RESET-MG: A Phase 1/2, Open-Label Study to Evaluate the Safety and Efficacy of Autologous CD19-specific Chimeric Antigen Receptor T Cells (CABA-201) in Participants With Generalized Myasthenia Gravis
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 24
- 试验地点
- 30
- 主要终点
- To evaluate incidence and severity of adverse events (AEs)
研究概览
简要总结
RESET-MG: A Phase 1/2 Open-Label Study to Evaluate the Safety and Efficacy of CABA-201 in Participants with Generalized Myasthenia Gravis
详细描述
Myasthenia gravis (MG) is a rare autoimmune disorder characterized by autoantibody responses that cause defective transmission of signals at the neuromuscular junction, resulting in a distinctive pattern of weakness. Patients with generalized MG (gMG) typically experience symptoms associated with ocular disease in addition to weakness of many other voluntary muscle groups, including extremity, bulbar, and respiratory muscles. MG is considered a classic example of a B-cell mediated autoimmune disease. Currently, there are no curative treatments for MG. This study is being conducted to evaluate the safety and efficacy of an investigational cell therapy, CABA-201, that can be given to patients with gMG. A single dose of CABA-201 in combination with cyclophosphamide (CY) and fludarabine (FLU) will be evaluated. In addition, escalating doses of CABA-201 will be evaluated in patients without CY and FLU preconditioning.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 and ≤70 years of age
- •Diagnosis of MG with generalized muscle weakness meeting criteria as defined by the MGFA class II, III , IVa, and IVb.
- •Diagnosis of seropositive (autoantibodies AChR, MuSK and/or LRP4) or seronegative MG
排除标准
- •Contraindication to leukapheresis
- •History of anaphylactic or severe systemic reaction to fludarabine, cyclophosphamide or any of their metabolites
- •Active infection requiring medical intervention at screening
- •Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, pulmonary, psychiatric, cardiac, neurological, or cerebral disease, including severe and uncontrolled infections, such as sepsis and opportunistic infections.
- •Concomitant medical conditions that, in the opinion of the investigator, might place the subject at unacceptable risk for participation in this study, interfere with the assessment of the effects or safety of the investigational product or with the study procedures
- •Significant lung or cardiac impairment
- •Prior solid organ (heart, liver, kidney, lung) transplant or hematopoietic cell transplant
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
CABA-201
AChR Antibody-Positive Cohort or AChR Antibody-Negative Cohort
干预措施: CABA-201 (Biological)
CABA-201, No Preconditioning
Infusion of CABA-201 with no preconditioning in subjects with gMG
干预措施: CABA-201 (Biological)
结局指标
主要结局
To evaluate incidence and severity of adverse events (AEs)
时间窗: Up to 28 days after CABA-201 infusion
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal result of an investigation), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. The term AE is used to include both serious and non-serious AEs.
次要结局
- To evaluate efficacy by change in Myasthenia Gravis - Activities of Daily Living (MG-ADL) score over time.(Up to 156 weeks)
- To evaluate efficacy by change in Quantitative Myasthenia Gravis (QMG) score over time.(Up to 156 weeks)
- To evaluate efficacy by change in Myasthenia Gravis Composite (MGC) score over time.(Up to 156 weeks)
- To evaluate disease-related biomarkers(Up to 156 weeks)
- To evaluate the incidence and severity of adverse events (AEs)(Up to 156 weeks)
- To characterize the pharmacodynamics (PD)(Up to 156 weeks)
- To characterize the pharmacokinetics (PK)(Up to 156 weeks)