Clinical trial NCT03837093: Low-dose IL-2 to the Kinetics of Regulatory T-cell in Healthy Volunteers
Official title: A Study of the Dose-response Relationship of Low-dose IL-2 to the Kinetics of Regulatory T-cell Response in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Low dose of IL-2
Healthy volunteers
Kinetic study
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Iltoo Pharma
First posted: 2019-02-11
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Variation of Tregs(in (expressed in % of CD4 and total)
timeFrame: from Day 1 to Day 5
Secondary outcomes:
measure: AUC corresponding to the évolution of residual values of tregs/CD4+
timeFrame: Day 5 to Day 60
measure: numbers of different circulating immune populations
timeFrame: baseline to Day 60
measure: levels of serum cytokine(pg)
timeFrame: from baseline to Day 60
measure: levels of serum chemokine
timeFrame: from baseline to Day 60
measure: composition of the intestinal microbiota
timeFrame: from baseline to Day 60
measure: adverse events, anti IL-2 autoantibodies
timeFrame: from baseline to Day 60
measure: levels of serum anti-IL-2 autoantibodies
timeFrame: from baseline to Day 60
Other outcomes:
Locations:
city: Paris
country: France
facility: Clinical Investigation Center Paris Est Hôpital Universitaire Pitié-Salpêtrière 83 bd de l'Hôpital 75013 Paris
Study officials:
affiliation: Investigation Center in Biotherapy et immunology Hôpital Universitaire Pitié-Salpêtrière 83 bd de l'Hôpital 75013 Paris l'hopital 75013 Paris
name: David Klatzmann, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinical Investigation Center Paris Est Hôpital Universitaire Pitié-Salpêtrière 83 bd de l'Hôpital 75013 Paris
name: Roberta Lorenzon, MD
role: STUDY_DIRECTOR
References: