Evaluation of Safety, Pharmacokinetics and Pharmacodynamics of Arnovie101, an mRNA-LNP-Based In Vivo CAR-T Therapy, for the Treatment of B Cell-Mediated Autoimmune Diseases (Systemic Lupus Erythematosus and Autoimmune Hemolytic Anemia)
This is an open lable and single arm study designed to evaluate the safety, PK and PD of Arnovie101 in B cell-mediated Autoimmune Disease
• Ability to voluntarily sign informed consent, including compliance with the requirements and restrictions listed in the Informed Consent Form (ICF) and this protocol.
• Male or female, aged 18 to 60 years (inclusive) at screening.
• Participants with relapsed/refractory SLE with at least 6 months of disease history and meeting the following criteria:
• A. Confirmed diagnosis of SLE according to the 2012 SLICC or 2019 EULAR/ACR revised criteria. SLEDAI-2K score ≥6 at screening. If the score includes low complement and/or anti-dsDNA antibodies, the clinical symptom score of SLEDAI-2K (excluding low complement and/or anti-dsDNA antibodies) should be ≥4. Poor response to standard therapy (at least two first-line treatments, including corticosteroids and immunosuppressants) and disease relapse after treatment.
• B. SLE: Stable standard therapy (including non-steroidal anti-inflammatory drugs, immunosuppressants, biologics, and glucocorticoids; oral glucocorticoid dose of prednisone or equivalent ≥7.5 mg/day and ≤30 mg/day; if combined with an immunosuppressant, no minimum daily dose requirement) for at least 8 weeks before screening, with current dose stable for at least 2 weeks and expected to remain stable during the study. Prior use of at least two immunosuppressants including hydroxychloroquine.
• C. Life expectancy \>6 months.
• Participants with AIHA meeting the following criteria:
• A. Participants with AIHA or Evans syndrome who have failed ≥3 lines of therapy.
• B. Failure of ≥3 lines of therapy must meet all of the following: hemoglobin \<10 g/dL with symptoms of anemia; failure of first-line corticosteroid therapy; failure of second-line rituximab therapy; failure of any one or more third-line regimens (splenectomy, cyclosporine, cyclophosphamide, azathioprine, mycophenolate mofetil, fludarabine, bortezomib, etc.).
• C. Life expectancy \>3 months.
• Adequate organ function:
• A. Renal function: Calculated creatinine clearance (Cockcroft-Gault) ≥30 mL/min without hydration support.
• B. Bone marrow function: Absolute neutrophil count (ANC) ≥1.0×10⁹/L, absolute lymphocyte count (ALC) ≥0.1×10⁹/L, hemoglobin (Hb) ≥60 g/L, platelet count (PLT) ≥20×10⁹/L. Coagulation: International normalized ratio (INR) or activated partial thromboplastin time (APTT) ≤1.5×ULN. Note: No blood transfusion, white blood cell growth factors (e.g., colony-stimulating factors), erythropoietin, or thrombopoietin within 7 days before the laboratory assessment.
• C. Hepatic function: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN, total bilirubin \<2.0 mg/dL (for participants with Gilbert's syndrome, total bilirubin \<3.0 mg/dL; except when caused by SLE itself).
• D. Pulmonary function: Dyspnea ≤CTCAE grade 1 and oxygen saturation (SpO₂) ≥92% on room air (measured by pulse oximeter).
• Female participants must meet the following criteria: 1) Not pregnant or breastfeeding; 2) Surgically sterile or postmenopausal for ≥2 years, or if of childbearing potential (including those postmenopausal \<2 years), have a negative serum pregnancy test (β-hCG) and agree to use effective contraception (e.g., condom, spermicide, or intrauterine device) during the study and for at least 12 months after the last dose. Use of progesterone-only contraceptives is not permitted; 3) Agree not to breastfeed during the study and for at least 12 months after the last dose.
• Male participants must meet the following criteria: If not surgically sterile and engaging in sexual activity that could lead to pregnancy, agree to use effective contraception (e.g., condom, spermicide) during the study and for at least 12 months after the last dose, and refrain from donating semen or sperm during the study and for 12 months after the last dose.