A Clinical Study Exploring the Safety, Efficacy and Cell Metabolic Dynamics of Universal CD19 / 20 Car-t Cell Injection in Moderate to Severe Refractory Systemic Lupus Erythematosus

Exclusion Criteria

• •3. Liver function: defined as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels ≤2× upper limit of normal (ULN), and total bilirubin levels ≤2× upper limit of normal (ULN)
• •4. Coagulation function: defined as an international normalized ratio (INR) or activated partial thromboplastin time (APTT) ≤1.5×ULN;
• •5. Lung function: When exposed to indoor air, the blood oxygen saturation (SpO2) is ≥92% (measured by a pulse oximeter);
• •6. Cardiac function: defined as having a left ventricular ejection fraction (LVEF) of ≥50% as assessed by echocardiography (ECHO) within the 8 weeks prior to screening.
• •Those who have suffered from severe lupus nephritis within the previous 2 months and require hemodialysis, or have received prednisone ≥100 mg/d or equivalent hormone treatment for ≥14 days;
• •Those who have undergone plasma exchange, plasma separation, hemodialysis within the previous 30 days, or those who have suffered from lupus crisis within the previous 30 days;
• •Screen for individuals with a history of ≥ Grade 2 bleeding within the previous 30 days or those requiring long-term anticoagulant therapy;
• •History of any of the following cardiovascular diseases within 30 days prior to screening: heart failure of NYHA class III or IV, myocardial infarction, unstable angina, uncontrolled or symptomatic atrial arrhythmias, any ventricular arrhythmias, or other clinically significant heart diseases;
• •Before screening, there were manifestations of the central nervous system caused by lupus, including but not limited to lupus headache, seizures, cognitive impairment, impaired intellectual function, and visual impairment;
• •Individuals with central nervous system diseases prior to screening include, but are not limited to: cerebrovascular accident, encephalitis, epilepsy, convulsion/seizure, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, central nervous system vasculitis, cognitive dysfunction, brain organic syndrome, or psychosis;
• •Screen for the absence of systemic active infections within the previous 2 weeks, including but not limited to active tuberculosis;
• •Previous exposure to CAR-T cell therapy or other gene-modified T cell therapies, or a history of major organ transplantation (such as heart, lung, kidney, liver) or hematopoietic stem cell/bone marrow transplantation;
• •Allergic or intolerant to diuretics, tocilizumab, or experiencing life-threatening allergic reactions, hypersensitivity reactions, or intolerance to CT1195E formulation or its excipients (including dimethyl sulfoxide (DMSO)), or having a history of other severe allergies such as anaphylactic shock;
• •Screen for individuals who have used targeted B-cell drugs such as rituximab within the previous 3 months;
• •Within 2 weeks prior to the infusion of CT1195E, the use of prednisone (or equivalent drugs) at a dosage of ≥10 mg/day is allowed. Physiological substitutes, topical, and inhaled steroids are also permitted;
• •Received T-cell-affecting immunosuppressants (mycophenolate mofetil, methotrexate, cyclosporine, azathioprine, leflunomide, tacrolimus) within 2 weeks before infusion of CT1195E;
• •Have received JAK inhibitors (such as tofacitinib, baricitinib, ruxolitinib, etc.) within 2 weeks before the infusion of CT1195E;
• •Have received attenuated live vaccine, inactivated vaccine, or RNA vaccine within one month before screening;
• •Suffered from malignant tumor within 2 years before signing the ICF. The following conditions are excluded: non-melanoma skin cancer that has undergone radical treatment, localized prostate cancer, biopsy-confirmed cervical carcinoma in situ or squamous intraepithelial lesion detected by cervical smear, and completely resected breast carcinoma in situ;
• •The participant has undergone major surgery within 4 weeks prior to signing the informed consent form, or plans to undergo major surgery during the study period, and the investigator believes that this would pose an unacceptable risk to the study participant;
• •During screening, there is evidence of HIV, syphilis infection, active hepatitis B virus infection (HBsAg positive and HBV-DNA above the detection limit), or active hepatitis C virus infection (both HCV antibody and HCV-RNA positive);
• •Those who participated in other clinical studies within the previous three months or are still within the five half-lives after the last dose;
• •Concurrent major chronic diseases that are not under control and that the investigator believes may increase the risk to study participants;
• •Subjects with a history or evidence of suicidal thoughts within the previous 6 months, or any suicidal behavior within the previous 12 months, are considered by the researchers to have a significant risk of suicide;
• •Pregnant or lactating women;
• •The researcher judges that the study participant has poor compliance, is unable or unwilling to adhere to the requirements of the study protocol, or has other reasons that make them unsuitable for participating in this clinical study.