Anti-CD19 CAR-T Cell Therapy in Participants With Moderate to Severe Active Systemic Lupus Erythematosus

Inclusion Criteria:

• 1.The subjects voluntarily participated in the experiment and signed the informedconsent.

2. Age ≥18 years old and ≤70 years old, regardless of gender. 3. Diagnosis of SLEaccording to the European League against Rheumatism (EULAR)/American College ofRheumatology (ACR) classification criteria 2019 or the 2012 International ClinicalCollaboration Group on Systemic Erythraeus (SLICC) criteria.
3. Prior to screening, patients must have been treated with glucocorticoids combinedwith immunosuppressants and/or biologics for at least 2 months, and the dose is stablefor >2 weeks, and the disease is still active (i.e., previous treatment withglucocorticoids + immunosuppressants or glucocorticoids + immunosuppressants +biologics, and any of the above drugs are not eligible for single drug use). Oralcorticosteroids must meet the following requirements: 1) Prednisone (or equivalent) ≥7.5mg/ day; 2) There is no minimum daily dose requirement for corticosteroids whenused in combination with immunosuppressants and/or biologics.
4. Screening is positive for antinuclear antibody (ANA), and/or anti-DS-DNA antibody,and/or anti-Smith antibody.
5. The SLEDAI-2K score in the screening period was >6, and the "clinical" SLEDAI-2Kscore was ≥4. Note: "Clinical" SLEDAI-2K is a score in the SLEDAI-2K score that does not include resultsattributable to any urine or laboratory tests (including immunological indicators) :
6. The BILAG2004 score meets at least one of the following conditions: a) ≥1 organ system BILAG2004 Class A disease b) ≥2 organ systems BILAG2004 Class B disease
7. Physician General assessment (PGA) score ≥1.0 (0-3 on visual analogue scale VAS) duringscreening.
8. Organ function and laboratory tests:
9. Liver function: alanine aminotransferase (ALT) and aspartate aminotransferase (AST≤3×upper normal limit (ULN), total bilirubin (TBIL) ≤2×ULN (except Gilbert syndrome).
10. Renal function: creatinine ≤1.5×ULN or creatinine clearance ≥40 ml/min.
11. Blood routine: neutrophil count ≥1×109/L, hemoglobin ≥60g/L, platelet count ≥20×109/L,lymphocyte count >0.3×109/L.
12. Coagulation function: International standardized ratio (INR) ≤ 1.5×ULN, or prothrombintime (PT) ≤ 1.5×ULN.
13. Blood oxygen saturation (SpO2) at rest in indoor air ≥92%.
14. Echocardiography showed left ventricular ejection fraction (LVEF) ≥50%. 10. The serumor urine pregnancy test results of fertile female subjects at the time of screeningwere negative.
15. Fertile women must consent to the use of highly effective contraceptive methodsfor contraception from at least 28 days before the start of the infusion until 12months after the RD06-04 reinfusion. Fertile men must consent to the use of aneffective barrier method of contraception from the start of DTP until 12 months afterRD06-04 reinfusion, and should not donate semen or sperm throughout the trial period.

Exclusion Criteria:

• 1. Combined with other autoimmune diseases, systemic treatment is required. 2.The presence of uncontrolled lupus crises within 8 weeks prior to screening,including acute lupus nephritis, severe neuropsychiatric lupus, severe hemolyticanemia, severe immune thrombocytopenia, agranulophilia, severe heart damage,severe lupus pneumonia, severe lupus hepatitis, and severe vasculitis, wasassessed by the investigators as not suitable for participation in this study.

3. Clinically significant central nervous system diseases or pathological changesnot caused by lupus prior to screening, including but not limited to:cerebrovascular accident, aneurysm, epilepsy, convulsions/convulsions, aphasia,stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease,cerebral organ syndrome, or psychosis.
4. Have a history of allogeneic bone marrow or stem cell transplantation or solidorgan transplantation (such as kidney, lung, heart, liver) or plan to undergosuch transplantation in the future.
5. Clinically significant cardiovascular dysfunction in the 12 months prior toscreening, including but not limited to: Class III or IV heart failure as definedby the New York Heart Association (NYHA), myocardial infarction, unstable angina,uncontrolled or symptomatic atrial arrhythmias, or any ventricular arrhythmias.
6. A history of malignant neoplasm within 5 years prior to signing the ICF, withthe exception of sufficiently treated or surgically resected non-melanoma skincancer or carcinoma in situ (e.g. cervical, bladder, breast) with no residualdisease.
7. Pregnant or lactating women. 8. A history of recurrent infections requiringhospitalization and intravenous antibiotics (e.g., 3 or more infections of thesame type in the past year).
8. There are active infections, such as infectious pneumonia and tuberculosis,that need systematic treatment within 2 weeks before the treatment.
9. Hepatitis B surface antigen (HBsAg) positive, or hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA test positive;Hepatitis C virus (HCV) antibody positive and peripheral blood HCV RNA positive;Human immunodeficiency virus (HIV) antibody positive.
10. Have received live attenuated vaccine within 4 weeks prior to treatment orplan to receive live attenuated vaccine during the course of the study.
11. Receiving high doses of corticosteroids (prednisone ≥60 mg/ day orequivalent) within 4 weeks prior to drenching, or failing to taper prednisone to ≤10 mg/ day 5 days prior to drenching.
12. As indicated in Table 3, tapering or elution of background therapy is notpossible prior to eluvial chemotherapy.
13. Were receiving renal replacement therapy in the 3 months prior to screeningor expected to require renal replacement therapy during the study period.
14. History of drug or alcohol abuse within 1 year prior to screening. 16.History or evidence of suicidal thoughts in the 6 months prior to screening, orany suicidal behavior in the 12 months prior to screening, is considered by theinvestigator to be a significant risk of suicide.
15. Use of other study drugs within 4 weeks or 5 half-lives (whichever is older)prior to screening.
16. A history of hypersensitivity or life-threatening reactions to any ingredientor preparation of an investigational drug or investigational treatment, includingchemotherapy. For more information about the ingredients of the investigationaldrug, see the Investigator's Manual (IB).
17. Any situation that the investigator believes may affect study participation,pose a safety risk to patients, or may confuse the interpretation of studyresults.