KYSA-5: A Phase 1/2, Open-Label, Multicentre Study of KYV 101, an Autologous Fully Human Anti-CD19 Chimeric Antigen Receptor T Cell (CD19 CAR T) Therapy, in Subjects With Systemic Sclerosis
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 4
- 主要终点
- Frequency of Dose-Limiting Toxicities (DLTs) at each dose level (Phase 1)
研究概览
简要总结
A Study of Anti-CD19 Chimeric Antigen Receptor T Cell Therapy for Subjects with Systemic Sclerosis
详细描述
SSc is an immune-mediated rheumatic disease that is characterized by fibrosis of the skin and internal organs and vasculopathy. B-cells play a role in SSc, and the disease is characterized by the presence of autoantibodies such as anti-Scl-70 and anti-RNAP III antibodies. CD19-targeted chimeric antigen receptor (CAR) T-cells harness the ability of cytotoxic T-cells to directly and specifically lyse target cells to effectively deplete B-cells in the circulation and in lymphoid and potentially non-lymphoid tissues. KYV-101, a fully human anti-CD19 CAR T-cell therapy, will be investigated in adult subjects with systemic sclerosis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Clinical diagnosis of SSc according to 2013 ACR/EULAR classification
- •Clinical disease as follows: Classified as diffuse cutaneous SSc; ≤ 6 years since first non-Raynaud's sign or symptom; active disease
- •Up to date on all recommended vaccinations per CDC or institutional guidelines for immune-compromised individuals
排除标准
- •Clinically significant ILD
- •Prior treatment with cellular therapy (CAR-T) or gene therapy product directed at any target
- •History of allogeneic or autologous stem cell transplant
- •Evidence of active hepatitis B or hepatitis C infection
- •Positive serology for HIV
- •Primary immunodeficiency
- •History of splenectomy
- •History of stroke, seizure, dementia, Parkinson's disease, coordination movement disorder, cerebellar diseases, psychosis, paresis, aphasia, and any other neurologic disorder investigator considers would increase the risk for the subject
- •Impaired cardiac function or clinically significant cardiac disease
- •Previous or concurrent malignancy with the following exceptions:
- •Adequately treated basal cell or squamous cell carcinoma (adequate wound healing is required prior to screening)
- •In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 3 years prior to screening
- •A primary malignancy which has been completely resected, or treated, and is in complete remission for at least 5 years prior to screening
研究组 & 干预措施
KYV-101 CAR-T cells with lymphodepletion conditioning (Phase 1)
Dosing with KYV-101 CAR T cells
干预措施: KYV-101 (Biological)
KYV-101 CAR-T cells with lymphodepletion conditioning (Phase 1)
Dosing with KYV-101 CAR T cells
干预措施: Standard lymphodepletion regimen (Drug)
KYV-101 CAR-T cells with lymphodepletion conditioning (Phase 2)
Recommended Phase 2 Dose
干预措施: KYV-101 (Biological)
KYV-101 CAR-T cells with lymphodepletion conditioning (Phase 2)
Recommended Phase 2 Dose
干预措施: Standard lymphodepletion regimen (Drug)
结局指标
主要结局
Frequency of Dose-Limiting Toxicities (DLTs) at each dose level (Phase 1)
时间窗: Up to 2 years
Incidence of adverse events and laboratory abnormalities (Phase 1)
时间窗: Up to 2 years
To evaluate efficacy of KYV-101(Phase 2)
时间窗: 52 weeks
via revised Composite Response Index in Systemic Sclerosis (rCRISS) 30/5
次要结局
- To evaluate efficacy of KYV-101 (Phase 1 and Phase 2)(12, 24, 52 weeks)
- To evaluate pharmacodynamics (PK) of KYV-101 in blood (Phase 1 and Phase 2)(Up to 2 years)
- To evaluate immunogenicity (humoral response) of KYV-101 (Phase 1 and Phase 2)(Up to 2 years)
- To define the Recommended Phase 2 Dose (RP2D) (Phase 1)(Up to 2 years)
- To evaluate pharmacodynamics (PD) of KYV-101 in blood (Phase 1 and Phase 2)(Up to 2 years)