Safety and Efficacy of S103 Cells in Progressive/Refractory Multiple Sclerosis

Who cannot join

• Subjects will be ineligible for inclusion in the study if they meet any of the following criteria prior to screening or at the baseline visit:
• The subject has any medical, psychological, or social condition that, in the investigator's opinion, may harm the subject, interfere with their ability to participate in the study, or result in poor protocol compliance;
• Female subjects who are pregnant or lactating, plans to become pregnant at any time within 12 months after receiving CAR-T cell treatment, or has a history of spontaneous or induced abortion within 4 weeks prior to screening;
• The subject has a clinically relevant active infection, such as sepsis, pneumonia, or a severe local abscess, or a serious infection requiring hospitalization or intravenous antibiotic treatment within 4 weeks prior to screening. Subjects are also excluded if they have a known immunodeficiency disorder including Human Immunodeficiency Virus (HIV), test positive for Hepatitis B surface antigen (HBsAg) or detectable Hepatitis B virus (HBV) DNA, test positive for Hepatitis C virus (HCV) antibody with detectable HCV RNA, test positive for syphilis during the screening period, or have an active or high-risk history of tuberculosis infection;
• The subject has previously received any Chimeric Antigen Receptor (CAR) T-cell therapy or other genetically modified cell therapies, or has a history of allogeneic hematopoietic stem cell transplantation (HSCT) or solid organ transplantation. Furthermore, subjects are excluded if they have received intravenous immunoglobulin (IVIG) or plasma exchange (PE) within 4 weeks prior to screening, or have received tocilizumab or eculizumab treatment within 3 months prior to screening;
• The subject is diagnosed with an active, severe autoimmune disease other than Multiple Sclerosis, such as Systemic Lupus Erythematosus or Rheumatoid Arthritis. This also includes the presence of other severe progressive neurodegenerative or central nervous system (CNS) disorders, such as Parkinson's disease, Alzheimer's disease, stroke, or active CNS tumors, that the investigator believes would confound the clinical assessment of Multiple Sclerosis. Additionally, a history of active malignancy within the past 5 years excludes the subject, with the exception of adequately treated basal cell or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix;
• The subject exhibits specific laboratory abnormalities or organ dysfunction during the screening period, including elevated liver enzymes with AST or ALT greater than 1.5 times the upper limit of normal (ULN), total bilirubin greater than 1.5 times the ULN, or a Creatinine Clearance (CrCl) of less than 60 mL/min. Exclusions also apply for an absolute neutrophil count (ANC) of less than 2.0 × 10^9/L, a platelet count of less than 100 × 10^9/L, hemoglobin levels below 100 g/L, or severe cardiovascular or pulmonary diseases, which include a Left Ventricular Ejection Fraction (LVEF) below 50%, unstable angina or myocardial infarction within the past 6 months, or a resting peripheral blood oxygen saturation (SpO2) of 91% or less;
• The subject has a known severe allergy, hypersensitivity, or intolerance to fludarabine, cyclophosphamide, or any excipients contained in the S103 CAR-T cell product, such as human serum albumin. Subjects are also excluded if they have received any live attenuated vaccine within 6 weeks prior to screening, or plan to receive a live vaccine during the study period.