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

Launched by THE FIRST PEOPLE'S HOSPITAL OF CHANGZHOU · Mar 5, 2025

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment approach for a serious condition called anti-N-Methyl-D-Aspartate Receptor (anti-NMDAR) encephalitis, which is an autoimmune disease affecting the brain. In this trial, researchers want to see if a combination of two therapies—one that targets specific immune cells (B cells) and another that targets plasma cells—can improve the health of patients with this condition. The goal is to reduce the harmful antibodies produced by these immune cells, which can cause severe symptoms and complications.

To participate in this trial, individuals must be 12 years or older and have a confirmed diagnosis of autoimmune encephalitis. They should have already received certain initial treatments, such as high-dose steroids or plasma exchange, and have a specific level of disability. Participants will receive the new treatment and will be closely monitored for its effects and safety. It’s important to note that individuals with certain health issues or who are pregnant or breastfeeding may not be eligible. This trial is currently recruiting participants, and those interested should speak with their healthcare provider for more information.

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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 ≥ 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 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.