Durable-Response Therapy Evaluation For Early or New-Onset Type 1 Diabetes - DEFEND
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 272
- 试验地点
- 110
- 主要终点
- Change From Baseline in 2-hour Mixed Meal Stimulated C-peptide Area Under Curve [AUC] (Normalized for 120-minute Time Interval) at Month 12
研究概览
简要总结
The purpose of this study is to find out if an 8-day series of otelixizumab infusions leads to greater improvement in insulin secretion as compared with placebo infusion. Insulin secretion will be assessed using mixed meal-stimulated C-peptide.
Subjects will be assigned to receive either otelixizumab or placebo at a ratio of 2:1 (2/3 otelixizumab, 1/3 placebo). These study agents will be administered as an addition to insulin, diet, and other physician determined standard of care treatments.
DEFEND-1 is now closed to enrollment.
DEFEND-2 will begin early in 2010. It is very similar to DEFEND-1 and will again require subjects with new onset type 1 diabetes. Please check back here for more details.
In the meantime, established and new onset type 1 diabetes patients in North America are welcome to consider the TTEDD study:
http://www.clinicaltrials.gov/ct2/show/NCT00451321?term=TTEDD\&rank=1
详细描述
The following visits are required:
- Screening Visits: 2 to 3 appointments will be conducted to determine eligibility. At 2 of these visits participants will drink a liquid meal and have blood tests done over the post-meal period.
- Dosing Visits: 8 outpatient visits on consecutive days, each lasting about 4-6 hours.
- Follow-up Visits: weekly for the first month, then every 2 weeks for 3 months, followed by monthly visits through 1 year. There will be 3 visits in the second year.
- The total duration of the study is 2 years.
- Glucose test strips, glucose monitors and PDAs to record insulin will be provided to all study subjects for the duration fo the study. Frequent glycemic monitoring will occur through lab testing and blood glucose self-monitoring to help facilitate tight glycemic control in all subjects.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 12 Years 至 45 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ages 12-45
- •Diagnosis of diabetes mellitus, consistent with ADA criteria
- •No more than 90 days between diagnosis and administration of study compounds
- •Requires insulin for type 1 diabetes mellitus, or has required insulin at some time between diagnosis and administration of study compounds.
- •Stimulated C-peptide level greater than 0.20 nmol/L and less than or equal to 3.50 nmol/L
- •Positive for one or more of the autoantibodies typically associated with T1DM: antibody to glutamic acid decarboxylase (anti-GAD); antibody to protein tyrosine phosphatase-like protein (anti-IA-2); zinc transporter autoantibodies (ZNT8); insulin autoantibodies (IAA). A subject who is positive for insulin autoantibodies (IAA) and negative for the other autoantibodies will only be eligible if the subject has used insulin for less than 7 days total.
排除标准
- •Other, significant medical conditions based on the study doctor's evaluation
研究组 & 干预措施
otelixizumab
otelixizumab
干预措施: otelixizumab infusion plus physician determined standard of care (Biological)
placebo
Placebo
干预措施: placebo infusion plus physician determined standard of care (Biological)
结局指标
主要结局
Change From Baseline in 2-hour Mixed Meal Stimulated C-peptide Area Under Curve [AUC] (Normalized for 120-minute Time Interval) at Month 12
时间窗: Baseline (0-120 minutes on Day 1) and Month 12 (0-120 minutes)
Mixed meal-stimulated C-peptide AUC was the area under the C-peptide/time curve from Time 0 to 120 minutes, calculated using the trapezoidal rule. This reported AUC was normalized for time interval by dividing it by 120 minutes. This normalized AUC was calculated for each participant at Baseline, Week 12, and at Months 6, 12, 18, and 24. Data has been presented for meal stimulated C-peptide Area under assessment performed at Month 12. Baseline assessments were carried out on the morning of Day 1, before the start of the first infusion of study drug. Change from Baseline was calculated by subtracting the Baseline value from the post-randomization value at Month 12.
次要结局
- Number of Participants Who Were Responders for (Glycosylated Hemoglobin) HbA1c/Insulin Use Response at Week 12 and Months 6 and 12(Week 12 and Months 6 and 12)
- Mean Daily Insulin Use at Week 12 and Months 6 and 12.(Week 12 and Months 6 and 12.)
- HbA1c Level at Week 12 and Months 6 and 12(Week 12 and Months 6 and 12)
- Number of Hypoglycemic Events Defined by Hypoglycemic Event Categories From Baseline Upto Month 12(Upto Month 12)
- Number of Participants With Hypoglycemic Events Defined by Hypoglycemic Event Categories From Baseline Upto Month 12(Upto Month 12)
- Number of Hypoglycemic Excursions (<=70 mg/dL) With Most Complete Glucose at Week 12 and Months 6 and 12.(Week 12 and Months 6 and 12.)
- Magnitude of Greatest Hypoglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.(Week 12 and Months 6 and 12.)
- Number of Participants With Hypoglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12(Week 12 and Months 6 and 12)
- Number of Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.(Week 12 and Months 6 and 12)
- Composite Rank Summary for C-Peptide AUC, HbA1c and Exogenous Insulin Use at Month 6 and Month 12(Month 6 and 12)
- Change From Baseline in Level of Cytokines Interleukin (IL-6), IL-10 and Tumor Necrosis Factor-alpha (TNF-a) at Day 1, Day 4, Day 8(Day 1, Day 4, Day 8)
- Percent Change From Baseline in Circulating Peripheral Lymphocytes CD4+CD25+FoxP3+ T Cells and CD4+CD25hiFoxP3+ T Cells in Type 1 Diabetes Mellitus (TIDM) up to Month 12(Baseline (pre-dose on Day 1) and up to 12 Months)
- Percent Change From Baseline in Cell-bound Otelixizumab on CD4+ T Cells at Day 1, Day 4, Day 8(Baseline (pre-dose on Day 1), Day 4 and Day 8)
- Percent Change From Baseline in CD3/TCR Saturation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8(Baseline (Pre-dose Day 1), Day 4, Day 8)
- Percent Change From Baseline in CD3/TCR Modulation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8(Baseline (Pre-dose Day 1), Day 4, Day 8)
- Magnitude of Greatest Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.(Week 12 and Months 6 and 12.)
- Number of Participants With Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12(Week 12 and Months 6 and 12)
- Change From Baseline in Average Daily Risk Range (ADRR) at Week 12 and Months 6 and 12.(Baseline (Day 1) and Week 12, Months 6 and 12.)
- Composite Rank Summary for HbA1c and Exogenous Insulin Use at Month 6 and Month 12(Month 6 and 12)