Durable-Response Therapy Evaluation For Early- or New-Onset Type 1 Diabetes
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 179
- 试验地点
- 1
- 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
DEFEND-2 is a Phase 3 confirmatory study for the Phase 3 DEFEND-1 study. The study objective is to find out if an 8-day series of otelixizumab infusions leads to greater improvement in insulin secretion as compared with placebo. 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 standard of care treatments.
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. Participants will also be required to wear a continuous glucose monitor for a short period of time.
- Dosing Visits: 8 outpatient visits on consecutive days, each lasting about 2-4 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 and glucose monitors will be provided to participants for the duration of the study. Frequent glycemic monitoring will occur through lab testing and blood glucose self-monitoring to help facilitate tight glycemic control in all subjects. Subjects will be asked to intermittently record their insulin doses using a telephone or web based system and continuous glucose monitoring will be performed every 6 months.
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 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ages 12-17
- •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. In Canada, has to be using insulin at the time of dosing.
- •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 (Biological)
placebo
placebo
干预措施: Placebo (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 (Day 1) and Month 12
C-peptide is a protein that shows how much insulin the body is producing. For 3 days before the mixed meal tolerance test participants were asked to eat a balanced diet. The test was performed only when the finger-stick blood glucose level was above 70 mg per deciliter (mg/dL) and no higher than 200 mg/dL. 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 AUC was normalized for time interval by dividing it by 120-minutes (the number of minutes over which it was determined), and was adjusted by inclusion of Baseline C-peptide AUC as a covariate in the analysis. Baseline was defined at Day 1. Change from Baseline was calculated by subtracting the value at Month 12 from the Baseline value.
次要结局
- Change From Baseline in 2 Hour Mixed Meal-stimulated C-peptide AUC (Normalized for 120-minute Time Interval) at Week 12 and 6 Months(Baseline (Day 1) and Week 12, Month 6)
- Change From Baseline in Stimulated C-Peptide Mean AUC at Week 12, Month 6, 12 and 18(Baseline (Day 1) and Week 12, Month 6, 12, 18)
- Number of Participants With Responder Status(Month 3, 6 and 12)
- Change From Baseline in Mean Daily Insulin Use Over 7 Consecutive Days During the 2 Weeks Prior to the Assessment(Baseline (Day 1) and Month 3, 6, 12)
- Change From Baseline in HbA1c Levels Over 7 Consecutive Days During the 2 Weeks Prior to the Assessment(Baseline (Day 1) and Month 3, 6, 12)
- Average Number of Severe Hypoglycemic Events and Documented Symptomatic Hypoglycemic Events From Baseline to Month 12(Baseline (Day 1) and Month 12)
- Percentage of Participants With Change From Baseline in Severe Hypoglycemic Events and Documented Symptomatic Hypoglycemic Events at Month 12(Baseline (Day 1) and Month 12)
- Composite Rank Sum: HbA1c and Exogenous Insulin Use at 6 and 12 Months(Month 6 and 12)
- Composite Rank Sum: C-Peptide AUC, HbA1c and Exogenous Insulin Use at 6 and 12 Months(Month 6 and 12)