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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: ILT101; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Paris, France, 75013
    • Clinical Investigation Center Paris Est Hôpital Universitaire Pitié-Salpêtrière 83 bd de l'Hôpital 75013 Paris

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo	Drug: Placebo; 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
Experimental: dose A; ILT-101	Drug: ILT101; 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; Other Names: low-dose IL-2
Experimental: dose B; ILT-101	Drug: ILT101; 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; Other Names: low-dose IL-2
Experimental: dose C; ILT-101	Drug: ILT101; 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; Other Names: low-dose IL-2
Experimental: dose D; ILT-101	Drug: ILT101; 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; Other Names: low-dose IL-2
Experimental: dose E; ILT-101	Drug: ILT101; 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; Other Names: low-dose IL-2

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Iltoo Pharma
• Investigators: Principal Investigator: David Klatzmann, MD, Investigation Center in Biotherapy et immunology Hôpital Universitaire Pitié-Salpêtrière 83 bd de l'Hôpital 75013 Paris l'hopital 75013 Paris; Study Director: Roberta Lorenzon, MD, Clinical Investigation Center Paris Est Hôpital Universitaire Pitié-Salpêtrière 83 bd de l'Hôpital 75013 Paris

Study record dates

Study Major Dates

• Study Start (Actual): June 6, 2019
• Primary Completion (Actual): March 3, 2021
• Study Completion (Actual): November 6, 2021

Study Registration Dates

• First Submitted: January 17, 2019
• First Submitted That Met QC Criteria: February 8, 2019
• First Posted (Actual): February 11, 2019

Study Record Updates

• Last Update Posted (Actual): December 30, 2021
• Last Update Submitted That Met QC Criteria: December 10, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Healthy volunteers; Low dose of IL-2; Kinetic study
• Other Study ID Numbers: APHP180274; 2018-004123-37 (EudraCT Number); MEDAECNAT-2018-11-0048 (Other Identifier: ANSM); 2-17-33 (Other Identifier: CPP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No