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

A Phase Ib/II Clinical Study to Evaluate the Safety and Efficacy of SYS6020 Injection in Patients With Relapsing/Refractory Multiple Sclerosis

This trial is an investigator-initiated, single-arm, open-label Phase Ib/II study to observe the safety, tolerability, PK/PD characteristics, immunogenicity, and the efficacy of SYS6020 injection in participants with relapsed/refractory multiple sclerosis. The study plans to enroll participants with progressive or relapsing multiple sclerosis.

The recommended dosing regimen is as follows: a single administration dose of 45×10^6 CAR-T cells/kg (allowing a fluctuation of ±20%), administered once a week for 6 consecutive doses.

To ensure participant safety, this study will establish a Safety Monitoring Committee (SMC). A staggered enrollment and dosing strategy will be adopted in the early stage. Two early safety evaluation will be established (after the first 3 enrolled participants complete their first 3 infusions of SYS6020, and after the first 3 enrolled participants complete their first 6 infusions of SYS6020) for comprehensive assessment.

The study plans to enroll 10-15 participants. Once the enrollment of 10-15 participants is complete, a comprehensive assessment may be conducted based on the actual progress of the study and combined with existing data. This will fully evaluate the safety, preliminary efficacy, and PK/PD/ADA data of the enrolled participants. If the overall safety of the participants is manageable, preliminary efficacy shows a positive trend, and there are value and necessity for further exploration, expanding the number of participants may be considered (up to a maximum of 25 participants in total).

Study Overview

• Status: Not yet recruiting
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Biological: SYS6020 injection

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Yuhang Cheng; Phone Number: +86-13125197960; Email: chengyh_tj@163.com

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430000
      • Tongji Hospital, Tongji Medical College of HUST
      • Principal Investigator: Daishi Tian, MD
      • Principal Investigator: Chuan Qin, MD
      • Contact: Yuhang Cheng; Phone Number: +86-13125197960; Email: chengyh_tj@163.com
      • Principal Investigator: Zhouping Tang, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 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:

  1. For progressive MS: evidence of worsening disability, such as an increased Expanded Disability Status Scale (EDSS) score.
  2. For RMS: at least one of the following:

  i. ≥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:

  1. 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;
  2. Total bilirubin ≤2 × upper limit of normal (ULN), and alanine aminotransferase and aspartate aminotransferase ≤3 × ULN;
  3. Serum creatinine ≤1.5 × ULN and creatinine clearance ≥40 mL/min by the Cockcroft-Gault formula;
  4. Activated partial thromboplastin time and international normalized ratio ≤1.5 × ULN;
  5. Oxygen saturation ≥90% on room air;
  6. 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.

Exclusion Criteria:

• 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:

  1. Clinically significant ventricular arrhythmia, second- or third-degree atrioventricular block, or another serious rhythm/conduction disorder;
  2. Resting QT interval corrected using Fridericia's formula >450 msec for men or >470 msec for women;
  3. Acute coronary syndrome, congestive heart failure, or another Grade ≥3 cardiovascular event within 6 months before first administration;
  4. Left ventricular ejection fraction <50%;
  5. 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;

  6. 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:

  1. Curatively treated basal cell carcinoma, localized cutaneous squamous cell carcinoma, or cervical carcinoma in situ completed >12 months before screening; or

  2. 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:

