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

Overview

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.

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.