Low Dose Interleukin-2 in Patients With Stable Ischaemic Heart Disease and Acute Coronary Syndromes
Condition: Ischemic Heart Disease
MeSH terms: Heart Diseases; Acute Coronary Syndrome; Myocardial Ischemia; Coronary Artery Disease; Ischemia
Study type: Interventional
Phase: Phase 1/Phase 2

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.
    

Intervention name(s): Proleukin; Placebo Injection
Intervention type(s): Drug; Drug
Intervention description(s): 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.; Dextrose 5%
Intervention MeSH terms: Aldesleukin
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment