A Clinical Study to Evaluate the Safety and Efficacy of GT802 Injection in the Treatment of Relapsing/Refractory Multiple Sclerosis

The study consists of three dose groups as follows:

Dose Level 1: Total dose of 8.5 mg, administered via 4 separate intravenous infusions at doses of 1.0 mg, 1.5 mg, 3.0 mg and 3.0 mg; Dose Level 2: Total dose of 13.5 mg, administered via 4 separate intravenous infusions at doses of 1.5 mg, 3.0 mg, 4.5 mg and 4.5 mg; De-escalation Dose: Total dose of 4.5 mg, administered via 4 separate intravenous infusions at doses of 0.5 mg, 1.0 mg, 1.5 mg and 1.5 mg.

It is planned to enroll 4-12 participants in total. The planned number of participants for each dose group is specified below:

Dose Level 1: 1-6 participants; Dose Level 2: 3-6 participants; De-escalation Dose: 1-6 participants.

Inclusion criteria

• 1. The participant or their legally authorized representative voluntarily signs a written informed consent form and is willing and able to comply with all study procedures specified in this protocol.
• 2. Aged between 18 and 65 years old inclusive at the time of informed consent signature, with no restriction on gender.
• 3. For any prior systemic therapy administered for the indication, a washout period of at least 4 weeks or 5 half-lives (whichever is shorter) must have elapsed prior to the participant's scheduled administration of study treatment.
• 4. Toxicities resulting from prior therapies must have stabilized and resolved to Grade ≤1, excluding clinically insignificant toxicities such as alopecia.
• 5. Confirmed diagnosis of relapsed/refractory multiple sclerosis with limited effective therapeutic options at present based on specified diagnostic criteria.
• 6. Screening laboratory test results shall meet the corresponding criteria (no corrective treatment with any blood products or cellular growth factors administered within 7 days prior to laboratory testing).
• 7. Pregnancy-related requirements:
• a. Serum beta human chorionic gonadotropin (β-hCG) pregnancy test result is negative as confirmed by the investigator at screening.
• b. Agree to refrain from breastfeeding throughout study participation for at least 1 year after infusion of GT802 Injection, or until two consecutive flow cytometry assays confirm the absence of GT802 cells (whichever occurs later).
• c. Male participants with sexual partners and female participants of childbearing potential must agree to use highly effective contraceptive methods (e.g., oral contraceptives, intrauterine devices, condoms) starting at screening and continuing for at least 1 year after infusion of GT802 Injection, or until two consecutive flow cytometry assays confirm the absence of GT802 cells (whichever occurs later). Male participants must agree to use condoms during sexual intercourse with pregnant females or females of childbearing potential for a minimum of 1 year after GT802 Injection infusion, even following successful vasectomy.

