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

Exclusion Criteria

• •Current presentation with cardiogenic shock (systolic blood pressure \<80 mm Hg, unresponsive to fluids, or necessitating catecholamines), severe congestive heart failure and/or pulmonary oedema
• •Known active bleeding or bleeding diatheses
• •Known active infection requiring antibiotic treatment
• •Severe hematologic abnormalities (haematocrit \<30% AND platelet cell count of \<100 × 10\^3/μL AND white blood cell count \<3.3 × 10\^3/μL )
• •Known malignancies requiring active treatment or follow up (However, patients with current/a history of localised basal or squamous cell skin cancer are not excluded from participation in this trial)
• •Known heart failure with impaired LV function: echocardiographic findings of LV EF \< 45%
• •Hypotension (Systolic BP\<100mm Hg, DBP\<50mmHg) at screening
• •Uncontrolled hypertension (\>160/100 mmHg) at screening
• •History of recurrent syncope (Electrocardiographic history suggestive of arrhythmia syncope (e.g. bifascicular block, sinus bradycardia \< 40 beats per minute in absence of sinoatrial block or medications, pre-excited QRS complex, abnormal QT interval, ST segment elevation leads V1 through V3 \[Brugada syndrome\], negative T wave in right precordial leads and epsilon wave \[arrhythmogenic right ventricular dysplasia/cardiomyopathy\]))
• •Known hepatic failure or abnormal LFTs at baseline (ALT \> 2 x ULN).
• •Elevated Total Bilirubin Levels, (TBL \> 1.5 x ULN) and Alkaline Phosphatase, ALP (ALP \> 1.5 x ULN), at baseline
• •Acute kidney injury or chronic kidney disease at Stage \> 3B (eGFR \< 45)
• •Respiratory failure
• •History of drug induced Stevens Johnson syndrome, Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), toxic epidermal necrolysis, or contrast allergy (requiring steroid treatment)
• •History of recurrent epileptic seizures in the previous 4 years; repetitive or difficult to control seizures, coma or toxic psychosis lasting \>48 hours
• •If known diabetic, uncontrolled diabetes defined as HbA1c \> 64 mmol/mol
• •Average corrected QT interval (QTc) \> 450 msecs using Bazett's formula using triplicate ECGs (or \> 480 msecs if bundle branch block)
• •Known chronic active hepatitis (B or C)
• •Known HIV infection
• •Current infection possibly related to recent or on-going immunosuppressive treatment
• •Known autoimmune disease requiring active immunosuppressive therapy
• •History of organ transplantation
• •Any oral or intravenous Immunosuppressive treatment including Prednisolone, hydrocortisone or disease modifying drugs such as Azathioprine, interferon-alpha, Cyclophosphamide or Mycophenolate. \[Other immunosuppressive therapies should be discussed with PI. Inhaled or topical steroids are permissible.\]
• •Known pregnancy at screening or visit 2 (where applicable)
• •On-going lactation
• •Inability to comply with trial procedures
• •Current participation in the active dosing phase of other interventional clinical trials
• •Contra indication to IL-2 treatment or hypersensitivity to IL-2 or to any of its excipients
• •Unwillingness or inability to provide written informed consent for participation
• •Known hyper- or hypothyroidism
• •Any medical history or clinically relevant abnormality that is deemed by the principal investigator/delegate and/or medical monitor to make the patient ineligible for inclusion because of a safety concern
• •Part B
• •ST elevation myocardial infarction (heart attack) on this admission.
• •Current presentation with cardiogenic shock (systolic blood pressure \<80 mm Hg, unresponsive to fluids, or necessitating catecholamines), electrical instability, severe congestive heart failure and/or pulmonary oedema
• •Known active bleeding or bleeding diatheses
• •Known active infection requiring antibiotic treatment
• •Severe hematologic abnormalities (haematocrit \<30% AND platelet cell count of \<100 × 10\^3/μL, white blood AND cell count \<3.3 × 10\^3/μL)
• •Known malignancies requiring active treatment or follow up (However, patients with current/a history of localised basal or squamous cell skin cancer are not excluded from participation in this trial)
• •Known heart failure with impaired LV function: echocardiographic findings of LV EF \< 35%
• •Hypotension (Systolic BP (SBP)\<100mm Hg, DBP\<50mmHg) at screening
• •Uncontrolled hypertension (\>160/100 mmHg) at screening
• •History of recurrent syncope (Electrocardiographic history suggestive of arrhythmia syncope (e.g., bifascicular block, sinus bradycardia \< 40 beats per minute in absence of sinoatrial block or medications, pre-excited QRS complex, abnormal QT interval, ST segment elevation leads V1 through V3 \[Brugada syndrome\], negative T wave in right precordial leads and epsilon wave \[arrhythmogenic right ventricular dysplasia/cardiomyopathy\]))
• •Known hepatic failure or abnormal LFTs at baseline (ALT \> 2 x ULN).
• •Elevated Total Bilirubin Levels, (TBL \> 1.5 x ULN) and Alkaline Phosphatase, ALP (ALP \> 1.5 x ULN), at baseline
• •Renal impairment at screening (Creatinine clearance \[Cockcroft-Gault\] \<45ml/min)
• •Acute respiratory failure
• •History of drug induced Stevens Johnson syndrome, Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), toxic epidermal necrolysis, or contrast allergy (requiring steroid treatment)
• •History of recurrent epileptic seizures in the previous 4 years; repetitive or difficult to control seizures, coma or toxic psychosis lasting \>48 hours
• •Average corrected QT interval (QTc) \> 450 msecs using Bazett's formula using triplicate ECGs (or \> 480 msecs if bundle branch block)
• •Known chronic active hepatitis (B or C)
• •Known HIV infection
• •Current infection possibly related to recent or on-going immunosuppressive treatment
• •Known autoimmune disease requiring active immunosuppressive therapy
• •History of organ transplantation
• •Any oral or intravenous immunosuppressive treatment including Prednisolone, hydrocortisone or disease modifying drugs such as Azathioprine, interferon-alpha, Cyclophosphamide or Mycophenolate. \[Other immunosuppressive therapies should be discussed with PI. Inhaled or topical steroids are permissible.\]
• •Known pregnancy at screening (where applicable)
• •On-going lactation
• •Inability to comply with trial procedures
• •Current participation in the active dosing phase of other interventional clinical trials
• •Contra indication to IL-2 treatment or hypersensitivity to IL-2 or to any of its excipients
• •Unwillingness or inability to provide written informed consent for participation
• •Known hyper- or hypothyroidism
• •Any medical history or clinically relevant abnormality that is deemed by the principal investigator/delegate and/or medical monitor to make the patient ineligible for inclusion because of a safety concern