Clinical Study of EVM18001 in the Treatment of Refractory Autoimmune Diseases

Inclusion Criteria

• •1. Voluntarily sign the Informed Consent Form (ICF), which must be signed by the participant or their legal guardian.
• •2. At the time of signing the ICF, the age must be between 18 and 70 years (inclusive), regardless of gender.
• •3. At screening, peripheral blood B cells must be CD19 positive, and T cells must express CD7.
• •4. Confirmed autoimmune diseases based on recognized diagnostic criteria, including:
• •* SLE: Diagnosed with SLE according to the 2012 Systemic Lupus International Collaborating Clinics (SLICC) or 2019 European League Against Rheumatism (EULAR)/ACR criteria;
• •* MG: Diagnosed with MG according to the Myasthenia Gravis Foundation of America (MGFA) clinical classification;
• •* SSc: Diagnosed with SSc according to the 2013 ACR/EULAR classification criteria.
• •5. History of autoimmune disease for at least 6 months before screening and meets any of the following criteria. Definitions of active refractory SLE, active refractory SSc, and active refractory MG are as follows:
• •* Definition of active refractory SLE: SLEDAI-2000 score ≥6; and disease activity or relapse persists after at least 3 months of standard therapy (glucocorticoids combined with at least 2 immunosuppressants, or at least 1 imunosuppressant and 1 targeted therapy).
• •* Definition of active refractory SSc: Patients meeting the 2013 ACR/EULAR classification criteria for SSc who still show disease activity or progression after at least 6 months of standard therapy (including steroids, immunosuppressants, vasodilators, or antifibrotic agents). Specific criteria include but are not limited to: mRSS increase ≥5 points or ≥25% from baseline; absolute value of predicted FVC% decrease ≥5%; DLCO% corrected for hemoglobin absolute value decrease ≥10%; new or worsening digital ulcers after ≥3 months of vasodilator therapy; persistent or recurrent organ involvement requiring intensified treatment.
• •* Definition of active refractory MG: Refers to generalized MG patients meeting MGFA diagnostic criteria with ongoing disease activity (MGFA II-IV, QMG ≥12, or MG-ADL ≥6), and includes at least one of the following: poor control after at least 12 months of standard therapy (including at least 2 immunosuppressants); need for ≥2 intravenous immunoglobulin (IVIG) or plasma exchange treatments in the past 12 months to control symptoms; relapse with prednisone ≥20 mg/day or reduction to \<10 mg/day; persistent or recurrent disease activity.
• •6. Patients must meet the following conditions for concomitant medication:
• •1. Corticosteroids must have been used for more than 6 weeks prior to screening and at a stable dose of ≤ 10 mg/day prednisone or equivalent for at least 14 days prior to administration of EVM18001. Concurrent treatment with topical or inhaled corticosteroids (or other immunomodulators) is allowed;
• •2. Continued use during treatment is allowed if antimalarial drugs (eg, hydroxychloroquine, chloroquine, etc.) are started ≥ 12 weeks prior to screening and maintained at a stable dose for ≥ 8 weeks (maximum dose limit: hydroxychloroquine, 400 mg/day; chloroquine, 500 mg/day).
• •7. Examination at screening meet any of the following criteria:
• •* SLE: positive for blood ANA, and/or positive for anti-dsDNA, anti-Smith antibodies;
• •* MG: Positive serology for anti-AChR antibodies or anti-musclespecific tyrosine kinase receptor (MuSK) antibodies.
• •8. Life expectancy greater than 6 months.
• •9. Bone marrow reserve and organ function are normal:
• •* Bone marrow function: defined as absolute neutrophil count (ANC) ≥ 1.0×109/L, absolute lymphocyte count (ALC) ≥0.5×109/L, hemoglobin (Hb) ≥80g/L, platelet count (PLT) ≥50×109/L. Blood transfusions and growth factors must not be used to meet these requirements within 7 days prior to screening for eligibility.
• •* Coagulation function: defined as international normalized ratio (INR) or activated partial thromboplastin time (aPTT) ≤ 1.5× upper limit of normal (ULN).
• •* Cardiac function: defined as left ventricular ejection fraction (LVEF) ≥ 45% as assessed by echocardiography (ECHO).
• •* Pulmonary function: defined as Common Terminology Criteria ≤for Adverse Events (CTCAE) Grade 1 dyspnea and oxygen saturation (SpO2) ≥ 92% (pulse oximetry) on room air.
• •* Hepatic function: defined as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5× ULN, total bilirubin \< 2.0mg/dL (total bilirubin of Gilbert syndrome trial participants \<3.0mg/dL).
• •* Renal function: defined as calculated creatinine clearance (Cockcroft-Gault) ≥ 50 mL/min without hydration assistance.
• •10. Female trial participants of childbearing potential:
• •* Negative serum β human chorionic gonadotropin (β-hCG) test at screening;
• •* Agree to use a highly effective method of contraception for the duration of study participation and for 12 months after EVM18001 last infusion.
• •11. Male trial participant whose partner is of childbearing potential who agrees to use a highly effective method of contraception during the study and 12 months after the last infusion of the EVM18001.