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Dose Finding Study of Il-2 at Ultra-low Dose in Children With Recently Diagnosed Type 1 Diabetes (DFIL2-Child)

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01862120
First Posted: May 24, 2013
Last Update Posted: April 19, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
December 10, 2012
May 24, 2013
April 19, 2016
June 2013
December 2016   (Final data collection date for primary outcome measure)
Treg response following the induction cure period [ Time Frame: day 5 ]
expressed as % total CD4 cells
Treg response following the induction cure period [ Time Frame: day 22 ]
expressed as % total CD4 cells
Complete list of historical versions of study NCT01862120 on ClinicalTrials.gov Archive Site
  • Fasting plasma concentration of C-peptide [ Time Frame: at Day 0, 99, 183, 267, 351, 436 ]
  • C-peptide AUC response to a mixed meal tolerance test [ Time Frame: at baseline, at months 6, 12, 15 ]
  • IDAA1C score [ Time Frame: at baseline, at months 3, 6, 9, 12, 15 ]
    is a score defined as A1C (percent) + [4 x insulin dose (units per kilogram per 24 h)] without unit
  • HbA1c [ Time Frame: at baseline, at months 3, 6, 9, 12, 15 ]
  • Treg response after the last administration [ Time Frame: day 351, day 436 ]
  • Treg response during the maintenance period compare to the baseline [ Time Frame: day 15, day 29, day 43, day 99, day 183, day 267 ]
    Treg response expressed as the % / CD4 will be measured several times
  • Fasting plasma concentration of C-peptide [ Time Frame: Baseline ]
  • Fasting plasma concentration of C-peptide [ Time Frame: 6 months ]
  • Fasting plasma concentration of C-peptide [ Time Frame: 12 months ]
  • Fasting plasma concentration of C-peptide [ Time Frame: day 466 ]
  • C-peptide AUC response to a mixed meal tolerance test [ Time Frame: Baseline ]
  • C-peptide AUC response to a mixed meal tolerance test [ Time Frame: 6 months ]
  • C-peptide AUC response to a mixed meal tolerance test [ Time Frame: 12 months ]
  • C-peptide AUC response to a mixed meal tolerance test [ Time Frame: day 466 ]
  • IDAA1C score [ Time Frame: Baseline ]
    is a score defined as A1C (percent) + [4 x insulin dose (units per kilogram per 24 h)] without unit
  • Fasting plasma concentration of C-peptide [ Time Frame: 3 months ]
  • Fasting plasma concentration of C-peptide [ Time Frame: 9 months ]
  • HbA1c [ Time Frame: Baseline ]
  • IDAA1C score [ Time Frame: 3 months ]
    is a score defined as A1C (percent) + [4 x insulin dose (units per kilogram per 24 h)] without unit
  • IDAA1C score [ Time Frame: 6 months ]
    is a score defined as A1C (percent) + [4 x insulin dose (units per kilogram per 24 h)] without unit
  • IDAA1C score [ Time Frame: 9 months ]
    is a score defined as A1C (percent) + [4 x insulin dose (units per kilogram per 24 h)] without unit
  • IDAA1C score [ Time Frame: 12 months ]
    is a score defined as A1C (percent) + [4 x insulin dose (units per kilogram per 24 h)] without unit
  • IDAA1C score [ Time Frame: day 466 ]
    is a score defined as A1C (percent) + [4 x insulin dose (units per kilogram per 24 h)] without unit
  • HbA1c [ Time Frame: 3 months ]
  • HbA1c [ Time Frame: 6 months ]
  • HbA1c [ Time Frame: 9 months ]
  • HbA1c [ Time Frame: 12 months ]
  • HbA1c [ Time Frame: day 466 ]
  • Treg response during the maintenance period [ Time Frame: month 1 from month 12 ]
    Treg response expressed as the % / CD4 will be measured several times (day 29, day 57, day 113, day 115, day 127, day 197, day 281, day 351, day 365,
  • Treg response after the last administration [ Time Frame: day 379 ]
  • Treg response after the last administration [ Time Frame: day 466 ]
Not Provided
Not Provided
 
Dose Finding Study of Il-2 at Ultra-low Dose in Children With Recently Diagnosed Type 1 Diabetes
Induction of Regulatory T Cells for the Treatment of Recently Diagnosed Type 1 Diabetes: Dose Finding Study of the Lowest Active Dose of IL-2 in Children
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.

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.

Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Type 1 Diabetes
  • Drug: 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).
  • 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).
  • 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).
  • 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).
  • Experimental: interleukin-2
    Dose D1 of interleukin-2
    Intervention: Drug: Dose D1 of interleukin-2
  • Experimental: Dose D2 of interleukin-2
    Dose D2 of interleukin-2
    Intervention: Drug: Dose D2 of Interleukin-2
  • Experimental: Dose D3 of interleukin-2
    Dose D3 of interleukin-2
    Intervention: Drug: Dose D3 of interleukin-2
  • Placebo Comparator: placebo
    placebo
    Intervention: Drug: placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
24
March 2017
December 2016   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
7 Years to 14 Years   (Child)
No
Contact information is only displayed when the study is recruiting subjects
France
 
 
NCT01862120
P101106
Yes
Not Provided
Not Provided
Assistance Publique - Hôpitaux de Paris
Assistance Publique - Hôpitaux de Paris
Not Provided
Principal Investigator: David Klatzmann, MD, PhD APHP
Assistance Publique - Hôpitaux de Paris
April 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP