Allogeneic anti‑CD19 CAR‑T therapy for refractory Graves' disease

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

This will try a single dose of donor‑derived anti‑CD19 CAR‑T cells to lower TSH‑receptor antibodies and control hyperthyroidism in people whose Graves' disease has not responded to standard treatments.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 5 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Shanghai Zhongshan Hospital (Academic / other)
• Drugs / interventions: CAR-T
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07129642 on ClinicalTrials.gov

What this trial studies

This early‑phase study gives one dose of allogeneic anti‑CD19 CAR‑T cells to people with refractory Graves' disease and follows them for changes in serum TRAb, FT3, FT4, clinical symptoms, and adverse events. The approach aims to deplete B cells that produce TSH‑receptor antibodies, the drivers of thyroid hormone overproduction and associated eye disease. Participants must have significantly elevated TRAb and detectable CD19 expression on peripheral B cells and will be followed with frequent clinic visits and laboratory monitoring. The trial is conducted at Zhongshan Hospital, Fudan University, and focuses on safety and signals of clinical effect rather than definitive efficacy.

Who should consider this trial

Good fit: Ideal candidates are adults with refractory Graves' disease (persistent or relapsing disease after prolonged antithyroid drugs or multiple radioiodine treatments) who have TRAb ≥5 IU/L and detectable CD19 on peripheral B cells and who can consent to close follow‑up.

Not a fit: Patients whose disease is well controlled, who have low or negative TRAb, or who lack detectable CD19‑expressing B cells are unlikely to benefit from this CD19‑targeted approach.

Why it matters

Potential benefit: If successful, the therapy could substantially lower TRAb levels and produce durable remission of hyperthyroidism in patients who have exhausted standard options.

How similar studies have performed: CD19‑directed CAR‑T has been highly effective in B‑cell cancers and has shown encouraging early results in some autoimmune disorders, but applying allogeneic anti‑CD19 CAR‑T to refractory Graves' disease is novel and largely untested.

Eligibility criteria

Inclusion Criteria:

* 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 Criteria:

* 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: 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;
* 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.

Where this trial is running

Shanghai, Shanghai Municipality

• Zhongshan Hospital Fudan University — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Principal investigator: Xiaoying LI, MD, PhD — Fudan University
• Study coordinator: Jingjing JIANG, MD, PhD

Conditions Graves Disease; CAR-T; refractory Graves disease; TSH receptor antibody