Dose Finding Study of Il-2 at Ultra-low Dose in Children With Recently Diagnosed Type 1 Diabetes

• Status: Completed
• Trial end date: 2017-03-16
• Target enrollment: 0
• Participant gender: All

Summary

Human recombinant interleukin-2 (rhIL-2) is a biological signalling protein playing a key role in the regulation of the immune system. At high doses, rhIL-2 activates the immune effectors T cells (TEFFS) while at low doses rhIL-2 induces and activates regulatory T cells (TREGS), a population of immune cells controlling the immune Teff response. In patients with Type 1 Diabetes (T1D), TREGS fail to control the autoimmune destruction by TEFFS of pancreatic beta-cells producing insulin. The investigator recently showed that rhIL-2 at low dose is well tolerated in patients with an autoimmune disease and in adults with established T1D, inducing TREGS without effects on TEFFS. The investigators aim to use rhIL-2 at low dose to induce/stimulate TREGS in young recently diagnosed T1D patients. This study will investigate the dose effect relationship of low dose rhIL-2 on TREG induction such as to optimize the risk benefit ratio of this treatment in T1D. Through Treg induction, the investigators aim to protect the remaining/regenerating pancreatic β-cells from autoimmune destruction, thus improving or even curing T1D.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Treatments: Interleukin-2

Criteria

Inclusion criteria :

• Age [7-13] years for girls and [7-14] years for boys

• With a T1D diagnosis (as ADA)

• Treated with insulin for ≤ 3 months,

• With at least one auto-antibody among: anti-insulin, anti-GAD, anti-IA2, anti-ZnT8 ;

• No clinically relevant abnormal findings for haematology, biochemistry, liver and kidney functions

• Informed consent signed by the patient, the parents, and the investigator before any intervention necessary for the trial.

Exclusion criteria :

• Contra-indications to IL-2 :

• Hyper sensibility to IL-2 or its excipients,

• Severe cardiopathy

• Previous organ allograft

• Ongoing infection requiring antibiotherapy,

• O2 Saturation ≤ 90 %

• Severe impairment of any vital organ

• Documented history of other auto-immune diseases (except for auto-antibodies for, IAA, GADA, IA-2A, anti-ZnT8A, and stable thyroiditis with normal TSH (<10 mUI/L), T3 and, T4 levels.

• Diabetes onset characteristics including:

• Continuous nocturnal polyuria ≥ 3 months ;

• Inaugural acidosis (with venous Ph < 7.25) ;

• HbA1c at diagnostic ≥ 13%;

• Weight loss ≥ 10 % at diagnosis ;

• Positive autoantibodies to 21-hydroxylase

• Stage 2 obesity

• Non authorized concomitant treatment : immuno-modulators, cytotoxic drugs, drug modifying plasma glycemia

• vaccination ≤ 4 weeks with life vaccin

• Positive serology (IgM) to the Epstein-Barr virus (EBV) and/or cytomegalovirus (CMV), reflecting an acute infection.

• Participation to another clinical investigation in previous 3 months

• No affiliation to National Health Insurance