A Study to Evaluate the Safety and Preliminary Efficacy of SYS6020 CAR T-cells in Patients With Refractory Generalized Myasthenia Gravis

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

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.

Study Overview

• Status: Recruiting
• Conditions: Myasthenia Gravis
• Intervention / Treatment: Biological: SYS6020 injection

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Jinan, China
    • Recruiting
    • Qilu Hospital, Shandong University
    • Contact: Chuanzhu Yan; Phone Number: 18561811888; Email: chuanzhuyan@163.com

Participation Criteria

Eligibility Criteria

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

Description

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>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 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SYS6020 injection: 2*106CAR+ T-cells per kg(dose level 1); Participants will undergo leukapheresis to isolate peripheral blood mononuclear cells to manufacture SYS6020 injection, during which no lymphodepleting chemotherapy will be performed. Participants will receive 3 doses treatment of SYS6020 injection, with a dose level of 2*106CAR+ 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.	Biological: SYS6020 injection; The SYS6020 is an injection of autologous CAR-T cells that have been temporarily transfected with LNP-mRNA targeting BCMA. Before each dosing, the infusion eligibility of SYS6020 is assessed by the investigator, and the eligible participants will receive 3 dosing SYS6020 injection treatment. The dosing interval is 7 days according to the protocol design.
Experimental: SYS6020 injection: 6*106CAR+ T-cells per kg(dose level 2); Participants will undergo leukapheresis to isolate peripheral blood mononuclear cells to manufacture SYS6020 injection, during which no lymphodepleting chemotherapy will be performed. Participants will receive 3 doses treatment of SYS6020 injection, with a dose level of 6*106CAR+ 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.	Biological: SYS6020 injection; The SYS6020 is an injection of autologous CAR-T cells that have been temporarily transfected with LNP-mRNA targeting BCMA. Before each dosing, the infusion eligibility of SYS6020 is assessed by the investigator, and the eligible participants will receive 3 dosing SYS6020 injection treatment. The dosing interval is 7 days according to the protocol design.
Experimental: SYS6020 injection: 1.8*107CAR+ T-cells per kg(dose level 3); 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 1.8*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.	Biological: SYS6020 injection; The SYS6020 is an injection of autologous CAR-T cells that have been temporarily transfected with LNP-mRNA targeting BCMA. Before each dosing, the infusion eligibility of SYS6020 is assessed by the investigator, and the eligible participants will receive 3 dosing SYS6020 injection treatment. The dosing interval is 7 days according to the protocol design.
Experimental: SYS6020 injection: 3.6*107CAR+ T-cells per kg(dose level 4); 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 3.6*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.	Biological: SYS6020 injection; The SYS6020 is an injection of autologous CAR-T cells that have been temporarily transfected with LNP-mRNA targeting BCMA. Before each dosing, the infusion eligibility of SYS6020 is assessed by the investigator, and the eligible participants will receive 3 dosing SYS6020 injection treatment. The dosing interval is 7 days according to the protocol design.
Experimental: SYS6020 injection: 5.4*107CAR+ T-cells per kg(dose level 5); 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.	Biological: SYS6020 injection; The SYS6020 is an injection of autologous CAR-T cells that have been temporarily transfected with LNP-mRNA targeting BCMA. Before each dosing, the infusion eligibility of SYS6020 is assessed by the investigator, and the eligible participants will receive 3 dosing SYS6020 injection treatment. The dosing interval is 7 days according to the protocol design.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The frequency and the grade of DLT and the incidence of adverse events and serious adverse events. (For the dose-escalation phase)	For the dose-escalation phase, the primary objective is to evaluate the safety of SYS6020, as measured by the frequency and nature of Dose-limiting toxicity (DLT) and the incidence of all adverse events and serious adverse events. DLT is defined as any adverse event related to SYS6020 that occurs within 28 days after the infusion of SYS6020 and that meets certain criteria.	12 months
