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 Active Idiopathic Inflammatory Myopathy or Juvenile Idiopathic Inflammatory Myopathy
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 74
- 试验地点
- 58
- 主要终点
- Phase 1/2: Incidence and severity of adverse events (AEs)
研究概览
简要总结
RESET-Myositis: Open-Label Study to Evaluate the Safety and Efficacy of CABA-201 in Subjects with Active Idiopathic Inflammatory Myopathy or Juvenile Idiopathic Inflammatory Myopathy
详细描述
Idiopathic inflammatory myopathies (IIMs, or myositis) are a group of rare autoimmune diseases characterized by inflammation and muscle weakness. Though the cause of IIM is not well understood, some subtypes of IIM, including dermatomyositis (DM), anti-synthetase syndrome (ASyS), immune-mediated necrotizing myopathy (IMNM), and juvenile idiopathic inflammatory myopathy (JIIM), are thought to involve B cells that cause the body to attack different tissues in the body. 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 DM, ASyS, IMNM, or JIIM 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
- 6 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult Cohorts
- •Inclusion Criteria:
- •Age ≥18 and ≤75
- •A clinical diagnosis of IIM, based on the 2017 The European League Against Rheumatism/American College of Rheumatology classification criteria
- •Diagnosis of DM, ASyS, or IMNM
- •Evidence of active disease, despite prior or current treatment with standard of care treatments, as defined by the presence of elevated creatine kinase (CK), DM rash, or active disease on muscle biopsy, magnetic resonance imaging (MRI), or electromyography
- •Presence of muscle weakness
- •Other protocol-defined criteria apply.
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
- •Previous CAR T cell therapy
- •Prior solid organ (heart, liver, kidney, lung) transplant or hematopoietic cell transplant
- •Other protocol-defined criteria apply.
- •Juvenile Cohort
- •Inclusion Criteria:
- •Age ≥6 and ≤17 years at enrollment
- •A clinical diagnosis of IIM, based on the 2017 The European League Against Rheumatism/American College of Rheumatology classification criteria
- •Evidence of active disease, despite prior or current treatment with standard of care treatments, as defined by the presence of elevated muscle enzymes, DM rash, or active disease on muscle biopsy, magnetic resonance imaging (MRI), or electromyography
- •Other protocol-defined criteria apply.
- •Exclusion Criteria:
- •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
- •Previous CAR T cell therapy
- •Prior solid organ (heart, liver, kidney, lung) transplant or hematopoietic cell transplant
- •Other protocol-defined criteria apply.
研究组 & 干预措施
CABA-201 Phase 2b - Sub-study 1
Infusion of CABA-201 following preconditioning with fludarabine and cyclophosphamide in subjects with DM and ASyS.
干预措施: CABA-201 following preconditioning with fludarabine and cyclophosphamide (Biological)
CABA-201 Phase 1/2
DM Cohort: Infusion of CABA-201 following preconditioning with fludarabine and cyclophosphamide in subjects with DM.
ASyS Cohort: Infusion of CABA-201 following preconditioning with fludarabine and cyclophosphamide in subjects with ASyS.
IMNM Cohort: Infusion of CABA-201 following preconditioning with fludarabine and cyclophosphamide in subjects with IMNM.
JIIM Cohort: Infusion of CABA-201 following preconditioning with fludarabine and cyclophosphamide in subjects with JIIM.
干预措施: CABA-201 following preconditioning with fludarabine and cyclophosphamide (Biological)
CABA-201 Phase 2b - Sub-study 2
Infusion of CABA-201 following preconditioning with fludarabine and cyclophosphamide in subjects with IMNM.
干预措施: CABA-201 following preconditioning with fludarabine and cyclophosphamide (Biological)
结局指标
主要结局
Phase 1/2: Incidence and severity of adverse events (AEs)
时间窗: Up to 28 days after CABA-201 infusion
Incidence and severity of AEs
Phase 2b Sub-study 1: Proportion of DM & ASyS subjects achieving at least a moderate Total Improvement Score (TIS) without any immunomodulatory medications and no or low dose of steroids
时间窗: Within 16 weeks
≥40 on the TIS, a composite measure ranging from 0 to 100, derived from six Core Set Measures, with higher scores indicating greater clinical improvement
Phase 2b Sub-study 2: Proportion of subjects with IMNM achieving at least a minimal TIS without any immunomodulatory medications and no or low dose of steroids
时间窗: Within 24 weeks
≥20 on the TIS, a composite measure ranging from 0 to 100, derived from six Core Set Measures, with higher scores indicating greater clinical improvement
次要结局
- To evaluate adverse events and laboratory abnormalities(Up to 156 weeks)
- To characterize the pharmacodynamics (PD)(Up to 156 weeks)
- To evaluate disease-related biomarkers of muscle inflammation(Up to 156 weeks)
- Incidence of adverse events and laboratory abnormalities(Up to 156 weeks (Phase 1/2) and through 52 weeks (Sub-study 1 and 2))
- Pharmacodynamics (PD)(Up to 156 weeks (Phase 1/2) and through 52 weeks (Sub-study 1 and 2))
- Pharmacokinetics (PK)(Up to 156 weeks (Phase 1/2) and through 52 weeks (Sub-study 1 and 2))
- Change in disease-related biomarkers of muscle inflammation(Up to 156 weeks (Phase 1/2))
- Change in autoantibody-related biomarkers(Up to 156 weeks (Phase 1/2))
- Proportion of DM subjects achieving at least a moderate TIS without any immunomodulatory medications and no or low dose of steroids(Week 16 (Sub-study 1))
- Mean change from baseline on the MMT-8 in subjects with DM and ASyS without any immunomodulatory medications and no or low dose of steroids(Week 16 (Sub-study 1))
- Proportion of DM and ASyS subjects achieving a major TIS response without any immunomodulatory medications and no or low dose of steroids(Week 16 (Sub-study 1))
- Proportion of subjects with DM & ASyS achieving moderate TIS without any immunomodulatory medications on no or low dose of steroids(Week 52 (Sub-study 1))
- Proportion of subjects with DM achieving moderate TIS without any immunomodulatory medications on no or low dose of steroids(Week 52 (Sub-study 1))
- Mean change from baseline on the MMT-8 in subjects with IMNM without any immunomodulatory medications and no or low dose of steroids(Week 24 (Sub-study 2))
- Proportion of subjects with IMNM achieving at least minimal TIS response without immunomodulatory medications and no or low dose of steroids(Week 52 (Sub-study 2))