Exclusion criteria

• 1. Contraindication or hypersensitivity reaction to any component of the investigational product.
• 2. Presence of any of the following conditions within 6 months prior to signing the informed consent form (ICF): uncontrolled congestive heart failure (New York Heart Association [NYHA] Class III-IV), angina pectoris, myocardial infarction, cardiomyopathy, stroke (lacunar infarction excluded), coronary/peripheral artery bypass graft surgery, clinically significant arrhythmias including but not limited to ventricular arrhythmias, markedly prolonged QT interval (QTc ≥ 500 ms corrected by Bazett's formula, to be judged by the investigator), poorly controlled hypertension (systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg), uncontrolled diabetes mellitus, diffuse pulmonary lesions, pulmonary insufficiency, or other clinically significant cardiac disorders.
• 3. History of active malignant tumor or any malignancy within 5 years prior to screening. The following are exceptions: early-stage malignancies treated with curative intent (carcinoma in situ or Stage I tumors, non-ulcerated primary melanoma with depth <1 mm and no lymph node involvement), basal cell carcinoma of the skin, cutaneous squamous cell carcinoma, cervical carcinoma in situ, or breast carcinoma in situ treated with potentially curative therapy.
• 4. Any other known autoimmune disease besides the study indication.
• 5. Requiring long-term administration of medications affecting blood coagulation.
• 6. Subjects with clinically evident bleeding symptoms or definite bleeding diathesis within 6 months before screening, such as gastrointestinal hemorrhage, hemorrhagic gastric ulcer, etc.; hereditary or acquired bleeding and thrombotic diatheses (e.g., hemophilia, coagulation disorders, hypersplenism, etc.); arterial or venous thromboembolic events occurring within 6 months prior to screening, including cerebrovascular diseases (cerebral hemorrhage, cerebral infarction, etc.), deep vein thrombosis and/or pulmonary embolism.
• 7. Presence of severe underlying medical conditions at screening, such as:
• a) Evidence of uncontrolled viral, bacterial, fungal or other infections requiring systemic intravenous therapy;
• b) Distinct clinical evidence of dementia or altered mental status;
• c) History of any other central nervous system disease or neurodegenerative disease, such as epilepsy, convulsive seizures, paralysis, aphasia, stroke, severe traumatic brain injury, dementia, Parkinson's disease, psychosis.
• 8. Positive test result for any of the following items:
• a) Positive human immunodeficiency virus (HIV) antibody;
• b) Positive hepatitis B surface antigen (HBsAg) and/or positive hepatitis B core antibody (HBcAb), with HBV-DNA above the lower limit of quantification of the assay;
• c) Positive hepatitis C virus (HCV) antibody, with HCV RNA above the lower limit of quantification of the assay;
• d) Positive syphilis antibody (excluding false-positive results caused by underlying diseases).
• 9. Positive cytomegalovirus (CMV)-DNA and Epstein-Barr virus (EBV)-DNA tests (plasma + peripheral blood mononuclear cells [PBMC]).
• 10. Active tuberculosis or latent tuberculosis infection without appropriate treatment prior to screening.
• 11. Received another investigational medicinal product within 4 weeks before ICF signature, or the interval from the last administration of the previous clinical trial drug to ICF signature is still within 5 half-lives of the drug (whichever is longer).
• 12. Received intravenous immunoglobulin (IVIG), plasma exchange or immunoadsorption therapy within 4 weeks prior to study treatment initiation.
• 13. Received B-cell-targeted therapy within 1 month prior to study treatment initiation, including but not limited to rituximab, belimumab, telitacicept, etc.
• 14. Received tacrolimus, cyclosporine, azathioprine, mycophenolate mofetil, mycophenolic acid, methotrexate, etc., within 2 weeks prior to study treatment initiation.
• 15. Received neonatal Fc receptor (FcRn) antagonist therapy (e.g., efgartigimod, etc.) within 2 weeks prior to study treatment initiation.
• 16. Received complement inhibition therapy (e.g., eculizumab, etc.) within 2 weeks prior to study treatment initiation.
• 17. Received systemic glucocorticoids at a daily dose ≥10 mg prednisone equivalent within 7 days prior to study treatment initiation (inhaled glucocorticoids excluded).
• 18. Received live attenuated vaccines or mRNA vaccines within 8 weeks before enrollment, or inactivated vaccines within 4 weeks before enrollment.
• 19. Underwent major surgery within 8 weeks prior to screening, or scheduled to receive surgical procedures during the study period.
• 20. History of solid organ transplantation, splenectomy, allogeneic or autologous stem cell transplantation.
• 21. Presence of any indwelling catheter or drainage tube (e.g., percutaneous nephrostomy tube, indwelling Foley catheter, biliary drainage tube, pleural/peritoneal/pericardial catheter). Dedicated central venous access catheters such as Port-a-Cath or Hickman catheter are permitted.
• 22. Uncontrolled massive serous effusions despite treatment (e.g., pleural effusion, ascites, pericardial effusion).
• 23. Prior administration of CAR-T products targeting any antigen or other gene-edited cellular biotherapies.
• 24. History of other autoimmune diseases (e.g., Crohn's disease, systemic lupus erythematosus, etc.) within the past 2 years that have caused end-organ damage or required systemic immunosuppression, except for the disease population specified in the inclusion criteria.
• 25. Any condition that, in the investigator's judgment, would interfere with the subject's full participation in the trial, confound study results, or render trial participation inconsistent with the subject's best interest.