Phase II Multiple Dose Treatment of Type 1 Diabetes Mellitus With hOKT3gamma1(Ala-Ala)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 10
- 试验地点
- 3
- 主要终点
- 4-hour C-peptide AUC
研究概览
简要总结
This is a phase II study to examine the clinical and immunological effects of humanized FcR non-binding anti-CD3 mAb in participants with Type 1 diabetes mellitus (T1DM), and to develop this therapy to prevent the immune destruction leading to β cell loss.
详细描述
This is a 2-arm, open-label phase II trial involving 0 or 3 cycles of treatment 6 months apart with hOKT3γ1 (Ala-Ala), over the first year of disease in participants with new onset T1DM. Each cycle consists of 12 daily doses of hOKT3γ1 (Ala-Ala).
Participants will be randomized in a ratio of 2:1 to either the experimental arm or the control arm and will be stratified by study site.
To be eligible, participants must be: male or female between 7-30 years of age, diagnosed with T1DM within the past 6 weeks, have a body weight ≥26 kg at the time of enrollment and have detectable anti-GAD, anti-ICA512/IA-2, or insulin autoantibodies (if the participant has been on insulin ≤10 days).
Participants randomized to the experimental group will start the first cycle of hOKT3γ1 (Ala-Ala) within 4-8 weeks of T1DM diagnosis. Each participant randomized to the experimental group will receive 3 cycles of drug treatment, separated by 6 months each. Each cycle consists of 12 days of drug treatment.
Both groups will undergo the Mixed Meal Stimulated C-Peptide Test and receive blood draws for mechanistic studies on the same schedule.
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
- None
入排标准
- 年龄范围
- 7 Years 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •diagnosed with T1DM within the past 6 weeks
- •have a body weight ≥26 kg at the time of enrollment
- •have detectable anti-GAD, anti-ICA512/IA-2, or insulin autoantibodies (if the participant has been on insulin ≤10 days).
排除标准
- •Pregnant or lactating females;
- •Prior OKT3 treatment;
- •Known hypersensitivity to murine products;
- •Uncompensated heart failure or fluid overload, recent myocardial infarction;
- •History of epilepsy, cancer, active infection, atopic disease, active Grave's disease, cystic fibrosis, sickle cell anemia, neuropathy, peripheral vascular disease, cerebrovascular disease, any concurrent autoimmune diseases, asthma;
- •Any medical condition that in the opinion of the investigator will interfere with safe completion of the trial;
- •Inability to give informed consent;
- •Prior participation in a clinical trial that could potentially affect diabetes or immunologic status;
- •Participation in a clinical trial within the last 6 weeks;
- •HIV positive;
- •Positive for Hepatitis B surface antigen or Anti-Hepatitis C antibody;
- •Seropositivity for Toxoplasmosis (IgG);
- •Lymphopenia (<1000 lymphocytes/microliter);
- •Thrombocytopenia (<150,000/mm3 platelets);
- •Anemia (Hgb < 10g/dL);
- •Vaccination with a live virus within the past 6 weeks;
- •Positive PPD skin test;
- •Any infectious mononucleosis-like illness within the 3 months prior to enrollment;
- •Serologic evidence of acute infection with EBV or CMV based on tests listed and as defined by the protocol.
研究组 & 干预措施
Treatment
干预措施: hOKT3gamma1(Ala-Ala) (Drug)
结局指标
主要结局
4-hour C-peptide AUC
时间窗: 24 months
次要结局
- Insulin usage(throughout study)