemorrhagic strokes comparing IL2 to placebo

**Time Frame:** 2 years from when initially dosed in preceding IVORY trial

**Description:** Number of haemorrhagic strokes comparing IL2 to placebo

**Measure:** Haemorrhagic strokes comparing IL2 to placebo

**Time Frame:** 5 years from when initially dosed in preceding IVORY trial

**Description:** Number of new atrial fibrillation diagnoses comparing IL2 to placebo

**Measure:** New atrial fibrillation diagnosis comparing IL2 to placebo

**Time Frame:** 1 year from when initially dosed in preceding IVORY trial

**Description:** Number of new atrial fibrillation diagnoses comparing IL2 to placebo

**Measure:** New atrial fibrillation diagnosis comparing IL2 to placebo

**Time Frame:** 2 years from when initially dosed in preceding IVORY trial

**Description:** Number of new atrial fibrillation diagnoses comparing IL2 to placebo

**Measure:** New atrial fibrillation diagnosis comparing IL2 to placebo

**Time Frame:** 5 years from when initially dosed in preceding IVORY trial

**Description:** Number of ventricular arrhythmia episodes (sustained ventricular tachycardia and ventricular fibrillation) comparing IL2 to placebo

**Measure:** Ventricular arrhythmia (sustained ventricular tachycardia and ventricular fibrillation) comparing IL2 to placebo

**Time Frame:** 1 year from when initially dosed in preceding IVORY trial

**Description:** Number of ventricular arrhythmia episodes (sustained ventricular tachycardia and ventricular fibrillation) comparing IL2 to placebo

**Measure:** Ventricular arrhythmia (sustained ventricular tachycardia and ventricular fibrillation) comparing IL2 to placebo

**Time Frame:** 2 years from when initially dosed in preceding IVORY trial

**Description:** Number of ventricular arrhythmia episodes (sustained ventricular tachycardia and ventricular fibrillation) comparing IL2 to placebo

**Measure:** Ventricular arrhythmia (sustained ventricular tachycardia and ventricular fibrillation) comparing IL2 to placebo

**Time Frame:** 5 years from when initially dosed in preceding IVORY trial

### Eligibility Module

**Eligibility Criteria:** 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

**Maximum Age:** 85 Years

**Minimum Age:** 18 Years

**Sampling Method:** NON_PROBABILITY_SAMPLE

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

**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.

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Cambridge

**Country:** United Kingdom

**Facility:** Addenbrooke's Hospital

**State:** Cambridgeshire

**Zip:** CB20QQ

#### Overall Officials

**Official 1:**

**Affiliation:** Cambridge University Hospitals NHS Foundation Trust

**Name:** Joseph Cheriyan, MBChB, FRCP

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**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.

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000004194

- Term: Disease

- ID: D000010335

- Term: Pathologic Processes

- ID: D000017202

- Term: Myocardial Ischemia

- ID: D000006331

- Term: Heart Diseases

- ID: D000002318

- Term: Cardiovascular Diseases

- ID: D000014652

- Term: Vascular Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC14

- Name: Heart and Blood Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M16355

- Name: Syndrome

- Relevance: HIGH

- As Found: Syndrome

- ID: M10293

- Name: Inflammation

- Relevance: HIGH

- As Found: Inflammation

- ID: M27545

- Name: Acute Coronary Syndrome

- Relevance: HIGH

- As Found: Acute Coronary Syndrome

- ID: M6546

- Name: Coronary Artery Disease

- Relevance: LOW

- As Found: Unknown

- ID: M19506

- Name: Myocardial Ischemia

- Relevance: LOW

- As Found: Unknown

- ID: M10543

- Name: Ischemia

- Relevance: LOW

- As Found: Unknown

- ID: M9419

- Name: Heart Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M17400

- Name: Vascular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T170

- Name: Acute Graft Versus Host Disease

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000054058

- Term: Acute Coronary Syndrome

- ID: D000013577

- Term: Syndrome

- ID: D000007249

- Term: Inflammation

### Intervention Browse Module - Ancestors

- ID: D000000970

- Term: Antineoplastic Agents

- ID: D000019380

- Term: Anti-HIV Agents

- ID: D000044966

- Term: Anti-Retroviral Agents

- ID: D000000998

- Term: Antiviral Agents

- ID: D000000890

- Term: Anti-Infective Agents

### Intervention Browse Module - Browse Branches

- Abbrev: Infe

- Name: Anti-Infective Agents

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Analg

- Name: Analgesics

### Intervention Browse Module - Browse Leaves

- ID: M225496

- Name: Aldesleukin

- Relevance: HIGH

- As Found: Platinum

- ID: M10411

- Name: Interleukin-2

- Relevance: LOW

- As Found: Unknown

- ID: M21350

- Name: Anti-HIV Agents

- Relevance: LOW

- As Found: Unknown

- ID: M25428

- Name: Anti-Retroviral Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4314

- Name: Antiviral Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4214

- Name: Anti-Infective Agents

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: C000082598

- Term: Aldesleukin

### Misc Info Module

- Version Holder: 2024-05-31
