Exploratory Clinical Study of CNCT19 Anti CD19 Cell Therapy in the Treatment of Refractory Autoimmune Diseases

Inclusion Criteria:

1. The enrolled subjects or their legal representatives signed informed consent form;

2. age range: 18-70 years (including 18 and 70 years), male or female;

3. Subjects with refractory systemic lupus erythematosus (lupus nephritis, immunethrombocytopenia) : Diagnosed with systemic lupus erythematosus according toAmerican College of Rheumatology (ACR) criteria, accompanied by lupus nephritis (SLE-LN) or immune thrombocytopenia (SLE-ITP) and receiving standard treatment;

4. Subjects with Refractory Systemic Lupus Erythematosus (Lupus Nephritis): Activeand biopsy-confirmed proliferative lupus nephritis grade III or IV or simplegrade V alone according to 2003 ISN/RPS criteria. Active renal disease wasdefined as a urine protein: creatinine ratio > 1.0 or proteinuria > 3.5grams/day.

5. Subjects with refractory systemic lupus erythematosus (thrombocytopenia): Atleast two consecutive blood routine examinations showed that platelet was lowerthan 50x109/L; Blood cell morphology of peripheral blood smear was normal. Thespleen is generally not enlarged; The morphological characteristics of bonemarrow cells were megakaryocytic increase or normal, accompanied by maturationdisorder. Platelet count > 10 x10^9 / L.

6. Subjects with refractory ANCA-associated vasculitis: diagnosis of ANCAglomerulonephritis (GN) or vasculitis based on the 2013 American Chapel HillConsensus Conference definition of AAV ;

• Relapsed or refractory AAV requiring treatment with cyclophosphamide orrituximab

• Newly diagnosed or recurrent AAV--, defined as accumulation of at least onemajor organ (e.g., kidney, lung, heart) requiring induction therapy withcyclophosphamide or rituximab;

• Anti-PR3 or anti-MPO positive (current or history);

5. Subjects with Refractory Dermatomyositis: Refractory MDA5-positive dermatomyositisis defined as active disease and meets the following conditions: adequatecorticosteroid therapy (greater than two to four weeks of conventionalcorticosteroid therapy or intolerance to such therapy) and/or

• Use of ≥ 1 conventional immunosuppressive agent (eg, methotrexate,azathioprine, tacrolimus, cyclosporine, mycophenolate mofetil, IVIG, anti-TNF,or rituximab) at a reasonable dose and duration (greater than two to four weeksor intolerance to therapy);

• Treatment with IVIG or cyclophosphamide for two to four weeks.

6. Women of childbearing potential must have a negative blood pregnancy test 7 daysprior to trial conditioning therapy; any male and female patients of childbearingpotential must agree to use an effective method of contraception throughout thestudy and for at least 1 year following reinfusion of CNCT19 CAR-T cells.Childbearing potential, in the judgment of the investigator, is biologically capableof bearing a living baby and sexually active. Female patients who were not ofchildbearing potential (ie, met at least 1 of the following criteria):

• Hysterectomy or oophorectomy, or

• Medically confirmed ovarian failure, or medically confirmed postmenopausal (cessation of menses for at least 12 consecutive months in the absence ofpathological or physiological causes).

7. Adequate organ function according to the following criteria:

• Aspartate aminotransferase (AST) ≤ 3 times of upper limit of normal (ULN);

• Alanine aminotransferase (ALT) ≤ 3 times ULN;

• Total serum bilirubin ≤ 2 times ULN unless the patient has documented Gilbert'ssyndrome; patients with Gilbert's syndrome who have bilirubin ≤ 3.0 times ULNand direct bilirubin ≤ 1.5 times ULN may be included;

• Serum creatinine ≤ 1.5 times ULN, or creatinine clearance ≥ 60 mL/min (Cockcroft and Gault formula), Patients with lupus nephritis may relax theconditions appropriately according to the judgment of the investigator;

• Must have minimal pulmonary reserve and oxygen saturation > 91% in anonoxygenated state;

• Lymphocyte count > 0.4 × 109/L.

Exclusion Criteria:

1. Patients with severe active central nervous system (CNS) lupus, including seizures,psychosis, cerebrovascular accident or CNS vasculitis requiring therapeuticintervention within 60 days after baseline;

2. Dialysis patients;

3. Pregnancy or lactation;

4. Concomitant uncontrollable infection (e.g., sepsis, bacteremia, fungemia,uncontrolled pulmonary infection, etc.);

5. Hepatitis B surface antigen (HBsAg) positive and hepatitis C (HCV) antibodypositive, human immunodeficiency virus (HIV) antibody positive, syphilis (TP)positive;

6. Major surgery that was assessed as unsuitable by the investigator within 4 weeksbefore screening;

7. Patient's heart meets any of the following:

• Left ventricular ejection fraction (LVEF) ≤ 45%;

• New York Heart Association (NYHA) Class III or IV congestive heart failure oractive cardiac disease;

• Serious arrhythmia requiring treatment (except atrial fibrillation, paroxysmalsupraventricular tachycardia);

• QTc interval ≥ 450 ms for males and ≥ 470 ms for females (QTcB = QT/RR1/2);

• Myocardial infarction, bypass surgery or stent surgery within 6 months prior tothe study;

• Other cardiac diseases that are not suitable for the study as judged by theinvestigator;

8. Received live vaccine within 6 weeks prior to screening.

9. Participation in other interventional clinical studies within 3 months prior to cellinfusion, treatment with an active experimental drug, or intentional participationin another clinical trial or treatment outside of that specified by the protocolthroughout the study period.

10. Patients with a history of epilepsy or other active central nervous system diseases;

11. Known hypersensitivity to the ingredients of the preparation used in the test;

12. Prior treatment with CAR-T cells.

13. Other conditions that the investigator considers inappropriate for participation inthis clinical trial.