E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067584 |
E.1.2 | Term | Type 1 diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1. To evaluate efficacy of ILT-101 for the preservation of residual pancreatic β cells function 2. To select the optimal regimen of administration of ILT- 101 |
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E.2.2 | Secondary objectives of the trial |
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 β 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. Throrough 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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Age 6-35 years, except for Germany, Belgium and Netherlands. -Male or female both using effective methods of contraception during treatment if sexually active -With type-1 diabetes -Newly diagnosed (ADA criteria) at most two months between insulin initiation and anticipated start of experimental treatment -Positive for one or more of the autoantibodies typically associated with T1D -With a detectable peak C-peptide concentration during a standardised MMTT (≥ 0.2pmol/ml) -Patients with a stable blood glucose level and seric glycemia between 60 mg/dL and 250 mg/dL verified at MMTT visit -Absence of clinically significant abnormal laboratory values in haematology, biochemistry, thyroid, liver and kidney function; -Normal cardiac function -Efficient contraception for potentially child-bearing patients -Free, informed and written consent |
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E.4 | Principal exclusion criteria |
- Children under the age of 12 years old cannot be included In Germany, Belgium and Netherlands - In case of ketoacidosis at diabetes diagnosis : Venous pH≤7.25 or undue ketonuria at diabetes diagnosis - Chronic adrenal insufficiency known or fasting ACTH ≥2.5 ULN normal at inclusion after control - Anti TPO present at inclusion and abnormal TSH - Anti-transglutaminase positive at inclusion - Hypersensitivity to the active substance or to any of the excipients - Any major health problem including asthma requiring treatment by corticosteroids (whatever route of administration) and including serious digestive malfunctions. - 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 - Children or adolescents with obesity grade>2, adult with 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 - 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) |
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E.5 End points |
E.5.1 | Primary end point(s) |
AUC (T0-T120) of serum C-peptide, determined after a mixed meal tolerance test at month 12, compared to baseline |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | 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 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |