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

Official title

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

Overview

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.

Interventions

• Biological allogenic anti-CD19/BCMA CAR-T
  Participants will receive a single infusion of allogenic anti-CD19/BCMA CAR-T (RD06-05).

Primary outcome measures

• Incidence and severity of treatment-emergent adverse events (AEs) [Time frame: From baseline to 12 months after infusion of CAR-T cells]
• Remission of Graves' disease [Time frame: From baseline to 12 months after infusion of CAR-T cells]

Secondary outcome measures (12)

• Proportion of participants with ≥50% reduction of anti-thyrotropin receptor antibody (TRAb) [Time frame: From baseline to 12 months after infusion of CAR-T cells]
• Proportion of participants with ≥50% reduction of thyroid stimulating immunoglobulin (TSI) [Time frame: From baseline to 12 months after infusion of CAR-T cells]
• Change of TRAb levels compared to baseline [Time frame: From baseline to 12 months after infusion of CAR-T cells]
• Change of TSI levels compared to baseline [Time frame: From baseline to 12 months after infusion of CAR-T cells]
• Change of thyroid gland volume compared to baseline [Time frame: From baseline to 12 months after infusion of CAR-T cells]
• Change of thyroid peroxidase antibody (TPOAb) levels compared to baseline [Time frame: From baseline to 12 months after infusion of CAR-T cells]
• Change of thyroglobulin antibody (TgAb) levels compared to baseline [Time frame: From baseline to 12 months after infusion of CAR-T cells]
• Change of serum free T3 (FT3) levels compared to baseline [Time frame: From baseline to 12 months after infusion of CAR-T cells]
• Change of serum free T4 (FT4) levels compared to baseline [Time frame: From baseline to 12 months after infusion of CAR-T cells]
• Cmax of CAR-T cells after infusion [Time frame: Day 0 to Day 28]
• Tmax of CAR-T cells after infusion [Time frame: Day 0 to Day 28]
• Dynamic change of circulating CAR-T cell count [Time frame: From baseline to 3 months after infusion]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Zhongshan Hospital Fudan University — Shanghai

Identifiers

NCT: NCT07261345 · B2025-711

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