A Phase 2/3, Randomized, Double-Blind, Multicenter, Multinational, 4-Arm, Controlled, Dose-Ranging Study to Evaluate Efficacy and Safety of 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
- 2 期
- 状态
- 已完成
- 发起方
- MacroGenics
- 入组人数
- 554
- 试验地点
- 115
- 主要终点
- Number of Subjects in Segment 2 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 protocol is to assess the efficacy, tolerability, and safety of MGA031 when administered according to 3 different MGA031 dosing regimens in children and adults with recent-onset (diagnosis within past 12 weeks) type 1 diabetes mellitus. All regimens will be administered as an addition to insulin and other standard of care treatments. Efficacy will be defined primarily by the capacity of MGA031 to markedly reduce typical insulin requirements while maintaining relatively normal blood sugar levels.
Other studies involving the study drug use the name hOKT3γ1 (Ala-Ala). MGA031, a humanized monoclonal antibody, is the name used for hOKT3γ1 (Ala-Ala) that is produced by MacroGenics, Inc. The United States Adopted Name (USAN) for MGA031 is teplizumab.
详细描述
The Protégé Study - A Multinational Clinical Trial of MGA031 for Preserving the Capability to Produce Insulin, Reducing Insulin Usage and Improving Blood Sugar Levels in Children and Adults With Recent-Onset Type 1 Diabetes Mellitus
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 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 must meet all of the following criteria:
- •Enrollment (Segment #1) or randomization (Segment #2) on Study Day 0 within 12 weeks of first visit to any physician for symptoms or signs of diabetes. Study Day 0 is the first day of study drug dosing.
- •Diagnosis of type 1 diabetes mellitus, according to the American Diabetes Association (ADA) criteria
- •Requirement for injected insulin therapy
- •Have a detectable fasting or stimulated C-peptide level (above the lower limit of detection of the assay)
- •One positive result on testing for any of the following antibodies:
- •islet-cell autoantibodies (ICA512/IA-2),
- •glutamic acid decarboxylase autoantibodies, or
- •insulin autoantibodies (if present during first 2 weeks, but not beyond 2 weeks, of insulin treatment)
- •Male or female
- •Subject must be in one of the following age groups:
- •Age 18-35 years
- •Age 12-17 years pending approval by Data Monitoring Committee
- •Age 8-11 years pending approval by Data Monitoring Committee
- •Body weight ≥ 36 kg
排除标准
- •Subjects must have none of the following:
- •Prior administration of a monoclonal antibody -- within the 1 year before enrollment or randomization at Study Day 0 -- that could potentially prevent or confound a therapeutic response to MGA031
- •Participation in any type of therapeutic drug or vaccine clinical trial within the 12 weeks before enrollment or randomization
- •Any medical condition that, in the opinion of the investigator, would interfere with safe completion of the trial
- •Pregnant or lactating females
- •Prior murine OKT®3 treatment at any time before enrollment or randomization
- •Current or planned therapy with exenatide or any other agents that stimulate pancreatic beta cell regeneration or insulin secretion
- •Current or planned therapy with inhaled insulin
- •Uncompensated heart failure, fluid overload, myocardial infarction or evidence of ischemic heart disease, or other serious cardiac disease within the 12 weeks before enrollment or randomization
- •History of epilepsy, cancer, cystic fibrosis, sickle cell anemia, neuropathy, peripheral vascular disease or cerebrovascular disease
- •Newly diagnosed hypothyroidism (not currently being treated but which, in the opinion of the investigator, should be treated) or active Graves' disease
- •Eczema, asthma or severe atopic disease requiring treatment within the 12 weeks before enrollment or randomization
- •Evidence of active infection, such as fever ≥ 38.0 degrees Celsius (100.5 degrees Fahrenheit)
- •Known or suspected infection with human immunodeficiency virus (HIV)
- •Evidence of active hepatitis B (HBV) or hepatitis C virus (HCV)
- •Evidence of active or latent tuberculosis
- •Vaccination with a live virus within the 8 weeks before enrollment or randomization or planned live virus vaccination continuing through week 52 of the study. Vaccination with an antigen or killed organism must not be given within 8 weeks before or planned within 8 weeks after each dosing cycle.
- •Any infectious mononucleosis-like illness within the 6 months before enrollment or randomization
- •Serologic and clinical evidence of acute infection with Epstein-Barr virus (EBV)
- •Serologic evidence of acute infection with cytomegalovirus (CMV)
研究组 & 干预措施
Double-blind Curtailed Herold Regimen
Full dose of teplizumab IV for 6 days followed by placebo for 8 days, repeated at Week 26
干预措施: Teplizumab (Biological)
Double-blind Herold Regimen
Full dose of teplizumab IV for 14 days, repeated at Week 26
干预措施: Teplizumab (Biological)
Double-blind 33.3% Herold Regimen
One third full dose of teplizumab IV for 14 days, repeated at Week 26
干预措施: Teplizumab (Biological)
Double-blind Placebo
Placebo IV dosing daily for 14 days repeated at Week 26
干预措施: Placebo (Drug)
Open-label Herold Regimen
Full dose of teplizumab IV for 14 days, repeated at Week 26
干预措施: Teplizumab (Biological)
结局指标
主要结局
Number of Subjects in Segment 2 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
This is a composite endpoint is based on the proportion of subjects who have both a total daily insulin dose \<0.5 U/Kg/day and an HbAlc level 6.5% at 52 weeks after randomization.
Number of Subjects in Segment 1 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 first dose
This is a composite endpoint based on the proportion of subjects who have both a total daily insulin dose \<0.5 U/Kg/day and an HbAlc level 6.5%
Mean HbA1c Change From Baseline in Segment 2
时间窗: 52 weeks after randomization
Comparison among study treatments of average change from baseline HbA1C. This endpoint will be assessed in a hierarchical manner only if the composite primary endpoint shows a statistically significant difference between arms
Mean HbA1c Change From Baseline in Segment 1
时间窗: 52 weeks after first dose
The average change in HbA1c levels after dosing.
次要结局
- Change From Baseline in C-peptide Area Under the Curve (AUC) in Segment 2(104 weeks after randomization)
- Change From Baseline in C-peptide AUC in Segment 1(104 weeks after first dose)
- Number of Subjects in Segment 2 With Both a Total Daily Insulin Dose of Less Than 0.5 U/kg/Day and HbA1c Level of Less Than 6.5%(104 weeks after randomization)
- Number of Subjects in Segment 1 With Both a Total Daily Insulin Dose of Less Than 0.5 U/kg/Day and HbA1c Level of Less Than 6.5%(104 weeks after first dose)
- Number of Subjects in Segment 2 With Both a Total Daily Insulin Dose of Less Than 0.5 U/kg/Day and HbA1c Level of Less Than 7.0%.(at 52 weeks after randomization)
- Number of Subjects in Segment 1 With Both a Total Daily Insulin Dose of Less Than 0.5 U/kg/Day and HbA1c Level of Less Than 7.0%.(52 weeks after first dose)
- Mean HbA1c Change From Baseline in Segment 2(at 104 weeks after randomization)
- Mean HbA1c Change From Baseline in Segment 1(104 weeks after first dose)