Safety, Efficacy and Cellular Metabolic Dynamics of ct1192 in Patients With Moderate to Severe Refractory SLE

Exclusion Criteria

• •1. Patients with severe lupus nephritis within the first 2 months of screening need to undergo hemodialysis or receive prednisone ≥ 100 mg/d or equivalent hormone therapy for ≥ 14 days;
• •2. Have undergone plasma exchange, plasma separation, hemodialysis within 30 days prior to screening, or have had lupus crisis within 30 days prior to screening;
• •3. Individuals with a history of ≥ grade 2 bleeding or requiring long-term anticoagulant therapy within the 30 days prior to screening;
• •4. Screening for a history of any of the following cardiovascular diseases within the previous 30 days: Grade III or IV heart failure defined by the New York Heart Association (NYHA), myocardial infarction, unstable angina, uncontrolled or symptomatic atrial arrhythmias, any ventricular arrhythmias, or other clinically significant heart diseases;
• •5. Prior to screening, central nervous system manifestations caused by lupus, including but not limited to lupus headache, epileptic seizures, cognitive impairment, impaired intellectual function, visual impairment, etc;
• •6. Individuals with central nervous system diseases prior to screening include but are not limited to: cerebrovascular accidents, encephalitis, epilepsy, seizures/convulsions, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar diseases, central nervous system vasculitis, cognitive dysfunction, organic brain syndrome, or psychiatric disorders;
• •7. No systemic active infections, including but not limited to active tuberculosis, within 2 weeks prior to screening;
• •8. Previously received CAR-T cell or other genetically modified T cell therapy, or have a history of major organ transplantation (such as heart, lung, kidney, liver) or hematopoietic stem cell/bone marrow transplantation;
• •9. Allergic or intolerant reactions to Qinglin drugs, tocilizumab, or life-threatening allergic reactions, hypersensitivity reactions, or intolerance to CT1192 preparations or their excipients (including dimethyl sulfoxide (DMSO)), or previous history of other severe allergies such as anaphylactic shock;
• •10. Screening for drugs targeting B cells, such as rituximab, that have been used within the previous 6 months;
• •11. Within the 12 weeks prior to screening, other biologics such as taceptil and belimumab have been used for treatment;
• •12. Hormone use ≥ 10 mg/day of prednisone (or equivalent) within 2 weeks prior to CT1192 infusion, with the use of physiological substitutes, topical and inhaled steroids allowed;
• •13. Received immunosuppressive agents that affect T cells (mycophenolate mofetil, methotrexate, cyclosporine, azathioprine, leflunomide, tacrolimus) within 2 weeks prior to CT1192 infusion;
• •14. Have received JAK inhibitors (tofacitinib, baritinib tablets, lukatinib, etc.) within 2 weeks prior to CT1192 infusion;
• •15. Have received attenuated live vaccine, inactivated vaccine or RNA vaccine within one month before screening;
• •16. Suffering from malignant tumors within 2 years prior to signing the ICF. Except for the following situations: non melanoma skin cancer that has undergone radical treatment, local prostate cancer, cervical carcinoma in situ confirmed by biopsy or squamous intraepithelial lesions detected by cervical smear, and breast carcinoma in situ that has been completely removed;
• •17. If a major surgery has been performed within 4 weeks prior to signing the informed consent form, or if a major surgery is planned during the study period, the researcher believes that it would pose unacceptable risks to the participants; During screening, there may be HIV, syphilis infection, active hepatitis B virus infection (HBsAg positive and HBV-DNA above the detection limit), or active hepatitis C virus infection (HCV antibody and HCV-RNA positive);
• •19\. Participate in other clinical studies within the first 3 months of screening or still within the five half lives after the last medication; 20. Merge major chronic diseases that have not been controlled and researchers believe may increase the risk for participants; 21. If there is a history or evidence of suicidal thoughts within the previous 6 months, or any suicidal behavior within the previous 12 months, the researcher believes that there is a significant risk of suicide; 22. Pregnant or lactating women; According to the researcher's assessment, participants have poor compliance, are unable or unwilling to comply with the requirements of the research protocol, or are not suitable to participate in this clinical study for other reasons.
• •5.5 Pre cleaning standard Before clearing, the following assessment needs to be completed. If the participant meets the following criteria, clearing can be performed. Otherwise, clearing cannot be performed or may need to be delayed.
• •1. Not using immunosuppressants in the week before Qinglin treatment;
• •2. Female participants with fertility potential who undergo pregnancy studies within 24 hours prior to the clearance of gonorrhea and have negative results;
• •3. Blood oxygen saturation ≥ 92% (under non auxiliary oxygen supply conditions);
• •4. Inactive or uncontrollable systemic infection; The use of anti infective drugs within 7 days before clearing gonorrhea must be reviewed by a medical inspector;
• •5. No signs of CNS disease or abnormal neurological examination results with clinical significance;
• •6. Serious abnormalities in heart, lung, liver, kidney function, and endocrine disorders, including but not limited to: newly developed arrhythmias or heart failure that cannot be controlled by medication; Hypotension requiring the use of vasopressors; Bacterial, fungal, or viral infections with increased activity/progression determined by researchers;
• •7. Researchers assess that participants are unable to comply with the requirements of the study protocol or are not suitable to continue the study in other situations.
• •If a participant shows obvious abnormalities such as symptoms, signs, or test results during or after clearing the lymphatic system, the researcher must communicate with the cooperating medical monitor to discuss whether the participant is suitable to continue receiving CT1192 cell infusion.