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

Phase 2

Completed

Interventions: Drug: Dose D3 of interleukin-2
Drug: Dose D2 of Interleukin-2
Drug: placebo
Drug: Dose D1 of interleukin-2

Brief 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.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Primary Outcome Measures

Name	Time	Method
Treg response following the induction cure period	day 5	expressed as % total CD4 cells

Secondary Outcome Measures

Name	Time	Method
Fasting plasma concentration of C-peptide	at Day 0, 99, 183, 267, 351, 436
C-peptide AUC response to a mixed meal tolerance test	at baseline, at months 6, 12, 15
IDAA1C score	at baseline, at months 3, 6, 9, 12, 15	is a score defined as A1C (percent) + \[4 x insulin dose (units per kilogram per 24 h)\] without unit
HbA1c	at baseline, at months 3, 6, 9, 12, 15
Treg response after the last administration	day 351, day 436
Treg response during the maintenance period compare to the baseline	day 15, day 29, day 43, day 99, day 183, day 267	Treg response expressed as the % / CD4 will be measured several times

Locations (6): CIC pédiatrique - CHU de Necker
🇫🇷
Paris, France
Service d'Endocrinologie Pédiatrique
🇫🇷
Le Kremlin Bicetre, France
Service de Pédiatrie - CHU de Nîmes
🇫🇷
Nimes, France
Service d'endocrinologie pédiatrique - CHU de Necker
🇫🇷
Paris, France
CIC 9202 CHU Rober Débré
🇫🇷
Paris, France
Service d'endocrinologie Diabétologie pédiatrique CHU Robert Débré
🇫🇷
Paris, France