Acute Coronary Syndrome (ACS) such as myocardial infarction and unstable angina MedDRA version: 20.0 Level: PT Classification code 10051592 Term: Acute coronary syndrome System Organ Class: 10007541 - Cardiac disorders
Conditions
Interventions
Trade Name: Proleukin
Product Name: Aldesleukin
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Aldesleukin
Concentration unit: IU international unit(s)
Concentration type:
Sponsors
Cambridge University Hospitals NHS Foundation Trust and University of Cambridge
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: To be included in the trial the participant must meet the following criteria: - Able to provide written informed consent to participate. - Age between 18 and 85 - Current admission (on the screening visit) with an ACS with symptoms suggestive of mycardial 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, 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 sterilisation OR iii. Peri-menopausal with a negative pregnancy test at screening (for the purposes of this trial, perimenopausal is defined as women with an appropriate clinical profile, e.g. age appropriate, history of vasomotor symptoms, irregular periods). These women will be expected 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 Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: - Current presentation (at screening) with cardiogenic shock (systolic blood pressure 48 hours - Uncontrolled hypotension (Systolic BP (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] 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 regular oral or intravenous immunosuppressive treatment including 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 breastfeeding women.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to compare the effect of low dose IL-2 against placebo on vascular inflammation using 18F-FDG PET/CT in ACS. ;Secondary Objective: 1. To determine if low dose IL-2 can increase Regulatory T cell (Treg) numbers sustainably over extended treatment 2. To determine the effect of low dose IL-2 on systemic inflammation measured by cardiovascular biomarkers (including but not limited to hsCRP, Troponin, BNP). 3. To determine the safety and tolerability of extended dosing of low dose IL-2 in patients with acute coronary syndrome ;Primary end point(s): Change in vascular inflammation (as measured by mean TBR max in the index vessel) on F-FDG PET/CT from baseline to follow-up scans. In detail, a region of interest (ROI) including arterial wall and lumen will be drawn on each axial slice of artery (ascending aorta and both carotid arteries) on the co-registered PET/CT scan and the maximum standardised uptake value (SUVmax) recorded. Subsequently, each ROI will be normalised by the blood FDG concentration in the superior vena cava or jugular vein (for carotids), to yield an arterial mean maximum tissue-to-blood ratio (TBR max) as a quantitative measure of arterial tracer uptake.The “index vessel” (defined as the arterial territory with the highest mean max TBR at baseline – left carotid, right carotid or ascending aorta) will be the primary outcome variable. All scans will be analysed by a central reader, anonymised to patient identifiable information (name, treatment group, and visit number). ;Timepoint(s) of evaluation of this end point: This will be assessed at Visit 15. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Change in mean max TBR in each arterial region Lymphocyte subsets (T effector (Teffs) cells), natural killer cells and B lymphocytes Change in percentage of Treg cell numbers Change in serum cardiac biomarkers Safety and tolerability of extended dosing of IL-2 in ACS patients;Timepoint(s) of evaluation of this end point: Change in TBR max between Visit 2 and Visit 15. Lymphocytes subsets and percentage change of Treg cell numbers: Change between Visit 3 and Visit 7, then Visit 8, Visit 10, Visit 12, Visit 14, Visit 15, Visit 16. Change in serum cardiac biomarkers: change beween Visit 3 and Visit 7, Visit 8, Visit 10, Visit 12, Visit 14, Visit 15, Visit 16. | — |
Countries
United Kingdom
Contacts
Public ContactCarrie Bayliss
Cambridge Clinical Trials Unit
Outcome results
None listed