Safety and Efficacy of S103 Cells in Progressive/Refractory Multiple Sclerosis (RESET-MS)

Safety and Efficacy of S103 Cells in Patients With Progressive or Refractory Multiple Sclerosis：An Open-Label, Single-Arm, Exploratory Clinical Study

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Multiple Sclerosis; Multiple Sclerosis (MS) Primary Progressive; Multiple Sclerosis (MS) Secondary Progressive; Refractory Multiple Sclerosis
• Intervention / Treatment: Drug: S103 cells

• Study Type: Interventional
• Enrollment (Estimated): 9
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Wen Jiang Dr.; Phone Number: 86 29 84771319; Email: jiangwen@fmmu.edu.cn
• Study Contact Backup: Name: Xiaodan Shi Dr.; Phone Number: +86 29 84771319; Email: Shixd999@163.com

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710032
      • Xijing Hospital
      • Contact: Wen Jiang, Dr.; Phone Number: +86 29 84771319; Email: jiangwen@fmmu.edu.cn
      • Contact: Xiaodan Shi, Dr.; Phone Number: +86 29 84771319; Email: Shixd999@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18 years and ≤75 years;
2. 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;
3. 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);
4. 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;
5. Male study participants must agree to take contraceptive measures during the treatment period and within 1 year after receiving study treatment, and are prohibited from donating sperm throughout the study period;
6. Women of childbearing potential (WOCBP) must agree to take contraceptive measures during treatment and for at least 1 year after receiving study treatment. Participants must have a negative serum pregnancy test result during screening; a negative urine pregnancy test result must be confirmed before receiving CAR-T for the first time.

Exclusion Criteria:

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:

1. 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;
2. 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;
3. 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;
4. 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;
5. 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;
6. 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;
7. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: S103 cells; subjects will undergo leukapheresis followed by lymphodepletion conditioning with cyclophosphamide and fludarabine, then receive S103 CAR-T cell infusion.	Drug: S103 cells; Dose 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From Day 1 up to Day 28 post S103 infusion
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	From Day 1 up to week 26 post S103 infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PD-soluble BCMA	The changes in concentration of BCMA in the peripheral blood after S103 infusion	From Day 1 up to week 26 post 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	From Day 1 up to Day 28 post S103 infusion
PD-NFL	The changes in peripheral blood neurofilament light chain(NfL) concentration in patients with MS	From Day 1 up to week 26 post S103 infusion
PD-OB	The changes in CSF Oligoclonal Bands index in patients with MS	From Day 1 up to week 26 post S103 infusion
Changes of Expanded Disability Status Scale（EDSS）scores	The EDSS score ranges from 0 to 10, with higher scores indicating worse disability. A negative change relative to baseline indicates clinical improvement. Disability worsening is defined as follows: an increase of at least 2.0 points if the baseline EDSS score is 0; an increase of at least 1.0 point if the baseline EDSS score is 1.0 to 5.0; and an increase of at least 0.5 points if the baseline EDSS score is 5.5 or higher.	From Day 1 up to week 26 post S103 infusion

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	From Day 1 up to week 26 post S103 infusion
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	From Day 1 up to week 26 post S103 infusion
MS: Annualized Relapse Rate (ARR)	Annualized relapse rate (ARR): Number of MS relapses divided by person-years of observation	From Day 1 up to 1 year post S103 infusion
Time to first relapse	Time from S103 infusion to the first relapse of MS	From Day 1 up to 1 year post S103 infusion
Imaging prognostic evaluation	Neurological imaging assessments before intervention and at 26 weeks after intervention, including: gadolinium-enhancing lesions, T2, SWI, and other relevant MRI sequences.	At baseline (pre-infusion), Day 28, and week 26 post S103 infusion
Percent of NEDA-3	The proportion of patients achieving no evidence of disease activity-3 (NEDA-3), defined as no relapse, no disability worsening, and no MRI activity	From Day 1 up to 1 year post S103 infusion
9-Hole Peg Test (9-HPT)	Change from baseline in the 9-Hole Peg Test (9-HPT), measured in seconds. A higher value indicates worse upper extremity function. A negative change from baseline indicates improvement.	At baseline (pre-infusion), Month 1, Month 3, and Month 6 post S103 infusion
Change in Timed 25-Foot Walk (T25-FW) Time	Change from baseline in the Timed 25-Foot Walk (T25-FW), measured in seconds. A higher value indicates worse ambulatory function. A negative change from baseline indicates improvement.	At Baseline (pre-infusion), Month 1, Month 3, and Month 6 post S103 infusion
Change in Mini-Mental State Examination (MMSE) Score	Change from baseline in the Mini-Mental State Examination (MMSE) score. Scores range from 0 to 30, with higher scores indicating better cognitive function. A positive change from baseline indicates improvement.	At Baseline (pre-infusion), Month 1, Month 3, and Month 6 post S103 infusion
Change in Montreal Cognitive Assessment (MoCA) Score	Change from baseline in the Montreal Cognitive Assessment (MoCA) score. Scores range from 0 to 30, with higher scores indicating better cognitive function. A positive change from baseline indicates improvement.	At Baseline (pre-infusion), Month 1, Month 3, and Month 6 post S103 infusion

Collaborators and Investigators

• Sponsor: Xijing Hospital
• Collaborators: Hebei Senlang Biotechnology Co., LTD

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2029

Study Registration Dates

• First Submitted: April 28, 2026
• First Submitted That Met QC Criteria: May 7, 2026
• First Posted (Actual): May 14, 2026

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Multiple Sclerosis; Safety and Efficacy; Progressive Multiple Sclerosis; Refractory Multiple Sclerosis; BCMA-CAR T Cells; Chimeric Antigen Receptor T-Cell Therapy
• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Chronic Disease; Disease Attributes; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Pathological Conditions, Signs and Symptoms; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive
• Other Study ID Numbers: KY20262101JIANGWEN

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No