European Phase-IIb Clinical Trial Evaluating Efficacy of Low Dose rhIL-2 in Patients With Recently-diagnosed Type 1 Diabetes DIABIL-2
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 141
- 试验地点
- 34
- 主要终点
- AUC (T0-T120) of serum C-peptide, determined after a mixed meal tolerance test at month 12, compared to baseline.
研究概览
简要总结
Type 1diabetes (T1D) is caused by autoimmune destruction of the pancreatic islet ß-cells, leading to an absolute deficiency in insulin.
In health, regulatory T cells (Tregs) suppress immune responses against normal tissues, and likewise prevent autoimmune diseases. Tregs are insufficient in T1D.
The investigators previously showed that administration of low doses of IL-2 induces selective expansion and activation of Tregs in mice and humans.
The investigators hypothesize that Tregs expansion and activation with low doses of IL2 could block the ongoing autoimmune destruction of insulin producing cells in patients with recently diagnosed T1D.
详细描述
Scientific justification:
Clinical and preclinical studies, together with supportive mechanistic data showing that Tregs are activated by much lower IL-2 concentration than effector T cells (Teffs), provide a strong rationale for studying efficacy of low dose IL2 to stop the autoimmune destruction of insulin-secreting beta cells in patient with recently diagnosed with T1D.
Primary objective:
- To evaluate efficacy of low dose IL-2 for the preservation of residual pancreatic β cells function
- To select the optimal regimen of administration of IL-2
Primary assessment criterion:
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 6 Years 至 35 Years（Child, Adult）
- 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
rhIL-2
- 0.5 MIU/m²/day of IL2 with a maximum of 1MIU/day in a volume of 1 ml for children and adolescents,
- 1MIU/day for adults.
Subcutaneous injection every day (5 days) then:
- Regimen A injection every two weeks between D15 and D351,
- Regimen B injections every week between D15 and D351
干预措施: rhIL-2 (Drug)
Placebo
Placebo with a identical formulation and regimen of injections i.e. Subcutaneous injection every day (5 days) then:
- Regimen A injection every two weeks between D15 and D351
- Regimen B injections every week between D15 and D351
干预措施: Placebo (Drug)
结局指标
主要结局
AUC (T0-T120) of serum C-peptide, determined after a mixed meal tolerance test at month 12, compared to baseline.
时间窗: Baseline, month12
次要结局
- AUC (T0-T120) of serum C-peptide after a mixed meal tolerance test after treatment discontinuation(month 15)
- Number of clinically significant symptomatic episodes of hypoglycaemia between each visit.(baseline, Day 1, Day 5, month 1, month 3, month 6, month 9, month 12, month 15, month 18, month 21)
- HbA1c and IDAA1c score(baseline, month 3, month 6, month 9, month 12, month 15)
- Change in trough level of Tregs (%CD4+ and absolute numbers) at month 1, month 3, month 6, month 9, month 12, compared to baseline; and then month 15 and 24 after treatment discontinuation.(Baseline, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15, Month 24)
- Cytokines and chemokines assays at day 5, month 1, month 3, month 6, month 9, and month 12 compared to baseline and then month 15 and month 24 after treatment discontinuation.(Baseline, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15, Month 24)
- Transcriptome analysis.(Baseline, Month 6, Month 12)
- Genotyping at baseline(baseline)
- Serum concentrations of C-peptide(month 3, month 6, month 9, month 15)
- Diabetic monitoring (insulin use)(baseline, Day 1, Day 5, month 1, month 3, month 6, month 9, month 12, month 15, month 18, month 21.)
- Number of hypoglycaemic episodes (< 0.5 g/L on capillary sample) over 15 days before each visit.(baseline, Day 1, Day 5, month 1, month 3, month 6, month 9, month 12, month 15, month 18, month 21)
- Change in Tregs (expressed as percentage of CD4 and absolute numbers) at day 5 compared to baseline.(Baseline, Day 5.)
- Change in Foxp3 gene methylation(Day 1, Day 5, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15)
- Treg phenotype and functionality in adults and adolescents only including pStat5 analysis(Day 1, Day 5, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15)
- Clinical examination.(Baseline Day 1, Day 5, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 24)
- Height/weight and pubertal stage especially for children and adolescents.(Baseline, Month 12, Month 24)
- Routine laboratory tests(Baseline Day 1, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 24)
- Haematology(Baseline Day 1, Day 5, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 24)
- Detection of IL-2 auto-antibodies(Day1, Month 6, Month 12)
- T cells repertory(Day 1, Day 5, Month 6, Month 12)
- Intestinal microbiota.(Baseline, Month 6, Month 12)
- Adverse event.(Baseline, Day 1, 2, 3, 4, 5, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 24)