Type 1 diabetes (T1D) is caused by the destruction of insulin-producing cells by effector T cells (Teffs), due to a deficiency of regulatory T cells (Tregs).
Ciclosporin effectively blocks the Teffs and controls diabetes, but cannot be considered as a long-term treatment. Low-dose interleukin-2 (ld IL-2) activates and expands Tregs in humans.
Hence, Ld IL-2 in patients in whom the autoimmune process was blocked early by a short treatment (2 months) of cyclosporine should restore immune homeostasis and maintain some insulin production over the long term.
• Age at inclusion between ≥ 16 years old (Tanner 5 pubertal stage) and ≤ 45 years old
Type 1 diabetes according to ADA criteria, with at least 1 positive autoantibody among the following: anti-islet, anti-GAD, anti-IA2, anti-ZnT8 and anti-insulin.
Diagnosis ≤ 3 months
No acid ketosis
Hypersensitivity to the active substance or to one of the excipients.
Signs of active infection requiring antibiotics
Documented history of clinical autoimmune disease
Oxygen saturation ≤ 90%
Parallel
Cyclosporin
Drug• Ciclosporin: 5mg/kg, twice a day, oral, between Day 1 and Day 60
ILT101
Drug• ILT-101: 1MIU/day in a volume of 1 ml; subcutaneous injection every day during 5 consecutive days and then every week between Day 63 and Day 354.
Placebo
Drug• Placebo with an identical formulation and regimen of injections i.e. Subcutaneous injection every day (5 consecutive days) then then every week between Day 63 and Day 354.
Treg variation
Change in Tregs values at Day 67 compared to Day 63 (post-ciclosporin value)
Change in Area under curve (AUC (T0-T120) of serum C-peptide at month 6
Change in Area under curve (AUC (T0-T120) of serum C-peptide after mixed-meal tolerance test compared to baseline 2\. Variation in HbA1c value (in %) 3. Variation in IDAA1c score (IDAA1c score = HbA1c (in %) + \[4 × insulin dose (in international units per kilogram per 24 h)\]. 4\. Change in Insulin requirement (insulin dose in international units per kilogram per 24 h 5. Change in Tregs values (in %/CD4+) at month 3, month 6, month 9, month 12 and after treatment interruption at month 18 and month 24 compared to baseline and post-cyclosporin values (Day 63)
Change in Area under curve (AUC (T0-T120) of serum C-peptide at month 12
Change in Area under curve (AUC (T0-T120) of serum C-peptide after mixed-meal tolerance test compared to baseline 2\. Variation in HbA1c value (in %) 3. Variation in IDAA1c score (IDAA1c score = HbA1c (in %) + \[4 × insulin dose (in international units per kilogram per 24 h)\]. 4\. Change in Insulin requirement (insulin dose in international units per kilogram per 24 h 5. Change in Tregs values (in %/CD4+) at month 3, month 6, month 9, month 12 and after treatment interruption at month 18 and month 24 compared to baseline and post-cyclosporin values (Day 63)
Change in Area under curve (AUC (T0-T120) of serum C-peptide at month 24
Change in Area under curve (AUC (T0-T120) of serum C-peptide after mixed-meal tolerance test compared to baseline 2\. Variation in HbA1c value (in %) 3. Variation in IDAA1c score (IDAA1c score = HbA1c (in %) + \[4 × insulin dose (in international units per kilogram per 24 h)\]. 4\. Change in Insulin requirement (insulin dose in international units per kilogram per 24 h 5. Change in Tregs values (in %/CD4+) at month 3, month 6, month 9, month 12 and after treatment interruption at month 18 and month 24 compared to baseline and post-cyclosporin values (Day 63)
Variation in HbA1c value (in %) during the treatment period and during the 1-year follow-up period compared to Baseline at day 63,
Variation in HbA1c value (in %) during the treatment period and during the 1-year follow-up period compared to baseline
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Assistance Publique - Hôpitaux de Paris
Lead sponsor
Iltoo Pharma
Collaborator
