This study is a single-center, open-label, single-arm, exploratory clinical study to evaluate the safety, tolerability, and preliminary efficacy of S103（BCMA-CAR T ）cells in the treatment of progressive or refractory multiple sclerosis. The study is a dose escalation trial in adult progressive and refractory MS patients. A standard "3+3" design will be used to perform dose escalation to explore the safety profile and dose-limiting toxicities (DLTs). A total of 9 MS patients who meet the inclusion criteria are expected to be recruited.
Age ≥18 years and ≤75 years;
The subject signs the informed consent form, is willing and able to comply with the protocol, complete the research assessments and return for follow-up;
To be diagnosed with Multiple Sclerosis (MS) according to the 2017 McDonald criteria, specifically including Progressive MS (Primary Progressive MS [PPMS] or Secondary Progressive MS [SPMS]) or Relapsing-Remitting MS (RRMS);
The subject must be assessed by the investigator as having progressive or refractory MS for which no effective standard therapy is available. For subjects with Relapsing MS (RMS), refractory/progressive disease is defined as having experienced at least 2 clinical relapses within the past 2 years, or at least 1 clinical relapse within the past 1 year accompanied by at least one gadolinium-enhancing lesion on MRI within the past year, despite treatment with standard disease-modifying therapies (DMTs). In addition, the subject must have an Expanded Disability Status Scale (EDSS) score between 2.0 and 7.0, inclusive, at both screening and baseline;
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;
Sequential
S103 cells
DrugDose Level 0 (De-escalation dose): 0.5×10\^6 CAR-T cells/kg Dose Level 1 (Starting dose): 1.0×10\^6 CAR-T cells/kg Dose Level 2 (Maximum dose): 2.0×10\^6 CAR-T cells/kg
Incidence and type of Dose-Limiting Toxicities (DLTs)
A DLTs is defined as any Grade 4 toxicity or Grade 3 toxicity lasting more than 7 days occurring within 28 days after BCMA-CAR T infusion that is related to the treatment (with specific exceptions for manageable CRS, neurotoxicity, and hematologic toxicities as defined in the protocol). This is used to determine the safety and tolerable dose.
Incidence and severity of AEs, including changes in vital signs, physical examination, laboratory parameters, Electrocardiograms and Echocardiograms.
To evaluate the AEs occurring within 6 months after S103 infusion
PD-soluble BCMA
The changes in concentration of BCMA in the peripheral blood after S103 infusion
PK-BCMA CAR-T cells
The concentration of BCMA-CAR T cells(cells/mL) in peripheral blood after administration was detected by flow cytometry
PD-NFL
The changes in peripheral blood neurofilament light chain(NfL) concentration in patients with MS
PD-OB
The changes in CSF Oligoclonal Bands index in patients with MS
Changes in proportion of peripheral blood immune cell subsets and inflammatory markers levels
Changes in proportion of peripheral blood immune cell subsets and inflammatory markers levels of subjects after infusion of S103
Changes in Cerebrospinal Fluid (CSF) parameters
Evaluation of central nervous system (CNS) microenvironment changes through lumbar puncture. Parameters include CSF cytology, biochemistry, cytokines, lymphocyte subsets, free kappa light chains, and oligoclonal band (OB) index， and multi-omics analysis of cerebrospinal fluid immune microenvironment
MS: Annualized Relapse Rate (ARR)
Annualized relapse rate (ARR): Number of MS relapses divided by person-years of observation
Time to first relapse
Time from S103 infusion to the first relapse of MS
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Xijing Hospital
Lead sponsor
Hebei Senlang Biotechnology Co., LTD
Collaborator
