Study conducted on humans in Europe to test the importance of a small molecule normally produced by the body, called Interleukin 2 (IL-2) to treat a specific type of diabetes (called type 1 diabetes)

• Register: EUCTR
• Last refreshed on: 2 August 2021
• Main ID: EUCTR2014-002522-12-DE
• Date of registration: 04/03/2015
• Prospective Registration: Yes
• Primary sponsor: Assistance Publique - Hôpitaux de Paris (AP-HP)
• Public title: Study conducted on humans in Europe to test the importance of a small molecule normally produced by the body, called Interleukin 2 (IL-2) to treat a specific type of diabetes (called type 1 diabetes)
• Scientific title: European phase-II clinical trial evaluating efficacy of low dose rhIL-2 in patients with recently diagnosed type 1 diabetes - DIABIL-2
• Date of first enrolment: 24/08/2015
• Target sample size: 138
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-002522-12
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Germany, Netherlands, Sweden

Contacts

• Name: Clinical Research and Development
• Affiliation: AP-HP

• Name: Clinical Research and Development
• Affiliation: AP-HP

Key inclusion & exclusion 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 < 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
Are the trial subjects under 18? yes
Number of subjects for this age range: 92
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 46
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 severe or evolutive auto-immune/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).


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

type -I diabetes
MedDRA version: 21.1 Level: PT Classification code 10067584 Term: Type 1 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Intervention(s)

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: mg/ml milligram(s)/millilitre
Concentration type: range
Concentration number: 1.50-3.00
Pharmaceutical form of the placebo: Lyophilisate for solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

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. 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.

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 Outcome(s)

Timepoint(s) of evaluation of this end point: Please refer to 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

Secondary ID(s)

2014-002522-12-BE

P121001

Source(s) of Monetary Support

FP7-Health-2012-innovation-1, European Commission

Ethics review

Status: Approved
Approval date: 24/08/2015
Contact: