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

• ClinicalTrials.gov Identifier: NCT03837093
• Recruitment Status: Completed
• First Posted: February 11, 2019
• Last Update Posted: December 30, 2021
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborator: Iltoo Pharma
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Healthy Volunteers	Drug: ILT101; Drug: Placebo	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Other
• 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
• Actual Study Start Date: June 6, 2019
• Actual Primary Completion Date: March 3, 2021
• Actual Study Completion Date: November 6, 2021

Arms and Interventions

Arm	Intervention/treatment
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 Name: 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 Name: 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 Name: 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 Name: 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 Name: low-dose IL-2
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

Outcome Measures

Primary Outcome Measures :

1. Variation of Tregs(in (expressed in % of CD4 and total) [ Time Frame: from Day 1 to Day 5 ]

Secondary Outcome Measures :

1. AUC corresponding to the évolution of residual values of tregs/CD4+ [ Time Frame: Day 5 to Day 60 ]
2. numbers of different circulating immune populations [ Time Frame: baseline to Day 60 ]
3. levels of serum cytokine(pg) [ Time Frame: from baseline to Day 60 ]
4. levels of serum chemokine [ Time Frame: from baseline to Day 60 ]
5. composition of the intestinal microbiota [ Time Frame: from baseline to Day 60 ]
6. adverse events, anti IL-2 autoantibodies [ Time Frame: from baseline to Day 60 ]
7. levels of serum anti-IL-2 autoantibodies [ Time Frame: from baseline to Day 60 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

France

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

Paris, France, 75013

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

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

More Information

• Responsible Party: Assistance Publique - Hôpitaux de Paris
• ClinicalTrials.gov Identifier: NCT03837093
• Other Study ID Numbers: APHP180274; 2018-004123-37 ( EudraCT Number ); MEDAECNAT-2018-11-0048 ( Other Identifier: ANSM ); 2-17-33 ( Other Identifier: CPP )
• First Posted: February 11, 2019
• Last Update Posted: December 30, 2021
• Last Verified: December 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Assistance Publique - Hôpitaux de Paris:

Low dose of IL-2; Healthy volunteers; Kinetic study