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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 6
- 主要终点
- Treg response following the induction cure period
研究概览
简要总结
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.
详细描述
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:
- Induction of TREGS following a cure of 5 days repeated once daily administration [day 1 - day 5].
- Maintenance of TREGS following repeated administration once every two weeks for one year [day 15 - day 337].
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 7 Years 至 14 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
interleukin-2
Dose D1 of interleukin-2
干预措施: Dose D1 of interleukin-2 (Drug)
Dose D2 of interleukin-2
Dose D2 of interleukin-2
干预措施: Dose D2 of Interleukin-2 (Drug)
Dose D3 of interleukin-2
Dose D3 of interleukin-2
干预措施: Dose D3 of interleukin-2 (Drug)
placebo
placebo
干预措施: placebo (Drug)
结局指标
主要结局
Treg response following the induction cure period
时间窗: day 5
expressed as % total CD4 cells
次要结局
- Fasting plasma concentration of C-peptide(at Day 0, 99, 183, 267, 351, 436)
- C-peptide AUC response to a mixed meal tolerance test(at baseline, at months 6, 12, 15)
- IDAA1C score(at baseline, at months 3, 6, 9, 12, 15)
- HbA1c(at baseline, at months 3, 6, 9, 12, 15)
- Treg response after the last administration(day 351, day 436)
- Treg response during the maintenance period compare to the baseline(day 15, day 29, day 43, day 99, day 183, day 267)