Recruiting
Early Phase 1
Allogeneic Anti-CD19/BCMA CAR-T for Refractory Graves' Disease
Condition(s) studied
Graves' Disease
Investigational drug(s) / intervention(s)
allogenic anti-CD19/BCMA CAR-T
allogenic anti-CD19/BCMA CAR-T: Participants will receive a single infusion of allogenic anti-CD19/BCMA CAR-T (RD06-05).
Study summary
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.
Eligibility
Inclusion Criteria (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.
Exclusion Criteria (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.
Primary outcome measure(s)
- Incidence and severity of treatment-emergent adverse events (AEs) — From baseline to 12 months after infusion of CAR-T cells
- Remission of Graves' disease — 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.
Trial sites (1)
| Facility | City | Region | Status |
|---|
| Zhongshan Hospital Fudan University |
Shanghai |
Shanghai Municipality |
Recruiting |
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