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DIABIL-2

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Ultra-low dose of IL-2 for the treatment of recently diagnosed type 1 diabetes

Coordinator: David KLATZMANN
Project Number: 305380
EC contribution: € 5,900,000.00
Project website: http://www.diabil-2.eu/


Concept

The discovery of regulatory T cells (Tregs) has revolutionized our understanding of autoimmune diseases. As T1D is caused by the failure of Tregs to block autoimmune destruction of pancreatic ß-cells, Treg stimulation has the potential to stop the process, preserve ß-cells’ insulin secretion, and likewise prevent or delay disease progression and improve clinical outcome for patients.

Background

Low-dose interleukin-2 (ld-IL2) was recently shown to stimulate Tregs without stimulating effector T cells. In NOD mice, ld-IL2 can prevent and cure T1D. In humans, (i) we showed that ld-IL2 is safe, induces Tregs and is associated with clinical improvement in patients with autoimmune vasculitis; and (ii) we performed a dose-finding study in T1D to define an ultra-low dose IL-2 (uld-IL2) that is well tolerated and induces Tregs’ numbers and functionality. With this strong background – a well defined mechanism of action; proof of concept in NOD mice; proof of principle in a clinical trial with another autoimmune disease; safety and activity/efficacy data in T1D – we propose a phase-II clinical trial testing the efficacy of uld-IL2 for preserving ß-cells.

Method

This will be a double-blind randomised placebo-controlled age-stratified (7-35 year) multicentre European trial assessing efficacy and safety of uld-IL2 (5x10e5 IU/m2/day) in 200 recently-diagnosed T1D patients. Our methodology strictly follows the Immunology of Diabetes Society consensus recommendations and European regulatory guidelines. The primary end-point is the change from baseline of AUC C-peptide during a mixed meal test at 1 year. The trial is precisely and conservatively powered to detect an effect size of d=0.5.

Impacts

If successful, this trial will have profound impacts for the management of patients with recently-diagnosed T1D, their families and EU economy. It will be a milestone towards preventing T1D in people at risk of this increasingly common childhood disease.

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