2023-505226-33-00招募中2 期
A multicenter, randomized, blinded, placebo controlled, phase II study to evaluate the safety and efficacy of cell therapy based with artificially expanded CD4+CD25+CD127- regulatory lymphocytes and anti-CD20 antibody in pediatric patients with presymptomatic diabetes type 1 (stage 1)
Poltreg S.A.9 个研究点 分布在 1 个国家目标入组 150 人开始时间: 2024年7月22日最近更新:
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 150
- 试验地点
- 9
- 主要终点
- Cumulative diabetes incidence [only the progression to stage 3 considered as diabetes incidence]. (The analysis will cover the 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)
研究概览
简要总结
To assess the safety and efficacy of the treatment used in the separate groups of pediatric participants with DM1 stage 1 treated with two-dose combination regimen of Tregs and rituximab over placebo, rituximab alone, and Tregs alone.
入排标准
- 年龄范围
- 0 years 至 17 years（0-17 Years）
- 接受健康志愿者
- 是
入选标准
- •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
- •25 ≤ 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 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])
排除标准
- •Refusal to participate in the trial or lack of a signed informed consent form
- •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
- •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
- •Elevated thrombotic activity/history of thrombosis episode
- •Any disease prior to inclusion in the trial currently requiring medication for more than 3 months in history
- •Diagnosed autoimmune disease other than type 1 diabetes mellitus, including a history of Hashimoto's disease and coeliac disease
- •Suspicion or diagnosis for a type of diabetes other than type 1 diabetes mellitus
- •Taking anti-diabetic medication (including insulin) in the last 4 weeks prior to trial inclusion
- •History of retinopathy
- •History of hypertension
- •Current or history of albuminuria
- •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
- •Breastfeeding
- •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
- •Excessive anxiety of the participant or his/her legal representatives regarding the procedures used in the trial
- •Any medical problem that, in the opinion of the investigator, may adversely affect the participant's health if included in the trial
- •Legal representatives and/or children over the age of 15 with an identified alcohol and/or psychoactive substance addiction
- •Age under 3 or above 18
- •History of disease of unknown etiology
- •History of Creutzfeldt-Jacob disease
- •History of progressive dementia or degenerative neurological disease, including of unknown origin
- •History of taking hormones derived from the human pituitary gland (e.g., growth hormone)
- •Treatment with immunosuppressants
- •History of corneal, scleral, and dural transplant or undocumented neurosurgery
- •History of occurrence of risk factors related to the participant's travel, where there is a possibility of exposure to regional infectious diseases
- •Physical signs that indicate the risk of an infectious disease
- •History of xenogeneic transplant
- •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 > 75 percentiles for defined age or weight of less than 20 kg
结局指标
主要结局
Cumulative diabetes incidence [only the progression to stage 3 considered as diabetes incidence]. (The analysis will cover the 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)
Cumulative diabetes incidence [only the progression to stage 3 considered as diabetes incidence]. (The analysis will cover the 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)
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
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
次要结局
- 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)
- 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
- 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 study
- 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%]
- 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
- Percentage of participants in each group who are still in stage 1 type 1 diabetes mellitus, i.e., presence of autoantibodies and normoglycemia
研究者
Information desk
Scientific
Poltreg S.A.
研究点 (9)
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