A Phase I Study to Evaluate BCMA-targeted Chimeric Antigen Receptor T Cell (SYS6020 Injection) in Patients With Refractory Generalized Myasthenia Gravis

CSPC ZhongQi Pharmaceutical Technology Co., Ltd.1 个研究点分布在 1 个国家目标入组 60 人开始时间: 2025年3月4日最近更新: 2026年8月12日

适应症

干预措施

试验速览

阶段: 1 期
状态: 招募中
发起方
入组人数: 60
试验地点: 1
主要终点: The frequency and the grade of DLT and the incidence of adverse events and serious adverse events. (For the dose-escalation phase)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This study is a single-arm, open, 2-stage (dose-escalation phase and dose-expansion phase), multi-center, phase I clinical trial to evaluate the safety and tolerance of SYS6020 injection in the participants with refractory systemic myasthenia gravis, and determine the recommended dose (RD) for subsequent studies of the product, and to preliminarily evaluate the clinical efficacy of the product, as well as to explore the pharmacokinetics and immunogenicity of the product in vivo.

The dose-escalation phase and dose-expansion phase include 7 periods, and they are respectively in sequence as follows: the screening period, apheresis period, pre-dosing assessment, SYS6020 injection infusion, DLT observation period, the primary follow-up period (6 months), and the long-term follow-up period (5 years). The DLT observation period is 28 days after receiving SYS6020 injection. The participants will not undergo lymphodepleting chemotherapy.

The efficacy and safety profile of the participants will be continuously assessed during the trial. Efficacy measurement includes the MG-ADL, QMG, MGC, MG-QoL 15R scale, MGFA clinical classification, and MGFA post-intervention state (MGFA PIS) grading scales, as well as self-antibodies, etc. Safety measurement includes vital signs, physical examination, laboratory tests, cytokines, and ECG, etc. The adverse events and concomitant therapy will be continuously collected during the trial. In addition, during the study period, blood samples will be collected from participants who have received SYS6020 treatment for PK/PD test, and immunogenicity test.

For the dose-escalation phase, 3 to 5 dose levels are proposed to be explored. The Safety Monitoring Committee (SMC) will discuss the safety data and make a decision if the next SYS6020 injection could be initiated or dose-escalation could be initiated. After the completion of the dose-escalation phase, the recommended doses would be determined for dose-expansion phase. For the dose-expansion phase, further safety and efficacy data will be collected among the participants who will receive the recommended dose of SYS6020 injection.

研究设计

研究类型: Interventional
分配方式: Non Randomized
干预模型: Sequential
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) The ages ≥18 and ≤ 70 years old;
•2) Diagnosed as generalized myasthenia gravis (GMG), the clinical classification of MGFA II-IVa;
•3) Diagnosed as refractory myasthenia gravis (refractory MG) ；
•4) QMG score >11 in the screening period and before apheresis;
•5) Positive acetylcholine receptor antibody (AChR-Ab) and/or muscle-specific receptor tyrosine kinase (MuSK) antibody in the screening period;
•6) The daily dose of concomitant glucocorticoid therapy must not exceed 20mg prednisone or equivalent within 7 days prior to apheresis;
•7) Participants have a thorough understanding of this clinical trial and voluntarily sign a written informed consent form.

排除标准

•1) Have been known to have allergic reactions, hypersensitivity, intolerance or contraindications to SYS6020（including its active ingredient and excipient dextran 40） or the drugs potentially used in the study, or who have had a previous history of severe allergic reactions;
•2) Participants with major chronic diseases that are not well-controlled and considered to increase the participant's risk potentially by the investigator;
•3) Participants with other autoimmune diseases that require systemic treatment. Participants with stable autoimmune thyroid diseases who have a normal thyroid function and are at a stable therapeutic dose are allowed to be enrolled.
•4) Participants with a severe recurrent infection during the screening period, or any active infection that the investigator considers may affect the patient's participation;
•Participants with a history of positive HIV; participants with positive HBsAg; participants with positive HBcAb and with HBV-DNA above the measurable limit;(Note: participants with positive HBV-DNA or HCV-RNA results within 6 months prior to ICF are excluded);
•6) Participants with a history of malignant tumors within the past 5 years or with current active malignant tumors. (Participants with successfully treated localized tumors, as well as participants with WHO histological type A, AB, B1 or B2thymoma, with no evidence of recurrence or metastasis for at least 1 year after complete resection assessed by the investigator , are allowed to be enrolled;)
•7) Any serious respiratory system disease.
•8) Participants with a history of serious cardiovascular disease, such as severe cardiac rhythm or conduction abnormalities.
•9) Abnormal laboratory findings with clinical significance, including ALT, AST>3*ULN； Scr>1.5*ULN； INR>1.5*ULN, and so on. .
•10) Individuals with potential disease conditions (including laboratory abnormalities) which are considered of clinical significance by the investigator; individuals with alcohol dependence or drug abuse .
•11) Individuals with a current psychotic disorder that interferes with adherence.
•12) Participants with a history of primary immunodeficiency disease, organ or hematopoietic stem cell/bone marrow transplantations before screening; or those planning to undergo a transplantation during the trial;
•13) Participants with a history of ≥ Grade 2 (CTCAE 5.0 standard) bleeding within 30 days before screening, or those requiring long-term continuous treatments with anticoagulant drugs.
•14) Participants who have received any CAR-T therapy or gene therapy before.
•15) Participants who have received intravenous injection of human immunoglobulin (IVIG) or plasmapheresis (PE), plasma separation, or hemodialysis within 1 month before apheresis.
•16) Participants who have used calcineurin inhibitors, or cyclophosphamide or neonatal Fc receptor antagonists within 3 weeks before apheresis. Participants who have used targeted B-cell biological agents such as rituximab within 3 months before apheresis. Participants who started receiving eculizumab treatment within 8 weeks before the first dosing；
•17) Any situations that the investigator believes that the participant is not suitable for this clinical trial for any other reasons.

研究组 & 干预措施

SYS6020 injection: 5.4*107CAR+ T-cells per kg(dose level 5)

Experimental

Participants will undergo leukapheresis to isolate peripheral blood mononuclear cells to manufacture SYS6020 injection, during which no lymphodepleting chemotherapy will be performed. Participants receive 3 doses of SYS6020 injection, with a dose level of 5.4*107CAR+ T-cells per kg. If one DLT occurs in three participants, additional 3 ones may be considered to be enrolled after SMC safety data review and make a determination.