💬In plain words
What the trial is, and whether it could suit you
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 sustain
Sign in to get the eligibility rules as simple questions to take to your doctor.
📋 Eligibility rules (as published)
Inclusion Criteria (Participants must meet all of the following criteria to be eligible for this study):
* 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.
Exclusion Criteria (Participants meeting any of the following criteria will be excluded from the study):
* 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.
* 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 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.
* 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.
* Any other condition that, in the opinion of the investigator, would make the participant unsuitable for the study.
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