In Vivo CAR-T for Refractory Graves' Disease

NCT07333677 | Recruiting Early Phase 1

• 1 other identifier: B2025-805
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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

Keywords

refractory Graves' disease; TSH receptor antibody; in vivo CAR-T

Outcome Measures

Primary Outcomes (2)

• Incidence and severity of Adverse Events (AEs)

  Assessment of the incidence and severity of treatment-emergent adverse events (AEs) occurring within 3 months after drug administration at the recommended dose.

  From baseline to 3 months after infusion of HN2301

• Remission of Graves' disease

  Proportion of remission will be calculated throughout 12 months after initial dose of HN2301. Remission is defined as euthyroid status without anti-thyroid medication.

  From baseline to 12 months after infusion of HN2301

Secondary Outcomes (14)

• Proportion of participants with ≥50% reduction of anti-thyrotropin receptor antibody (TRAb)

  From baseline to 12 months after infusion of HN2301

• Proportion of participants with ≥50% reduction of thyroid stimulating immunoglobulin (TSI)

  From baseline to 12 months after infusion of HN2301

• Change of TRAb levels compared to baseline

  From baseline to 12 months after infusion of HN2301

• Change of TSI levels compared to baseline

  From baseline to 12 months after infusion of HN2301

• Change of thyroid gland volume compared to baseline

  From baseline to 12 months after infusion of HN2301

Study Arms (1)

In Vivo CAR-T Therapy for Refractory Graves' Disease

EXPERIMENTAL

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

Biological: In Vivo CAR-T Therapy

Interventions

In Vivo CAR-T Therapy BIOLOGICAL

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

Also known as: HN2301

In Vivo CAR-T Therapy for Refractory Graves' Disease

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

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

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: SPONSOR

Study Record Dates

• First Submitted: December 20, 2025
• First Posted: January 12, 2026
• Study Start: January 29, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: March 19, 2026

Record last verified: 2025-11

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)