Safety and Efficacy of PRG-2311 for Refractory Lupus Nephritis and IgG4-Related Disease

Inclusion Criteria:

1. Age ≥ 18 years old;

2. If the kidneys are involved, estimate the glomerular filtration rate (eGFR) to be ≥ 15 mL/minute/1.73 m2;

3. The following test values within 3 days before the collection of mononuclear cellsmeet the following standards:

4. Absolute lymphocyte count: ≥ 0.5 × 10 ^ 9/L [The use of granulocytecolony-stimulating factor (G CSF) is allowed, but subjects are not allowed toreceive this supportive treatment within 7 days before the screening periodlaboratory examination];

5. Absolute neutrophil count: ≥ 1.0 × 10 ^ 9/L [The use of granulocytecolony-stimulating factor (G-CSF) is allowed, but subjects are not allowed toreceive this supportive treatment within 7 days before the screening periodlaboratory examination];

6. Platelets: Subject platelet count ≥ 50 × 10 ^ 9/L (subjects are not allowed toreceive blood transfusion support within 7 days before the screening periodlaboratory examination);

7. Hemoglobin: ≥ 8.0 g/dL (allowing the use of recombinant human erythropoietin) [subjects have not received red blood cell (RBC) infusion within 7 days priorto the screening period laboratory examination];

8. Creatinine clearance rate: (CrCl) or glomerular filtration rate (GFR) (Cockcroft Gault formula) ≥ 30 mL/min;

9. Total bilirubin (serum): Total bilirubin (serum) ≤ 1.5 × ULN; Bloodbilirubin>1.5 × Gilbert subjects from ULN can be enrolled with the consent ofthe sponsor AST and ALT: ≤ 3.0 × ULN;

10. Plasma prothrombin time (PT), international standardized ratio (INR), partialprothrombin time (APTT): PT ≤ 1.5 × ULN, APTT ≤ 1.5 × ULN, INR ≤ 1.5 × ULNWilling to sign an informed consent form.

11. Fertile men and women of childbearing age must agree to use effective contraceptionfrom the time they sign an informed consent and up to 1 year after the study drug isused. Blood pregnancy tests for women of reproductive age at the time of screeningand before cell infusion must be negative.

12. The patients or their guardians agree to participate in the clinical study and signthe informed consent, indicating that they understand the purpose and procedure ofthe clinical study and are willing to participate in the study.

• for refractory LN

1. According to the 2019 American Society of Rheumatology (ACR) criteria,diagnosed with systemic lupus erythematosus, within 6 months prior toinfusion, confirmed by renal tissue biopsy according to the 2003International Society of Nephrology (ISN)/Society of Nephropathology (RPS)criteria as active, proliferative lupus nephritis (LN), type III or IV, ortype III/IV combined with type V, or type V. And have received standardtreatment that is ineffective or relapses after disease remission.
2. Positive anti-nuclear antibodies (ANA) and/or anti-dsDNA antibodies duringthe screening period.
3. The SLE Disease Activity Index (SLEDAI-2000) score during the screeningperiod is ≥ 8. SLEDAI-2000 clinical score ≥ 6 points, but low complementand/or anti ds-DNA positivity can be selected.

• for refractory IgG4-RD

1. According to the 2019 ACR/EULAR criteria, diagnosed with IgG4-RD;
2. The clinical manifestations were recurrent or refractory IgG4-RD;
3. IgG4-RD response index (RI) ≥2, the disease is in the active stage;
4. meet the clinical phenotype of Mikulitz/systemic

Exclusion Criteria:

Subjects who meet any of the following criteria should be excluded from this study:

1. Pregnant or lactating women;

2. A history of malignant tumors within 5 years （①Carcinoma in situ of the cervix thathas undergone curative treatment for more than 12 months prior to screening, ②Basalcell or squamous cell carcinoma of the skin that has been treated therapeutically, ③Prostate cancer that has been treated with radical prostatectomy or curativeradiation therapy for more than 3 years prior to screening has no known recurrenceand is not currently receiving treatment；④have had surgery for thyroid cancer, andhave not evidence of active disease）;

3. Received any B-cell depletion biologic therapy (for example, rituximab, ocrelizumab,obinutuzumab, ofatumumab, inebilizumab, etc) in the 6 months prior to CAR-Treinfusion, unless B-cell recovery was demonstrated;

4. Received immunosuppressant therapy within 3 days prior to CAR-T reinfusion, orsystemic corticosteroid therapy (>10 mg/ day of prednisone or equivalent doses ofother corticosteroids) within 3 days prior to CAR-T reinfusion;

5. Received live vaccine or live therapeutic STDS within 2 weeks prior to screening;

6. The presence of chronic and active hepatitis B (except for HBV DNA testing below 500IU/ml), hepatitis C (HCV), human immunodeficiency virus (HIV) infection, orsyphilis infection;

7. With an active infection that requires intravenous antibiotics or hospitalization;

8. Obvious evidence of cardiovascular disease as follows: a N-terminal B-typenatriuretic peptide (NT proBNP)>8500ng/L; b. The New York Heart Association (NYHA)classifies heart failure as Grade IV; c. Patients who received hospitalization forunstable angina or myocardial infarction within 6 months prior to the firstadministration, or patients who received percutaneous cardiac intervention andreceived the most recent stent placement within 6 months or coronary artery bypassgrafting within 6 months;

9. People who have a known allergy, hypersensitivity, intolerance, or contraindicationto any component of PRG-2311 or the drugs that may be used in the study, includingfludarabine, cyclophosphamide, tolumab, or albumin, or who have had a prior severeallergic reaction;

10. Patients with other conditions determined by the investigator to be unsuitable forlymphocyte clearance or cell infusion, or who are otherwise unsuitable for studyparticipation.