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 Subjects With Systemic Sclerosis
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 37
- 试验地点
- 12
- 主要终点
- To evaluate incidence of adverse events
研究概览
简要总结
RESET-SSc: A Phase 1/2 Open-Label Study to Evaluate the Safety and Efficacy of CABA-201, a CD19-CAR T cell therapy, in Subjects with Systemic Sclerosis
详细描述
Systemic sclerosis (SSc), also known as scleroderma , is a rare autoimmune disorder characterized by autoantibody production and abnormal B cell function. Though the cause of SSc is not well understood, it is thought to involve B cells that cause the body to attack different tissues in one's own body, causing skin and organ fibrosis. This study is being conducted to evaluate the safety and efficacy of an investigational therapy, CABA-201, a CD19-CAR T cell therapy, that can be given to patients with SSc who have active disease. A single dose of CABA-201 in combination with cyclophosphamide (CY) and fludarabine (FLU) will be evaluated.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 and ≤75
- •A clinical diagnosis of SSc, based on the 2013 American College of Rheumatology and European League Against Rheumatism classification criteria.
- •Early active disease
- •Evidence of significant skin, pulmonary, or cardiac involvement
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 visit
- •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
- •Severe lung or cardiac impairment
- •Previous CAR T cell therapy
- •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 Phase 2b - Sub-study
Infusion of CABA-201 with preconditioning in subjects with SSc
干预措施: CABA-201 (Biological)
CABA-201 Phase 1/2
Severe Skin Cohort: Infusion of CABA-201 with preconditioning in subjects with SSc with severe skin involvement
Organ Cohort: Infusion of CABA-201 with preconditioning in subjects with SSc with organ involvement
干预措施: CABA-201 (Biological)
结局指标
主要结局
To evaluate incidence of adverse events
时间窗: Up to 28 days after CABA-201 infusion
Incidence and severity of AEs
Phase 1/2: To evaluate incidence of adverse events
时间窗: Up to 28 days after CABA-201 infusion
Incidence and severity of AEs
Phase 2b Sub-study: To evaluate the efficacy of CABA-201 on % predicted forced vital capacity (FVC) in SSc-ILD subjects
时间窗: Week 52
Mean change from baseline in % predicted FVC without any immunomodulatory or anti-fibrotic medications and on no or low dose of steroids
次要结局
- To characterize the pharmacokinetics (PK)(Up to 156 weeks)
- To evaluate efficacy(Up to 156 weeks)
- To evaluate adverse events and laboratory abnormalities(Up to 156 weeks)
- To characterize the pharmacodynamics (PD)(Up to 156 weeks)
- To evaluate adverse events and laboratory abnormalities(Up to 156 weeks (Phase 1/2) and through 104 weeks (Sub-study))
- To characterize the pharmacodynamics (PD)(Up to 156 weeks (Phase 1/2) and through 104 weeks (Sub-study))
- To characterize the pharmacokinetics (PK)(Up to 156 weeks (Phase 1/2) and through 104 weeks (Sub-study))
- To evaluate efficacy(Up to 156 weeks (Phase 1/2) and at Week 52 (Sub-study))
- Mean change from baseline in Modified Rodnan Skin Score (mRSS)(Week 52 (Sub-study))