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

Sponsor
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Study ID
NCT06688435
Phase
PHASE1
Status
Recruiting
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Conditions

  • Myasthenia Gravis

Eligibility Criteria

Sex
ALL
Age
18 Years - 65 Years
Healthy Volunteers
Not accepted

Interventions

  • SYS6020 injection — BIOLOGICAL
    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.

Study Details

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.

Key Dates

First listed
Nov 14, 2024
Start date
Jan 8, 2025
Status verified
Aug 2025
Primary completion
Dec 1, 2028
Completion
May 1, 2033

Study Design

Enrollment
50 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • 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.
  • 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.
  • 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.
  • 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.
  • 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.

Primary Outcome Measure

The frequency and the grade of DLT and the incidence of adverse events and serious adverse events. (For the dose-escalation phase) [ Time Frame: 12 months ]

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