Treatment of Presymptomatic (Stage 1) Type 1 Diabetes Pediatric Patients With Treg Cell Preparations and Anti-CD20 Antibody

NCT06688331 | Recruiting Phase 2 DMC

• 2 other identifiers: PTG007-DM1-preTREG-0012023-505226-33-00
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 8

Brief Summary

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 6-16 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.

Conditions

Presymptomatic Diabetes Type 1 (Stage 1); Diabetes Mellitus, Type I; Diabetes Mellitus, Type 1

Keywords

PreTreg; Tregs; Prediabetes; presymptomatic

Outcome Measures

Primary Outcomes (2)

• Number of days from day 0 to the day of first dysglycemia (stage 2 of type 1 diabetes mellitus) in each group

  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)

  From day "0" (the day of administration of the first dose of Treg preparation) to the end of participation in the trial at month 60

• Number of adverse events reported 1 year, 2 years after the first dose of Tregs and 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)

  From enrollment to the end of participation in the trial at month 60 (day "0" is the day of administration of the first dose of Treg preparation)

Secondary Outcomes (7)

• Percentage of participants in each group who are in stage 2 type 1 diabetes mellitus, i.e., presence of autoantibodies, dysglycemia or stage 3 at year 1 and every year thereafter after the first dose of Tregs/placebo

  From day "0" (the day of administration of the first dose of Treg preparation) to the end of participation in the trial at month 60

• 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 group)

  From day "0" (the day of administration of the first dose of Treg preparation) to the end of participation in the trial at month 60

• 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

  From day "0" (the day of administration of the first dose of Treg preparation) to the end of participation in the trial at month 60

• Daily dose of insulin per kg body weight (DDI) 1 year, 2 years after the first dose of Tregs, and annually thereafter until the end of the trial

  From day "0" (the day of administration of the first dose of Treg preparation) to the end of participation in the trial at month 60

• Number of participants in remission 1 year, 2 years after the first dose of Tregs, and annually thereafter until the end of the trial, [remission defined as daily insulin dose is less than 0.5U/kg/day with an HbA1c level less than 6.5%]

  From day "0" (the day of administration of the first dose of Treg preparation) to the end of participation in the trial at month 60

Study Arms (4)

TregsCD20

EXPERIMENTAL

Infusion of Treg preparation at "day 0" + 4 doses of antiCD20 antibody; second infusion of Treg preparation at time "+90±30days" Interventions: ex vivo expanded CD4+CD25+CD127- regulatory T cells (Tregs) + Anti-CD20 (rituximab)

Tregs only

EXPERIMENTAL

Infusion of Treg preparation at "day 0" + 4 doses of placebo; second infusion of Treg preparation at time "+90±30 days"

Biological: ex vivo expanded CD4+CD25+CD127- regulatory T cells (Tregs); Other: Placebo

CD20 only

EXPERIMENTAL

Infusion of Treg sham at "day 0" + 4 doses of antiCD20 antibody; second infusion of Treg sham at time "+90±30days"

Biological: Anti-CD20 (rituximab); Other: Treg sham

Control group

PLACEBO COMPARATOR

Infusion of Treg sham at "day 0" + 4 doses of placebo; second infusion of Treg sham at time "+90±30days"

Other: Placebo; Other: Treg sham

Interventions

ex vivo expanded CD4+CD25+CD127- regulatory T cells (Tregs) BIOLOGICAL

regulatory T cells with the phenotype CD3(+)CD4(+)CD25(high)CD127(-)doublet(-)lin(-)

