In Vivo CAR-T for Refractory Graves' Disease

NCT ID: NCT07333677

Last Updated: 2026-01-12

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-31
• Study Completion Date: 2027-12-31

Brief Summary

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.

Conditions

Graves' Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

In Vivo CAR-T Therapy for Refractory Graves' Disease

Participants with refractory Graves' disease will receive three to five intraveneous administrations of In Vivo CAR-T (HN2301).

Group Type: EXPERIMENTAL

In Vivo CAR-T Therapy

Intervention Type: BIOLOGICAL

Participants will receive 3 to 5 intravenous administrations of HN2301, given once every 2 days, according to the study dosing regimen.

Interventions

In Vivo CAR-T Therapy

Participants will receive 3 to 5 intravenous administrations of HN2301, given once every 2 days, according to the study dosing regimen.

Intervention Type: BIOLOGICAL

Other Intervention Names

HN2301

Eligibility Criteria

Inclusion Criteria

• 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

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Zhongshan Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Zhongshan Hospital Fudan University

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Jingjing JIANG, MD, PhD

Role: CONTACT

jiang.jingjing@zs-hospital.sh.cn

86-021-64041990

Facility Contacts

Jingjing JIANG, MD, PhD

Role: primary

jiang.jingjing@zs-hospital.sh.cn

86-021-64041990

Other Identifiers

B2025-805

Identifier Type: -

Identifier Source: org_study_id