POLTREG-T1D for Type 1 diabetes mellitus (stage 1)|Prediabetes

Inclusion criteria

• {"criterion_text":"- Age 3-18\n- 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\n- Venous access to guarantee blood donation\n- 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\n- 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)\n- Insulin independence\n- C-peptide levels ≥ 1.0 ng/ml in fasting and post-stimulation tests increase ≥ 100%\n- 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)\n- HbA1c level (%) <5,7% (acc. to ADA)\n- Positive autoantibody titres (ICA, IAA, GAD, IA-2/ICA512, ZnT8) - low titers of two or more antibodies (2 times the normal or higher); 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)\n- 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])"}

Exclusion criteria

• {"criterion_text":"- Refusal to participate in the trial or lack of a signed informed consent form\n- History of hypersensitivity to anti-CD20 or other components of the preparation\n- History of hypersensitivity to penicillin and/or streptomycin\n- 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.\n- Active infection with the EBV or CMV virus (positive IgM)\n- Any fungal, parasitic, viral, or bacterial infection\n- History of past or active cancer\n- Anemia, lymphopenia, neutropenia, or thrombocytopenia defined as a blood cell count below the lower limit of normal for age found within the last 6 weeks prior to trial inclusion\n- Elevated thrombotic activity/history of thrombosis episode\n- Any disease reported in the medical history prior to inclusion in the trial that has required continuous treatment for more than 3 months with medication directly affecting the immune system (e.g., immunosuppressive, immunomodulatory or immunostimulatory therapy). This does not include chronic treatment with drugs without a primary immunological mechanism of action.\n- Diagnosed autoimmune disease other than type 1 diabetes mellitus, including a history of Hashimoto's disease and coeliac disease\n- Suspicion or diagnosis for a type of diabetes other than type 1 diabetes mellitus\n- Taking anti-diabetic medication (including insulin) in the last 4 weeks prior to trial inclusion\n- History of retinopathy\n- History of hypertension\n- Current or history of albuminuria\n- For women in childbearing potential/menstruating women: pregnancy (from medical interview) or unwillingness to exercise sexual restraint or use effective forms of contraception for the duration of the trial and up to 4 months after completion, if applicable\n- Breastfeeding\n- For males over 15 years of age: expressed intention to have offspring or donate sperm during the trial or within 4 months after the end of the trial, if applicable\n- Excessive anxiety of the participant or his/her legal representatives regarding the procedures used in the trial\n- Any medical problem that, in the opinion of the investigator, may adversely affect the participant's health if included in the trial\n- Legal representatives and/or children over the age of 15 with an identified alcohol and/or psychoactive substance addiction\n- Age under 3 or above 18\n- History of disease of unknown etiology\n- History of Creutzfeldt-Jacob disease\n- History of progressive dementia or degenerative neurological disease, including of unknown origin\n- History of taking hormones derived from the human pituitary gland (e.g., growth hormone)\n- Treatment with immunosuppressants\n- History of corneal, scleral, and dural transplant or undocumented neurosurgery\n- History of occurrence of risk factors related to the participant's travel, where there is a possibility of exposure to regional infectious diseases\n- Physical signs that indicate the risk of an infectious disease\n- History of xenogeneic transplant\n- 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)\n- C-peptide levels < 1.0 ng/ml fasting and in post-stimulation tests increase < 100%\n- Glucose levels in venous blood ≥ 100mg% fasting\n- Glucose levels in venous blood after 1 and 2 hours in OGTT ≥ 200mg%\n- Glycated hemoglobin level (HbA1c) in venous blood ≥ 5,7%\n- BMI < 5th percentile or > 95th percentile for age or body weight < 20 kg"}

Primary endpoints

• {"endpoint_text":"- Percentage 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.","definition_or_measurement_approach":"Measured as the percentage of participants in each randomized group classified by diabetes stage at the end of the trial based on presence of autoantibodies and glycaemia (normoglycemia vs dysglycemia) according to trial definitions."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Count of adverse events reported at specified timepoints (1 year, 2 years after first dose of Tregs, and at end of trial) compared across treatment and control arms."}

