Allogeneic dual CD19/BCMA CAR-T therapy for refractory Graves' disease

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

This will test an off-the-shelf CAR-T treatment that targets CD19 and BCMA to see if it can produce lasting remission in people whose Graves' disease has not responded to standard medications.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 4 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Shanghai Zhongshan Hospital (Academic / other)
• Drugs / interventions: CAR-T
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07261345 on ClinicalTrials.gov

What this trial studies

This early-phase 1, single-site study gives an allogeneic CAR-T product that targets both CD19 and BCMA to people with refractory Graves' disease to determine early safety and signs of benefit. Participants must have persistent or relapsing disease despite prolonged antithyroid drug therapy and positive TRAb. The dual-target approach aims to remove pathogenic B cells and antibody-secreting plasma cells to lower TRAb levels and reduce thyroid overactivity. The trial will monitor adverse events, immune-related toxicities, thyroid function, and antibody titers to gather preliminary evidence of sustained remission.

Who should consider this trial

Good fit: Ideal candidates are adults with refractory Graves' disease who have positive TRAb and either have been on antithyroid drugs for three years without meeting drug discontinuation criteria or have had two or more relapses after stopping medication, and who can consent and comply with follow-up.

Not a fit: Patients with active or uncontrolled infections, a history of severe drug allergies or certain central nervous system disorders, or those who have not met the refractory criteria are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, the treatment could produce durable remission, reduce or eliminate the need for long-term antithyroid drugs, and lower the risk of complications from ongoing antibody-driven disease.

How similar studies have performed: CAR-T approaches for autoimmune diseases are an emerging area with early signals in other conditions, but dual CD19/BCMA allogeneic CAR-T for Graves' disease is largely novel and untested in humans.

Eligibility criteria

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.

Where this trial is running

Shanghai, Shanghai Municipality

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

Study contacts

• Study coordinator: Jingjing JIANG, MD, PhD

Conditions Graves' Disease; CAR-T; TSH receptor antibody; refractory Graves' disease