A Phase 3, Randomized, Double-Blind, Multinational, Placebo-Controlled Study to Evaluate Efficacy and Safety of Teplizumab (MGA031), a Humanized, FcR Non-Binding, Anti-CD3 Monoclonal Antibody, in Children and Adults With Recent-Onset Type 1 Diabetes Mellitus
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- MacroGenics
- 入组人数
- 254
- 试验地点
- 118
- 主要终点
- Proportion of Subjects With Both a Total Daily Insulin Dose of Less Than 0.5 U/kg/Day and Hemoglobin A1c (HbA1c) Level of Less Than 6.5%.
研究概览
简要总结
The primary purpose of this study is to determine whether teplizumab (MGA031) infusions lead to greater reductions in insulin requirements in conjunction with near normal blood sugar control compared to placebo in patients recently diagnosed with type 1 diabetes.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 8 Years 至 35 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects 8-35 years old
- •Body weight > 36 Kg
- •Diagnosis of diabetes mellitus according to the American Diabetes Association (ADA) criteria
- •Randomization on Study Day 0 within 12 weeks of first visit to any physician for symptoms or signs of diabetes
- •Requires insulin for T1DM or has required insulin at some time between diagnosis and administration of study drug
- •Detectable fasting or stimulated C-peptide level (above the lower limit of the reportable range of the assay) at screening
- •Diagnosis of T1DM as evidenced by one positive result on testing for any of the following antibodies at screening:
- •Islet-cell autoantibodies 512 (ICA512)/islet antigen-2 (IA-2),
- •Glutamic acid decarboxylase (GAD) autoantibodies, or
- •Insulin autoantibodies (in subjects on insulin for more than 2 weeks, ICA512/IA-2 or GAD must be positive).
排除标准
- •Prior administration of a monoclonal antibody-within the 1 year before randomization
- •Participation in any type of therapeutic drug or vaccine clinical trial within the last 12 weeks before randomization at Study Day 0
- •Any medical condition that, in the opinion of the investigator, would interfere with safe completion of the trial
- •Pregnant females or lactating females who intend to provide their own breast milk to the baby during the study
- •Current therapy with GLP-1 receptor agonists (e.g., exenatide or pramlintide), or any other agents that might stimulate pancreatic beta cell regeneration or insulin secretion
- •Current treatment with oral antidiabetic agents
- •Evidence of active or latent tuberculosis
- •Vaccination with a live virus or organism within the 8 weeks before randomization continuing through Week 52 of the study.
- •Influenza vaccination with a killed virus, including booster vaccinations, within 4 weeks before or after each dosing cycle.
- •Vaccination with other antigens or killed organisms within 8 weeks before or after each dosing cycle
- •Any infectious mononucleosis-like illness within the 6 months before randomization
研究组 & 干预措施
Herold Regimen
14-day cycle of teplizumab consisting of daily IV doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, and 413 µg/m2 on Study Days 1-4, respectively, and one dose of 826 µg/m2 on each of Study Days 5-14. Repeat at Week 26
干预措施: Teplizumab Herold Regimen (Biological)
33.3% Herold Regimen
Subjects received a 14-day cycle of teplizumab consisting of daily IV doses of 17 µg/m2, 34 µg/m2, 68 µg/m2, and 136 µg/m2 on Study Days 1-4, respectively, and one dose of 273 µg/m2 on each of Study Days 5-14. Repeat at Week 26
干预措施: Teplizumab 33.3% Herold Regimen (Biological)
Curtailed Herold Regimen
Subjects received a 6 day cycle of teplizumab consisting of daily IV doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, and 413 µg/m2 on Study Days 1-4, respectively, and one dose of 826 µg/m2 on each of Study Days 5-6, followed by 8 days of IV placebo (Study Days 7-14). Repeat at Week 26
干预措施: Teplizumab Curtailed Herold Regimen (Biological)
Placebo
14-day cycle of placebo consisting of daily IV doses. Repeat at Week 26
干预措施: Placebo (Drug)
结局指标
主要结局
Proportion of Subjects With Both a Total Daily Insulin Dose of Less Than 0.5 U/kg/Day and Hemoglobin A1c (HbA1c) Level of Less Than 6.5%.
时间窗: 52 weeks after randomization
Mean Change From Baseline in HbA1c Between Teplizumab and Placebo
时间窗: 52 weeks after randomization
次要结局
- The Mean HbA1c Change From Baseline(104 weeks after randomization)
- The Change in Beta-cell Function as Measured by C-peptide Secretory Response Following a Mixed Meal(104 weeks after randomization)
- The Proportion of Subjects Who Have Both a Total Daily Insulin Dose < 0.5 U/Kg/Day and Hemoglobin A1c (HbA1c) Level < 7.0%(52 weeks after randomization)
- Mean Number of Total, Major, Minor and Nocturnal Hypoglycemia Events(Throughout the study up to 2 years)
- Number of Participants With Adverse Events(throughout the study, up to 104 weeks)
- Number of Participants With Serious Adverse Events(throughout the study, up to 104 weeks)
- Mean Number of Daily Insulin Injections(52 weeks after randomization)
- Number of Subjects With Both a Total Daily Insulin Dose of Less Than 0.5 U/kg/Day and Hemoglobin A1c (HbA1c) Level of Less Than 6.5%.(104 weeks after randomization)