Phase 3 Randomized Double-Blind Multinational Placebo-Controlled Study to Evaluate Efficacy and Safety of Teplizumab, a Humanized Fc Receptor (FcR) Non-Binding Anti-cluster of Differentiation 3 (CD3) Monoclonal Antibody, in Children and Adolescents With Newly Diagnosed Type 1 Diabetes
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 328
- 试验地点
- 121
- 主要终点
- Change in C-peptide ln(AUC+1) Standardized by Duration of the Mixed Meal Tolerance Test (MMTT)
研究概览
简要总结
The purpose of this study is to determine whether teplizumab slows the loss of β cells and preserves β cell function in children and adolescent 8-17 years old who have been diagnosed with T1D in the previous 6 weeks..
Subjects will receive two courses of either teplizumab or placebo treatment 6 months apart.
详细描述
This is a Phase 3, randomized, double-blind, placebo-controlled, multinational, multi-center study to evaluate the efficacy and safety of teplizumab, a humanized, anti-CD3 monoclonal antibody, in children and adolescents ages 8 through 17 recently diagnosed with type 1 diabetes (within 6 weeks of diagnosis). Approximately 300 participants will be randomized at a ratio of 2:1 to either the teplizumab group or the placebo group.
Teplizumab or matching placebo will be administered in two courses 6 months apart. Each course of treatment will include daily infusions for 12 days. The total study duration for each participant will be up to 86 weeks.
The primary objective is to determine whether two courses of teplizumab administered 6 months apart slows the loss of β cells and preserves β cell function over 18 months (78 weeks) in children and adolescents 8-17 years old who have been diagnosed with T1D in the previous 6 weeks.
The secondary objectives are to evaluate improvements in key clinical parameters of diabetes management, to determine the safety and tolerability of teplizumab, and to evaluate the pharmacokinetics (PK) and immunogenicity of teplizumab
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
- 8 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Is 8 to 17 years of age, inclusive, at the time of randomization/initiation of study drug administration.
- •Has received a diagnosis of type 1 diabetes (T1D) according to the criteria from the American Diabetes Association.
- •Is able to be randomized and initiate study drug within 6 weeks (42 days) of the formal T1D diagnosis.
- •Has a peak stimulated C-peptide of ≥0.2 pmol/mL from a mixed meal tolerance test (MMTT) at screening.
- •Has a positive result on testing for T1D-related autoantibodies.
排除标准
- •Has any autoimmune disease other than T1D with the exception of stable thyroid or celiac disease.
- •Has an active infection and/or fever.
- •Has a history of or serologic evidence at screening of current or past infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV).
- •An individual who has a medical, psychological or social condition that, in the opinion of the Principal Investigator, would interfere with safe and proper completion of the trial.
结局指标
主要结局
Change in C-peptide ln(AUC+1) Standardized by Duration of the Mixed Meal Tolerance Test (MMTT)
时间窗: Baseline to Week 78
The area under the concentration-time curve (AUC) of C-peptide was measured after a 4-hour mixed meal tolerance test (MMTT) and is a measure of endogenous insulin production and β cell function. The AUC was computed using the trapezoidal rule and standardized by the duration of the MMTT test, i.e., AUC was divided by the last blood sample collection time (240 minutes or the last collection time for 4h MMTT).
次要结局
- Number of Participants With Adverse Events of Special Interest (AESIs)(During the entire study (from the first dose to the last study contact, up to 78 Weeks))
- Anti-teplizumab Antibody (ADA) Titers After Treatment Courses(Baseline through 78 Week)
- Change in Glycated Hemoglobin (HbA1c) Levels (%)(Baseline to Week 78)
- Time in Range for Glycemia Control(Week 78)
- Teplizumab Serum Concentrations(Pre-dose samples collected on Days 1, 4, 9, 12 and 28 for each of the two treatment courses, and one post-dose sample collected on Day 9 during the first treatment course.)
- Average Daily Exogenous Insulin Use(Week 78)
- Rate of Clinically Important Hypoglycemic Events(During the entire study (from the first dose to the last study contact, up to 78 Weeks))
- Incidence of Anti-drug Antibodies (ADA) After Treatment Courses(From baseline through Week 78)