CD19/BCMA-Targeted Universal CAR-T Cell Injection for the Treatment of Autoimmune Diseases

Ki vehet részt

• General Inclusion Criteria (All Patients); Voluntarily provides written informed consent; Age ≥18 and ≤70 years, any gender; Adequate organ function:; ALT and AST ≤3×ULN; total bilirubin ≤2×ULN (excluding Gilbert syndrome); Creatinine ≤1.5×ULN or creatinine clearance ≥40 mL/min; Neutrophils ≥1×10⁹/L; hemoglobin ≥60 g/L; platelets ≥20×10⁹/L; lymphocytes >0.3×10⁹/L; INR ≤1.5×ULN or PT ≤1.5×ULN; Resting room-air SpO₂ ≥92%; LVEF ≥50% on echocardiogram; Negative serum or urine pregnancy test for females of childbearing potential at screening; Highly effective contraception required from 28 days before lymphodepletion until 12 months after RD06-05 infusion for females; effective barrier contraception required from lymphodepletion until 12 months after RD06-05 infusion for males, with no sperm donation during the study
• For SLE Patients; Diagnosis of SLE per 2019 EULAR/ACR or 2012 SLICC criteria; Active disease despite ≥2 months of stable (≥2 weeks) treatment with glucocorticoids plus immunosuppressants and/or biologics; prednisone ≥7.5 mg/day or equivalent; Positive ANA, anti-dsDNA antibody, and/or anti-Smith antibody at screening; SLEDAI-2K >6 and clinical SLEDAI-2K ≥4 at screening. Patients with lupus nephritis (proteinuria >0.5 g/24h, UPCR >500 mg/g, or active urinary sediment) are exempt from clinical SLEDAI-2K requirement; Physician Global Assessment (PGA) ≥1.0 (0-3 VAS) at screening
• For SSc Patients; Diagnosis of SSc per 2013 ACR/EULAR criteria; Diffuse cutaneous SSc at screening; Active disease defined by at least one of: new SSc within 2 years; new/worsening skin or thoracic/abdominal involvement within 6 months; worsening skin thickening (mRSS ≥2); tendon friction rubs within 3 months; worsening respiratory symptoms with FVC decline ≥5% predicted or DLCO decline ≥10% predicted; or ILD progression on HRCT compared to 12 months prior; Refractory or relapsing disease after >6 months of conventional therapy including glucocorticoids, cyclophosphamide, immunosuppressants, and/or biologics
• For AAV Patients; Diagnosis of ANCA-associated vasculitis (MPA, GPA, EGPA) per 2022 ACR/EULAR criteria; Positive MPO-ANCA or PR3-ANCA; BVAS with at least 1 major item, 3 minor items, or 2 renal items; Failure of standard of care: no remission after ≥4 months of glucocorticoids plus cyclophosphamide/rituximab; relapse after prior remission; or persistent active disease despite ≥6 months of SOC
• For IIM Patients; Diagnosis of IIM (DM, ASS, IMNM) per 2017 ACR/EULAR criteria (probability ≥55%); Active disease defined by ≥2 abnormal core measures, or active myositis on muscle MRI, or active inflammation on muscle biopsy within 16 weeks; Positive myositis-specific autoantibodies; Refractory or relapsing disease after ≥6 months of conventional therapy including glucocorticoids, immunosuppressants, and/or biologics
• For pSS Patients; Diagnosis of primary Sjögren's syndrome per 2016 ACR/EULAR criteria; Positive anti-SSA/Ro antibody; ESSDAI ≥6 at screening; Refractory or relapsing disease after ≥6 months of conventional therapy including glucocorticoids, immunosuppressants, and/or biologics

Ki nem vehet részt

• General Exclusion Criteria (All Patients):; Coexisting autoimmune disease confounding disease activity/safety (stable ≥3 months may be eligible with approval); Anti-CD20 mAb/T-cell engager within 3 months; CD19/BCMA-targeted therapy within 6 months (exception with CD19⁺ B-cell > LLN and approval); Rapidly progressive glomerulonephritis (RPGN); NYHA III/IV heart failure; severe cardiac disease within 12 months; Severe CNS disease impairing compliance/assessments; Malignancy history (except cured non-melanoma skin cancer/carcinoma in situ, disease-free ≥3 years); Primary immunodeficiency; Uncontrolled infection (uncomplicated UTI/upper respiratory infection permitted); Positive HIV; positive HCV (except undetectable RNA); positive syphilis; Positive HBsAg; positive HBcAb (except undetectable HBV DNA); Positive EBV/CMV DNA/IgM at screening; Active/recurrent tuberculosis; Prior CAR-T or genetically modified immune cell therapy; Live attenuated vaccine within 4 weeks before enrollment; Hypersensitivity to cell therapy product components; Tacrolimus hypersensitivity or ≥Grade 3 toxicity requiring hospitalization; Other clinical trial participation within 30 days before screening; Pregnant/breastfeeding; childbearing potential unwilling to use effective contraception; Any other ineligible condition (investigator judgment)
• Exclusion Criteria for SLE; Active/unstable neuropsychiatric SLE requiring intervention within 90 days; Anti-BAFF/APRIL therapy within required washout period; multiple NSAIDs within 14 days; inability to hold NSAIDs; intra-articular glucocorticoids within 6 weeks; immunosuppressants exceeding dose limits; hydroxychloroquine dose adjustment within 8 weeks; ACEI/ARB/SGLT2i adjustment within 4 weeks
• Exclusion Criteria for AAV; Alveolar hemorrhage requiring invasive ventilation beyond screening; Dialysis/plasmapheresis within 12 weeks; Renal transplantation history; Cyclophosphamide within 12 weeks; immunosuppressant discontinuation required 1 week before lymphodepletion; High-dose IV glucocorticoids within 4 weeks; Oral glucocorticoids >60mg prednisone equivalent daily for >6 weeks; Specific immunosuppressants/biologics within 4 weeks; Concomitant strong CYP3A4 inducers
• Exclusion Criteria for SSc; Significant respiratory disease other than ILD; FVC <50% or DLCO <40% predicted at screening/baseline; Lung transplantation listing/expected within 12 months; Scleroderma renal crisis within 6 months; Scleroderma-like disorders; Prior chlorambucil, bone marrow transplantation, or total lymphoid irradiation
• Exclusion Criteria for pSS; Active fibromyalgia interfering with assessment/requiring medication adjustment (stable permitted); Cyclophosphamide within 12 weeks; immunosuppressant discontinuation required 1 week before lymphodepletion; High-dose glucocorticoids (≥60mg/day) within 4 weeks
• Exclusion Criteria for IIM; Severe rhabdomyolysis or CK ≥120×ULN at screening; FVC ≤50% predicted or DLCO ≤40% predicted at screening