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

NCT04241601 | Completed Phase 2 DMC

• 2 other identifiers: IVORY2017-005130-27
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Acute Coronary Syndromes

Keywords

Acute Coronary Syndromes

Outcome Measures

Primary Outcomes (1)

• Change in vascular inflammation

  Vascular inflammation (as measured by mean TBR max in the index vessel) is measured by mean TBR max in the index vessel by 18F-FDG PET/CT

  Baseline: Visit 2, day -6-0, and Follow Up: Visit 15, day 61

Secondary Outcomes (29)

• Change in mean TBR max in each arterial region

  Baseline: Visit 2, day -6-0, and Follow Up: Visit 15, day 61

• Change in lymphocyte subsets

  Throughout treatment period: Visit 3, day 1; Visit 7, day 5; Visit 8, day 12; Visit 10, day 26; Visit 12, day 40; Visit 14, day 54, Visit 15, day 61

• Change in percentage of Treg cells between low dose IL-2 and placebo

  Throughout treatment period: Visit 3, day 1; Visit 7, day 5; Visit 8, day 12; Visit 10, day 26; Visit 12, day 40; Visit 14, day 54, Visit 15, day 61.

• Extended dosing of IL-2 in ACS patients safety and tolerability: Incidence of Adverse Events

  Visit 1 (day -14-0) through to Visit 16 (day 82)

• Extended dosing of IL-2 in ACS patients safety and tolerability: Incidence of injection site reaction

  All dosing visit: Visit 3 (day 1) through to Visit 14 (day 54)

Other Outcomes (8)

• Change in serum cardiac biomarkers: hsCRP

  Throughout treatment period: Visit 3, day 1; Visit 7, day 5; Visit 8, day 12; Visit 10, day 26; Visit 12, day 40; Visit 14, day 54; Visit 15, day 61.

• Change in serum cardiac biomarkers: IL-6

  Throughout treatment period: Visit 3, day 1; Visit 7, day 5; Visit 8, day 12; Visit 10, day 26; Visit 12, day 40; Visit 14, day 54; Visit 15, day 61.

• Change in serum cardiac biomarkers: Troponin I

  Throughout treatment period: Visit 3, day 1; Visit 7, day 5; Visit 8, day 12; Visit 10, day 26; Visit 12, day 40; Visit 14, day 54; Visit 15, day 61.

Study Arms (2)

low dose interleukin-2

ACTIVE COMPARATOR

Commercially available aldesleukin with a UK marketing authorisation will be used and will be initially prepared as per SmPC. Active and Placebo doses appearing identical at point of issue and administration.

Drug: Interleukin-2 [IL-2]

Placebo

PLACEBO COMPARATOR

Commercially available dextrose 5% injection with a UK marketing authorisation at equivalent dose volume will be used for the placebo formulation. Placebo and Active doses appearing identical at point of issue and administration.

Other: Placebo Dextrose 5% solution

Interventions

Interleukin-2 [IL-2] DRUG

Active Comparator: IL-2 plays a key role in Treg cell development, expansion, survival and suppressive function

Also known as: Aldesleukin

low dose interleukin-2

Placebo Dextrose 5% solution OTHER

Placebo Comparator: Dextrose 5% solution

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• High sensitivity C-reactive protein of \>2 mg/L at any point from index admission for acute event to screening (inclusive).
• Willingness and possibility to start dosing within 14 days from initial date of admission to the primary hospital for ACS.
• Able to comply with all trial mandated visits.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Cambridge University Hospitals NHS Foundation Trust: lead

Study Sites (1)

Addenbrooke's Hospital

Cambridge, Cambridgeshire, CB20QQ, United Kingdom

Location

Related Publications (3)

• Sriranjan-Rothwell RS, Zhao TX, Hoole SP, Bond SJ, Tarkin JM, Brubert J, Hubsch A, Helmy J, Bumanlag-Amis E, Jalaludeen N, Templin H, Jiang W, Tedgui A, Zhao X, Nus M, Warnes V, Krishnan U, O'Brien JW, Wall C, Rudd JHF, Cheriyan J, Mallat Z; IVORY investigators. Anti-inflammatory therapy with low-dose IL-2 in acute coronary syndromes: a randomized phase 2 trial. Nat Med. 2026 Jan 8. doi: 10.1038/s41591-025-04090-y. Online ahead of print.

  PMID: 41507574 DERIVED

• Tsiantoulas D, Binder CJ. Identifying the sensor elements of regulatory T cells in atherosclerosis. Nat Cardiovasc Res. 2024 Feb;3(2):106-107. doi: 10.1038/s44161-023-00416-6. No abstract available.

  PMID: 39196191 DERIVED

• Sriranjan R, Zhao TX, Tarkin J, Hubsch A, Helmy J, Vamvaka E, Jalaludeen N, Bond S, Hoole SP, Knott P, Buckenham S, Warnes V, Bird N, Cheow H, Templin H, Cacciottolo P, Rudd JHF, Mallat Z, Cheriyan J. Low-dose interleukin 2 for the reduction of vascular inflammation in acute coronary syndromes (IVORY): protocol and study rationale for a randomised, double-blind, placebo-controlled, phase II clinical trial. BMJ Open. 2022 Oct 7;12(10):e062602. doi: 10.1136/bmjopen-2022-062602.

  PMID: 36207050 DERIVED

MeSH Terms

Conditions

Acute Coronary Syndrome

Interventions

Interleukin-2; aldesleukin; Solutions

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors; Pharmaceutical Preparations

Study Officials

• Joseph Cheriyan, MBChB,FRCP

  Cambridge Unversity Hospitals NHS Foundation Trust; Unversity of Cambridge

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The trial will be double-blind, with active and placebo doses appearing identical at point of issue and administration. The CUH central pharmacy will be unblinded and provided with a copy of the concealment list. Data analysis for the trial will be performed by a statistician who will be unblinded after the database lock. The statistician, or delegate, may be unblinded for individual patients after their treatment period has concluded, to facilitate rapid reporting of safety events.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant Physician & Clinical Pharmacologist/Affiliated Assoc Professor

Model Details: a randomised, double-blind, placebo controlled, parallel group experimental medicine trial

Study Record Dates

• First Submitted: December 9, 2019
• First Posted: January 27, 2020
• Study Start: August 5, 2020
• Primary Completion: January 25, 2023
• Study Completion: January 25, 2023
• Last Updated: June 10, 2024

Record last verified: 2024-06

Locations

GB (1)