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Dose Finding Study of Il-2 at Ultra-low Dose in Children With Recently Diagnosed Type 1 Diabetes

NCT ID: NCT01862120

Last Updated: 2020-11-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-06-27

Study Completion Date

2017-03-16

Brief Summary

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Human recombinant interleukin-2 (rhIL-2) is a biological signalling protein playing a key role in the regulation of the immune system. At high doses, rhIL-2 activates the immune effectors T cells (TEFFS) while at low doses rhIL-2 induces and activates regulatory T cells (TREGS), a population of immune cells controlling the immune Teff response. In patients with Type 1 Diabetes (T1D), TREGS fail to control the autoimmune destruction by TEFFS of pancreatic beta-cells producing insulin. The investigator recently showed that rhIL-2 at low dose is well tolerated in patients with an autoimmune disease and in adults with established T1D, inducing TREGS without effects on TEFFS. The investigators aim to use rhIL-2 at low dose to induce/stimulate TREGS in young recently diagnosed T1D patients. This study will investigate the dose effect relationship of low dose rhIL-2 on TREG induction such as to optimize the risk benefit ratio of this treatment in T1D. Through Treg induction, the investigators aim to protect the remaining/regenerating pancreatic β-cells from autoimmune destruction, thus improving or even curing T1D.

Detailed Description

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Main objective:

Define the lowest dose of rhIL-2 inducing TREGS in children with recently diagnosed type 1 diabetes.

Conduct of the study:

Three doses will be studied versus placebo in parallel groups of six patients. Each dose or placebo will be studied according to three periods of treatment:

1. Induction of TREGS following a cure of 5 days repeated once daily administration \[day 1 - day 5\].
2. Maintenance of TREGS following repeated administration once every two weeks for one year \[day 15 - day 337\].

At each treatment period, Treg response and tolerance will be evaluated. In addition, overall response on T1D parameters will be assessed throughout the study.

Conditions

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Type 1 Diabetes

Keywords

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Recently diagnosed Regulatory T Cells Tolerance Induction Paediatrics Low dose IL-2

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants

Study Groups

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interleukin-2

Dose D1 of interleukin-2

Group Type EXPERIMENTAL

Dose D1 of interleukin-2

Intervention Type DRUG

subcutaneous injection of Interleukin-2 during 5 days, once daily repeated administration(Induction period). At day 15 single administration of Interleukin-2 every two weeks during one year (maintenance period).

Dose D2 of interleukin-2

Dose D2 of interleukin-2

Group Type EXPERIMENTAL

Dose D2 of Interleukin-2

Intervention Type DRUG

subcutaneous injection of Interleukin-2 during 5 days, once daily repeated administration(Induction period). At day 15 single administration of Interleukin-2 every two weeks during one year (maintenance period).

Dose D3 of interleukin-2

Dose D3 of interleukin-2

Group Type EXPERIMENTAL

Dose D3 of interleukin-2

Intervention Type DRUG

subcutaneous injection of Interleukin-2 during 5 days, once daily repeated administration(Induction period). At day 15 single administration of Interleukin-2 every two weeks during one year (maintenance period).

placebo

placebo

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

subcutaneous injection of Interleukin-2 during 5 days, once daily repeated administration(Induction period). At day 15 single administration of Interleukin-2 every two weeks during one year (maintenance period).

Interventions

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Dose D1 of interleukin-2

subcutaneous injection of Interleukin-2 during 5 days, once daily repeated administration(Induction period). At day 15 single administration of Interleukin-2 every two weeks during one year (maintenance period).

Intervention Type DRUG

placebo

subcutaneous injection of Interleukin-2 during 5 days, once daily repeated administration(Induction period). At day 15 single administration of Interleukin-2 every two weeks during one year (maintenance period).

Intervention Type DRUG

Dose D2 of Interleukin-2

subcutaneous injection of Interleukin-2 during 5 days, once daily repeated administration(Induction period). At day 15 single administration of Interleukin-2 every two weeks during one year (maintenance period).

Intervention Type DRUG

Dose D3 of interleukin-2

subcutaneous injection of Interleukin-2 during 5 days, once daily repeated administration(Induction period). At day 15 single administration of Interleukin-2 every two weeks during one year (maintenance period).

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Age \[7-13\] years for girls and \[7-14\] years for boys

* With a T1D diagnosis (as ADA)
* Treated with insulin for ≤ 3 months,
* With at least one auto-antibody among: anti-insulin, anti-GAD, anti-IA2, anti-ZnT8 ;
* No clinically relevant abnormal findings for haematology, biochemistry, liver and kidney functions
* Informed consent signed by the patient, the parents, and the investigator before any intervention necessary for the trial.

Exclusion Criteria

* Contra-indications to IL-2 :

* Hyper sensibility to IL-2 or its excipients,
* Severe cardiopathy
* Previous organ allograft
* Ongoing infection requiring antibiotherapy,
* O2 Saturation ≤ 90 %
* Severe impairment of any vital organ
* Documented history of other auto-immune diseases (except for auto-antibodies for, IAA, GADA, IA-2A, anti-ZnT8A, and stable thyroiditis with normal TSH (\<10 mUI/L), T3 and, T4 levels.
* Diabetes onset characteristics including:

* Continuous nocturnal polyuria ≥ 3 months ;
* Inaugural acidosis (with venous Ph \< 7.25) ;
* HbA1c at diagnostic ≥ 13%;
* Weight loss ≥ 10 % at diagnosis ;
* Positive autoantibodies to 21-hydroxylase
* Stage 2 obesity
* Non authorized concomitant treatment : immuno-modulators, cytotoxic drugs, drug modifying plasma glycemia
* vaccination ≤ 4 weeks with life vaccin
* Positive serology (IgM) to the Epstein-Barr virus (EBV) and/or cytomegalovirus (CMV), reflecting an acute infection.
* Participation to another clinical investigation in previous 3 months
* No affiliation to National Health Insurance
Minimum Eligible Age

7 Years

Maximum Eligible Age

14 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David Klatzmann, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

APHP

Locations

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Service d'Endocrinologie Pédiatrique

Le Kremlin-Bicêtre, , France

Site Status

Service de Pédiatrie - CHU de Nîmes

Nîmes, , France

Site Status

CIC pédiatrique - CHU de Necker

Paris, , France

Site Status

Service d'endocrinologie pédiatrique - CHU de Necker

Paris, , France

Site Status

CIC 9202 CHU Rober Débré

Paris, , France

Site Status

Service d'endocrinologie Diabétologie pédiatrique CHU Robert Débré

Paris, , France

Site Status

Countries

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France

References

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Rosenzwajg M, Salet R, Lorenzon R, Tchitchek N, Roux A, Bernard C, Carel JC, Storey C, Polak M, Beltrand J, Amouyal C, Hartemann A, Corbeau P, Vicaut E, Bibal C, Bougneres P, Tran TA, Klatzmann D. Low-dose IL-2 in children with recently diagnosed type 1 diabetes: a Phase I/II randomised, double-blind, placebo-controlled, dose-finding study. Diabetologia. 2020 Sep;63(9):1808-1821. doi: 10.1007/s00125-020-05200-w. Epub 2020 Jul 1.

Reference Type DERIVED
PMID: 32607749 (View on PubMed)

Other Identifiers

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P101106

Identifier Type: -

Identifier Source: org_study_id