KYSA-6: A Phase 2/3, Open-Label, Randomized, Controlled, Multicenter Study of KYV-101, an Autologous Fully Human Anti-CD19 Chimeric Antigen Receptor T-cell (CD19 CAR T) Therapy, Versus Ongoing Standard-Of-Care Immunosuppressive Therapy in Patients With Generalized Myasthenia Gravis
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 66
- 试验地点
- 31
- 主要终点
- Incidence and severity of adverse events (AEs) and laboratory abnormalities (Phase 2)
研究概览
简要总结
A Study of the Anti-CD 19 Chimeric Antigen Receptor T Cell Therapy for Patients with Myasthenia Gravis
详细描述
Myasthenia gravis (MG) is a chronic autoimmune disease that affects the neuromuscular junction and is characterized by muscle weakness. B cells play a role in MG, and the disease is characterized by the presence of autoantibodies such as anti-AChR and anti-MuSK antibodies. CD-19 target chimeric antigen receptor (CAR) T cells harness the ability of cytotoxic T cells to directly and specifically lyse target cells to effectively deplete both normal and autoreactive B cells in the circulation as well as impacted lymphoid and potentially non-lymphoid tissues. KYV-101 (mivocabtagene autoleucel [miv-cel])), a fully human anti-CD19 CAR T-cell therapy, will be investigated in adult subjects with myasthenia gravis (MG).
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Presence of autoantibodies to AChR or MuSK
- •Myasthenia Gravis Foundation of America (MGFA) Class II-IV
- •MG-Activities of Daily Living (MG-ADL) total score of ≥6 at screening and confirmed at baseline visit
- •QMG total score of ≥11 at screening an confirmed at baseline visit
- •Failed treatment with 2 or more immunosuppressive/immunomodulatory therapies, or failed at least 1 immunosuppressive therapy and required chronic plasmapheresis, or IVIG (or subcutaneous or intramuscular Ig) to control symptoms
- •On a stable dose of glucocorticoids and/or other immunotherapies for ≥1 month prior to screening. For patients treated with azathioprine, a stable dose for ≥2 months prior to screening is required
- •No change in dose of acetylcholinesterase inhibitors for ≥2 weeks prior to screening
- •No use of intravenous immune globulin (IVIG) or plasmapheresis (PLEX) within 4 weeks of screening or pre-dose baseline (unless this is part of their SOC treatment regimen)
- •No use of rituximab (or any other anti-CD20 or CD19 monoclonal antibody) within 12 weeks prior to screening
- •Able and willing to attend the necessary visits to the study site
排除标准
- •Unable to washout or interrupt autoimmune disease therapy prior to apheresis and/or baseline if required
- •Co-occurring neurological autoimmune disease (ie, Lambert-Eaton Myasthenic Syndrome) or any disease affecting the neuromuscular junction or muscle causing weakness (eg, myositis, myopathy, motor neuropathy)
- •History of stroke (with residual sequalae and/or risk for recurrence), seizure (even if well controlled on antiepileptics), neurodegenerative disease, altered mental status (unexplained and/or recent/current), or uncontrolled/severe psychiatric disease
- •Any serious and/or uncontrolled medical condition that, in the investigator's judgment, would cause unacceptable safety risk, interfere with study procedures or results, or compromise compliance with the protocol, including but not limited to, clinically significant cardiac or pulmonary disease
- •History of primary immunodeficiency, organ or allogeneic bone marrow transplant, or splenectomy
- •Active, uncontrolled, viral, bacterial, or systemic fungal infection or recent history of repeated infections
- •Thymectomy <12 months of screening or planned during the study
- •Prior treatment with gene therapy product or cellular immunotherapy (eg, CAR T) requiring vector integration and directed at any target
- •Patients requiring chronic anticoagulation therapy that cannot be discontinued for medical procedures
研究组 & 干预措施
KYV-101 CAR-T cells with lymphodepletion conditioning
Phase 2: Dosing with KYV-101 CAR-T cells
