NCT07129642招募中早期 1 期
The Efficacy and Safety of Allogenic Anti-CD19 CAR-T Cell Therapy for Refractory Graves' Disease
Shanghai Zhongshan Hospital1 个研究点 分布在 1 个国家目标入组 5 人开始时间: 2025年8月10日最近更新:
干预措施
相关药物
试验速览
- 阶段
- 早期 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Remission of Graves disease
研究概览
简要总结
Graves' disease is an autoimmune disease. The TSH receptor antibody(TRab) produced by B cells drives the production of thyroid hormone, which causes systemic disorders and thyroid eye disease. The purpose of this study is to investigate the efficacy and safety of allogeneic anti-CD19 CAR-T for refractory Graves' disease.
The participants with refractory Graves' disease will receive a single dose of allogeneic anti-CD19 CAR-T and be regularly seen for the change of serum TRab, FT3, FT4 and clinical presentations, as well as any adverse events.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects with refractory Graves disease, which is defined as meeting any one of the following criteria: a. Failure to discontinue medication after continuous standard antithyroid therapy for ≥ 3 years; b. Hyperthyroid state requiring medication after receiving ≥ 2 times of radioiodine therapy (with the last dose of radioiodine administered at least 6 months prior); c. Relapse ≥ 2 times after cessation of medication upon meeting the criteria for treatment discontinuation.
- •Serum TRAb ≥ 3 times greater than normal range (≥ 5 IU/L)
- •Positive expression of CD19 on peripheral blood B cells determined by flow cytometry.
- •Participation in this clinical study is willing to sign an informed consent with good compliance with treatment and follow-up.
- •(Criteria for treatment discontinuation is define as receiving continuous anti-thyroid drug therapy for ≥18 months, and maintaining euthyroid status for ≥6 months, plus negative TRAb and TSI. Relapse is defined as recurrence of hyperthyroidism and positive TRAb/TSI after meeting the criteria for treatment discontinuation and stopping medication.)
排除标准
- •History of severe drug allergies or allergic constitution;
- •Presence or suspicion of uncontrolled infections requiring intravenous treatment (fungal, bacterial, viral or other);
- •Presence of central nervous system disorders (including epilepsy, psychosis, cerebrovascular accident, encephalitis, CNS vasculitis, etc);
- •Presence of clinically significant heart diseases (e.g., angina pectoris, myocardial infarction, heart failure, severe arrhythmias, etc);
- •Subjects with congenital immunoglobulin deficiency;
- •Patients with malignant tumors;
- •Subjects who are:
- •HBsAg or HBcAb positive with detectable peripheral blood HBV DNA;
- •HCV antibody positive with detectable HCV RNA;
- •Positive HIV antibody;
- •Syphilis test positive;
- •Subjects with psychiatric disorders or severe cognitive dysfunction;
- •Hematopoietic function: a. White blood cell count < 3.5×10^9/L b. Neutrophil count < 1.5 x 10^9/L; c. Hemoglobin < 110g/L.
- •Liver function: ALT> 3×ULN, AST > 3×ULN, TBIL > 2.5×ULN.
- •Renal function: creatinine clearance rate (CrCl) < 60 ml/minute (calculated based on Cockcroft/Fault formula).
- •Cardiac function: LVEF < 55%
- •Coagulation function: International standardized ratio (INR) ≥ 1.5×ULN, prothrombin time(PT) >1.5 × ULN.
- •Participation in other clinical trials within 3 months prior to enrollment;
- •Pregnancy or planning pregnancy;
- •Other conditions considered by investigators as unsuitable for participation.
研究组 & 干预措施
Intervention Arm
Experimental
干预措施: Allogeneic CAR-T (Biological)
结局指标
主要结局
Remission of Graves disease
时间窗: From baseline to 12 months after infusion of CAR-T cells
Sustained euthyroid status without anti-thyroid medication for ≥3 months
Incidence of Adverse Events
时间窗: From baseline to 6 months after infusion of CAR-T cells
Assessed using the CTCAE v5.0 standards
次要结局
- PK parameters - CAR gene copy number(From baseline to 3 months after infusion of CAR-T cells)
- PK parameters - CAR-T cell count(From baseline to 3 months after infusion of CAR-T cells)
- Anti-Thyrotropin receptor antibody (TRAb)(From baseline to 12 months after infusion of CAR-T cells)
- Thyroid stimulating immunoglobulin (TSI)(From baseline to 12 months after infusion of CAR-T cells)
- thyroid peroxidase antibody (TPOAb)(From baseline to 12 months after infusion of CAR-T cells)
- Thyroglobulin antibody (TgAb)(From baseline to 12 months after infusion of CAR-T cells)
- Thyroid volume(From baseline to 12 months after infusion of CAR-T cells)
研究者
Xiaoying Li
Professor
Shanghai Zhongshan Hospital
研究点 (1)
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