In Vivo CAR-T for Refractory Graves' Disease
ConditionGraves' Disease
Trial statusRecruiting
Trial phaseEarly Phase 1
Trial typeInterventional
Biological sexAll
Age18-75
SponsorShanghai Zhongshan Hospital
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Design model
Single group
Treatments tested in this trial
In Vivo CAR-T Therapy
Biological/VaccineParticipants will receive 3 to 5 intravenous administrations of HN2301, given once every 2 days, according to the study dosing regimen.
Treatment groups
5 Participants
are divided into 1 treatment groupGroup A: In Vivo CAR-T Therapy for Refractory Graves' DiseaseExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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.
Time frame
From baseline to 3 months after infusion of HN23012
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.
Time frame
From baseline to 12 months after infusion of HN2301Secondary outcomes
1
Proportion of participants with ≥50% reduction of anti-thyrotropin receptor antibody (TRAb)
Percentage of participants achieving a ≥50% reduction of TRAb throughout 12 months after initial dose of HN2301, as compared with baseline.
Time frame
From baseline to 12 months after infusion of HN23012
Proportion of participants with ≥50% reduction of thyroid stimulating immunoglobulin (TSI)
Percentage of participants achieving a ≥50% reduction of TSI througout 12 months after initial dose of HN2301, as compared with baseline.
Time frame
From baseline to 12 months after infusion of HN23013
Change of TRAb levels compared to baseline
TRAb levels will be measured from baseline to 12 months after initial dose of HN2301
Time frame
From baseline to 12 months after infusion of HN23014
Change of TSI levels compared to baseline
TSI levels will be measured from baseline to 12 months after initial dose of HN2301
Time frame
From baseline to 12 months after infusion of HN2301Sponsors and contacts
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Source ClinicalTrials.gov