What side effects are associated with this type of intervention?

B cell depleting therapies, such as Inebilizumab and Rituximab, are commonly associated with side effects including infusion reactions (fever, chills, and rash), increased risk of infections due to immunosuppression, and potential allergic reactions. Other side effects may include fatigue, nausea, and headache. In rare cases, more severe complications like progressive multifocal leukoencephalopathy (PML) have been reported. It is important for patients to discuss these potential risks with their healthcare provider.

What prior FDA approvals exist?

The FDA has approved several treatments for encephalitis, particularly those targeting B cells through monoclonal antibodies. Rituximab, an anti-CD20 monoclonal antibody, is one such treatment that has been used for autoimmune encephalitis, including NMDAR encephalitis. Rituximab works by depleting B cells, similar to the investigational agent inebilizumab, which targets CD19. These therapies aim to reduce the autoimmune response by eliminating B cells that produce harmful antibodies.

What other types of research exist?

Promising, novel alternatives to Inebilizumab for Encephalitis patients in 2024 include Rituximab, which is another B cell depleting agent, and potentially high-dose cyclophosphamide or glucocorticoids, which have been used in other autoimmune conditions affecting the central nervous system.

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Monoclonal Antibodies

Inebilizumab for NMDAR Encephalitis (ExTINGUISH Trial)

Phase 2

Recruiting

Led By Stacey L Clardy, MD, PhD

Research Sponsored by University of Utah

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Diagnosis of NMDAR encephalitis, defined by subacute onset of change in mental status consistent with autoimmune encephalitis and a positive cell-based assay for anti-NMDA receptor IgG antibody in the CSF confirmed in study-specified laboratories

Received IVIg at a minimum dose of 2 g/kg or plasma exchange/plasmapheresis with a minimum of 5 treatments within 30 days before randomization

Must not have

Presence of an active or chronic serious infection

Recent history (last 5 years) of herpes simplex virus encephalitis or known central nervous system demyelinating disease

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 96 weeks

Summary

This trial is testing a new drug called inebilizumab for patients with severe anti-NMDAR encephalitis, a serious brain disease. The drug aims to reduce specific immune cells that cause the disease. Researchers hope this will improve symptoms and outcomes for these patients.

Who is the study for?

Adults diagnosed with NMDAR encephalitis who've had recent standard treatments can join. They must be able to attend study visits, agree to use effective contraception if applicable, and not receive other immunomodulatory therapies during the trial. Exclusions include a history of certain infections or diseases, recent participation in another clinical trial, pregnancy, specific prior treatments, and severe allergies.

What is being tested?

The trial is testing Inebilizumab against a placebo in patients already receiving standard care for NMDAR encephalitis. The main goal is to see how well participants recover over 16 weeks by looking at changes in their disability levels measured by the modified Rankin score.

What are the potential side effects?

While specific side effects are not listed here, Inebilizumab may cause reactions related to the immune system since it's designed to modify immune responses. This could potentially lead to infusion-related reactions or increase susceptibility to infections.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have been diagnosed with NMDAR encephalitis confirmed by a specific test.

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I have received IVIg or undergone plasma exchange at least 5 times in the last 30 days.

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I am 18 years old or older.

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I agree to use effective birth control if I can have children and am sexually active.

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I am a man who can father children and will use effective birth control.

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I agree not to take other immune therapies for NMDAR encephalitis during the study.

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I've had high-dose steroids via IV in the last month.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a serious ongoing infection.

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I have not had herpes brain infection or nerve damage diseases in the last 5 years.

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My NMDAR encephalitis has come back within the specified time.

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I have a condition that makes me more likely to get infections.

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I have a history of cancer, but it may fit the exceptions.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 96 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~96 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and 96 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change of modified Rankin score at 16 weeks

Inebilizumab safety measures by the number of treatment-emergent adverse events and serious adverse events

Secondary study objectives

Clinical Assessment Scale in Autoimmune Encephalitis (CASE) Score (continuous logistic regression), corrected from baseline value to week 24 (weeks 6 and 16).

Cognitive outcome at week 24 as measured by mean scaled score on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) + components of Delis-Kaplan Executive Function System (D-KEFS).

Proportion of participants who meet the protocol-defined criteria for needing rescue therapy at week 6.

+3 more

Trial Design

2Treatment groups

Active Control

Placebo Group

Group I: InebilizumabActive Control1 Intervention

Approximately 58 patients will receive Inebilizumab in addition to first line immunotherapy. (Approximately 116 participants will be randomized in a 1:1 ratio to 2 treatment groups; approximately 58 participants to each treatment group). All participants will also receive a 3 day course of IVIg.

Group II: PlaceboPlacebo Group1 Intervention

Approximately 58 patients will receive placebo in addition to first line immunotherapy. (Approximately 116 participants will be randomized in a 1:1 ratio to 2 treatment groups; approximately 58 participants to each treatment group). All participants will also receive a 3 day course of IVIg.

0 / 12Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Encephalitis, including corticosteroids, intravenous immunoglobulin (IVIG), plasmapheresis, and B-cell depletion therapies like Inebilizumab, primarily work by modulating the immune system. Inebilizumab, an anti-CD19 monoclonal antibody, depletes B cells, which are key players in the autoimmune response that can cause Encephalitis. Corticosteroids reduce inflammation by suppressing the overall immune response, IVIG provides a pool of antibodies that can neutralize harmful autoantibodies, and plasmapheresis removes these autoantibodies from the blood. These mechanisms are crucial for Encephalitis patients as they help to control the immune-mediated damage to the brain, thereby reducing symptoms and preventing further neurological deterioration.

Long-term efficacy and safety of inebilizumab in neuromyelitis optica spectrum disorder: Analysis of aquaporin-4-immunoglobulin G-seropositive participants taking inebilizumab for ⩾4 years in the N-MOmentum trial.B-cell-targeted treatment for multiple sclerosis: mechanism of action and clinical data.