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

NCT07261345 | Recruiting Early Phase 1

• 1 other identifier: B2025-711
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Graves' Disease

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Incidence and severity of treatment-emergent adverse events (AEs)

  From baseline to 12 months after infusion of CAR-T cells

• Remission of Graves' disease

  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.

  From baseline to 12 months after infusion of CAR-T cells

Secondary Outcomes (17)

• Proportion of participants with ≥50% reduction of anti-thyrotropin receptor antibody (TRAb)

  From baseline to 12 months after infusion of CAR-T cells

• Proportion of participants with ≥50% reduction of thyroid stimulating immunoglobulin (TSI)

  From baseline to 12 months after infusion of CAR-T cells

• Change of TRAb levels compared to baseline

  From baseline to 12 months after infusion of CAR-T cells

• Change of TSI levels compared to baseline

  From baseline to 12 months after infusion of CAR-T cells

• Change of thyroid gland volume compared to baseline

  From baseline to 12 months after infusion of CAR-T cells

Other Outcomes (2)

• BCR repertoire dynamics (Exploratory)

  From baseline to 12 months after infusion

• TCR repertoire dynamics (Exploratory)

  From baseline to 12 months after infusion

Study Arms (1)

Intervention Arm

EXPERIMENTAL

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

Biological: allogenic anti-CD19/BCMA CAR-T

Interventions

allogenic anti-CD19/BCMA CAR-T BIOLOGICAL

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

Intervention Arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead

Study Sites (1)

Zhongshan Hospital Fudan University

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

MeSH Terms

Conditions

Graves Disease

Condition Hierarchy (Ancestors)

Exophthalmos; Orbital Diseases; Eye Diseases; Goiter; Thyroid Diseases; Endocrine System Diseases; Hyperthyroidism; Autoimmune Diseases; Immune System Diseases

Central Study Contacts

Jingjing JIANG, MD, PhD

CONTACT

86-021-64041990; jiang.jingjing@zs-hospital.sh.cn

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2025
• First Posted: December 3, 2025
• Study Start: December 19, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: January 5, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: After publication.
• Access Criteria: IPD and supporting information will be avaible to researchers upon reasonable request (e.g. with a practical and meaningful research proposal).

Locations

CN (1)