Also known as: Tregs, regulatory T cells

Tregs only

Anti-CD20 (rituximab) BIOLOGICAL

rituximab

Also known as: Mabthera

CD20 only

Placebo OTHER

intrevenous 0,9% NaCl

Control group; Tregs only

Treg sham OTHER

intrevenous 0,9% NaCl

CD20 only; Control group

Eligibility Criteria

• Age: 6 Years - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age 6-16
• ≤ BMI ≤ 75 percentile (acc. to OLAF) 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
• C-peptide levels ≥ 1.0 ng/ml (central laboratory limit of normal) in fasting and post-stimulation tests increase ≥ 100%
• Participant has not yet been diagnosed with stage 2 or 3 type 1 diabetes mellitus (no history of dysglycemia, no history of clinical symptoms of type 1 diabetes mellitus)
• HbA1c level (%) \<5,7% (acc. to ADA)
• Positive autoantibody titres (ICA, IAA, GAD, IA-2/ICA512, ZnT8) - low titers of two or more antibodies (2-4 times the normal\*); if high titer of one of the antibodies (≥ 4 times the norm, not applicable to ICA) re-screening allowed (the participant can be included in the trial only after confirming two or more antibodies)
• Ability to give informed consent by the child's legal representatives (and the child himself or herself if he or she is over the age of 13 at the time of the trial \[according to local law\])
• Ability of the child's legal representatives to manage diabetes, defined as blood glucose levels control at least three times a day and the ability to dose insulin correctly.
• Venous access to guarantee blood donation

You may not qualify if:

• 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 6 or above 16
• 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)
• C-peptide levels \< 1.0 ng/ml fasting and in post-stimulation tests increase \< 100%
• Glucose levels in venous blood ≥ 100mg% fasting
• Glucose levels in venous blood after 1 and 2 hours in OGTT ≥ 200mg%
• Glycated hemoglobin level (HbA1c) in venous blood ≥ 5,7%
• BMI \< 25 or \> 75th percentile for a given age or weight of less than 20 kg
• History of hypersensitivity to anti-CD20 or other components of the preparation
• History of hypersensitivity to penicillin and/or streptomycin
• Past or active infection with HBV, HCV, HIV, HTLV I/II, mycobacterium tuberculosis, syphilis. Laboratory evidence of infection without the need for clinical signs and symptoms is sufficient for diagnosis.
• Active infection with the EBV or CMV virus (positive IgM)
• Any fungal, parasitic, viral, or bacterial infection
• History of past or active cancer

Sponsors & Collaborators

• PolTREG S.A.: lead
• Invicta Sp. z o.o.: collaborator
• Medical Research Agency, Poland: collaborator
• Clinmark Clinical Research: collaborator

Study Sites (8)

Uniwersytecki Dzieciecy Szpital Kliniczny Im. L. Zamenhofa W Bialymstoku

Bialystok, 15-269, Poland

RECRUITING

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-211, Poland

RECRUITING

Gornoslaskie Centrum Zdrowia Dziecka Im. Sw. Jana Pawla II Samodzielny Publiczny Szpital Kliniczny Nr 6 Slaskiego Uniwersytetu Medycznego W Katowicach

Katowice, 40-752, Poland

NOT YET RECRUITING

Uniwersytet Medyczny W Lodzi

Lodz, 90-419, Poland

RECRUITING

Uniwersytecki Szpital Dzieciecy w Lublinie

Lublin, 20-093, Poland

RECRUITING

Uniwersytecki Szpital Kliniczny w Opolu

Opole, 45-401, Poland

RECRUITING

Centrum Medyczne Medyk Sp. z o.o. S.K.

Rzeszów, 35-326, Poland

RECRUITING

Uniwersytecki Szpital Kliniczny Im. Jana Mikulicza-Radeckiego We Wroclawiu

Wroclaw, 50-556, Poland

RECRUITING

Related Links

• CTIS

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Prediabetic State

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Piotr Trzonkowski, Prof

  PolTREG S.A.

  STUDY DIRECTOR

• Artur Bossowski, Prof

  Uniwersytecki Dzieciecy Szpital Kliniczny Im. L. Zamenhofa W Bialymstoku

  PRINCIPAL INVESTIGATOR

• Wojciech Mlynarski, Prof

  Uniwersytet Medyczny W Lodzi

  STUDY CHAIR

Central Study Contacts

Marta Druch, Clinical Trial Director

CONTACT

+48731471845; m.druch@poltreg.com

Grzegorz Orlik, Medical Director

CONTACT

+48790680020; g.orlik@poltreg.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Blinding: The following roles indicated below will not be made aware of the treatment group assignment during the trial: * participant * legal representatives * site staff excluding pharmacists (applies to anti-CD20 only)
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Trial type: Prospective randomized, placebo-controlled, parallel group, blinded trial. Control method: placebo, active comparator, sham procedure.

Study Record Dates

• First Submitted: November 12, 2024
• First Posted: November 14, 2024
• Study Start: March 12, 2025
• Primary Completion (Estimated): December 1, 2032
• Study Completion (Estimated): December 1, 2032
• Last Updated: January 16, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

PL (8)