Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01862120
First received: December 10, 2012
Last updated: June 13, 2014
Last verified: June 2014

December 10, 2012
June 13, 2014
June 2013
September 2014   (final data collection date for primary outcome measure)
Treg response following the induction cure period [ Time Frame: day 22 ] [ Designated as safety issue: No ]
expressed as % total CD4 cells
Same as current
Complete list of historical versions of study NCT01862120 on ClinicalTrials.gov Archive Site
  • Fasting plasma concentration of C-peptide [ Time Frame: Baseline ] [ Designated as safety issue: Yes ]
  • Fasting plasma concentration of C-peptide [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Fasting plasma concentration of C-peptide [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Fasting plasma concentration of C-peptide [ Time Frame: day 466 ] [ Designated as safety issue: Yes ]
  • C-peptide AUC response to a mixed meal tolerance test [ Time Frame: Baseline ] [ Designated as safety issue: Yes ]
  • C-peptide AUC response to a mixed meal tolerance test [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • C-peptide AUC response to a mixed meal tolerance test [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • C-peptide AUC response to a mixed meal tolerance test [ Time Frame: day 466 ] [ Designated as safety issue: Yes ]
  • IDAA1C score [ Time Frame: Baseline ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
  • Fasting plasma concentration of C-peptide [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]
  • HbA1c [ Time Frame: Baseline ] [ Designated as safety issue: Yes ]
  • IDAA1C score [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    is a score defined as A1C (percent) + [4 x insulin dose (units per kilogram per 24 h)] without unit
  • HbA1c [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
  • HbA1c [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • HbA1c [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]
  • HbA1c [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • HbA1c [ Time Frame: day 466 ] [ Designated as safety issue: Yes ]
  • Treg response during the maintenance period [ Time Frame: month 1 from month 12 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Treg response after the last administration [ Time Frame: day 466 ] [ Designated as safety issue: No ]
Same as current
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. Acute tolerance following a single administration at day 1 [day 1- day 15].
  2. Induction of TREGS following a cure of 5 days repeated once daily administration [day 15 - day 30].
  3. Maintenance of TREGS following repeated administration once every two weeks for one year [day 30 - day 360].

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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Type 1 Diabetes
  • Drug: Dose D1 of interleukin-2
    Interleukin-2 by subcutaneous injection with: Single administration at day 1, followed at day 15 by an induction treatment of 5 days once daily repeated administration, and at day 30 by a maintenance treatment with a single administration every two weeks during one year.
    Other Name: IL2
  • Drug: placebo
    subcutaneous injection with: Single administration at day 1, followed at day 15 by an induction treatment of 5 days, and at day 30 by a maintenance treatment with a single administration every two weeks during one year.
  • Drug: Dose D2 of Interleukin-2
    Interleukin-2 by subcutaneous injection with: Single administration at day 1, followed at day 15 by an induction treatment of 5 days, and at day 30 by a maintenance treatment with a single administration every two weeks during one year.
  • Drug: Dose D3 of interleukin-2
    Interleukin-2 by subcutaneous injection with: Single administration at day 1, followed at day 15 by an induction treatment of 5 days, and at day 30 by a maintenance treatment with a single administration every two weeks during one year.
    Other Name: Il2
  • 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.
 
Recruiting
24
December 2014
September 2014   (final data collection date for primary outcome measure)

Inclusion criteria :

  • Age [7-12] years;

    • 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
Both
7 Years to 12 Years
No
Contact: David Klatzmann, MD, PhD +33(0) 1 42 17 74 61 David.klatzmann@upmc.fr
France
 
NCT01862120
P101106
Yes
Assistance Publique - Hôpitaux de Paris
Assistance Publique - Hôpitaux de Paris
Not Provided
Principal Investigator: David Klatzmann, MD, PhD APHP
Assistance Publique - Hôpitaux de Paris
June 2014

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