SYS6020 CAR T-cell therapy for 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 trial will try SYS6020 CAR T-cell infusion in adults with refractory generalized myasthenia gravis to see if it is safe and reduces symptoms.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd. (Industry-sponsored)
• Drugs / interventions: rituximab, eculizumab, CAR-T, cyclophosphamide, prednisone, chemotherapy
• Locations: 1 site (Jinan)
• Trial ID: NCT06688435 on ClinicalTrials.gov

What this trial studies

This is a single-arm, open-label Phase I trial with a two-stage design consisting of dose-escalation followed by dose-expansion to determine a recommended dose for future studies. Participants undergo screening, apheresis to collect cells, pre-dosing assessments, a single SYS6020 infusion, a 28-day dose-limiting toxicity observation window, a primary 6-month follow-up, and long-term follow-up for up to 5 years. No lymphodepleting chemotherapy is given before infusion. The study will monitor safety and tolerance, collect preliminary efficacy data, and explore pharmacokinetics and immunogenicity of SYS6020 in vivo.

Who should consider this trial

Good fit: Adults aged 18–65 with generalized, refractory myasthenia gravis (MGFA II–IV), a QMG score >11, positive AChR or MuSK antibodies, and a stable glucocorticoid dose ≤40 mg prednisone equivalent for ≥4 weeks may qualify.

Not a fit: Patients outside the age range, with mild or seronegative disease, unstable steroid dosing, known allergy to SYS6020 components (including dextran 40), or other exclusion criteria are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, SYS6020 could provide a durable reduction in disease activity for adults with refractory generalized myasthenia gravis who have not responded to standard therapies.

How similar studies have performed: Similar CD19-targeted CAR T-cell therapies have produced promising remissions in some refractory autoimmune diseases in small studies, but CAR T use in myasthenia gravis remains early and largely untested in larger trials.

Eligibility criteria

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.

Where this trial is running

Jinan

• Qilu Hospital, Shandong University — Jinan, China (Recruiting)

Conditions Myasthenia Gravis