A Phase lb Open-Label Study Evaluating the Safety and Efficacy of the Combination of CLBR00l, an Engineered Autologous T Cell Product, and SWI019, a CD19-directed Antibody-based Biologic With or Without Lymphodepletion in Subjects With Autoimmune Disorders Including Systemic Lupus Erythematosus, Systemic Sclerosis, or Idiopathic Inflammatory Myositis
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 入组人数
- 12
- 主要终点
- Number of subjects with adverse events
研究概览
简要总结
The goal of this clinical trial is to evaluate CLBR001 and SWI019 as a treatment for patients with autoimmune disorders, including systemic lupus erythematosus, systemic sclerosis, and idiopathic inflammatory myositis. Patients will be randomized 1:1 lymphodepletion vs no lymphodepletion arm. Patients will be administered a single infusion of CLBR001 cells followed by cycles of SWI019 with regular assessments of safety and disease response to treatment.
The goals are to establish the safety and efficacy of the combination therapy and determine if lymphodepletion is required for efficacy.
详细描述
CLBR001 + SWI019 is novel switchable CAR-T cell combination therapy comprised of an autologous CAR (chimeric antigen receptor)-T product (CLBR001, the switchable CAR-T cell [sCAR-T]) and SWI019 (the "switch" biologic molecule). SWI019 acts as an adapter molecule that controls the activity of the CLBR001 CAR-T cell product.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Women or men age ≥18 of age at time of consent.
- •Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of this study.
- •Adequate hematological, liver, pulmonary, and cardiac function
- •Willing to participate to participate in long term follow up study.
- •Confirmed diagnosis of moderate to severe systemic lupus erythematosus with lupus nephritis, systemic lupus erythematosus with extrarenal lupus, systemic sclerosis, and idiopathic inflammatory myositis.
- •Failed at least two immunosuppressive treatments
排除标准
- •Inability to tolerate washout of prior therapy.
- •Not willing/understanding the requirements of the clinical study
- •Dependent on hemodialysis for a period of greater or equal to 3 months.
- •Known hypersensitivity to prednisone or to both tocilizumab siltuximab.
- •Have received plasmapheresis within 14 days prior to informed consent.
- •Active bacterial, viral and/or fungal infection.
- •Prior autologous/allogeneic stem cell transplant or solid organ transplant.
- •Prior lentiviral or retroviral based therapy including CAR-T cell therapy.
- •History or concurrent malignancy with active treatment in the past 5 years
- •HIV-1 and HIV-2 antibody positive subjects.
- •History of central nervous system diseases (such as seizure, psychosis, organic brain syndrome or cerebrovascular accident).
研究组 & 干预措施
CLBR001 + SWI019 following Lymphodepletion
Subjects who are randomized into the lymphodepletion arm will undergo 3 days of lymphodepletion conditioning therapy consisting of fludarabine and cyclophosphamide prior to treatment with CLBR001+SWI019.
干预措施: CLBR001 + SWI019 (Combination Product)
CLBR001 + SWI019 without Lymphodepletion
Subjects who are randomized into the NO lymphodepletion arm will receive treatment with CLBR001+SWI019 without lymphodepletion administered prior.
干预措施: CLBR001 + SWI019 (Combination Product)
结局指标
主要结局
Number of subjects with adverse events
时间窗: To 1 year post CLBR001 administration
To assess the safety and tolerability in subjects by evaluating the frequency, relatedness, severity and duration of adverse events (assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0, with exception of Cytokine Release Syndrome (CRS) or Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS) which will be graded by American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading criteria).
次要结局
- Evaluate the efficacy of CLBR001 + SWI019 in autoimmune disease(1 year post CLBR001 administration)
- Quantification of white blood cells (WBCs)(1 year post CLBR001 administration)
- Evaluate the pharmacokinetics (PK) of CLBR001 and SWI019: Maximum Concentration (Cmax)(1 year post CLBR001 administration)
- Number of subjects with Clinical Response(1 year post CLBR001 administration)
- Evaluate the pharmacokinetics (PK) of CLBR001 and SWI019: Time to Peak Drug Concentration (Tmax)(1 year post CLBR001 administration)
- Evaluate the pharmacokinetics (PK) of CLBR001 and SWI019: Area Under the Curve (AUC)(1 year post CLBR001 administration)
- Evaluate the pharmacokinetics (PK) of CLBR001 and SWI019: Half-life (t1/2)(1 year post CLBR001 administration)
- Assess immunogenicity of CLBR001 and SWI019(1 year post CLBR001 administration)