E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
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 | 20.0 |
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 |
|
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 |
|
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. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 < 1). The following methods are acceptable: Oral , injectable, or implanted hormonal contraceptives (with the exception of oral minipills ie low-dose gestagens which are not acceptable (lynestrenol and norestisteron), Intrauterine device, Intrauterine system (for example, progestin-releasing toit),
-beta HCG negative at inclusion;
-With type-1 diabetes:
Newly diagnosed (ADA criteria) at most three 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 glycaemia between 60 mg/dL and 250 mg/dL verified at MMTT visit
- Absence of clinically significant abnormal laboratory values (out of range and associated with clinical symptoms or signs) in haematology,
biochemistry, thyroid, liver and kidney function;
- Normal cardiac function: no documented history of heart disease and absence of family history of sudden death, normal ECG especially QTc duration within normal value (<480ms)
- Free, informed and written consent |
|
E.4 | Principal exclusion criteria |
Children under the age of 6 years old cannot be included
- Patient who, before inclusion, have been treated with other antidiabetic 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 severe or evolutive autoimmune/ auto-inflammatory 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). |
|
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 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
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 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 32 |
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
|
The end of the trail will be at the last visit (visit 59, month 24) |
|
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 | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |