Dose Finding Study of Il-2 at Ultra-low Dose in Children With Recently Diagnosed Type 1 Diabetes
Condition: Type 1 Diabetes
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      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:

        1. Induction of TREGS following a cure of 5 days repeated once daily administration [day 1
           - day 5].

        2. 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.
    

Intervention name(s): Dose D1 of interleukin-2; placebo; Dose D2 of Interleukin-2; Dose D3 of interleukin-2
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): subcutaneous injection of Interleukin-2 during 5 days, once daily repeated administration(Induction period). At day 15 single administration of Interleukin-2 every two weeks during one year (maintenance period).; subcutaneous injection of Interleukin-2 during 5 days, once daily repeated administration(Induction period). At day 15 single administration of Interleukin-2 every two weeks during one year (maintenance period).; subcutaneous injection of Interleukin-2 during 5 days, once daily repeated administration(Induction period). At day 15 single administration of Interleukin-2 every two weeks during one year (maintenance period).; subcutaneous injection of Interleukin-2 during 5 days, once daily repeated administration(Induction period). At day 15 single administration of Interleukin-2 every two weeks during one year (maintenance period).
Intervention MeSH terms: Interleukin-2
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: Recently diagnosed; Regulatory T Cells; Tolerance Induction; Paediatrics; Low dose; IL-2