CD19/BCMA CAR-T Cell Therapy for Refractory/Moderate-to-severe Systemic Lupus Erythematosus

Prior treatment

• Diagnosis of active severe lupus nephritis within 8 weeks prior to screening, requiring medications prohibited by the research protocol for active nephritis, hemodialysis or prednisone ≥ 100 mg/d, or equivalent glucocorticoid therapy for ≥14 days;
• Any attempted suicide or suicidal ideation within the past year prior to screening;
• Presence of SLE or non-SLE related central nervous system diseases or pathological changes within 8 weeks prior to screening;
• Previous or current diagnosis of non-SLE-related inflammatory arthropathy or skin diseases;
• Subjects with malignancy within 5 years prior to screening;
• Have received plasma exchange, plasma separation, hemodialysis, or intravenous immunoglobulin (IVIG) within 14 days prior to screening;
• Previous or current diagnosis of acute or chronic illnesses unrelated to SLE with obviously unstable or uncontrollable clinical symptoms;
• Have received live/attenuated vaccination within 4 weeks prior to screening or plan to receive live/attenuated vaccination throughout the study;
• Have received intra-articular, intramuscular or intravenous glucocorticoids within 4 weeks prior to screening;
• Have received any commercially available Janus kinase (JAK) inhibitor or Bruton tyrosine kinase (BTK) inhibitor within 12 weeks prior to screening;
• Have received B-cell targeted therapy prior to screening;
• Have received a biologic agent other than B-cell targeted therapy within 5 half-lives prior to screening;
• Previously received therapies with CAR-T cells or other genetically modified T cells;
• Have received therapeutic dose of corticosteroids within 7 days prior to leukapheresis or within 72 hours prior to infusion;
• Subjects that have donated blood for ≥ 400mL or had a significant blood loss equivalent to at least 400mL within 4 weeks prior to screening, or have received blood transfusion within 8 weeks, or plan to donate blood during the study period;
• History of ≥grade 2 bleeding within 4 weeks prior to screening or need for long-term continuous anticoagulant therapy;
• Subjects that have undergone any major surgeries within 12 weeks prior to screening, or those who are scheduled to undergo major surgery during the study period;
• History of drug abuse within 12 weeks prior to screening;
• Subjects that have participated in other clinical trials within 3 months prior to screening and/or currently participated in other clinical trials (those who do not receive study drugs are excluded);

Other illness

• History of vital organ transplantation or hematopoietic stem cell/or bone marrow transplantation;
• History of lymphoproliferative diseases;
• Other autoimmune diseases requiring systemic therapy;
• Subjects with positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and HBV DNA titer in peripheral blood higher than the lower limit of research institution's test range. Subjects with positive hepatitis C virus (HCV) antibodies, human immunodeficiency virus (HIV) antibodies, or syphilis;
• Active or latent tuberculosis at screening;
• Severe lupus cardiac damage at screening;
• Presence of uncontrollable infections at screening, requiring antibiotic therapy;
• History of any significant drug allergy or intolerance;

Other

• Abnormalities in major organ function at screening;
• Severe lupus lung damage at screening;
• Female subjects who are pregnant or lactating, or intend to conceive within 2 years after the cell infusion; male patients whose female partners intend to conceive within 2 years after the cell infusion;
• Presence of other circumstances that make the subjects not eligible for participation in the study, in the opinion of the researchers.

• Participants or their legal guardians understand and voluntarily sign the informed consent form, and be able to complete all the documents, procedures, follow-up examinations and treatments specified in the study protocol, with good compliance;
• Age range from 18 to 70 years old, regardless of gender;
• Participants diagnosed with SLE according to the 2019 European League Against Rheumatism (EULAR)/the American College of Rheumatology (ACR) SLE criteria at least 24 weeks prior to screening;
• Refractory/moderate-to-severe SLE needs to meet the following criteria at screening: SELENA-SLEDAI score \> 6 points; PGA ≥ 1 points; BILAG-2004 organ system scores of at least 1 A or 2 B;Have received at least 12 weeks of standardized treatment for SLE prior to screening but lack efficacy;
• Participants with fertility agree to take effective contraceptive measures throughout the study and within 3 months after the last follow-up visit.