  1. Positive hepatitis B surface antigen;
  2. 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;

  3. 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SYS6020 injection; Use this field to provide additional information about the arm, including a description of the intervention(s) administered. Participants will receive a single administration dose of 45×10^6 CAR-T cells/kg (allowing a fluctuation of ±20%), administered once a week for 6 consecutive doses	Biological: SYS6020 injection; SYS6020 injection is an injection of autologous CAR-T cells that have been temporarily transfected with LNP-mRNA targeting BCMA. The eligible participants will receive a single administration dose of 45×10^6 CAR-T cells/kg (allowing a fluctuation of ±20%), administered once a week for 6 consecutive doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability	Incidence, severity, and relationship of adverse events and serious adverse events, and incidence of clinically significant laboratory abnormalities.	From informed consent through Month 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to 12-Week Confirmed Disability Progression (CDP) in Participants with Progressive Multiple Sclerosis	Time to protocol-defined worsening in Expanded Disability Status Scale (EDSS) score sustained for at least 12 weeks in participants with SPMS or PPMS	Month 24
Annualized Relapse Rate (ARR) in Participants with Relapsing Multiple Sclerosis	Number of protocol-defined relapses divided by total participant-years of follow-up	Time Frame: Month 24
Change from Baseline in EDSS(Expanded Disability Status Scale) Score	The EDSS ranges from 0 to 10, with higher scores indicating greater neurological disability.	Baseline and Months 1, 3, 6, 9, 12, 18, and 24
Proportion of Participants with an Improvement of at Least 1.0 Point in EDSS(Expanded Disability Status Scale) Score	The EDSS ranges from 0 to 10, with higher scores indicating greater neurological disability.	Baseline and Months 1, 3, 6, 9, 12, 18, and 24
Proportion of Participants Without Confirmed Disability Progression		Baseline and Months 1, 3, 6, 9, 12, 18, and 24
RMS: Proportion of Participants Who Remain Relapse-Free		Baseline and Months 1, 3, 6, 9, 12, 18, and 24
Change from Baseline in Timed 25-Foot Walk(T25FW)	Measured in seconds. A longer completion time indicates worse walking performance.	Baseline and Months 1, 3, 6, 9, 12, 18, and 24
Change from Baseline in Nine-Hole Peg Test(9HPT)	Measured in seconds. A longer completion time indicates worse upper-extremity and manual dexterity performance.	Baseline and Months 1, 3, 6, 9, 12, 18, and 24
Change from Baseline in Multiple Sclerosis Functional Composite (MSFC) Score Description	The MSFC score has no fixed minimum or maximum value, and higher scores indicate better neurological function.	Baseline and Months 1, 3, 6, 9, 12, 18, and 24
Change from Baseline in Modified Fatigue Impact Scale (MFIS) Score	The 21-item MFIS total score ranges from 0 to 84, with higher scores indicating a greater impact of fatigue on daily functioning.	Baseline and Months 1, 3, 6, 9, 12, 18, and 24
Change from Baseline in VAS (Visual Analog Scale) Score	Scores range from 0 to 10. Higher scores indicate greater pain severity.	Baseline and Months 1, 3, 6, 9, 12, 18, and 24
Change from Baseline in Multiple Sclerosis Quality of Life-54 (MSQOL-54) Score	Scores range from 0 to 100, with higher scores indicating better quality of life.	Baseline and Months 1, 3, 6, 9, 12, 18, and 24
Change from Baseline in 36-Item Short Form Health Survey Score (SF-36)	The SF-36 includes eight domains. Each domain score ranges from 0 to 100, with higher scores indicating better health status.	Baseline and Months 1, 3, 6, 9, 12, 18, and 24
Change from Baseline in T2-Weighted Lesion Volume		Baseline and Months 3, 6, 12, 18, and 24
PMS: Brain Volume Loss from Baseline		Baseline and Months 3, 6, 12, 18, and 24
Number of New or Enlarging T2-Weighted Lesions		Baseline and Months 3, 6, 12, 18, and 24
RMS: Gadolinium-Enhancing Lesion Outcomes		Baseline and Months 3, 6, 12, 18, and 24
PK: BCMA CAR Transgene Copy Number in Peripheral Blood	Quantified using quantitative polymerase chain reaction (qPCR)	Before and immediately after the first, second, third, and fifth infusions; at 1, 2, 6, 24, 48, and 72 hours after the first and second infusions; and at 1 and 2 hours after the third and fifth infusions, as protocol specified.
PK：BCMA CAR-Positive Cells in Peripheral Blood	The absolute count and percentage of circulating BCMA CAR-positive cells in peripheral blood will be measured using flow cytometry	Before and immediately after, and at 1 and 2 hours after the first, second, third, and fifth infusions.
PK: BCMA CAR Transgene Copy Number in Cerebrospinal Fluid	Quantified using qPCR	At screening and within 1 to 3 hours after the fifth infusion
Change from Baseline in Peripheral Blood B-Cell Subsets		Baseline and Day 15, Months 1, 3, 9, 18, and 24
Change from Baseline in Immunoglobulin Levels		Baseline and Months 1, 3, 6, 9, 12, 18, and 24
Incidence of Anti-CAR Antibodies		Baseline and Day 15, Months 1, 3, 6, 9, 12, 18, and 24

Collaborators and Investigators

• Sponsor: Tongji Hospital
• Collaborators: CSPC Baike (Shandong) Bio-Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Daishi Tian, MD, Tongji Hospital; Principal Investigator: Chuan Qin, MD, Tongji Hospital; Principal Investigator: Zhouping Tang, MD, Tongji Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): September 16, 2026
• Primary Completion (Estimated): February 7, 2029
• Study Completion (Estimated): February 7, 2029

Study Registration Dates

• First Submitted: July 30, 2026
• First Submitted That Met QC Criteria: August 5, 2026
• First Posted (Actual): August 10, 2026

Study Record Updates

• Last Update Posted (Actual): August 10, 2026
• Last Update Submitted That Met QC Criteria: August 5, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: SYS6020, BCMA, Autologous CAR-T Cell Therapy, mRNA CAR-T, Multiple Sclerosis, Primary Progressive Multiple Sclerosis, Secondary Progressive Multiple Sclerosis
• 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: SYS6020-005

Drug and device information, study documents

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