A Phase 1/2, Open-label, Safety and Dosing Study of Autologous CART Cells (Desmoglein 3 Chimeric Autoantibody Receptor T Cells [DSG3-CAART] or CD19-specific Chimeric Antigen Receptor T Cells [CABA-201]) in Subjects With Active, Pemphigus Vulgaris
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 26
- 主要终点
- Adverse events, including Dose Limit Toxicity
研究概览
简要总结
A phase 1/2, open-label, safety and dosing study of autologous CART cells (desmoglein 3 chimeric autoantibody receptor T cells [DSG3-CAART] or CD19-specific Chimeric Antigen Receptor T cells [CABA-201]) in subjects with active, pemphigus vulgaris
详细描述
Pemphigus vulgaris (PV) is a B-cell mediated autoimmune disorder in which painful blisters are formed on the skin or mucosal membrane, including the mouth, nose, throat, eyelids, anus, and genitals.
This phase 1/2 study is being conducted in two parts. The first part is the main study conducted to find the maximum tolerated dose and optimal fractionated infusion schedule of an investigational cell therapy, DSG3-CAART, that can be given to patients with mucosal PV who are inadequately managed by standard therapies. This study is closed to enrollment.
The second part is a sub-study is being conducted to investigate if CABA-201, also called resecabtagene autoleucel, or "rese-cel", can be safely administered while achieving clinical responses without the need for preconditioning in mucosal-dominant PV (mPV) and mucocutaneous PV (mcPV) patients. This sub-study is open to enrollment.
DSG3-CAART or CABA-201 may potentially lead to complete and durable remission of disease.
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
- •for DSG3-CAART: Closed to enrollment
- •Confirmed diagnosis of mPV by prior or screening biopsy and prior positive anti- DSG3 antibody ELISA
- •mPV inadequately managed by at least one standard immunosuppressive therapies
- •Active mPV at screening
- •Anti-DSG3 antibody ELISA positive at screening
- •Inclusion Criteria for CABA-201 sub-study: Open to enrollment
- •Confirmed diagnosis of PV by prior or screening biopsy and prior positive DSG3 ELISA, IIF, and/or DIF
- •PV inadequately managed by at least one standard immunosuppressive therapy
- •Active PV at screening
- •DSG3 ELISA positive at screening
排除标准
- •Active cutaneous lesions associated with PV that indicates mucocutaneous rather than mucosal-dominant disease
- •Rituximab in last 12 months unless PV symptoms have recently worsened or anti-DSG3 antibody titers have recently increased
- •Prednisone > 0.25mg/kg/day
- •Other autoimmune disorder requiring immunosuppressive therapies
- •Investigational treatment in last 3 months
- •Exclusion Criteria for CABA-201 sub-study
- •Have paraneoplastic pemphigus or active malignancy (not including non-melanoma skin cancer) or malignancy diagnosed within the previous 5 years
- •Have received rituximab or other anti-CD20 or anti-CD19 therapies in last 12 months unless anti-DSG3 antibody titers have recently increased or PV symptoms have recently worsened
- •Prednisone > 0.25mg/kg/day
- •Other autoimmune disorder requiring immunosuppressive therapies
- •Treatment with any investigational agent within 4 weeks or 5 half-lives, whichever is longer.
研究组 & 干预措施
CABA-201
Infusion of CABA-201 with or without cyclophosphamide and fludarabine preconditioning, or with or without cyclophosphamide preconditioning.
This sub-study is open to enrollment.
干预措施: CABA-201 (Biological)
DSG3-CAART
Single or multiple intravenous infusion(s) of DSG3-CAART at varying dose levels.
This study is now closed to enrollment.
干预措施: DSG3-CAART (Biological)
结局指标
主要结局
Adverse events, including Dose Limit Toxicity
时间窗: 3 months
Incidence of adverse events that are related to DSG3-CAART therapy
For CABA-201 Sub-study: To evaluate adverse events reported by subjects
时间窗: Up to 28 days after CABA-201 infusion
Incidence and severity of AEs
次要结局
- For CABA-201 Sub-study: To evaluate autoantibody -related biomarkers(Up to 156 Weeks)
- For CABA-201 Sub-study: To characterize the pharmacokinetics (PK)(Up to 156 weeks)
- Total DSG3-CAART positive cells(Baseline)
- Pemphigus Disease Area Index (PDAI)(Up to 36 months)
- Clinical remission: complete remission off therapy and complete remission on minimal therapy(Up to 36 months)
- For CABA-201 Sub-study: To evaluate adverse events reported by subjects(Up to 156 weeks after CABA-201 infusion)
- For CABA-201 Sub-study: To characterize the pharmacodynamics (PD)(Up to 156 weeks)
- Change in DSG3 autoantibody titer(Up to 36 months)
- Time to clinical remission and time to serologic remission(up to 36 months)
- For CABA-201 Sub-study: To evaluate efficacy(Up to 156 Weeks)
- Percent of CAAR-transduced cells(Baseline)
- Cellular kinetics profile of DSG3-CAART(Up to 36 months)
- Serologic remission(Up to 36 months)
- Duration of clinical remission and duration of serologic remission(up to 36 months)