The ExTINGUISH Trial of Inebilizumab in NMDAR Encephalitis
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age12+
SponsorUniversity of Utah
About this trial
Determine the difference in the modified Rankin score at 16 weeks in participants with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis treated with "first-line" immunomodulatory therapies provided as standard-of-care, and either inebilizumab (investigational agent) or placebo.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
A subacute onset of change in mental status consistent with autoimmune encephalitis,
A positive cell-based assay for anti-NMDA receptor IgG antibody in the CSF confirmed in study-specified laboratories.
Participants, ≥ 12 years of age at the time of informed consent. Participants under 18 years of age must weigh ≥40 kilograms.
Written informed consent and any locally required authorization (e.g., Health Insurance Portability and Accountability Act [HIPAA] in the United States of America [USA], European Union [EU] Data Privacy Directive in the EU) obtained from the participant/legal representative prior to performing any protocol-related procedures, including screening evaluations.
Disqualifiers
Any condition that, in the opinion of the Investigator, would interfere with the evaluation or administration of the IP, interpretation of participant safety or study results, or would make participation in the study an unacceptable risk. This specifically includes recent history (last 5 years) of herpes simplex virus encephalitis or known central nervous system demyelinating disease (e.g., multiple sclerosis).
Presence of an active or chronic infection that is serious in the opinion of the Investigator.
History of solid organ or cell-based transplantation.
Concurrent/previous enrollment in another clinical study involving an investigational treatment within 4 weeks or 5 published half-lives of the investigational treatment, whichever is longer, prior to randomization.
Trial design
Design model
Parallel
Treatments tested in this trial
Inebilizumab
DrugRCP: Blinded treatment on Day 1, Day 15, * Inebilizumab group: Inebilizumab 300 mg intravenous (IV) * Placebo group: IV matching placebo Prior to enrollment, all participants will receive standard of care, including high-dose corticosteroids (minimum of 3 days of treatment, 1 g methylprednisolone daily or equivalent) AND either IVIg (total dose range between 1.2 and 2 g/kg) OR plasmapheresis (defined as 5 or 6 exchanges). Rescue therapy will be given to participants in either treatment group based on the results of the Week 6 assessments. Rescue therapy is cyclophosphamide 750 mg/m2 IV followed by additional doses every 28-30 days until the mRS score is ≤ 3 (at site Principal Investigator's discretion under standard of care).
Placebo
DrugThe placebo group will receive IV matching placebo on Day 1 and Day 15,
Treatment groups
116 Participants
are divided into 2 treatment groupsGroup A: InebilizumabActive comparator 1 intervention
Group B: PlaceboPlacebo comparator 1 intervention
Trial outcomes
Primary outcomes
1
Change of modified Rankin score at 16 weeks
Change in modified Rankin score (mRS) (0 to 6; 0=normal and 6=death) at 16 weeks determined by rank analyses, integrating need for rescue therapy and time to achievement of the mRS.
Time frame
16 weeks2
Inebilizumab safety measures by the number of treatment-emergent adverse events and serious adverse events
Inebilizumab safety, as measured by the number of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs)
Time frame
96 weeksSecondary outcomes
1
Time to mRS ≤ 2, corrected for baseline value.
Time to mRS ≤ 2, corrected for baseline value.
Time frame
96 weeks2
Clinical Assessment Scale in Autoimmune Encephalitis (CASE) Score (continuous logistic regression), corrected from baseline value to week 24 (weeks 6 and 16).
Clinical Assessment Scale in Autoimmune Encephalitis (CASE) Score (ranges of 0 to 27 with 0 being normal and 27 being worse)(continuous logistic regression), corrected from baseline value to week 24 (weeks 6 and 16).
Time frame
16 weeks3
mRS at week 6 as measured by proportional odds logistic regression/shift analysis.
mRS at week 6 as measured by proportional odds logistic regression/shift analysis.
Time frame
6 weeks4
Proportion of participants who meet the protocol-defined criteria for needing rescue therapy at week 6.
Proportion of participants who meet the protocol-defined criteria for needing rescue therapy at week 6.
Time frame
6 weeksSponsors and contacts
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Source ClinicalTrials.gov