Safety and Efficacy of Combined B Cell Depleting theRapy And Daratumumab In Autoimmune Encephalitis

Inclusion Criteria:

1. Aged 12 years and above

2. Meet the diagnosis of autoimmune encephalitis and the target antigen is a neuronalsurface antigen

3. Have received at least 3 days of 500-1000mg high-dose methylprednisolone impulsetreatment and IVIG (0.4g/kg/d for 5 consecutive days) or at least 5 plasmaexchange/immunoadsorption or at least 2 times of efgartigimod treatment

4. mRS ≥ 4 points

5. Informed consent or guardian signed informed consent

Exclusion Criteria:

1. Severe active or chronic infection in the opinion of the investigator.

2. Concurrently/previously participated in another clinical study involvinginvestigational therapy within 4 weeks or 5 published half-lives of theinvestigational therapy (whichever is longer) before randomization.

3. Women who are lactating or pregnant, or intend to become pregnant at any time withinsix months from study enrollment to the last dose of study drug.

4. Known history of allergy or reaction to any component of the investigational drugformulation, or history of allergic reaction after any biological treatment.

5. Any of the following at screening (one repeat test may be performed during the samescreening period to confirm results prior to randomization): Aspartate aminotransferase (AST) > 2.5 × upper limit of normal (ULN) Alanine aminotransferase (ALT) > 2.5 × upper limit of normal (ULN) Total bilirubin > 1.5 × ULN (unless due to Gilbert's syndrome) Platelet count < 75,000/μL (or < 75 × 109/L) Hemoglobin < 8 g/dL (or < 80 g/L) Total white blood cell count < 2,500 cells/mm3 Total immunoglobulins < 600 mg/dL Absolute neutrophil count < 1200 cells/μL CD4 T lymphocyte count < 300 cells/µL Receipt of any experimental B cell depleting agent, unless CD19 B Cell levels havereturned to above the lower limit of normal before randomization A history of severedrug allergies or anaphylaxis to two or more foods or drugs (including knownsensitivity to acetaminophen/paracetamol, diphenhydramine or equivalentantihistamines, and methylprednisolone or equivalent glucocorticoids). A known history of primary immunodeficiency (congenital or acquired) or underlyingconditions, such as human immunodeficiency virus (HIV) infection or splenectomy,that predispose the participant to infection. Any of the following received within 3 months before randomization Natalizumab (Tysabri®) Cyclosporin Methotrexate Mitoxantrone Cyclophosphamide Azathioprine

6. Confirmed positive hepatitis B serology (hepatitis B surface antigen and coreantigen) and/or positive hepatitis C PCR at screening.

7. History of cancer, other than ovarian or extraovarian teratoma (also known asdermoid cyst) or germ cell tumor, or cutaneous squamous cell carcinoma or cutaneousbasal cell carcinoma. Treatment of squamous cell carcinoma and basal cell carcinomashould have documented successful curative treatment more than 3 months beforerandomization.

8. Received any live or attenuated vaccine (inactivated vaccine is acceptable) within 3weeks before enrollment.

9. Received BCG vaccine within 1 year before enrollment.