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

Conditions

• Anti-N-Methyl-D-Aspartate Receptor Encephalitis

Eligibility Criteria

Sex

ALL

Age

12 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Ofatumumab combined with daratumumab — DRUG
  All participants will begin acute first-line therapy prior to randomization, and participants who were receiving oral or intravenous corticosteroids at baseline will need to taper their doses according to a standard taper schedule starting 4 weeks after randomization (week 4). Patients will be randomly assigned to receive ofatumumab followed by daratumumab or ofatumumab followed by repeated intravenous globulin. The ofatumumab group will receive subcutaneous ofatumumab at weeks 0, 1, 2, 4, 8, 12, 16, 20, and 24, while the ofatumumab-daratumumab group will receive daratumumab intravenously (on the second day of ofatumumab) in addition to ofatumumab, with a dose of 8 mg/kg at weeks 0, 1, 2, and 4, and a dose of 4 mg/kg at weeks 8, 12, 16, 20, and 24. The study will investigate the effects of up to 24 cycles of daratumumab.
• Ofatumumab — DRUG
  All participants were started on acute first-line therapy before randomization, and participants who were receiving oral or intravenous glucocorticoids at baseline were required to taper their doses according to a standard taper schedule starting 4 weeks after randomization (week 4). Ofatumumab was administered subcutaneously at weeks 0, 1, 2, 4, 8, 12, 16, 20, and 24 in the ofatumumab group.
• Repeated intravenous immunoglobulin/plasma exchange therapy — DRUG
  Repeated intravenous immunoglobulin/plasma exchange therapy

Study Details

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.

Key Dates

Start date

Nov 8, 2024

Status verified

Jul 2025

Primary completion

Nov 8, 2026

Completion

Nov 8, 2027

Study Design

Enrollment

200 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: B cell depleting agent（ofatumumab）combined with daratumumab treatment group
  The group receiving B cell depletion plus daratumumab will receive daratumumab intravenously (on the second day of ofatumumab) in addition to ofatumumab, with a dose of 8 mg/kg at weeks 0, 1, 2, and 4, and a dose of 4 mg/kg at weeks 8, 12, 16, 20, and 24. The study will investigate the effect of up to 24 cycles of daratumumab
• Active Comparator: Ofatumumab treatment group
  Ofatumumab group received subcutaneous injection of ofatumumab at weeks 0, 1, 2, 4, 8, 12, 16, 20, and 24
• Active Comparator: Repeated intravenous immunoglobulin/plasma exchange therapy group
  At least two cycles of intravenous immunoglobulin/plasma exchange therapy

Primary Outcome Measure

Time to mRS<=2, i.e. the proportion of patients with mRS scores of 0-2 [ Time Frame: week 16 ]

Central Contacts

• Wei Xie
  +86051968872122
  [email protected]