A Phase I/IIa Clinical Study to Evaluate Universal Allogeneic CAR-T Cells (QT-019B) Targeting CD19 and BCMA for the Treatment of Refractory Systemic Lupus Erythematosus
This study is a single-arm, open-label clinical study designed to evaluate the safety and tolerability of QT-019B in subjects with refractory SLE and to determine the RD. The study has two phases: dose escalation and dose expansion, with a planned enrollment of 18-24 subjects.
• 1\. Age ≥18 years and ≤65 years at screening, gender is not limited.
• 2\. Subjects diagnosed with systemic lupus erythematosus according to the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) SLE classification criteria.
• 3\. Meets the criteria for refractory SLE: a) Must have received adequate standard treatment prior to screening, including glucocorticoids, immunosuppressants, biologics. b) Refractory SLE is defined as a failure to respond, or a documented adverse event or intolerance to glucocorticoids combined with other immunosuppressive therapies. The patient should have had received treatment with courses of at least two different non glucocorticoid immunosuppressive therapies (not necessarily simultaneously), at least one of which is a B cell-depleting biological agent such as belimumab, rituximab (unless such drugs are deemed contraindicated by the investigator or such drugs are not readily available to the patient).
• 4\. Positive serological test during the screening period, for at least one of the following autoantibodies: antinuclear antibodies (ANA) at a titer of ≥1:80, or anti dsDNA (above the ULN), or anti-Sm (above the ULN), or other disease related autoantibodies (abovethe ULN).
• 5\. At screening: a) SLE with or without Lupus Nephritis with SLEDAI-2K≥6. b) Severe, refractory SLE-ITP which is characterized by platelet count \< 30×109/L, or \< 50×109/L accompanied by a bleeding tendency.
• 6\. Important organ functions during the screening period must meet the following requirements (excluding abnormalities related to SLE): a) Bone marrow function must meet the following: a. Neutrophil count ≥0.5×109/L; b. Hemoglobin ≥ 60g/L. b) Liver function: Alanine aminotransferase (ALT) ≤ 2×ULN, Aspartate aminotransferase (AST) ≤ 2×ULN, Total bilirubin (TBil) ≤ 2×ULN. c) Renal function: Creatinine clearance (CrCl) ≥ 30 ml/min (Cockcroft/Gault formula).
• 7\. Female subjects of childbearing potential and male subjects whose partners are women of childbearing potential must use medically approved contraceptive measures or abstain from sex during the study treatment period and for at least 12 months after the end of the study treatment; female subjects of childbearing potential must have a negative serum HCG test within 7 days prior to study enrollment and must not be breastfeeding.
• 8\. Voluntarily participate in this clinical study, sign the informed consent form, have good compliance, and cooperate with follow-up.