In Vivo CAR-T for Refractory Graves' Disease

A vizsgálat adatai

Ki végzi

Shanghai Zhongshan Hospital

Azonosító

NCT07333677

A regiszteradat frissítve

2026. március 19.

Eredeti leírás

Graves' disease is an autoimmune thyroid disorder characterized by the production of autoantibodies against the thyroid-stimulating hormone receptor (TRAb), leading to excessive thyroid hormone secretion and systemic manifestations. A subset of patients develop refractory disease, failing to achieve durable remission despite prolonged antithyroid therapy.A teljes eredeti leírásKevesebb

A Safety and Efficacy Study of in Vivo CAR-T (HN2301) for Refractory Graves' Disease

Graves' disease is an autoimmune thyroid disorder characterized by the production of autoantibodies against the thyroid-stimulating hormone receptor (TRAb), leading to excessive thyroid hormone secretion and systemic manifestations. A subset of patients develop refractory disease, failing to achieve durable remission despite prolonged antithyroid therapy.

This study aims to evaluate the safety and efficacy of HN2301, an in vivo CAR-T therapy in which host T lymphocytes are engineered and transformed to functional CAR-T cells via CD8 antibody-coated LNP delivery of CD19 CAR-mRNA. Participants with refractory Graves' disease will receive three to five administrations of HN2301 and will be regularly monitored for changes in thyroid function, TRAb levels, clinical response, and treatment-related adverse events. The study will provide preliminary evidence on whether HN2301 can induce sustained remission of refractory Graves' disease.

Bevonási feltételek: Age 18-75 years (inclusive), male or female; Refractory Graves' disease, defined as meeting at least one of the following: a) Continuous antithyroid drug (ATD) therapy for ≥3 years without achieving criteria for ATD discontinuation; b) Meeting criteria for ATD discontinuation but experiencing ≥2 relapses after ATD withdrawal; Positive serum TRAb; Willing to use effective contraception for 12 months after study drug administration; Voluntarily agrees to participate in the study, has signed the informed consent form, and is able to comply with study procedures and follow-up requirements.

Kizáró feltételek: Receipt of any mRNA-LNP product or other lipid nanoparticle (LNP)-based therapy within the past 2 years; Receipt of a live vaccine within 30 days prior to screening; History of severe drug allergy or known allergic predisposition; Presence or suspected presence of uncontrolled active infection; History of major organ transplantation (e.g., heart, lung, liver, kidney) or bone marrow/hematopoietic stem cell transplantation; Presence of significant heart disease, such as angina, myocardial infarction, heart failure, or clinically significant arrhythmias; History of malignant tumors; Positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with peripheral blood HBV DNA above the detection limit; positive hepatitis C virus (HCV) antibody with detectable HCV RNA; positive human immunodeficiency virus (HIV) antibody; or positive syphilis test; Presence of psychiatric disorders or severe cognitive impairment; Any other condition that, in the opinion of the investigator, would make the participant unsuitable for the study; Hematologic dysfuction at screening, defined as any of the following: a. Neutrophil count < 1.8 × 10⁹/L, b. Hemoglobin < 110 g/L, c. Platelet count < 50 × 10⁹/L; Impaired liver function, defined as any of the following: Alanine aminotransferase (ALT) > 3 × ULN, Aspartate aminotransferase (AST) > 3 × ULN, Total bilirubin > 2.5 × ULN; Impaired renal function: 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; Pregnant or breastfeeding women.

ClinicalTrials.gov NCT07333677