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

NCT07129642 | Recruiting Early Phase 1 DMC

• 1 other identifier: B2025-217R
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

Graves' disease is an autoimmune disease. The TSH receptor antibody(TRab) produced by B cells drives the production of thyroid hormone, which causes systemic disorders and thyroid eye disease. The purpose of this study is to investigate the efficacy and safety of allogeneic anti-CD19 CAR-T for refractory Graves' disease. The participants with refractory Graves' disease will receive a single dose of allogeneic anti-CD19 CAR-T and be regularly seen for the change of serum TRab, FT3, FT4 and clinical presentations, as well as any adverse events.

Conditions

Graves Disease

Keywords

CAR-T; refractory Graves disease; TSH receptor antibody

Outcome Measures

Primary Outcomes (2)

• Remission of Graves disease

  Sustained euthyroid status without anti-thyroid medication for ≥3 months

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

• Incidence of Adverse Events

  Assessed using the CTCAE v5.0 standards

  From baseline to 6 months after infusion of CAR-T cells

Secondary Outcomes (7)

• Anti-Thyrotropin receptor antibody (TRAb)

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

• Thyroid stimulating immunoglobulin (TSI)

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

• thyroid peroxidase antibody (TPOAb)

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

• Thyroglobulin antibody (TgAb)

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

• Thyroid volume

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

Study Arms (1)

Intervention Arm

EXPERIMENTAL

Biological: Allogeneic CAR-T

Interventions

Allogeneic CAR-T BIOLOGICAL

The participants will receive one dose of allogeneic CAR-T

Intervention Arm

Eligibility Criteria

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

You may qualify if:

• 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.)

You may not qualify if:

• 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;

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

Study Officials

• Xiaoying LI, MD, PhD

  Fudan University

  PRINCIPAL INVESTIGATOR

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: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 6, 2025
• First Posted: August 19, 2025
• Study Start: August 10, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): March 31, 2027
• Last Updated: August 19, 2025

Record last verified: 2025-08

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)