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

Официальное название

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

Обзор

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.

Вмешательства

• Биопрепарат Allogeneic CAR-T
  The participants will receive one dose of allogeneic CAR-T

Первичные конечные точки

• Remission of Graves disease [Срок оценки: From baseline to 12 months after infusion of CAR-T cells]
• Incidence of Adverse Events [Срок оценки: From baseline to 6 months after infusion of CAR-T cells]

Вторичные конечные точки (7)

• Anti-Thyrotropin receptor antibody (TRAb) [Срок оценки: From baseline to 12 months after infusion of CAR-T cells]
• Thyroid stimulating immunoglobulin (TSI) [Срок оценки: From baseline to 12 months after infusion of CAR-T cells]
• thyroid peroxidase antibody (TPOAb) [Срок оценки: From baseline to 12 months after infusion of CAR-T cells]
• Thyroglobulin antibody (TgAb) [Срок оценки: From baseline to 12 months after infusion of CAR-T cells]
• Thyroid volume [Срок оценки: From baseline to 12 months after infusion of CAR-T cells]
• PK parameters - CAR gene copy number [Срок оценки: From baseline to 3 months after infusion of CAR-T cells]
• PK parameters - CAR-T cell count [Срок оценки: From baseline to 3 months after infusion of CAR-T cells]

Критерии участия

Критерии включения

• 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.)

Критерии исключения

• 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;
• Other conditions considered by investigators as unsuitable for participation.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Zhongshan Hospital Fudan University — Шанхай

Идентификаторы

NCT: NCT07129642 · B2025-217R

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