KYSA-1: A Phase 1/2, Open-Label, Multicenter Study of KYV-101, an Autologous Fully-Human Anti-CD19 Chimeric Antigen Receptor T-Cell (CD19 CAR T) Therapy, in Subjects With Refractory Lupus Nephritis
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 12
- 主要终点
- Incidence adverse events (AEs) and laboratory abnormalities (Phase 1 and Phase 2)
研究概览
简要总结
A Study of Anti-CD19 Chimeric Antigen Receptor T Cell Therapy for Subjects With Refractory Lupus Nephritis
详细描述
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a wide spectrum of organ involvement and disease severity. Renal involvement (categorized as lupus nephritis [LN]) may occur in approximately 50% of SLE patients and is marked by proteinuria, microscopic hematuria, and varying degrees of renal insufficiency. B cells play a central role in the pathogenesis of SLE and LN, with autoantibodies developing as an early finding, and local, tissue resident B cells producing pathogenic autoantibodies and driving inflammation and tissue damage over time. 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 refractory lupus nephritis.
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
- •Age ≥18 years
- •Clinical diagnosis of SLE according to 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria
- •Biopsy-proven proliferative LN Class III or IV according to 2018 International Society of Nephrology/Renal Pathology Society (ISN/RPS) criteria
- •Positive anti-nuclear antibody (ANA) (titer ≥1:80 ), anti-dsDNA (≥30 IU/mL on enzyme-linked immunosorbent assay [ELISA]), or anti-Smith at screening or by documented medical history
- •Up to date on recommended vaccinations, including against coronavirus disease 2019 (COVID-19)/ severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), per Centers for Disease Control and Prevention (CDC) or institutional guidelines for immune compromised individuals
排除标准
- •Rapidly progressive glomerulonephritis; history of or currently active severe central nervous system (CNS) lupus, including cerebritis, cerebrovascular accident, and seizures
- •Prior treatment with cellular immunotherapy (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 2)
Recommended Phase 2 Dose
干预措施: KYV-101 anti-CD19 CAR-T cell therapy (Biological)
KYV-101 CAR-T cells with lymphodepletion conditioning (Phase 1)
Dosing with KYV-101 CAR T cells
干预措施: KYV-101 anti-CD19 CAR-T cell therapy (Biological)
KYV-101 CAR-T cells with lymphodepletion conditioning (Phase 2)
Recommended Phase 2 Dose
干预措施: Standard lymphodepletion regimen (Drug)
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)
结局指标
主要结局
Incidence adverse events (AEs) and laboratory abnormalities (Phase 1 and Phase 2)
时间窗: Up to 2 years
Frequency of dose limiting toxicities at each dose level (Phase 1)
时间窗: Up to 2 years
To Evaluate efficacy (Phase 2)
时间窗: Up to 52 Weeks
Complete renal response rates (CRR)
次要结局
- To characterize the pharmacokinetics (PK) (Phase 1 and Phase 2)(Up to 2 years)
- To characterize the pharmacodynamics (PD) (Phase 1 and Phase 2)(Up to 2 months)
- To evaluate efficacy (Phase 2)(Up to 52 weeks)
- To evaluate the 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 assess PRO after infusion of KYV-101 (Phase 1 and Phase 2)(Up to 2 years)
- To evaluate disease related biomarkers (Phase 1 and Phase 2)(Up to 2 years)
- To evaluate efficacy (Phase 1 and Phase 2)(Up to 2 years)
- To characterize the pharmacodynamics (PD) (Phase 1 and Phase 2)(Up to 2 years)
- To evaluate efficacy (Phase 1 and Phase 2)(12, 24, and 52 weeks)