Overview

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.

Eligibility

Inclusion Criteria:

• 1) The ages ≥18 and ≤ 65 years old;
• 2)Diagnosed as generalized myasthenia gravis (GMG), the clinical classification of MGFA II-IV；
• 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 40mg prednisone or equivalent dose and the dose have to be stable for ≥4 weeks prior to baseline.
• 7) Participants have a thorough understanding of this clinical trial and voluntarily sign a written informed consent form.

Exclusion Criteria:

• 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;
• 5)Participants with a history of positive HIV; participants with positive HBsAg; participants with positive HBcAb and with HBV-DNA above the measurable limit;
• 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 those with thymomas classified as A, AB and B1 subtypes according to the WHO pathological classifications, 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>3ULN； Scr>1.5ULN； 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 and 8 weeks before the first dosing. 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.