Low-dose IL-2 to the Kinetics of Regulatory T-cell in Healthy Volunteers

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and the dose-response relationship of ILT-101 to blood Tregs.

Detailed Description
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In the healthy physiological state, there is homeostasis between regulatory T cells (Tregs) and effector T cells (Teffs) which is deregulated in autoimmune diseases (AID). The existence of an AID indicates a lack of Tregs. Our team has discovered that low-dose interleukin-2 (ld-IL2) activates and specifically increases Tregs in humans and thus may improve AID. Exploiting this potential requires i) to better target the dose with the best benefit / risk ratio and also ii) to better understand the mechanism of action of this molecule through clinical trials of ld-IL2 in progress, including in type 1 diabetes, multiple sclerosis and systemic lupus erythematosus. During these clinical trials, a very thorough immunological follow-up is carried out in order to discover biomarkers of treatment efficacy. Exploitation of these results will benefit both the cross-analysis of the effects of IL-2 in these 3 diseases with distinct pathophysiologies, but also very importantly a comparison with the effects of ld-IL2 at the healthy volunteer. These analyzes should make it possible to define the most effective dose of IL-2.

Official Title
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A Study of the Dose-response Relationship of Low-dose IL-2 to the Kinetics of Regulatory T-cell Response in Healthy Volunteers

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: ILT101
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Without any chronic diseases diagnosed (including allergies); Effective contraception> 2 weeks before the first administration of the experimental drug or its placebo and β-hCG negative at the verification of the selection criteria; Affiliated to a social security system; Free, informed and written consent, signed by the subject and the investigator, before any action required by the research. Not taking any treatment Exclusion Criteria: Subject in a period of exclusion of participation in other biomedical research; Participation in another research ≤ 1 month and during the study except for research Transimmunom (Non-interventional research involving the human person); known antecedents of autoimmune diseases; Hypersensitivity to any of the excipients of the investigational drug (mannitol, sodium laurilsulfate, monosodium phosphate dihydrate, disodium phosphate dihydrate); Evolutionary infection requiring treatment; Viral infection and benign infection less than 2 months old; Venous capital not allowing blood samples; Pregnant or lactating women; Men and women of childbearing potential without effective contraception during the study; Live attenuated virus vaccination in the month prior to inclusion or during the study; Surgical intervention ≤ 2 months or planned during the study; Psychiatric pathology or drug addiction that may impair ability to comply with protocol requirements or give informed consent; Presence or history of cancer that has not been cured for less than 5 years, except in situ cervical cancer, or basocellular cancer; Subject under a legal protection measure.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: dose A<br>ILT-101 | Drug: ILT101<br>* Subcutaneous injections starting with induction course with once-daily administration for 5 consecutive days, followed by maintenance course with once every weeks administration during three weeks<br>* Other names: low-dose IL-2;|
| Experimental: dose B<br>ILT-101 | Drug: ILT101<br>* Subcutaneous injections starting with induction course with once-daily administration for 5 consecutive days, followed by maintenance course with once every weeks administration during three weeks<br>* Other names: low-dose IL-2;|
| Experimental: dose C<br>ILT-101 | Drug: ILT101<br>* Subcutaneous injections starting with induction course with once-daily administration for 5 consecutive days, followed by maintenance course with once every weeks administration during three weeks<br>* Other names: low-dose IL-2;|
| Experimental: dose D<br>ILT-101 | Drug: ILT101<br>* Subcutaneous injections starting with induction course with once-daily administration for 5 consecutive days, followed by maintenance course with once every weeks administration during three weeks<br>* Other names: low-dose IL-2;|
| Experimental: dose E<br>ILT-101 | Drug: ILT101<br>* Subcutaneous injections starting with induction course with once-daily administration for 5 consecutive days, followed by maintenance course with once every weeks administration during three weeks<br>* Other names: low-dose IL-2;|
| Experimental: Placebo<br> | Drug: Placebo<br>* Subcutaneous injections starting with induction course with once-daily administration for 5 consecutive days, followed by maintenance course with once every weeks administration during three weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Variation of Tregs(in (expressed in % of CD4 and total) |  | from Day 1 to Day 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC corresponding to the évolution of residual values of tregs/CD4+ |  | Day 5 to Day 60 | 
| numbers of different circulating immune populations |  | baseline to Day 60 | 
| levels of serum cytokine(pg) |  | from baseline to Day 60 | 
| levels of serum chemokine |  | from baseline to Day 60 | 
| composition of the intestinal microbiota |  | from baseline to Day 60 | 
| adverse events, anti IL-2 autoantibodies |  | from baseline to Day 60 | 
| levels of serum anti-IL-2 autoantibodies |  | from baseline to Day 60 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Low dose of IL-2, Healthy volunteers, Kinetic study