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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Graves' Disease
• Intervention / Treatment: Biological: allogenic anti-CD19/BCMA CAR-T

• Study Type: Interventional
• Enrollment (Estimated): 4
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Jingjing JIANG, MD, PhD; Phone Number: 86-021-64041990; Email: jiang.jingjing@zs-hospital.sh.cn

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Recruiting
      • Zhongshan Hospital Fudan University
      • Contact: Jingjing JIANG, MD, PhD; Phone Number: 86-021-64041990; Email: jiang.jingjing@zs-hospital.sh.cn
      • Principal Investigator: HUIJIE ZHANG, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention Arm; Participants will receive a single dose of allogenic anti-CD19/BCMA CAR-T (RD06-05).	Biological: allogenic anti-CD19/BCMA CAR-T; Participants will receive a single infusion of allogenic anti-CD19/BCMA CAR-T (RD06-05).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of TRAb levels compared to baseline	TRAb levels will be measured from baseline to 12 months after infusion of CAR-T cells	From baseline to 12 months after infusion of CAR-T cells
Change of TSI levels compared to baseline	TSI levels will be measured from baseline to 12 months after infusion of CAR-T cells	From baseline to 12 months after infusion of CAR-T cells
Change of thyroid peroxidase antibody (TPOAb) levels compared to baseline	TPOAb levels will be measured from baseline to 12 months after infusion of CAR-T cells	From baseline to 12 months after infusion of CAR-T cells
Change of serum free T3 (FT3) levels compared to baseline	FT3 levels will be measured from baseline to 12 months after infusion of CAR-T cells	From baseline to 12 months after infusion of CAR-T cells
Change of serum free T4 (FT4) levels compared to baseline	FT4 levels will be measured from baseline to 12 months after infusion of CAR-T cells	From baseline to 12 months after infusion of CAR-T cells
Cmax of CAR-T cells after infusion	Peak peripheral blood concentration of CAR-T cells (RD06-05 ) following infusion, measured by flow cytometry.	Day 0 to Day 28
Tmax of CAR-T cells after infusion	Time to reach maximum observed concentration (Tmax) of CAR-T cells (RD06-05).	Day 0 to Day 28
Dynamic change of circulating CAR-T cell count		From baseline to 3 months after infusion
Dynamic change of peripheral B lymphocyte cell counts		From baseline to 12 months after infusion of CAR-T cells.
Dynamic change of serum interleukin-6		From baseline to 3 months after infusion of CAR-T cells.
Dynamic change of serum tumor necrosis factor α (TNF-α)		From baseline to 3 months after infusion of CAR-T cells.
Proportion of participants with ≥50% reduction of anti-thyrotropin receptor antibody (TRAb)	Percentage of participants achieving a ≥50% reduction of TRAb throughout 12 months after infusion of CAR-T, as compared with baseline.	From baseline to 12 months after infusion of CAR-T cells
Proportion of participants with ≥50% reduction of thyroid stimulating immunoglobulin (TSI)	Percentage of participants achieving a ≥50% reduction of TSI throughout 12 months after infusion of CAR-T, as compared with baseline.	From baseline to 12 months after infusion of CAR-T cells
Change of thyroid gland volume compared to baseline	Size of the thyroid will be measured and calculated by ultrasound from baseline to 12 months after infusion of CAR-T cells	From baseline to 12 months after infusion of CAR-T cells
Change of thyroglobulin antibody (TgAb) levels compared to baseline	TgAb levels will be measured from baseline to 12 months after infusion of CAR-T cells.	From baseline to 12 months after infusion of CAR-T cells
Dynamic change of CAR transgene copy number		From baseline to 3 months after infusion
Dynamic change of serum immunoglobulin levels		From baseline to 12 months after infusion

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
BCR repertoire dynamics (Exploratory)	High-throughput sequencing of B-cell receptor (BCR) repertoires	From baseline to 12 months after infusion
TCR repertoire dynamics (Exploratory)	High-throughput sequencing of T-cell receptor (TCR) repertoires	From baseline to 12 months after infusion

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: November 23, 2025
• First Submitted That Met QC Criteria: November 23, 2025
• First Posted (Estimated): December 3, 2025

Study Record Updates

• Last Update Posted (Actual): January 5, 2026
• Last Update Submitted That Met QC Criteria: January 1, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: CAR-T; TSH receptor antibody; refractory Graves' disease
• Additional Relevant MeSH Terms: Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Eye Diseases; Exophthalmos; Orbital Diseases; Goiter; Hyperthyroidism; Thyroid Diseases; Graves Disease
• Other Study ID Numbers: B2025-711

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All IPD that underlie results in a publication
• IPD Sharing Time Frame: After publication.
• IPD Sharing Access Criteria: IPD and supporting information will be avaible to researchers upon reasonable request (e.g. with a practical and meaningful research proposal).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No