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

Main objective:

Define the lowest dose of rhIL-2 inducing TREGS in children with recently diagnosed type 1 diabetes.

Conduct of the study:

Three doses will be studied versus placebo in parallel groups of six patients. Each dose or placebo will be studied according to three periods of treatment:

• Induction of TREGS following a cure of 5 days repeated once daily administration [day 1 - day 5].
• Maintenance of TREGS following repeated administration once every two weeks for one year [day 15 - day 337].

At each treatment period, Treg response and tolerance will be evaluated. In addition, overall response on T1D parameters will be assessed throughout the study.

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