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Acute Coronary SyndromesPhase 2IVORYNCT04241601

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

A Phase 2 study testing Interleukin-2 [IL-2] in people with Acute Coronary Syndromes, run by Cambridge University Hospitals NHS Foundation Trust at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 85 years
Conditions the study is for
Acute Coronary Syndromes
What is being tested?
Interleukin-2 [IL-2]
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
60 participants
Where
1 siteUnited Kingdom
Study dates
5 Aug 2020to 25 Jan 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
  • 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 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.

Who cannot join

  • 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.
Show all 23Show fewer
  • 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.
  • Diabetics on oral hypglycaemics/diet control with HbA1c (DCCT) >8% (OR HbA1c (IFCC) >64mmol/mol) at screening. Diabetics on insulin are excluded from the study.
  • 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.
  • Patients who are COVID-19 PCR positive at the time of screening.
  • Known severe allergy to the CT-contrast agents.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

  • Addenbrooke's Hospital

    Cambridge, Cambridgeshire, CB20QQ

Other trials in United Kingdom

About this study

Official title: Low-dose Interleukin-2 for the Reduction of Vascular Inflammation in Acute Coronary Syndromes

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.

Read the detailed description

A heart attack occurs when there is reduced blood flow to heart muscle cells which results from narrowings or blockages in walls of blood vessels supplying the heart, due to fatty deposits and inflammatory cells that build up over time. This build-up leads to heart muscle damage called a heart attack. The immune system plays an important role in both the development of the narrowings and the damage to the heart muscle during a heart attack. Studies have shown that there is a lower level of protective immune cells called regulatory T-cells (Tregs) in heart attack patients. Increasing the number of circulating Tregs may have a direct effect in reducing the inflammation in arteries, preventing further narrowings in blood vessels and improving heart muscle function.

Aldesleukin, also known as interleukin-2 (IL-2), is a medicine that stimulates the production of Treg cells when given at low doses and is the drug being tested in this trial. IL-2 is licensed for the treatment of kidney cancer where it is given at much higher doses than planned in this trial. It appears to be safe and well tolerated at low doses while increasing Treg cells.

IVORY will be conducted in patients presenting with a heart attack (Acute Coronary Syndrome (ACS)). Approximately, 60 patients will be randomized to receive either low dose IL-2 or placebo. It is a Phase 2, randomised, double- blinded, placebo-controlled experimental trial. Total study duration for each participant will be approximately 13 weeks.

Participants will undergo two PET/CT (Positron emission tomography-computed tomography) scans to observe change of inflammation in the blood vessels from baseline between the two trial groups (Primary Endpoint).

Being tested
Interleukin-2 [IL-2], Placebo Dextrose 5% solution
Keywords
Acute Coronary Syndromes
Medical subject headings
Acute Coronary Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Interleukin-2 [IL-2]Drug

    Also called Aldesleukin

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

  • Placebo Dextrose 5% solutionOther

    Placebo Comparator: Dextrose 5% solution

Study groups in NCT04241601
Study groupRoleWhat they receive
low dose interleukin-2Active comparatorCommercially 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.
Receives: Drug: Interleukin-2 [IL-2]
PlaceboPlacebo comparatorCommercially 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.
Receives: Other: Placebo Dextrose 5% solution

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

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

Secondary outcomes (29)

  1. Change in mean TBR max in each arterial region

    Change in mean max TBR in each arterial region individually restricted to those slices with TBR>1.6

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

  2. Change in lymphocyte subsets

    Lymphocyte subsets:T effector [Teffs] cells defined as central memory and effector memory T cells in the non-Treg gated T cells. Evaluated by flow cytometry

    Measured: 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

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

    Treg cells are defined as CD3+CD4+CD25highCD127low cells within the CD3+CD4+ T cell gate. Evaluated by flow cytometry

    Measured: 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.

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

    Number of incidences of adverse events is assessed via adverse change in routine test results and patient consultation. Events will be catalogued using MedDRA coding.

