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

Официальное название

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

Обзор

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.

Вмешательства

• Препарат 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

Первичные конечные точки

• Incidence and type of Dose-Limiting Toxicities (DLTs) [Срок оценки: 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. [Срок оценки: From Day 1 up to week 26 post S103 infusion]

Вторичные конечные точки (5)

• PD-soluble BCMA [Срок оценки: From Day 1 up to week 26 post S103 infusion]
• PK-BCMA CAR-T cells [Срок оценки: From Day 1 up to Day 28 post S103 infusion]
• PD-NFL [Срок оценки: From Day 1 up to week 26 post S103 infusion]
• PD-OB [Срок оценки: From Day 1 up to week 26 post S103 infusion]
• Changes of Expanded Disability Status Scale（EDSS）scores [Срок оценки: From Day 1 up to week 26 post S103 infusion]

Критерии участия

Критерии включения

• 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;
• 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;
• 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.

Критерии исключения

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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Xijing Hospital — Сиань

Идентификаторы

NCT: NCT07587125 · KY20262101JIANGWEN

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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