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

Not Yet RecruitingPhase 1, Phase 2

Sponsor: Tongji Hospital

Conditions: Multiple Sclerosis

Interventions: SYS6020 injection

Countries: China

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).

Eligibility overview

Sex: ALL

Age: 18 Years to 65 Years

Healthy volunteers: No

Study type: INTERVENTIONAL

Eligibility criteria

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.

Locations (1)

Wuhan, Hubei, China