Combining B Cell Depletion Therapy with Daratumumab for Autoimmune Encephalitis

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

This study is testing a new treatment that combines two therapies to see if it can help people with severe autoimmune encephalitis feel better by targeting harmful cells in their bodies.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 200 (estimated)
• Ages: 12 Years and up
• Sex: All
• Sponsor: The First People's Hospital of Changzhou (Academic / other)
• Drugs / interventions: Natalizumab, Methotrexate, Cyclophosphamide, ofatumumab, daratumumab, rituximab, tocilizumab, immunotherapy
• Locations: 2 sites (Zhengzhou, Henan and 1 other locations)
• Trial ID: NCT06867991 on ClinicalTrials.gov

What this trial studies

This study investigates the safety and efficacy of a treatment regimen that combines B cell depletion therapy using ofatumumab with plasma cell depletion therapy using daratumumab for patients suffering from severe anti-N-Methyl-D-Aspartate Receptor (NMDAR) autoimmune encephalitis. The approach aims to eliminate pathogenic B cells and plasma cells responsible for producing harmful autoantibodies. Participants will receive high-dose methylprednisolone and intravenous immunoglobulin or plasma exchange prior to the treatment. The study seeks to provide a structured evaluation of this combined therapy in a Phase 3 setting.

Who should consider this trial

Good fit: Ideal candidates include individuals aged 12 years and older diagnosed with autoimmune encephalitis and exhibiting severe symptoms.

Not a fit: Patients with severe active infections or those who are pregnant or lactating may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve outcomes for patients with severe autoimmune encephalitis by targeting the underlying immune dysfunction.

How similar studies have performed: While various therapies for autoimmune encephalitis have been explored, this specific combination of therapies has not been previously tested in a high-quality randomized controlled trial.

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.

Where this trial is running

Zhengzhou, Henan and 1 other locations

• The First Affiliated Hospital of Zhengzhou University — Zhengzhou, Henan, China (Recruiting)
• The First People's Hospital of Changzhou — Changzhou, Jiangsu, China (Recruiting)

Study contacts

• Study coordinator: Wei Xie

Conditions Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Ofatumumab; Daratumumab; severe autoimmune encephalitis