An Exploratory Study of CD19/CD22/BCMA CAR-T Cells (BZE2204) in Subjects With Relapsed or Refractory Autoimmune Diseases

Inclusion Criteria

• •1. Males or females, aged 18-70 years old
• •2. Adequate bone marrow, hepatic, renal, coagulation and pulmonary function defined as:
• •* Bone marrow reservation: absolute neutrophil count (ANC) ≥1 ×10\^9/L; absolute lymphocyte count (ALC)≥ 0.5 ×10\^9/L; hemoglobulin ≥80 g/L; platelets ≥50 ×10\^9/L(except for ITP);
• •* Hepatic function: i: Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 5 upper limit of normal(ULN) (except for elevations are evaluated to be related to autoimmune disease by investigators)and ii: total bilirubin ≤ 2 ULN, (except for Gilbert's syndrome patients, those with total bilirubin ≤ 3 ULN and direct bilirubin ≤ 1.5 ULN can be enrolled).
• •* Renal function: serum creatinine ≤ 1.5 ULN , or estimated glomerular filtration rate(eGFR) ≥ 60 mL/min/1.73m2 \[eGFR=186×age\^-0.203×SCr\^-1.154（mg/dl）,female×0.742\]
• •* Coagulation function: International normalized ratio (INR) or prothrombin time (PT) ≤1.5 ULN
• •* Pulmonary function: Have the minimum level of pulmonary reserve, defined as ≤ CTCAE (Common Terminology Criteria for Adverse Events) grade 1 dyspnea and the SaO2(oxygen saturation)≥ 91% on room air
• •3. Life expectancy \> 6 months
• •4. Subjects with relapsed or refractory active IIM also need meet following criteria:
• •* Subjects with suspected or confirmed dermatomyositis(DM), polymyositis(PM), anti-synthetase syndrome(ASS) and immune-mediated necrotizing myopathy(IMNM, need to be assessed by the investigator that the patient has no safety instability) based on the 2017 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria
• •* Positive (+ or above) for at least one myositis-specific antibody (MSA) or myositis-associated antibody (MAA), including anti-TIF-1γ, NXP-2, Mi-2α, Mi-2β, MDA-5, SAE-1/2, SRP, HMGCR, Jo-1, PL-7, PL-12, HA, EJ, OJ, KS, Zo, Tyr, PM-Scl100, PM-Scl75, SSA/Ro-52, SSB/LA, Ku, RNA-PIII, cN1A, etc
• •* At screening, the subject must have moderate to severe IIM, defined as manual muscle testing (MMT) ≤ 141 and 2 of the following criteria are met; or CT suggests active interstitial lung disease(ILD)
• •1. Physician global activity assessment (PGA) ≥ 2 cm (Visual analogue scale VAS 10 cm);
• •2. Patient global activity assessment (PtGA) ≥ 2 cm ( VAS 10 cm scale);
• •3. Extramuscular global assessment (Myositis Disease Activity Assessment Tool \[MDAAT\]) ≥ 2.0 cm (VAS 10 cm scale);
• •4. Health assessment questionnaire (HAQ) \> 0.25;
• •5. Elevation in one or more muscle enzymes (CK, LDH, AST, ALT) is ≥ 1.5 ULN;
• •* Lack of efficacy or intolerance to corticosteroids and at least 1 immunosuppressant or biologic agents
• •5. Subjects with relapsed or refractory active ITP also need meet following criteria
• •* Diagnosed with ITP for more than 3 months, including primary ITP and ITP secondary to autoimmune diseases
• •* Platelets \<50 ×10\^9/L with at least twice tests(≥24h interval)
• •* At least one platelet glycoprotein specific autoantibody positive
• •* Lack of efficacy for first line of therapy, or lack of efficacy/relapse post splenectomy
• •6. Subjects with relapsed or refractory active SLE also need meet following criteria
• •* Diagnosed with SLE according to the 2019 EULAR/ACR classification criteria for at least 6 months
• •* Positive autoantibodies: antinuclear antibody (ANA) and/or anti-double strand-DNA(dsDNA) antibody and/or anti-Smith(Sm) antibody
• •* SLEDAI-2K scores ≥8 at screening. If the scores for low complement and/or anti-ds-DNA antibody are available, the SLEDAI-2K scores for clinical symptoms (except low complement and/or anti-ds-DNA antibody) should be ≥6
• •* Proliferative class III or IV , or class III+V or IV+V lupus nephritis(LN) confirmed by biopsies within 12 months; urine protein \> 1.0g/24h or urine protein creatinine ratio (UPCR) \>1000mg/g and PGA\>1
• •* Lack of efficacy or intolerance to at least one immunosuppressant and/or one biologic in medical history; for LN patients, relapse during maintenance post induction therapy is also eligible.