Response rate at 12 months after dosing （For the dose-expansion phase)	Response rate is defined as: The score of Myasthenia Gravis Activities of Daily Living Scale (MG-ADL) and Quantitative Myasthenia Gravis score (QMG) is decreased by ≥2 points from baseline to 12 months after dosing; or; The score of Myasthenia Gravis Composite Scale (MGC) is decreased by ≥3 points from baseline to 12 months after dosing; or; The concentration of specific autoantibodies (i.e., AChR-Ab or MuSK-Ab) is decreased by ≥50% from baseline to 12 months after dosing.	12months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of MG-ADL score sdecline≥2	The proportion of participants achieving a decline of 2 points or more in MG-ADL from baseline to 6 months and 12 months after dosing (as dose-escalation phase endpoints only); The proportion of participants achieving a decline of 2 points or more in MG-ADL from baseline to 6 months after dosing (as dose-expansion phase endpoints only)	6 months, 12 months
the proportion of QMG score decline≥2	The proportion of participants achieving a decline of 2 points or more in QMG from baseline to 6 months and 12 months after dosing (as dose-escalation phase endpoints only); The proportion of participants achieving a decline of 2 points or more in QMG from baseline to 6 months after dosing (as dose-expansion phase endpoints only)	6 months, 12 months
The proportion of MGC score decline≥3	The proportion of participants achieving a decline of 3 points or more in MGC from baseline to 6 months and 12 months after dosing (as dose-escalation phase endpoints only); The proportion of participants achieving a decline of 3 points or more in MGC from baseline to 6 months after dosing (as dose-expansion phase endpoints only)	6 months, 12 months
The mean change of MG-ADL score	the mean change of MG-ADL score from baseline to 6 months and 12 months after dosing (as two-phase joint-endpoints)	6 months, 12 months
The mean change of QMG score	the mean change of QMG score from baseline to 6 months and 12 months after dosing (as two-phase joint-endpoints)	6 months, 12 months
The mean change of MG QoL-15R score	the mean change of MG QoL-15R from baseline to 6 months and 12 months after dosing (as two-phase joint-endpoints)	6 months, 12 months
The mean change of MGC score	the mean change of MGC from baseline to 6 months and 12 months after dosing (as two-phase joint-endpoints)	6 months, 12 months
The mean change of MGFA clinical classification	the mean change of MGFA clinical classification from baseline to 6 months and 12 months after dosing (as two-phase joint-endpoints)	6 months, 12 months
The mean change of MGFA PIS grading	the mean change of MGFA PIS grading from baseline to 6 months and 12 months after dosing (as two-phase joint-endpoints)	6 months, 12 months
The mean change of hand grip strength	the mean change of hand grip strength from baseline to 6 months and 12 months after dosing (as two-phase joint-endpoints)	6 months, 12 months
The mean change of vital capacity	the mean change of vital capacity from baseline to 6 months and 12 months after dosing (as two-phase joint-endpoints)	6 months, 12 months
The proportion of participants with concentration titer change of myasthenia gravis-specific autoantibody	the proportion of participants whose AChR-Ab or MuSK-Ab concentrations titer is declined by ≥50% from baseline to 12 weeks after dosing (as two phase joint-endpoints)	12 weeks
The incidence of AE and SAE	the incidence of all the adverse events (AE) and serious adverse events (SAE) during 12 months after dosing. (as two phase joint-endpoints)	12 months
the pharmacokinetic parameters of SYS6020 injection	the concentrations and pharmacokinetic parameters of SYS6020 CAR+ cells, as well as the gene copies of CAR targeting BCMA.	12 months

Collaborators and Investigators

• Sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): May 1, 2033

Study Registration Dates

• First Submitted: November 6, 2024
• First Submitted That Met QC Criteria: November 12, 2024
• First Posted (Actual): November 14, 2024

Study Record Updates

• Last Update Posted (Actual): August 6, 2025
• Last Update Submitted That Met QC Criteria: August 1, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Manifestations; Pathologic Processes; Neoplasms by Site; Neoplasms; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases; Autoimmune Diseases of the Nervous System; Neurodegenerative Diseases; Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; Muscle Weakness; Myasthenia Gravis
• Other Study ID Numbers: SYS6020-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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