NCT03113773

Low Dose Interleukin-2 in Patients With Stable Ischaemic Heart Disease and Acute Coronary Syndromes

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 41 (actual)
• Sponsor: Cambridge University Hospitals NHS Foundation Trust · Academic / Other
• Sex: All
• Age: 18 Years – 85 Years
• Healthy volunteers: Not accepted

Summary

The mainstay for treatment for acute coronary syndrome (ACS) focusses on re-establishing and maintaining the patency of vessels following coronary plaque disruption, through the use of anti-platelets and anticoagulants. Despite advances in management ACS still carries a high risk of morbidity and mortality, thus future management is likely to target other pathways. Recent studies indicate that CD4+ T cells, and more specifically Treg cells, are important for the control of post-ischemic immune responses and the promotion of myocardial healing. The investigators therefore hypothesise that expansion of Treg cells in patients with ACS dampens the activation of the immune response and promotes both plaque and myocardial healing. The investigators hypothesise that this can be achieved through subcutaneous administration of low doses of interleukin-2 (IL-2). IL-2 supplementation appears to be an attractive therapeutic option playing a key role in Treg cell development, expansion, survival and suppressive function.

Detailed description

This Phase I/II trial will carefully examine the safety of low-dose IL-2 in cardiovascular patients where it is currently contraindicated. The planned doses will be given to the trial patients once a day, over five days as subcutaneous injections \[ i) Part A : Repeated doses will be given in the range of 0.3x10\^6 IU up to a maximum of 3.0x10\^6 IU (total of 25 completed patients across 5 groups: 3:2 randomisation IL-2:placebo) ii) Part B : Repeated doses will be given at doses not exceeding the maximum dose used in Part A (total of 32 completed patients across 4 groups: 6:2 randomisation IL-2:placebo)\]. These doses have been chosen on the basis of safety and tolerability data from published clinical studies. In the low dose IL-2 studies evaluated, there were a low rate of adverse events (AEs) in all of the studies with the most commonly reported AEs being injection site reactions, fatigue, fever, nausea and vomiting. A low percentage of serious adverse events (SAEs) were recorded in a GVHD (graft-versus-host disease)-risk study and these SAEs included haemorrhage (CNS), anorexia, and infection (colitis). The experimental and clinical background in low-dose IL-2 therapy suggests a potential clinical utility of Treg cell expansion in patients with ACS. Administration of low doses of IL-2 in various clinical settings appears to be safe and remarkably efficacious at promoting selective expansion of Treg cells with preserved suppressive function. This is the first trial to assess the mechanism of action of IL-2 therapy in cardiovascular patients. The aim of Part A of this clinical trial is to assess the safety of low-dose IL-2 as well as the proof of mechanism in patients with stable ischaemic heart disease. Part B aims to assess the safety and efficacy of, and increase in Treg as a result of this drug supplementation, in the setting of ACS. The investigators hypothesize that low doses of IL-2 in patients with ACS can increase Treg number and function, and ultimately promote plaque stabilisation and myocardial healing (this will be further addressed in future studies). In this context, it may improve patient recovery and limit the occurrence/recurrence of major clinical events.

Conditions

• Ischemic Heart Disease

Interventions

Type	Name	Description
DRUG	Proleukin	Patients will be treated with subcutaneous injections of IL-2 (range 0.3 X 10\^6 - 3.0 X 10\^6 IU) or placebo once daily for five consecutive days during the trial.A maximum dose of 3.0 X 10\^6 IU will be allowed per day.
DRUG	Placebo Injection	Dextrose 5%

Timeline

• Start date: 2017-05-11
• Primary completion: 2019-02-21
• Completion: 2019-02-21
• First posted: 2017-04-14
• Last updated: 2021-09-14

Locations

1 site across 1 country: United Kingdom