Inebilizumab for NMDAR Encephalitis

(ExTINGUISH Trial)

Recruiting at 39 trial locations

Overseen By Ka-Ho Wong, MBA

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Utah

Must be taking: Methylprednisolone, IVIg, Plasmapheresis

Must not be taking: Biologic B cell-depleting, Methotrexate

Disqualifiers: Pregnancy, Active infection, Transplant history, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

116 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding inebilizumab, an investigational medication, to standard treatments benefits people with anti-NMDA receptor (NMDAR) encephalitis, a brain inflammation that alters mental status. Participants will receive either inebilizumab or a placebo, alongside standard care, to compare recovery over 16 weeks. Individuals who have experienced significant mental changes due to NMDAR encephalitis and have undergone certain standard treatments might be suitable candidates. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group.

Do I need to stop my current medications for this trial?

The trial requires participants to stop other immunomodulatory therapies for NMDAR encephalitis during the study. However, it does not specify if you need to stop other medications, so it's best to discuss your specific situation with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that inebilizumab is under investigation as a potential treatment for NMDAR encephalitis, a serious brain condition. Previous studies found that inebilizumab effectively targets certain immune cells, which might help reduce disease symptoms. The ongoing ExTINGUISH trial is carefully monitoring patients using standard safety measures.

As a Phase 2 trial, earlier studies have already assessed the basic safety of inebilizumab in humans. It has generally been well-tolerated, but researchers continue to collect more information on side effects. For those considering joining a trial, this phase indicates that inebilizumab has passed initial safety checks, though more detailed safety information is still being gathered. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for NMDAR encephalitis?

Inebilizumab is unique because it specifically targets CD19, a protein found on the surface of B cells, which are implicated in NMDAR Encephalitis. Most current treatments focus on broad immunosuppression or plasma exchange, which can have widespread effects on the immune system. By contrast, Inebilizumab offers a more targeted approach, potentially leading to fewer side effects and more effective management of the condition. Researchers are excited about this treatment because its precise action on B cells could mean better outcomes for patients and a new direction for treating autoimmune diseases like NMDAR Encephalitis.

What evidence suggests that inebilizumab could be an effective treatment for NMDAR encephalitis?

Research has shown that inebilizumab, one of the treatments under study in this trial, might help treat NMDAR encephalitis. This treatment targets and reduces certain immune cells called CD19+ B cells, which play a role in the disease. Studies have found that inebilizumab can significantly and lastingly decrease these cells. This effect may help improve symptoms and possibly lead to better long-term results for patients. If successful, inebilizumab could become a promising new option for people with this condition. Participants in this trial will receive either inebilizumab or a placebo, in addition to first-line immunotherapy. ^{1 2 3 4 5}

Who Is on the Research Team?

Stacey L Clardy, MD, PhD

Principal Investigator

University of Utah

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

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

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

Written informed consent and any locally required authorization obtained from the participant/legal representative prior to performing any protocol-related procedures, including screening evaluations

Exclusion Criteria

Severe drug allergic history or anaphylaxis to two or more food products or medicines

I have not received a live vaccine recently.

I have received the specific treatments required before being randomly assigned to a trial group.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either inebilizumab or placebo in addition to first-line immunotherapy, including a 3-day course of IVIg

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with primary outcomes assessed at 16 weeks and additional assessments at 24 and 96 weeks

96 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Inebilizumab
• Placebo

Trial Overview 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.

How Is the Trial Designed?

Group I: Inebilizumab Active Control 1 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: Placebo Placebo Group 1 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.

Inebilizumab is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Uplizna for:

• Neuromyelitis optica spectrum disorder (NMOSD) in adults who are anti-aquaporin-4 (AQP4) antibody positive

Approved in European Union as Uplizna for:

• Neuromyelitis optica spectrum disorder (NMOSD) in adults who are anti-aquaporin-4 (AQP4) antibody positive

Approved in Canada as Uplizna for:

• Neuromyelitis optica spectrum disorder (NMOSD) in adults who are anti-aquaporin-4 (AQP4) antibody positive

Who Is Running the Clinical Trial?

University of Utah

Lead Sponsor

Trials

1,169

Recruited

1,623,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40625668/

A Phase-2B Double-Blind Randomized International ... Inebilizumab may be an efficacious treatment for patients with NMDAR encephalitis, with the potential to achieve early robust and sustained suppression CD19+ ...

2. neurology.org neurology.org/doi/10.1212/WN9.0000000000000007

The ExTINGUISH Trial Inebilizumab may be an efficacious treatment for patients with NMDAR encephalitis, with the potential to achieve early robust and sustained ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04372615

NCT04372615 | The ExTINGUISH Trial of Inebilizumab in ... The ExTINGUISH Trial will prospectively study an optimized B-cell depletion therapy to promote better long-term outcomes in NMDAR encephalitis, to determine ...

4. yalemedicine.org yalemedicine.org/clinical-trials/the-extinguish-trial-of-inebilizumab-in-nmdar-encephalitis-extinguish

The ExTINGUISH Trial of Inebilizumab in NMDAR ... The ExTINGUISH Trial will randomize 116 participants with moderate-to-severe NMDAR encephalitis to receive either inebilizumab or placebo in addition to first- ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S147149142500214X

Review Anti-N-methyl-d-aspartate receptor encephalitis Although ~80% of patients achieve favorable functional outcomes, persistent neuropsychiatric and cognitive deficits may impact quality of life, ...