Graves' DiseaseEarly Phase 1NCT07333677
In Vivo CAR-T for Refractory Graves' Disease
A Early Phase 1 study testing In Vivo CAR-T Therapy in people with Graves' Disease, run by Shanghai Zhongshan Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Graves' Disease
- What is being tested?
- In Vivo CAR-T Therapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteChina
- Study dates
- 29 Jan 2026to Dec 2027
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Zhongshan Hospital Fudan University
Shanghai, Shanghai Municipality, 200032
Jingjing JIANG, MD, PhD, 86-021-64041990, jiang.jingjing@zs-hospital.sh.cn
HUIJIE ZHANG, MD, PhD
About this study
Official title: 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.
- Conditions
- Graves' Disease
- Being tested
- In Vivo CAR-T Therapy
- Keywords
- refractory Graves' disease, TSH receptor antibody, in vivo CAR-T
- Medical subject headings
- Graves Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
In Vivo CAR-T TherapyBiological
Also called HN2301
Participants will receive 3 to 5 intravenous administrations of HN2301, given once every 2 days, according to the study dosing regimen.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Biological: In Vivo CAR-T Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: From baseline to 12 months after infusion of HN2301
Secondary outcomes (14)
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.
Measured: From baseline to 12 months after infusion of HN2301
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.
Measured: From baseline to 12 months after infusion of HN2301
Change of TRAb levels compared to baseline
TRAb levels will be measured from baseline to 12 months after initial dose of HN2301
Measured: From baseline to 12 months after infusion of HN2301
Change of TSI levels compared to baseline
TSI levels will be measured from baseline to 12 months after initial dose of HN2301
Measured: From baseline to 12 months after infusion of HN2301
Change of thyroid gland volume compared to baseline
Size of thyroid will be measured and calculated by ultrasound from baseline to 12 months after initial dose of HN2301
Measured: From baseline to 12 months after infusion of HN2301
Change of thyroid peroxidase antibody (TPOAb) levels compared to baseline
TPOAb levels will be measured from baseline to 12 months after initial dose of HN2301
Measured: From baseline to 12 months after infusion of HN2301
Change of Thyroglobulin antibody (TgAb) levels compared to baseline
TgAb levels will be measured from baseline to 12 months after initial dose of HN2301
Measured: From baseline to 12 months after infusion of HN2301
Proportion of CAR-T cells generated in peripheral blood after HN2301 administration
Proportion of CAR-T cells generated in peripheral blood after infusion of HN2301
Measured: Day 0 to Day 14
Time to peak CAR-T Cell generation in peripheral blood after HN2301 administration
Time to reach the peak level of CAR-T cells generated in peripheral blood after infusion of HN2301
Measured: Day 0 to Day 14
Dynamic change of CAR gene copy number in peripheral blood after HN2301 administration
Measured: Day 0 to Day 14
Dynamic change of peripheral blood B lymphocyte cell count after HN2301 administration
Measured: From baseline to 12 months after infusion of HN2301
Dynamic change of serum interleukin-6 after HN2301 administration
Measured: From baseline to 12 months after infusion of HN2301
Dynamic change of serum tumor necrosis factor α (TNF-α) after HN2301 administration
Measured: From baseline to 12 months after infusion of HN2301
Dynamic change of serum immunoglobulin levels after HN2301 administration
Measured: From baseline to 12 months after infusion of HN2301
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2026
- Study start29 Jan 2026
- Primary completionJun 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Graves' DiseaseStudies of the same condition, open and under way.
- More trials run by Shanghai Zhongshan HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Zhongshan Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07333677
- Sponsor's protocol ID
- B2025-805
- Status last verified
- Nov 2025
- First submitted
- 20 Dec 2025
- Last updated
- 19 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All IPD that underlie results in a publication
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Safety and Efficacy Study of in Vivo CAR-T (HN2301) for Refractory Graves' Disease
- ClinicalTrials.gov ID
- NCT07333677
- Acronym / sponsor ID
- B2025-805
- Conditions
- Graves' Disease
- Keywords
- refractory Graves' disease, TSH receptor antibody, in vivo CAR-T
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 5 participants (estimated)
- Lead sponsor
- Shanghai Zhongshan HospitalUniversity, hospital or other
- Study start
- 29 Jan 2026 (actual)
- Primary completion
- Jun 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 12 Jan 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| In Vivo CAR-T Therapy for Refractory Graves' Disease | Experimental | Biological: In Vivo CAR-T TherapyParticipants with refractory Graves' disease will receive three to five intraveneous administrations of In Vivo CAR-T (HN2301). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| In Vivo CAR-T TherapyAlso: HN2301Participants will receive 3 to 5 intravenous administrations of HN2301, given once every 2 days, according to the study dosing regimen. | Biological | In Vivo CAR-T Therapy for Refractory Graves' Disease |
Primary outcome
Incidence and severity of Adverse Events (AEs)
Time frame: From baseline to 3 months after infusion of HN2301
Assessment of the incidence and severity of treatment-emergent adverse events (AEs) occurring within 3 months after drug administration at the recommended dose.
Remission of Graves' disease
Time frame: From baseline to 12 months after infusion of HN2301
Proportion of remission will be calculated throughout 12 months after initial dose of HN2301. Remission is defined as euthyroid status without anti-thyroid medication.
14 secondary outcomes
Proportion of participants with ≥50% reduction of anti-thyrotropin receptor antibody (TRAb)
Time frame: From baseline to 12 months after infusion of HN2301
Proportion of participants with ≥50% reduction of thyroid stimulating immunoglobulin (TSI)
Time frame: From baseline to 12 months after infusion of HN2301
Change of TRAb levels compared to baseline
Time frame: From baseline to 12 months after infusion of HN2301
Change of TSI levels compared to baseline
Time frame: From baseline to 12 months after infusion of HN2301
Change of thyroid gland volume compared to baseline
Time frame: From baseline to 12 months after infusion of HN2301
Change of thyroid peroxidase antibody (TPOAb) levels compared to baseline
Time frame: From baseline to 12 months after infusion of HN2301
Change of Thyroglobulin antibody (TgAb) levels compared to baseline
Time frame: From baseline to 12 months after infusion of HN2301
Proportion of CAR-T cells generated in peripheral blood after HN2301 administration
Time frame: Day 0 to Day 14
Time to peak CAR-T Cell generation in peripheral blood after HN2301 administration
Time frame: Day 0 to Day 14
Dynamic change of CAR gene copy number in peripheral blood after HN2301 administration
Time frame: Day 0 to Day 14
Dynamic change of peripheral blood B lymphocyte cell count after HN2301 administration
Time frame: From baseline to 12 months after infusion of HN2301
Dynamic change of serum interleukin-6 after HN2301 administration
Time frame: From baseline to 12 months after infusion of HN2301
Dynamic change of serum tumor necrosis factor α (TNF-α) after HN2301 administration
Time frame: From baseline to 12 months after infusion of HN2301
Dynamic change of serum immunoglobulin levels after HN2301 administration
Time frame: From baseline to 12 months after infusion of HN2301
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2026.
- Individual participant dataSharing planned: Yes. All IPD that underlie results in a publication
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing In Vivo CAR-T Therapy in people with Graves' Disease, run by Shanghai Zhongshan Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 19 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jingjing JIANG, MD, PhD (86-021-64041990, jiang.jingjing@zs-hospital.sh.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence and severity of Adverse Events (AEs) (time frame: From baseline to 3 months after infusion of HN2301). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2026.