干预措施: Standard lymphodepletion regimen (Drug)
KYV-101 Treatment
Phase 3
干预措施: Standard lymphodepletion regimen (Drug)
Standard of Care
Phase 3 Optional crossover to receive KYV-101 Treatment after 24 weeks
干预措施: Standard of Care Treatment (Drug)
Standard of Care
Phase 3 Optional crossover to receive KYV-101 Treatment after 24 weeks
干预措施: Standard lymphodepletion regimen (Drug)
Standard of Care
Phase 3 Optional crossover to receive KYV-101 Treatment after 24 weeks
干预措施: KYV-101 (Biological)
KYV-101 CAR-T cells with lymphodepletion conditioning
Phase 2: Dosing with KYV-101 CAR-T cells
干预措施: KYV-101 (Biological)
KYV-101 Treatment
Phase 3
干预措施: KYV-101 (Biological)
结局指标
主要结局
Incidence and severity of adverse events (AEs) and laboratory abnormalities (Phase 2)
时间窗: 18 months
Efficacy of KYV-101 via Myasthenia Gravis Activities of Daily Living (MG-ADL) change from baseline for KYV-101 Treatment arm to Standard of Care arm (Phase 3)
时间窗: 24 weeks
Efficacy of KYV-101 via Quantitative Myasthenia Gravis (QMG) change from baseline for KYV-101 Treatment arm to Standard of Care arm (Phase 3)
时间窗: 24 weeks
Efficacy of KYV-101 via Myasthenia Gravis Activities of Daily Living (MG-ADL) change from baseline (Phase 2)
时间窗: 24 weeks
Incidence and severity of adverse events (AEs) and laboratory abnormalities (Phase 2)
时间窗: 2 years
Efficacy of KYV-101 via Myasthenia Gravis Activities of Daily Living (MG-ADL) change from baseline (Phase 2)
时间窗: 24 weeks
Efficacy of KYV-101 via Myasthenia Gravis Activities of Daily Living (MG-ADL) change from baseline for KYV-101 Treatment Arm to Standard of Care Arm (Phase 3)
时间窗: 24 weeks
Efficacy of KYV-101 via Quantitative Myasthenia Gravis (QMG) change from baseline for KYV-101 Treatment arm to Standard of Care arm
时间窗: 24 weeks
次要结局
- Efficacy of KYV-101 via Myasthenia Gravis Composite (MGC) score change from baseline for KYV-101 Treatment arm to Standard of Care arm (Phase 3)(24 weeks)
- Incidence and severity of adverse events (AEs) and laboratory abnormalities (Phase 3)(18 months)
- Efficacy of KYV-101 via Proportion of patients with a ≥3 point improvement from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) for KYV-101 Treatment arm to Standard of Care arm (Phase 3)(24 weeks)
- Efficacy of KYV-101 via Myasthenia Gravis Quality of Life 15-item Scale (MG-QoL 15r) change from baseline for KYV-101 Treatment arm to Standard of Care arm (Phase 3)(24 weeks)
- Efficacy of KYV-101 via Percent change from baseline in anti acetylcholine receptors (anti-AChR) antibody levels for KYV-101 Treatment arm to Standard of Care arm (Phase 3)(24 weeks)
- Efficacy of KYV-101 via Percent change from baseline in anti muscle-specific tyrosine kinase (anti-MuSK) antibody levels for KYV-101 Treatment arm to Standard of Care arm (Phase 3)(24 weeks)
- Efficacy of KYV-101 via Myasthenia Gravis Composite (MGC) score change from baseline for KYV-101 arm to Standard of Care arm (Phase 3)(24 weeks)
- Efficacy of KYV-101 via Percent change from baseline in anti acetylcholine receptors (anti-AChR) antibody levels for KYV-101 Treatment arm to Standard of Care arm (Phase 3)(24 weeks)
- Efficacy of KYV-101 via Percent change from baseline in anti muscle-specific tyrosine kinase (anti-MuSK) antibody levels for KYV-101 Treatment arm to Standard of Care arm (Phase 3)(24 weeks)
- Efficacy of KYV-101 via Proportion of patients with a ≥3 point improvement from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) for KYV-101 Treatment arm to Standard of Care arm (Phase 3)(24 weeks)
- Efficacy of KYV-101 via Proportion of patients with minimal symptom expression (MSE) for KYV-101 Treatment arm to Standard of Care arm (Phase 3)(24 weeks)
- Efficacy of KYV-101 via Myasthenia Gravis Quality of Life 15-item Scale (MG-QoL 15r) change from baseline for KYV-101 Treatment arm to Standard of Care arm (Phase 3)(24 weeks)
- Incidence and severity of adverse events (AEs) and laboratory abnormalities (Phase 3)(2 years)