Low-dose Interleukin-2 for the Reduction of Vascular Inflammation in Acute Coronary Syndromes - IVORY (IVORY)

Low-dose Interleukin-2 for the Reduction of Vascular Inflammation in Acute Coronary Syndromes - IVORY (IVORY)

Brief Summary:
Acute coronary syndromes (ACS) result from coronary plaque(s) disruption, which initiates a thrombotic process leading to partial or complete obstruction of the vessel lumen with subsequent myocardial ischaemia and necrosis. The mainstay of treatment is currently focused on the re-establishment and maintenance of coronary artery patency using anti-platelets and anticoagulants with or without mechanical dilatation and stenting of the culprit artery. Despite important advances in management, ACS still carries a risk of substantial morbidity and mortality. The improved efficacy of novel anti-platelet and anticoagulant agents have been limited by increased risk of haemorrhagic events. Future breakthroughs in management are most likely to arise from targeting other relevant pathophysiological pathways. Particularly, the immune response which is an important process that has been neglected in the management of patients with ACS.

In this trial the investigators investigate the efficacy of low dose IL-2 compared with placebo in patients with ACS.

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 (IL-2), is a medicine that stimulates the production of Treg cells when given at low doses and is the drug being tested in this trial. IL-2 is licensed for the treatment of kidney cancer where it is given at much higher doses than planned in this trial. It appears to be safe and well tolerated at low doses while increasing Treg cells.

IVORY will be conducted in patients presenting with a heart attack (Acute Coronary Syndrome (ACS)). Approximately, 60 patients will be randomized to receive either low dose IL-2 or placebo. It is a Phase 2, randomised, double- blinded, placebo-controlled experimental trial. Total study duration for each participant will be approximately 13 weeks.

Participants will undergo 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 (Primary Endpoint).


Study Type: Interventional (Clinical Trial)
Estimated Enrollment: 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: a randomised, double-blind, placebo controlled, parallel group experimental medicine trial
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: The trial will be double-blind, with active and placebo doses appearing identical at point of issue and administration. The CUH central pharmacy will be unblinded and provided with a copy of the concealment list. Data analysis for the trial will be performed by a statistician who will be unblinded after the database lock.

The statistician, or delegate, may be unblinded for individual patients after their treatment period has concluded, to facilitate rapid reporting of safety events.

Primary Purpose: Treatment
Official Title: Low-dose Interleukin-2 for the Reduction of Vascular Inflammation in Acute Coronary Syndromes
Actual Study Start Date: August 5, 2020
Estimated Primary Completion Date: January 1, 2024
Estimated Study Completion Date: January 1, 2024

Arm:
- Active Comparator: low dose interleukin-2
- Placebo Comparator: Placebo

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