type -I diabetes MedDRA version: 20.0 Level: PT Classification code 10067584 Term: Type 1 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Product Name: ILT-101
Pharmaceutical Form: Lyophilisate for solution for injection
INN or Proposed INN: Aldesleukin
CAS Number: 8000048-25-1
Other descriptive name: INTERLEUKIN-2
Concentration unit: m
Sponsors
Assistance Publique - Hôpitaux de Paris (AP-HP)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Age 6-35 years old. -Male or female both using effective methods of contraception during treatment if sexually active. -Specifically; Females (if sexually active) with childbearing potential must use contraceptive methods that are considered as highly-effective (pearl index =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: -Children under the age of 6 years old cannot be included -Patient who, before inclusion, have been treated with other anti-diabetic medication than Insulin for more than 3 months consecutively - Chronic adrenal insufficiency known or fasting ACTH =2.5 ULN normal at inclusion after control - Anti TPO present at inclusion and abnormal TSH and T4 - Anti-transglutaminase positive at inclusion - Hypersensitivity to the active substance or to any of the excipients - Any major health problem including: any major auto-immune/autoinflammatory disease (other than type 1 diabetes) present at inclusion, any significant respiratory disease (such as moderate or severe COPD or asthma) only if requiring the chronic use of corticosteroids (whatever route of administration) and serious digestive malfunctions. -Patient with existing malignancy or history of malignancy - Major psychosocial instability with expected lack of compliance with insulin treatment, psychiatric pathology of patient or parents, or major problems of family dynamics - Signs of active infection - Any patient with obesity defined as BMI = 35 - Existence of a serious malfunction of a vital organ - History of organ allograft - Use of treatments not allowed in the Study - Vaccination with alive attenuated virus within 4 weeks of the first injection of the induction period and during the whole maintenance period - Pregnant female (confirmed by laboratory testing) or lactating - Participation in another clinical trial in the previous 3 months - Lack of affiliation to a social security scheme (as a beneficiary or assignee)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To evaluate efficacy of ILT-101 for the preservation of residual pancreatic ß cells function 2. To select the optimal regimen of administration of ILT-101;Secondary Objective: To assess: 1. Tregs expansion after an induction period and during maintenance therapy, 2. Safety of low-dose rhIL-2 during the treatment period (1 year) and 1 year after its discontinuation 3. Relation between Tregs expansion and preservation of residual pancreatic ß cells function 4. Clinical and biological responses according to (i) pubertal stage group, (i) time from diagnosis to treatment initiation, (iii) biomarkers of responses Immunomonitoring: 5. Thorough evaluation of the effects of low dose rhIL-2 on disease-specific immune responses 6. identification of immune biomarkers for predicting/monitoring safety and efficacy of low dose rhIL- 2 treatment.;Primary end point(s): AUC (T0-T120) of serum C-peptide, determined after a mixed meal tolerance test at month 12, compared to baseline;Timepoint(s) of evaluation of this end point: 12 months after baseline | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): · Serum concentrations of C-peptide after a 10 to 12-h fast, month 3, month 6, month 9, month 12, compared to baseline; and then month 15 and 24 during discontinuation period · AUC (T0-T120) of serum C-peptide after a mixed meal tolerance test after treatment discontinuation at month 15 (adults only) and at month 24 (V60) · Diabetic monitoring will include assessment of daily insulin use at each visit · HbA1c and IDAA1c score at month 3, month 6, month 9, month 12, compared to baseline; and then month 15 and 24 during discontinuation period · Number of hypoglycaemic episodes (< 0.5 g/L on capillary sample) over 15 days before each visit compared to baseline; and after treatment discontinuation · Number of clinically significant symptomatic episodes of hypoglycaemia between each visit · Change in Tregs (expressed as percentage of CD4 and absolute numbers) at day 5 compared to baseline. · Change in trough level of Tregs (%CD4+ and absolute numbers) at month 1, month 3, month 6, month 9, month 12, compared to baseline; and then month 15 and 24 after treatment discontinuation · Change in Tregs Foxp3 gene methylation at day 5, month 1, month 3, month 6, month 9, month 12 compared to baseline and then month 15 and month 24 after treatment discontinuation · Cytokines and chemokines assays at day 5, month 1, month 3, month 6, month 9, month 12 compared to baseline and then month 15 and month 24 after treatment discontinuation · Transcriptome analysis at day 5, month 1, month 3, month 6, month 9, month 12 compared to baseline and then month 15 and month 24 after treatment discontinuation · Genotyping: only at baseline · Treg phenotype and functionality in adults and adolescents only including pStat5 analysis day 5, month 1, month 3, month 6, month 9, month 12 compared to baseline and then month 15 and month 24 after treatment discontinuation. . Pharmacokinetic of IL2 will be performed (in patients from regimen A only) on day 1 at T0 | — |
Countries
Belgium, France, Germany, Netherlands, Sweden, Switzerland
Contacts
Public ContactClinical Research and Development
AP-HP
Outcome results
None listed