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

• Status: Recruiting
• Trial end date: 2024-01-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Cambridge University Hospitals NHS Foundation Trust
• Treatments: Aldesleukin; Interleukin-2

Criteria

Inclusion Criteria:

• Able to provide written informed consent to participate.

• Current admission (on the screening visit) with an acute coronary syndrome - ST elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (NSTEMI), or unstable angina (UA) with symptoms suggestive of myocardial ischaemia lasting 10 minutes or longer with the patient at rest or with minimal effort AND EITHER i. elevated levels of TnI on admission OR ii. dynamic changes in ECG (new ST-T changes or T-wave inversion).

• Where applicable, to be included in the trial women must be:

i) Postmenopausal (for the purposes of this trial, postmenopausal is defined as being amenorrhoeic for greater than 2 years with an appropriate clinical profile, e.g. age appropriate, history of vasomotor symptoms) OR ii) Have had a documented hysterectomy and/or bilateral oophorectomy or sterilised OR iii) Peri-menopausal with a negative pregnancy test at screening (for the purposes of inclusion in this trial. Peri-menopausal is defined as women with an appropriate clinical profile, e.g. age appropriate, history of vasomotor symptoms, irregular periods). They will also have to comply with the use of contraception for the duration of the trial and undergo additional pregnancy tests during and after treatment.

• High sensitivity C-reactive protein of >2 mg/L at screening.

• Willingness and possibility to start dosing within 8 days from initial date of admission to the primary hospital for ACS.

• Able to comply with all trial mandated visits.

Exclusion Criteria:

• Current presentation (at screening) with cardiogenic shock (systolic blood pressure <80 mm Hg, unresponsive to fluids, or necessitating catecholamines).

• Current presentation with cardiac arrest.

• Signs or symptoms of active infection requiring intravenous antibiotic treatment at screening.

• History of malignancies requiring active treatment (However, patients with a history of treated localised basal or squamous cell skin cancer are not excluded from participation in this trial).

• History of solid organ transplantation or other bone marrow transplantation.

• History of recurrent epileptic seizures in the previous 4 years; repetitive or difficult to control seizures, coma or toxic psychosis lasting >48 hours.

• Uncontrolled hypotension (Systolic BP (SBP)<80mmHg or DBP<50mmHg) OR uncontrolled hypertension (SBP>180 or DBP>120 mmHg) at screening.

• Average corrected QT interval (QTc) > 450 msecs using Bazett's formula from average of triplicate ECGs (or > 480 msecs if bundle branch block).

• Renal impairment defined as Creatinine clearance [Cockcroft-Gault] <45ml/min at screening.

• Liver dysfunction (defined as ALT > 2xULN) at screening.

• Evidence of cholestasis defined as elevated Total Bilirubin Levels, (TBL > 1.5 x ULN) and Alkaline Phosphatase, ALP (ALP > 1.5 x ULN), at screening.

• Known hypothyroidism or hyperthyroidism.

• Known autoimmune disease requiring active immunosuppressive treatment.

• Any oral or intravenous immunosuppressive treatment including regular prednisolone, hydrocortisone or disease modifying drugs. [Inhaled or topical steroids are permissible].

• Patients on cytotoxic drugs and interferon-alpha.

• Known Type 1 or Type 2 diabetes mellitus.

• Contraindication to IL-2 treatment or hypersensitivity to IL-2 or to any of its excipients.

• Participation in a previous research trial in the last 3 years which involved exposure to significant ionising radiation (i.e. cumulative research radiation dose >5 mSv)

• Participation in a clinical trial where the patient has received a drug or new chemical entity within 30 days or 5 half-lives, or twice the duration of the biological effect of the drug (whichever is longer) prior to the first dose of trial medication, Visit 3 (Day 1).

• Any medical history or clinically relevant abnormality that is deemed by the principal investigator/delegate to make the patient ineligible for inclusion because of a safety concern.

• Pregnant women or breast feeding women.