NCT07756268尚未招募1 期
A Phase Ib/II Clinical Study to Evaluate the Safety and Efficacy of SYS6020 Injection in Patients With Relapsing/Refractory Multiple Sclerosis
适应症
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Safety and tolerability
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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:
- •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.
- •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.
- •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.
- •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.
排除标准
- •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.
- •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.
- •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:
- •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.
- •Severe recurrent infections or any active infection that may interfere with study participation.
- •13. Any of the following viral hepatitis findings:
- •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.)
- •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.
- •Previous CAR-T-cell therapy other than SYS6020 or previous gene therapy.
- •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.
结局指标
主要结局
Safety and tolerability
时间窗: From informed consent through Month 24
Incidence, severity, and relationship of adverse events and serious adverse events, and incidence of clinically significant laboratory abnormalities.
次要结局
- Change from Baseline in Modified Fatigue Impact Scale (MFIS) Score(Baseline and Months 1, 3, 6, 9, 12, 18, and 24)
- Time to 12-Week Confirmed Disability Progression (CDP) in Participants with Progressive Multiple Sclerosis(Month 24)
- Annualized Relapse Rate (ARR) in Participants with Relapsing Multiple Sclerosis(Time Frame: Month 24)
- Change from Baseline in EDSS(Expanded Disability Status Scale) Score(Baseline and Months 1, 3, 6, 9, 12, 18, and 24)
- RMS: Gadolinium-Enhancing Lesion Outcomes(Baseline and Months 3, 6, 12, 18, and 24)
- Proportion of Participants with an Improvement of at Least 1.0 Point in EDSS(Expanded Disability Status Scale) Score(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)(Baseline and Months 1, 3, 6, 9, 12, 18, and 24)
- Change from Baseline in Nine-Hole Peg Test(9HPT)(Baseline and Months 1, 3, 6, 9, 12, 18, and 24)
- Change from Baseline in Multiple Sclerosis Functional Composite (MSFC) Score Description(Baseline and Months 1, 3, 6, 9, 12, 18, and 24)
- Change from Baseline in VAS (Visual Analog Scale) Score(Baseline and Months 1, 3, 6, 9, 12, 18, and 24)
- Change from Baseline in Multiple Sclerosis Quality of Life-54 (MSQOL-54) Score(Baseline and Months 1, 3, 6, 9, 12, 18, and 24)
- Change from Baseline in 36-Item Short Form Health Survey Score (SF-36)(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)
- PK: BCMA CAR Transgene Copy Number in Peripheral Blood(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(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(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)
研究者
研究点 (1)
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