eligibility_summary
Inclusion: ≥12, autoimmune encephalitis (neuronal surface antigen), after high-dose steroids+IVIG or ≥5 PLEX/IA or ≥2 efgartigimod, mRS ≥3 with neuropsychiatric symptoms, consent. Exclusion: active infection, recent investigational therapy, pregnancy/lactation, drug/biologic allergy, abnormal LFTs/cytopenias/low Ig/ANC/CD4, ongoing B-cell depletion, immunodeficiency/HIV/splenectomy, recent immunosuppressants, HBV/HCV+, cancer (except teratoma/treated skin SCC/BCC), recent live/BCG vaccines.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
NCT06867991 is a Phase 3, randomized, open-label trial in severe anti‑NMDAR autoimmune encephalitis. Interventions: 1) Ofatumumab—fully human anti‑CD20 monoclonal antibody (B‑cell–depleting via complement/ADCC), 2) Ofatumumab + Daratumumab—human anti‑CD38 monoclonal antibody (plasma cell–depleting via CDC/ADCC/ADCP and apoptosis, also modulates certain T‑cell functions), versus 3) repeated IVIG/plasma exchange (IVIG immunomodulation, PLEX removes circulating antibodies). Targets/pathways: depletion of CD20+ B cells (autoreactive B‑cell pool) and CD38+ plasma cells, particularly long‑lived intrathecal/meningeal/brain‑resident plasma cells sustaining pathogenic anti‑NMDAR IgG, suppression of humoral autoimmunity and intrathecal antibody production, possible T‑cell functional effects via CD38 targeting. IVIG/PLEX act on circulating autoantibodies and complement pathways. Goal: faster clinical improvement by eliminating autoantibody‑producing cells and reducing anti‑NMDAR antibody burden.