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

Objective

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 (6-35 year), multicentre European trial assessing efficacy and safety of uld-IL2 (0.5M IU/m2/day with a maximum of 1 MIU/m2/day for adult patients) in 138 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.

Call for proposal

FP7-HEALTH-2012-INNOVATION-1
See other projects for this call

Coordinator

ASSISTANCE PUBLIQUE HOPITAUX DE PARIS
Address
3 Avenue Victoria
75000 Paris
France
Activity type
Research Organisations
EU contribution
€ 2 925 549,60
Administrative Contact
Catherine Tostain Desmares (Ms.)

Participants (6)

INSERM TRANSFERT SA
France
EU contribution
€ 310 193
Address
Rue Watt 7
75013 Paris
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Florence Chung (Dr.)
THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE

Participation ended

United Kingdom
EU contribution
€ 3 137,96
Address
Trinity Lane The Old Schools
CB2 1TN Cambridge
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Renata Schaeffer (Ms.)
UNIVERSITATSSPITAL BASEL
Switzerland
EU contribution
€ 360 000
Address
Hebelstrasse 32
4031 Basel
Activity type
Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments)
Administrative Contact
Marc Donath (Prof.)
ILTOO PHARMA
France
EU contribution
€ 2 040 211,44
Address
47/83 Boulevard De L'hopital
75013 Paris
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Jérémie Mariau (Mr.)
DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG

Participation ended

Germany
EU contribution
€ 73 571,20
Address
Im Neuenheimer Feld 280
69120 Heidelberg
Activity type
Research Organisations
Administrative Contact
Ina Krischek (Dr.)
ACADEMISCH ZIEKENHUIS LEIDEN
Netherlands
EU contribution
€ 187 336,80
Address
Albinusdreef 2
2333 ZA Leiden
Activity type
Higher or Secondary Education Establishments
Administrative Contact
W.M. Schaap (Mr.)