Allogeneic Anti-CD19 CAR-T for Refractory Graves' Disease

Trial details

Who runs it

Shanghai Zhongshan Hospital

Trial code

NCT07129642

Record updated

19 August 2025

Original description

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.Read full original descriptionShow less

The Efficacy and Safety of Allogenic Anti-CD19 CAR-T Cell Therapy for Refractory Graves' Disease

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.

Inclusion: 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.).

Exclusion: Participation in other clinical trials within 3 months prior to enrollment; 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); Patients with malignant tumors; Subjects who are: 1. HBsAg or HBcAb positive with detectable peripheral blood HBV DNA; 2. HCV antibody positive with detectable HCV RNA; 3. Positive HIV antibody; 4. Syphilis test positive; Subjects with psychiatric disorders or severe cognitive dysfunction; Other conditions considered by investigators as unsuitable for participation; 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; Subjects with congenital immunoglobulin deficiency; Pregnancy or planning pregnancy.

ClinicalTrials.gov NCT07129642