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

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

    Location of injection site will be recorded as will incidences of induration, redness and swelling at the injection site

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

  6. Extended dosing of IL-2 in ACS patients safety and tolerability: Full Blood Count: total white cell count

    Haematology tests - full blood count: Total white cell count (WBC), in 10^9/L

    Measured: Baseline, Visit 3 (day 1) thorugh Visit 14 (day 54) and Visit 16 (day 82 when clinically indicated and patient attends hospital)

  7. Extended dosing of IL-2 in ACS patients safety and tolerability: Full Blood Count: Red cell count

    Haematology tests - full blood count: Red cell count (RBC), in 10^12/L

    Measured: Baseline, Visit 3 (day 1) thorugh Visit 14 (day 54) and Visit 16 (day 82 when clinically indicated and patient attends hospital)

  8. Extended dosing of IL-2 in ACS patients safety and tolerability: Full Blood Count: Haemoglobin

    Haematology tests - full blood count: Haemoglobin (Hb), in g/L

    Measured: Baseline, Visit 3 (day 1) thorugh Visit 14 (day 54) and Visit 16 (day 82 when clinically indicated and patient attends hospital)

  9. Extended dosing of IL-2 in ACS patients safety and tolerability: Full Blood Count: Platelets

    Haematology tests - full blood count: Platelet Count, in 10^9/L

    Measured: Baseline, Visit 3 (day 1) thorugh Visit 14 (day 54) and Visit 16 (day 82 when clinically indicated and patient attends hospital)

  10. Extended dosing of IL-2 in ACS patients safety and tolerability: Differential blood count - Neutrophils

    Haematology tests - differential blood count: Neutrophils, in 10^9/L

    Measured: Baseline, Visit 3 (day 1) thorugh Visit 14 (day 54) and Visit 16 (day 82 when clinically indicated and patient attends hospital)

  11. Extended dosing of IL-2 in ACS patients safety and tolerability: Differential blood count - Lymphocytes

    Haematology tests - differential blood count: Lymphocytes, in 10^9/L

    Measured: Baseline, Visit 3 (day 1) thorugh Visit 14 (day 54) and Visit 16 (day 82 when clinically indicated and patient attends hospital)

  12. Extended dosing of IL-2 in ACS patients safety and tolerability: Differential blood count - Monocytes

    Haematology tests - differential blood count: Monocytes, in 10^9/L

    Measured: Baseline, Visit 3 (day 1) thorugh Visit 14 (day 54) and Visit 16 (day 82 when clinically indicated and patient attends hospital)

  13. Extended dosing of IL-2 in ACS patients safety and tolerability: Differential blood count - Eosinophils

    Haematology tests - differential blood count: Eosinophils, in 10^9/L

    Measured: Baseline, Visit 3 (day 1) thorugh Visit 14 (day 54) and Visit 16 (day 82 when clinically indicated and patient attends hospital)

  14. Extended dosing of IL-2 in ACS patients safety and tolerability: Differential blood count - Basophils

    Haematology tests - differential blood count: Basophils, in 10^9/L

    Measured: Baseline, Visit 3 (day 1) thorugh Visit 14 (day 54) and Visit 16 (day 82 when clinically indicated and patient attends hospital)

  15. Extended dosing of IL-2 in ACS patients safety and tolerability: Clinical biochemistry - Urea

    Clinical biochemistry test: level of urea, in mmol/L

    Measured: Baseline, Visit 3 (day 1) through Visit 14 (day 54) and Visit 16 (day 82 when clinically indicated and patient attends hospital)

  16. Extended dosing of IL-2 in ACS patients safety and tolerability: Clinical biochemistry - Creatinine

    Clinical biochemistry test: level of creatinine, in µmol/L

    Measured: Baseline, Visit 3 (day 1) through Visit 14 (day 54) and Visit 16 (day 82 when clinically indicated and patient attends hospital)

  17. Extended dosing of IL-2 in ACS patients safety and tolerability: Clinical biochemistry test for liver function - ALT

    Clinical biochemistry blood test for liver function: Alanine Aminotransferase (ALT), in µ/L

    Measured: Baseline, Visit 3 (day 1) through Visit 14 (day 54) and Visit 16 (day 82 when clinically indicated and patient attends hospital)

  18. Extended dosing of IL-2 in ACS patients safety and tolerability: Clinical biochemistry test for liver function - ALP

    Clinical biochemistry blood test for liver function: Alkaline Phosphatase (ALP), in µ/L

    Measured: Baseline, Visit 3 (day 1) through Visit 14 (day 54) and Visit 16 (day 82 when clinically indicated and patient attends hospital)

  19. Extended dosing of IL-2 in ACS patients safety and tolerability: Clinical biochemistry test for liver function - Albumin

