NCT07261345招募中早期 1 期
The Safety and Efficacy of Allogenic Anti-CD19/BCMA 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 4 人开始时间: 2025年12月19日最近更新:
干预措施
试验速览
- 阶段
- 早期 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 4
- 试验地点
- 1
- 主要终点
- Incidence and severity of treatment-emergent adverse events (AEs)
研究概览
简要总结
Graves' disease is an autoimmune thyroid disorder in which autoantibodies against the thyroid-stimulating hormone receptor (TRAb) lead to excessive thyroid hormone production and systemic complications, as well as thyroid eye disease and pretibial myxedema in some cases. Patients with refractory Graves' disease often fail to achieve durable remission despite prolonged antithyroid medication.
This study aims to evaluate the safety and efficacy of RD06-05, an allogeneic dual CD19/BCMA CAR-T therapy, in participants with refractory Graves' disease, and will provide preliminary evidence on whether dual-targeting CAR-T therapy can induce sustained remission of refractory Graves' disease.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •(Participants must meet all of the following inclusion criteria to be eligible for this study):
- •Refractory Graves' disease, defined as meeting at least one of the following: a) Continuous treatment with antithyroid drugs (ATDs) for ≥3 years without achieving criteria for drug discontinuation. b) Meeting criteria for drug discontinuation but experiencing ≥2 relapses after withdrawal.
- •Positive serum TRAb.
- •Willing to voluntarily participate in this clinical study, able to sign informed consent, and compliant with follow-up requirements.
排除标准
- •(Participants will be excluded if any of the following conditions apply):
- •History of severe drug allergies or allergic constitution.
- •Presence or suspected presence of uncontrolled or active infections (including bacterial, fungal, viral, or other pathogens) requiring systemic or intravenous treatment.
- •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.
- •Subjects with malignancy (current or past), except for conditions deemed cured and with no risk of recurrence based on investigator assessment.
- •Positive viral serology, including any of the following: Hepatitis B surface antigen (HBsAg)-positive, or hepatitis B core antibody (HBcAb)-positive with HBV DNA above the upper limit; Hepatitis C virus (HCV) antibody-positive with detectable HCV RNA; Human immunodeficiency virus (HIV) antibody-positive; Positive syphilis test.
- •Severe psychiatric disorder or significant cognitive impairment that may affect compliance.
- •Hematologic dysfunction, including: a) White blood cell count < 3.5 × 10⁹/L; b) Neutrophil count < 1.8 × 10⁹/L; c) Hemoglobin < 110 g/L.
- •Hepatic dysfunction, defined as any of the following: Alanine aminotransferase (ALT) > 3 × ULN; Aspartate aminotransferase (AST) > 3 × ULN; Total bilirubin (TBIL) > 2.5 × ULN.
- •Renal dysfunction: creatinine clearance rate (CrCl) < 60 mL/min (Cockcroft-Gault formula).
- •Left ventricular ejection fraction (LVEF) < 55%.
- •Coagulation abnormalities, defined as either: International normalized ratio (INR) > 1.5 × ULN; Prothrombin time (PT) > 1.5 × ULN.
- •Participation in another clinical trial within 3 months prior to enrollment.
- •Pregnant or breastfeeding women, or women planning to become pregnant.
- •Any other condition that, in the opinion of the investigator, would make the participant unsuitable for the study.
研究组 & 干预措施
Intervention Arm
Experimental
Participants will receive a single dose of allogenic anti-CD19/BCMA CAR-T (RD06-05).
干预措施: allogenic anti-CD19/BCMA CAR-T (Biological)
结局指标
主要结局
Incidence and severity of treatment-emergent adverse events (AEs)
时间窗: From baseline to 12 months after infusion of CAR-T cells
Remission of Graves' disease
时间窗: From baseline to 12 months after infusion of CAR-T cells
Proportion of remission will be calculated throughout 12 months after infusion of CAR-T cells. Remission is defined as euthyroid status without anti-thyroid medication.
次要结局
- Proportion of participants with ≥50% reduction of anti-thyrotropin receptor antibody (TRAb)(From baseline to 12 months after infusion of CAR-T cells)
- Proportion of participants with ≥50% reduction of thyroid stimulating immunoglobulin (TSI)(From baseline to 12 months after infusion of CAR-T cells)
- Change of TRAb levels compared to baseline(From baseline to 12 months after infusion of CAR-T cells)
- Change of thyroglobulin antibody (TgAb) levels compared to baseline(From baseline to 12 months after infusion of CAR-T cells)
- Change of serum free T3 (FT3) levels compared to baseline(From baseline to 12 months after infusion of CAR-T cells)
- Change of serum free T4 (FT4) levels compared to baseline(From baseline to 12 months after infusion of CAR-T cells)
- Change of TSI levels compared to baseline(From baseline to 12 months after infusion of CAR-T cells)
- Change of thyroid gland volume compared to baseline(From baseline to 12 months after infusion of CAR-T cells)
- Change of thyroid peroxidase antibody (TPOAb) levels compared to baseline(From baseline to 12 months after infusion of CAR-T cells)
- Dynamic change of circulating CAR-T cell count(From baseline to 3 months after infusion)
- Dynamic change of serum immunoglobulin levels(From baseline to 12 months after infusion)
- Cmax of CAR-T cells after infusion(Day 0 to Day 28)
- Tmax of CAR-T cells after infusion(Day 0 to Day 28)
- Dynamic change of serum tumor necrosis factor α (TNF-α)(From baseline to 3 months after infusion of CAR-T cells.)
- Dynamic change of CAR transgene copy number(From baseline to 3 months after infusion)
- Dynamic change of peripheral B lymphocyte cell counts(From baseline to 12 months after infusion of CAR-T cells.)
- Dynamic change of serum interleukin-6(From baseline to 3 months after infusion of CAR-T cells.)
研究者
研究点 (1)
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