IL-2 Therapy for Acute Coronary Syndromes: Trial Results
study design and oversight
Table of Contents
IVORY was a parallel-group, double-blind, randomized, placebo-controlled, phase 2 trial (ClinicalTrials.gov registration: NCT04241601)48.this was an investigator-led trial and the funders had no role in the design, conduct or data analysis of the trial. It was conducted across two sites in the United Kingdom: Cambridge University Hospitals NHS Foundation Trust and Royal Papworth Hospital; 1,383 visits were carried out to complete the trial. The trial protocol was designed by the investigators (see Supplementary Facts for the protocol). The trial received favorable ethical opinion from the Yorkshire and Humber-Sheffield ethics committee (19/YH/0171) as well as regulatory approval by the Medicines and Healthcare products Regulatory Authority (MHRA). the trial was conducted in accordance with the principles of the Declaration of Helsinki and the International Council for Harmonisation Guideline for Good Clinical Practice. Written informed consent was obtained from all patients before carrying out any study procedures for both IVORY and IVORY-FINALE. An self-reliant data and safety monitoring committee (M. Marber, M. Dewey, R. Choudhury, G. Lombardi and E. Robinson) reviewed cumulative safety data to safeguard the well-being of the patients.
All patients, clinical investigators and research personnel carrying out study visits or undertaking immune profiling, biomarker and[[[[18F]FDG PET-CT image analysis were blinded to treatment allocation. Treatment was administered as subcutaneous injections which looked identical (colorless liquid) at equal dose volumes. The PET-CT scans were analyzed with all patient identifiers (including trial identification numbers) and scan dates removed. Therefore, the PET-CT scan analyzers were blinded to the treatment allocation, patient identification details and dates of the scan.
IVORY-FINALE (clinicaltrials.gov registration: NCT06427694) is a prospective observational study in which cardiovascular clinical outcome data are collected for patients who completed the IVORY trial (Extended Data Fig. 2). The study received favorable ethical opinion from the West Midlands-Edgbaston ethics committee (24/WM/0059) as well as research governance approval by the Health Research Authority (HRA).All prespecified clinical events for patients who completed the IVORY trial were included in this analysis, from the start of the IVORY trial (V1 onwards). The data were collected and analyzed by a team blinded to treatment allocation. A blinded,independent,clinical endpoint adjudication committee reviewe
To ensure accurate serial measures,a number of approaches were employed,such as using a standardized validated imaging protocol with mandated[[[[18F]FDG uptake times,injected dose and reconstruction parameters,a single dedicated scanner and a phantom study before the start for quantification accuracy.
Dosing commenced within 14 days of admission with ACSs. On completion of dosing, a post-treatment[[[[18F]FDG PET-CT scan was undertaken. immunophenotyping (Extended Data Fig. 6) was carried out at the start and end of the induction phase, at alternate visits during the maintenance phase and at approximately 1 week after cessation of treatment. Information with respect to the antibodies used for the FACS can be found in the Reporting Summary. The following antibodies were used according to the manufacturer’s instructions: CD196 phycoerythrin (PE) (20 μl in 100 μl of blood; BD Pharmingen, cat. no. 551773, clone 11A9), CD25 BB515 (5 μl in 100 μl of blood; BD Horizon, cat. no. 564467, clone 2A3), CD194 BB700 (5 μl in 100 μl of blood; BD Pharmingen, cat no. 566475,clone 1G1),CD197 Pe-Cy7 rat (5 μl in 100 μl of blood; BD Pharmingen,cat.no. 557648, clone 3D12), CD185 AF647 rat (5 μl in 100 μl of blood; BD Pharmingen, cat. no. 558113, clone RF8B2), CD4 AF700 (5 μl in 100 μl of blood; BD Pharmingen, cat. no. 557922,clone RPA-T4),CD45RA APC-H7 (5 μl in 100 μl of blood; BD Pharmingen,cat. no. 560674, clone HI100), CD183 BV421 (5 μl in 100 μl of blood; BD Horizon, cat.no. 562558, clone 1C6/CXCR3), CD3 BV510 (5 μl in 100 μl of blood; BD Horizon, cat. no. 563109, clone UCHT1), CD127 BV605 (5 μl in 100 μl of blood; BD Horizon, cat. no. 562662, clone HIL-7R-M21), CD8 BV711 (5 μl in 100 μl of blood; BD Horizon, cat. no. 563677, clone RPA-T8) and CD279 BV786 (5 μl in 100 μl of blood; BD horizon, cat. no. 563789, clone EH12.1).
Patients who completed the IVORY trial were afterward invited and then enrolled into the IVORY-FINALE study once written consent had been obtained. A telephone questionnaire was conducted to collect initial clinical outcome data. This was corroborated with medical notes (primary and/or secondary care) before declaration and reviewed by a clinical endpoint adjudication committee
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