    Clinical biochemistry blood test for liver function: Albumin, in g/L

    Measured: Baseline, Visit 3 (day 1) through Visit 14 (day 54) and Visit 16 (day 82 when clinically indicated and patient attends hospital)

  20. Extended dosing of IL-2 in ACS patients safety and tolerability: Clinical biochemistry test for liver function - Bilirubin

    Clinical biochemistry blood test for liver function: Bilirubin, in µmol/L

    Measured: Baseline, Visit 3 (day 1) through Visit 14 (day 54) and Visit 16 (day 82 when clinically indicated and patient attends hospital)

  21. Extended dosing of IL-2 in ACS patients safety and tolerability: Thyroid function

    A thyroid function blood test of level of TSH (thyroid-stimulating hormone) in the blood will be performed. T4 (Thyroxine) will be performed if TSH is abnormal.

    Measured: Visit 1 (day -14-0)

  22. Extended dosing of IL-2 in ACS patients safety and tolerability: Electrical activity of the heart recorded using a 12-lead electrocardiogram

    12-lead ECG recording - QTcB (Corrected QT using Bazett's formula) intervals, in ms

    Measured: Baseline, Visit 3 (day 1) through Visit 14 (day 54), and Visit 16 (day 82 when clinically indicated and patient attends hospital)

  23. Extended dosing of IL-2 in ACS patients safety and tolerability: Blood pressure assessment

    Blood pressure will be assessed using systolic and diastolic pressure measured in mmHg.

    Measured: Baseline, Visit 3 (day 1) through Visit 14 (day 54), and Visit 16 (day 82 when clinically indicated and patient attends hospital)

  24. Extended dosing of IL-2 in ACS patients safety and tolerability: Heart rate assessment

    Heart rate assessed using bpm

    Measured: Baseline, Visit 3 (day 1) through Visit 14 (day 54), and Visit 16 (day 82 when clinically indicated and patient attends hospital)

  25. Extended dosing of IL-2 in ACS patients safety and tolerability: Respiratory rate assessment

    Measured using breaths per minute

    Measured: Baseline, Visit 3 (day 1) through Visit 14 (day 54), and Visit 16 (day 82 when clinically indicated and patient attends hospital)

  26. Extended dosing of IL-2 in ACS patients safety and tolerability: Oxygen saturation assessment

    Assessment of oxygen saturation and measured in percentage

    Measured: Baseline, Visit 3 (day 1) through Visit 14 (day 54), and Visit 16 (day 82 when clinically indicated and patient attends hospital)

  27. Extended dosing of IL-2 in ACS patients safety and tolerability: Physical examination evaluation - Gastrointestinal

    Incidences of a abdominal distention, palpations and/or patient self-report of physical discomfort or pain

    Measured: Baseline, Visit 3 (day 1) through Visit 14 (day 54), and Visit 16 (day 82 when clinically indicated and patient attends hospital)

  28. Extended dosing of IL-2 in ACS patients safety and tolerability: Physical examination evaluation - Skin

    Incidences of ISR lesions, nodules and/or bruising

    Measured: Baseline, Visit 3 (day 1) through Visit 14 (day 54), and Visit 16 (day 82 when clinically indicated and patient attends hospital)

  29. Extended dosing of IL-2 in ACS patients safety and tolerability: Incidence of cardiovascular events

    Occurrence of another important cardiovascular event(s) such a myocardial infarction. These will be captured through AEs and SAEs

    Measured: Visit 2 (day -6-0) and Visit 15 (day 61)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2020
  2. Study start5 Aug 2020
  3. Primary completion25 Jan 2023
  4. Study completion25 Jan 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
a randomised, double-blind, placebo controlled, parallel group experimental medicine trial
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04241601
Sponsor's protocol ID
IVORY
Other IDs
2017-005130-27, 2017
Acronym
IVORY
Status last verified
Jun 2024
First submitted
9 Dec 2019
Last updated
10 Jun 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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 Feb;32(2):624-632. doi: 10.1038/s41591-025-04090-y. Epub 2026 Jan 8.

    PubMed 41507574

  • 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.

    PubMed 39196191

  • 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.

    PubMed 36207050

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Interleukin-2 [IL-2] in people with Acute Coronary Syndromes, run by Cambridge University Hospitals NHS Foundation Trust at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in vascular inflammation (time frame: Baseline: Visit 2, day -6-0, and Follow Up: Visit 15, day 61). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04241601, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jun 2024.

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