IVORY
Research type
Research Study
Full title
Low-dose interleukin-2 for the reduction of vascular inflammation in Acute Coronary Syndromes (IVORY)
IRAS ID
220945
Contact name
Joseph Cheriyan
Contact email
Sponsor organisation
Cambridge University Hospitals NHS Foundation Trust and University of Cambridge
Eudract number
2017-005130-27
Duration of Study in the UK
3 years, 1 months, 8 days
Research summary
Research Summary:
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 diagnosed with narrowings/blockages in walls of blood vessels to the heart (Acute Coronary Syndrome (ACS)). 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 10 weeks. Participants will undergo two non-invasive vascular imaging scans (echogram or ECHO) and two invasive PET/CT (Positron emission tomography–computed tomography) scans to observe change of inflammation in the blood vessels from baseline between the two trial groups. A series of other medical assessments will also be carried out during this time.
Summary of Results:
What the study was about Inflammation in the walls of the arteries plays a big part in heart attacks and related conditions (together called acute coronary syndromes, or ACS). The IVORY trial tested whether a very low dose of a drug called interleukin-2 (IL-2) could calm that inflammation down.
IL-2 is a natural signalling molecule in the body. At low doses it boosts a type of white blood cell called a regulatory T cell (or "Treg"), which acts like a brake on the immune system — dialling inflammation down rather than up.
How the study was done
We recruited patients who had recently had an ACS and who still had raised levels of CRP in their blood, a marker showing that inflammation was still active.
Patients were split into two groups at random, with an equal chance of being in either. One group received low-dose IL-2 injections; the other received a dummy (placebo) injection. Neither the patients nor the doctors knew who was getting which — this is what "double-blind" means, and it keeps expectations from influencing the results.
Treatment started with a daily injection for five days, then dropped to one injection a week for seven weeks.
To measure inflammation in the arteries, we used a type of scan called 18F-FDG-PET/CT, which highlights areas where immune cells are most active. Each patient was scanned before treatment started and again after it finished. We focused on whichever artery (the main artery leaving the heart, or the arteries in the neck) was the most inflamed at the start.
What we found
We assessed 106 patients, 69 were assigned to a treatment group, 63 started treatment, and 60 finished the trial (31 on IL-2, 29 on placebo). The two groups were well matched at the start, so any difference at the end is more likely to be down to the drug.
• Arterial inflammation was significantly lower at the end of treatment in the IL-2 group than in the placebo group.
• The more inflamed a patient's arteries were to begin with, the bigger the benefit they appeared to get.
• IL-2 raised the number of regulatory T cells (the immune "brakes") in the blood, without increasing the inflammation-driving cells. This is what we'd hoped to see, and suggests the drug worked the way we expected.
• Side effects were mild and short-lived, and there were no more infections in the IL-2 group than in the placebo group — an important check, since a drug acting on the immune system could in principle leave people more vulnerable to infection.
What it means
In people who have had an acute coronary syndrome, low-dose IL-2 appears safe and reduced inflammation in the arteries compared with placebo.
Reducing inflammation on a scan is not the same as preventing heart attacks, however. Larger and longer trials are now needed to find out whether this treatment actually improves patients' long-term heart health.REC name
Yorkshire & The Humber - Sheffield Research Ethics Committee
REC reference
19/YH/0171
Date of REC Opinion
21 Jun 2019
REC opinion
Favourable Opinion