Presentation

Background and Purpose: The lack of approved therapies for anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis has led to substantial variability in treatment. High-quality data is needed to guide treatment and optimize long-term outcomes in recovering patients. Inebilizumab is a humanized anti-CD19 monoclonal antibody that can be administered intravenously with good CSF penetration with high target engagement, and may be an efficacious treatment for NMDAR encephalitis. ExTINGUISH is to assess the safety and efficacy of inebilizumab in patients with NMDAR encephalitis.

Methods: The ExTINGUISH trial is a Phase-2B randomized double-blind placebo-controlled trial designed to evaluate the safety and efficacy of inebilizumab 300 mg for the acute treatment of moderate-to-severe NMDAR encephalitis. 120 participants will be enrolled at 39 US and two European sites (Barcelona, Spain; Rotterdam, The Netherlands). All patients will receive standard “first-line” immunotherapies prior to randomization as well as intravenous immune globulin (IVIg) at Day 22. Cyclophosphamide IV rescue therapy will be provided after 6 weeks to patients who fail to respond to initial treatments. Motor, cognitive, and functional outcomes will be assessed over a minimum of 24 weeks. Study operations are supported via the NINDS-supported NeuroNEXT infrastructure.

Results: Primary outcomes will be ascertained at 16 weeks using the change in the modified Rankin scale (adjusted for rescue therapy) and accepted safety measures. Comprehensive neuropsychological tests and quality of life/ functional indices will be measured across study participation (secondary outcomes). Currently, trial enrollment is ongoing. Trial design and baseline demographic will be presented.

Conclusion: ExTINGUISH Trial findings will immediately influence patient care while informing the design and implementation of future clinical trials in autoimmune encephalitis.