Secondary endpoints

• {"endpoint_text":"- 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 group)","definition_or_measurement_approach":"Calculated as total days from diagnosis of stage 2 to onset of stage 3 in each group, normalized to person-days in each group."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Measurement of fasting and post-MMTT C-peptide AUC at 1 year, 2 years and annually thereafter; comparisons between treatment and control arms."}
• {"endpoint_text":"- Daily average 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 in each arm of the trial","definition_or_measurement_approach":"Average daily insulin dose per kg body weight assessed at specified intervals (1 year, 2 years, annually) for each arm."}
• {"endpoint_text":"- Number of participants per arm 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%]","definition_or_measurement_approach":"Count of participants meeting remission criteria (DDI <0.5 U/kg/day and HbA1c <6.5%) at each timepoint per arm."}
• {"endpoint_text":"- Assessment of the incidence and severity of adverse events associated with the administration of Treg preparation or anti-CD20 antibody, primarily the effects of immunosuppression: incidence of infections of any etiology and de novo tumors detected","definition_or_measurement_approach":"Recording and grading incidence and severity of adverse events, with particular focus on infections and new tumors associated with immunosuppression, compared across arms."}
• {"endpoint_text":"- Number of days from day 0 to the day of first dysglycemia (stage 2 of type 1 diabetes mellitus) in each group.","definition_or_measurement_approach":"Time-to-event measured as days from day 0 to first dysglycemia (stage 2) for participants in each group."}
• {"endpoint_text":"- Cumulative diabetes incidence [only the progression to stage 3 considered as diabetes incidence].","definition_or_measurement_approach":"Cumulative incidence of diabetes defined as progression to stage 3; proportion/time-to-progression comparisons between arms."}

Poland

Earliest CTIS Part Ii Submission Date

01-07-2024

Latest Decision Or Authorization Date

23-03-2026

Processing Time Days

630

Number Of Sites

10

Number Of Participants

150

Primary sponsor

Full Name

Poltreg S.A.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Poland

Contract research organisations

Name

Clinmark Sp. z o.o.

Responsibilities

Multiple sponsorDuties including monitoring/auditing of sites and operational trial support (sponsorDuties codes: 1,3,6,7,8,10,14,15); contact: clinmark@clinmark.org

Name

Cefea Sp. z o.o. sp.k.

Responsibilities

Logistics and IMP handling including purchase, repackaging and labeling and storage/transport for IMPs/placebos/AxMP (sponsorDuties codes: 14,15); contact: biuro@cefea.pl

Third parties

• {"country":"Poland","full_name":"Cefea Sp. z o.o. sp.k.","duties_or_roles":"sponsorDuties codes: 14, 15; value for code 15: \"Purchase, repackaging and labeling without compromising the integrity of the immediate packaging and storage and transportation of one of the IMPs, one of the placebos and the AxMP\"; contact: biuro@cefea.pl","organisation_type":"Pharmaceutical company"}
• {"country":"Poland","full_name":"Medyczne Laboratoria Diagnostyczne INVICTA","duties_or_roles":"sponsorDuties code: 4; contact: bok@invicta.pl","organisation_type":"Industry"}
• {"country":"Poland","full_name":"Clinmark Sp. z o.o.","duties_or_roles":"sponsorDuties codes: 1, 10, 14, 15 (value: auditing of the sites), 3, 6, 7, 8; contact: clinmark@clinmark.org","organisation_type":"Pharmaceutical company"}
• {"country":"Poland","full_name":"Uniwersyteckie Centrum Kliniczne","duties_or_roles":"sponsorDuties code: 4; contact: labimmunologia@uck.gda.p","organisation_type":"Hospital/Clinic/Other health care facility"}