A Phase 1, Open-label, Safety and Dose-finding Study of Autologous Muscle-specific Tyrosine Kinase Chimeric Autoantibody Receptor T Cells (MuSK-CAART) in Subjects With Anti-MuSK-antibody-positive Myasthenia Gravis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 7
- 试验地点
- 5
- 主要终点
- Adverse events
研究概览
简要总结
Muscle-specific tyrosine kinase (MuSK) myasthenia gravis (MG) is a rare but potentially severe disease, in which patients develop pathogenic autoantibodies that specifically target the MuSK protein in the neuromuscular junction. This phase 1 study is being conducted to evaluate the safety of various dosing regimens of an investigational cell therapy, MuSK-CAART, that can be given to patients with anti-MuSK antibody positive Myasthenia Gravis (MuSK MG), who have active disease. Various dosing regimens of MuSK-CAART alone, in combination with cyclophosphamide (CY), and in combination with CY and fludarabine (FLU) will be evaluated. Treatment with MuSK-CAART may potentially lead to complete and durable remission of disease.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of MuSK-type MG with at least 1 prior positive anti-MuSK antibody test.
- •History of a negative anti-AChR (acetylcholine receptor) antibody test.
- •Positive anti-MuSK antibody test at screening
- •MG severity Class I to IVa on the MGFA (Myasthenia Gravis Foundation of America) Clinical Classification
排除标准
- •Rituximab in the last 12 months.
- •Prednisone > 0.25mg/kg/day [in Part A]
- •Other autoimmune disorder requiring immunosuppressive therapies.
- •Investigational treatment for MG in the past 12 weeks.
- •Absolute lymphocyte count < 500/µL at screening.
研究组 & 干预措施
MuSK-CAART
Cohort A: Infusion of MuSK-CAART at various dose levels with or without pre-treatment (6 groups planned).
Cohort B: Infusion of MuSK-CAART at the dose regimen selected from Part A.
干预措施: MuSK-CAART (Biological)
结局指标
主要结局
Adverse events
时间窗: 3 months
Incidence of adverse events (AEs), including dose-limiting toxicities (DLTs) and AEs that are related to MuSK-CAART.
次要结局
- Total MuSK-CAART positive cells(Baseline)
- Percent of CAAR-transduced cells(Baseline)
- Change in MuSK autoantibody titer(Up to 36 months)
- Cellular kinetics profile of MuSK-CAART(Up to 36 months)