The main purpose of the study is to check:
* Can therapy with a preparation of regulatory cells (Tregs lymphocytes) and/or an anti-CD20 antibody preparation (rituximab) be successfully used in children with pre-diabetes to treat or delay type 1 diabetes? * Is therapy with a preparation of regulatory cells (Tregs lymphocytes) and/or a preparation of antiCD20 antibodies (rituximab) safe for children with pre-diabetes, and what side effects may be associated with it? The study will include patients at high risk for type 1 diabetes whose laboratory tests have confirmed preserved normal/high insulin production. First (part 1 of the study), tests will be performed to determine the risk of the disease (determination of autoantibodies that characterize the autoimmune background).
In order to confirm the effectiveness of the therapy, not all patients will receive the study treatment. The study will be a so-called blinded randomized trial. This means that in this trial, all participants will undergo the same study procedures, but the participant will be randomly assigned to one of four (4) groups that will receive different treatment regimens before entering the study.
The participant will be randomly assigned to one of four groups:
* Group I will receive a preparation of regulatory cells (Tregs lymphocytes) along with a preparation of antiCD20 antibodies, * Group II will receive a preparation of regulatory cells (Tregs lymphocytes) together with an inert substance (placebo) * Group III will receive a preparation of antiCD20 antibodies along with a sham treatment (inert substance) * Group IV will receive an agent containing an inert substance and sham treatment.
Approximately 150 patients aged 3-18 who are at risk of developing type 1 diabetes will be enrolled in the study, which will last up to 96 months. Each enrolled participant will remain in the study for up to five years.
Age 3-18
5 ≤ BMI ≤ 95 percentile (acc. to OLAF, or WWF in the case of children under six years old) with a lower weight threshold of 20 kg
Venous plasma glucose levels < 100mg% at fasting (70 to 100 mg/dl) and normal glucose tolerance test (at 120 minutes glycaemia <140 mg/dl) (acc. to PTD)
Insulin independence
Refusal to participate in the trial or lack of a signed informed consent form
Suspicion or diagnosis for a type of diabetes other than type 1 diabetes mellitus
Age under 3 or above 18
IgA deficiency or history of other diagnosed immunodeficiency (max. 7 infections/year allowed, and the prognosis should indicate that the patient will remain in the study throughout its duration)
Parallel
ex vivo expanded CD4+CD25+CD127- regulatory T cells (Tregs)
Biological/Vaccineregulatory T cells with the phenotype CD3(+)CD4(+)CD25(high)CD127(-)doublet(-)lin(-)
Anti-CD20 (rituximab)
Biological/Vaccinerituximab
Placebo
Other interventionintrevenous 0,9% NaCl
Treg sham
Other interventionintrevenous 0,9% NaCl
% of participants in each group who are still in stage 1 type 1 diabetes mellitus, i.e., presence of autoantibodies and normoglycemia or in stage 2 type 1 diabetes mellitus, i.e., presence of autoantibodies, dysglycemia or stage 3 at the end of the trial
To assess the safety and efficacy of the treatment used in the separate groups of participants treated with combined treatment with Treg preparation and rituximab antibody or Treg preparation or rituximab antibody or the control (placebo/Tregs sham)
Number of adverse events reported 1 year, 2 years after the first dose of Tregs and at the end of the trial comparing to control arms
To assess the safety and efficacy of the treatment used in the separate groups of participants treated with combined treatment with Treg preparation and rituximab antibody or Treg preparation or rituximab antibody or the control (placebo/Tregs sham)
Pace of diabetes development. Total number of days from the date of diagnosis of stage 2 to the date of onset of full-blown type 1 diabetes mellitus (stage 3 of type 1 diabetes mellitus) in each group (normalized to the number of person/days in each grou
Additional measures to assess the safety and efficacy of the treatment used in the separate groups of pediatric participants treated with combined treatment with Treg preparation and rituximab antibody or Treg preparation or rituximab antibody or the control (placebo/ Tregs sham) in preserving β-cell function
Number of days from day 0 to the day of first dysglycemia (stage 2 of type 1 diabetes mellitus) in each group
Additional measures to assess the safety and efficacy of the treatment used in the separate groups of pediatric participants treated with combined treatment with Treg preparation and rituximab antibody or Treg preparation or rituximab antibody or the control (placebo/ Tregs sham) in preserving β-cell function
Cumulative diabetes incidence [only the progression to stage 3 considered as diabetes incidence]
Additional measures to assess the safety and efficacy of the treatment used in the separate groups of pediatric participants treated with combined treatment with Treg preparation and rituximab antibody or Treg preparation or rituximab antibody or the control (placebo/ Tregs sham) in preserving β-cell function
C-peptide levels [fasting/post MMTT stimulation (AUC)] 1 year, 2 years after the first dose of Tregs and then annually until the end of the trial comparing to control arms
Additional measures to assess the safety and efficacy of the treatment used in the separate groups of pediatric participants treated with combined treatment with Treg preparation and rituximab antibody or Treg preparation or rituximab antibody or the control (placebo/ Tregs sham) in preserving β-cell function
Click on the lead sponsor to view all of their trials.
PolTREG S.A.
Lead sponsor
Invicta Sp. z o.o.
Collaborator
Medical Research Agency, Poland
Collaborator
Clinmark Clinical Research
Collaborator
