NCT01862120

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
24

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Jun 2013

Typical duration for phase_2

Geographic Reach
1 country

6 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 10, 2012

Completed
6 months until next milestone

First Posted

Study publicly available on registry

May 24, 2013

Completed
1 month until next milestone

Study Start

First participant enrolled

June 27, 2013

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 8, 2016

Completed
8 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 16, 2017

Completed
Last Updated

November 12, 2020

Status Verified

November 1, 2020

Enrollment Period

3 years

First QC Date

December 10, 2012

Last Update Submit

November 10, 2020

Conditions

Type 1 Diabetes

Keywords

Recently diagnosedRegulatory T CellsTolerance InductionPaediatricsLow doseIL-2

Outcome Measures

Primary Outcomes (1)

  • Treg response following the induction cure period

    expressed as % total CD4 cells

    day 5

Secondary Outcomes (6)

  • Fasting plasma concentration of C-peptide

    at Day 0, 99, 183, 267, 351, 436

  • C-peptide AUC response to a mixed meal tolerance test

    at baseline, at months 6, 12, 15

  • IDAA1C score

    at baseline, at months 3, 6, 9, 12, 15

  • HbA1c

    at baseline, at months 3, 6, 9, 12, 15

  • Treg response after the last administration

    day 351, day 436

  • +1 more secondary outcomes

Study Arms (4)

interleukin-2

EXPERIMENTAL

Dose D1 of interleukin-2

Drug: Dose D1 of interleukin-2

Dose D2 of interleukin-2

EXPERIMENTAL

Dose D2 of interleukin-2

Drug: Dose D2 of Interleukin-2

Dose D3 of interleukin-2

EXPERIMENTAL

Dose D3 of interleukin-2

Drug: Dose D3 of interleukin-2

placebo

PLACEBO COMPARATOR

placebo

Drug: placebo

Interventions

Dose D1 of interleukin-2DRUG

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).

interleukin-2
placeboDRUG

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
Dose D2 of Interleukin-2DRUG

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 D3 of interleukin-2DRUG

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

Eligibility Criteria

Age7 Years - 14 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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.

You may not qualify if:

  • 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
  • +5 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

Service d'Endocrinologie Pédiatrique

Le Kremlin-Bicêtre, 94275, France

Location

Service de Pédiatrie - CHU de Nîmes

Nîmes, 30029 cedex 9, France

Location

CIC pédiatrique - CHU de Necker

Paris, 75015, France

Location

Service d'endocrinologie pédiatrique - CHU de Necker

Paris, 75015, France

Location

CIC 9202 CHU Rober Débré

Paris, 75019, France

Location

Service d'endocrinologie Diabétologie pédiatrique CHU Robert Débré

Paris, 75019, France

Location

Related Publications (1)

  • 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.

    PMID: 32607749DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesAutoimmune DiseasesImmune System Diseases

Study Officials

  • David Klatzmann, MD, PhD

    APHP

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 10, 2012

First Posted

May 24, 2013

Study Start

June 27, 2013

Primary Completion

July 8, 2016

Study Completion

March 16, 2017

Last Updated

November 12, 2020

Record last verified: 2020-11

Locations

FR(6)