Phase Ib/II Study of SYS6020 in Relapsing/Refractory Multiple Sclerosis

Laborértékek

• 1\. Uncontrolled significant chronic disease that, in the investigator's opinion, may increase the participant's risk.
  • 2\. Another autoimmune disease requiring systemic treatment, except adequately treated autoimmune thyroid disease with stable treatment and normal thyroid function.
  • 3\. History of primary immunodeficiency, organ transplantation, or hematopoietic stem cell/bone marrow transplantation, or planned transplantation during the study.
  • 4\. Current psychotic disorder. 5. Suicidal ideation within 6 months before informed consent, suicidal behavior within 12 months before informed consent, or a significant suicide risk in the investigator's opinion.
  • 6\. Alcohol or drug abuse/dependence likely to impair study compliance. 7. Stroke, transient ischemic attack, or another active central nervous system disorder unrelated to neuroimmunological disease within 6 months before enrollment.
  • 8\. Significant cardiovascular disease, including:
  • Clinically significant ventricular arrhythmia, second- or third-degree atrioventricular block, or another serious rhythm/conduction disorder;
  • Resting QT interval corrected using Fridericia's formula \>450 msec for men or \>470 msec for women;
  • Acute coronary syndrome, congestive heart failure, or another Grade ≥3 cardiovascular event within 6 months before first administration;
  • Left ventricular ejection fraction \<50%;
  • Risk factors for QT prolongation or arrhythmia, including heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or use of QT-prolonging medications;
  • Poorly controlled hypertension, defined as systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg.
  • 9\. Major surgery or invasive intervention within 4 weeks before leukapheresis, or planned systemic or local tumor resection during the study.
  • 10\. Grade ≥2 bleeding within 30 days before screening or a need for continuous long-term anticoagulant therapy.
  • 11\. Active malignancy or history of malignancy, except:
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  • Curatively treated basal cell carcinoma, localized cutaneous squamous cell carcinoma, or cervical carcinoma in situ completed \>12 months before screening; or
  • Other malignancies with curative treatment completed ≥5 years before screening. 12. Severe recurrent infections or any active infection that may interfere with study participation.
  • 13\. Any of the following viral hepatitis findings:
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  • Positive hepatitis B surface antigen;
  • Positive hepatitis B core antibody with hepatitis B virus DNA above the lower limit of quantification or 1000 copies/mL (500 IU/mL), whichever is lower;
  • Positive hepatitis C virus antibody with hepatitis C virus RNA above the lower limit of quantification or 1000 copies/mL, whichever is lower.
  • (Participants with detectable hepatitis B virus DNA or hepatitis C virus RNA within 6 months before screening who subsequently became undetectable after antiviral treatment are also excluded.) 14. History of human immunodeficiency virus infection or positive HIV test at screening.
  • 15\. Inability or unwillingness to receive investigator-required prophylaxis against Pneumocystis jirovecii, herpes simplex virus, or herpes zoster; or a positive confirmatory syphilis test.
  • 16\. Positive human T-cell lymphotropic virus type 1/2 antibody, cytomegalovirus immunoglobulin M, or Epstein-Barr virus immunoglobulin M.
  • 17\. Active bacterial, fungal, or viral infection requiring intravenous antimicrobial therapy within 2 weeks before leukapheresis, or another infection considered clinically relevant by the investigator. Prophylactic antimicrobial treatment without clinical evidence of active infection is permitted.
  • 18\. Receipt of a live vaccine within 4 weeks before leukapheresis or planned live vaccination during the study. Messenger RNA vaccines are not considered live vaccines.
  • 19\. Previous or active tuberculosis infection or a positive T-SPOT test. 20. Previous CAR-T-cell therapy other than SYS6020 or previous gene therapy. 21. Renal replacement therapy within 3 months before screening or anticipated need for renal replacement therapy during the study.
  • 22\. Intravenous immunoglobulin, plasma exchange, plasmapheresis, or hemodialysis within 1 month before leukapheresis.
  • 23\. Prednisone ≥20 mg/day, or equivalent corticosteroid dose, within 7 days before leukapheresis.
  • 24\. Calcineurin inhibitors, such as tacrolimus or cyclosporine, or cyclophosphamide within 3 weeks before leukapheresis.
  • 25\. Receipt of an investigational product within 4 weeks before screening, unless at least 5 half-lives have passed since last dose, or concurrent participation in another interventional clinical study. Observational studies and follow-up periods of completed interventional studies are permitted.
  • 26\. Known allergy, hypersensitivity, intolerance, or contraindication to SYS6020 or its components, including dextran 40; to study-related medications such as acetaminophen or tocilizumab; to beta-lactam antibiotics; or a history of severe allergic reactions.
  • 27\. Other drug allergies suggesting an allergic predisposition in the investigator's opinion, or a positive dextran 40 skin test at screening.
  • 28\. Any other condition that, in the investigator's opinion, makes the participant unsuitable for the study.

• 1\. Male or female participants aged 18-65 years at the time of signing informed consent.
  • 2\. Diagnosis of progressive multiple sclerosis (primary progressive MS \[PPMS\] or secondary progressive MS \[SPMS\]) or relapsing multiple sclerosis (RMS) according to the 2024 McDonald criteria.
  • 3\. Inadequate response to at least one disease-modifying therapy (DMT) administered for ≥6 months:
  • For progressive MS: evidence of worsening disability, such as an increased Expanded Disability Status Scale (EDSS) score.
  • For RMS: at least one of the following:
  • ≥2 relapses within 2 years before screening; ii. ≥1 relapse within 1 year before screening; or iii. Gadolinium-enhancing lesions on MRI within 1 year before screening. 4. Positive cerebrospinal fluid oligoclonal bands or an elevated immunoglobulin G index, documented previously or during screening.
  • 5\. Typical MS lesions on brain and/or spinal cord MRI, documented previously or during screening.
  • 6\. Screening EDSS score of 3.0-7.0. 7. Adequate baseline organ function, including:
  • Absolute lymphocyte count ≥0.3 × 10⁹/L, absolute neutrophil count ≥1.0 × 10⁹/L, platelet count ≥50 × 10⁹/L, and hemoglobin ≥80 g/L, without red blood cell or platelet transfusion or colony-stimulating factor within 7 days before testing;
  • Total bilirubin ≤2 × upper limit of normal (ULN), and alanine aminotransferase and aspartate aminotransferase ≤3 × ULN;
  • Serum creatinine ≤1.5 × ULN and creatinine clearance ≥40 mL/min by the Cockcroft-Gault formula;
  • Activated partial thromboplastin time and international normalized ratio ≤1.5 × ULN;
  • Oxygen saturation ≥90% on room air;
  • Serum potassium ≥3.0 mmol/L and calcium ≥2.0 mmol/L. 8. Participants of reproductive potential must use reliable contraception during the study and for at least 2 years after the last SYS6020 infusion. Women must not donate oocytes and men must not donate sperm for assisted reproduction during this period. Women of childbearing potential must have a negative serum pregnancy test at screening and a negative serum or urine pregnancy test before leukapheresis.