NCT06867991 Safety and Efficacy of Combined B Cell Depleting theRapy And Daratumumab In Autoimmune Encephalitis

Eligibility & Interventions

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What to Expect as a Participant

You will actively receive the study intervention — which may be a drug, biologic, device, or procedure.

Phase 3 trials are large pivotal studies comparing the treatment to current standard of care or placebo. Your participation directly contributes to the evidence needed for regulatory approval.

This trial targets 200 participants in total. It began in 2024-11-08 with a primary completion date of 2026-11-08.

Brief Summary

Autoimmune encephalitis is an autoimmune disease of the central nervous system that targets neuronal autoantigens. Anti-neuronal autoantibodies are produced in patients, with anti-NMDAR antibody being the most common.Anti-NMDAR encephalitis can be severe and life-threatening. Anti-NMDAR autoantibodies against neurons are pathogenic and are mainly produced by autoreactive B cells and plasma cells. Therefore, early elimination of these abnormal immune cells is crucial for rapid improvement of the patient's condition. This study aims to explore the efficacy and safety of B cell depletion therapy (ofatumumab) followed by plasma cell depletion therapy (daratumumab) in the treatment of severe anti-NMDAR autoimmune encephalitis.

Eligibility Criteria

Inclusion Criteria: 1. Aged 12 years and above 2. Meet the diagnosis of autoimmune encephalitis and the target antigen is a neuronal surface antigen 3. Have received at least 3 days of 500-1000mg high-dose methylprednisolone impulse treatment and IVIG (0.4g/kg/d for 5 consecutive days) or at least 5 plasma exchange/immunoadsorption or at least 2 times of efgartigimod treatment 4. mRS ≥ 3 points and neuropsychiatric manifestations inadequate to symptomatic treatment 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 involving investigational therapy within 4 weeks or 5 published half-lives of the investigational therapy (whichever is longer) before randomization. 3. Women who are lactating or pregnant, or intend to become pregnant at any time within six months from study enrollment to the last dose of study drug. 4. Known history of allergy or reaction to any component of the investigational drug formulation, or history of allergic reaction after any biological treatment. 5. Any of the following at screening (one repeat test may be performed during the same screening 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 have returned to above the lower limit of normal before randomization A history of severe drug allergies or anaphylaxis to two or more foods or drugs (including known sensitivity to acetaminophen/paracetamol, diphenhydramine or equivalent antihistamines, and methylprednisolone or equivalent glucocorticoids). A known history of primary immunodeficiency (congenital or acquired) or underlying conditions, 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 core antigen) and/or positive hepatitis C PCR at screening. 7. History of cancer, other than ovarian or extraovarian teratoma (also known as dermoid cyst) or germ cell tumor, or cutaneous squamous cell carcinoma or cutaneous basal cell carcinoma. Treatment of squamous cell carcinoma and basal cell carcinoma should have documented successful curative treatment more than 3 months before randomization. 8. Received any live or attenuated vaccine (inactivated vaccine is acceptable) within 3 weeks before enrollment. 9. Received BCG vaccine within 1 year before enrollment.

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