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RecruitingNCT04372615ExTINGUISHUpdated Jul 1, 2025

The ExTINGUISH Trial of Inebilizumab in NMDAR Encephalitis

A Phase 2 interventional study of Inebilizumab and Placebo in Autoimmune Encephalitis and Encephalitis, sponsored by University of Utah. Recruiting at 39 sites in 3 countries. Open to participants aged 12 Years and older. Per ClinicalTrials.gov, last updated 2025-07-01.

Sponsored by University of Utah · Phase 2, Interventional, and Treatment

From the registry’s dates

  • Started Mar 2022; still recruiting 4 years 7 months later.
Phase
Phase 2
Study type
Interventional
Enrollment
116
Allocation
Randomized
Ages
12 Years and older
Sex
All
01

Study summary

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.

Read the detailed description

N-methyl-D-aspartate receptor (NMDAR) encephalitis is one of the most common causes of autoimmune encephalitis, with prevalence exceeding herpes encephalitis in industrialized nations. Typically, the disease affects patients age 10-50 causing prominent psychiatric symptoms, altered consciousness, seizures, movement disorders and life-threatening dysautonomia. Intensive care, including cardiorespiratory support is required in 75% of cases. The diagnosis is confirmed by detection of IgG autoantibodies against central nervous system NMDAR in the cerebrospinal fluid. Despite the severity of the illness, NMDAR encephalitis is a treatable neurological disease, with retrospective case series establishing the benefit of off-label intravenous steroids and immunoglobulins. These treatments are presumed to work through effects on IgG NMDAR autoantibody levels in the CSF, although prospective data informing predictors of treatment responses are limited. Even with prompt treatment, \~50% of patients remain disabled, requiring prolonged hospital admissions. Various off-label therapies have been proposed as "second-line" treatments in NMDAR encephalitis. The majority of second-line treatments target circulating B-cells with various degrees of blood brain penetrance and efficacy, and poor consensus on the timing, dose and route of delivery of candidate agents. High-quality evidence is needed to inform the treatment of NMDAR encephalitis. Inebilizumab is a promising therapeutic monoclonal antibody for the treatment of NMDAR encephalitis. This humanized monoclonal antibody against the B-cell surface antigen CD19 was recently shown to be safe and efficacious in the treatment of neuromyelitis optica spectrum disorder-another antibody-mediated disorder of the central nervous system. Compared to other off label B-cell depleting therapies, such as rituximab, inebilizumab not only depletes CD20+ B-cells, but also CD20- plasmablasts and plasma cells, resulting in robust and sustained suppression of B-cell expression. The ExTINGUISH Trial will randomize 116 participants with moderate-to-severe NMDAR encephalitis to receive either inebilizumab or placebo in addition to first-line therapies. Patient outcomes will be ascertained at standard intervals using the modified Rankin scale and accepted safety measures (primary outcomes at 16 weeks), together with comprehensive validated neuropsychological tests, bedside cognitive screening tools, quality of life/ functional indices, and outcome prediction measures. Clinical data will be combined with quantitative measures of NMDAR autoantibody titers and cytokines implicated in B-cell activation and antibody production within the intrathecal compartment to identify treatment responders, inform the biologic contributors to outcomes, and evaluate for biomarkers that may serve as early predictors of favorable outcomes in future clinical trials in NMDAR encephalitis. The ExTINGUISH Trial will prospectively study an optimized B-cell depletion therapy to promote better long-term outcomes in NMDAR encephalitis, to determine more meaningful cognitive endpoints, and to identify better biologic biomarkers to predict outcome.

02

Conditions studied

  • Autoimmune Encephalitis
  • Encephalitis

Keywords

  • Inebilizumab
  • NMDAR encephalitis
  • Autoimmune Encephalitis
  • Rare Disease
03

In context

Autoimmune Diseases of the Nervous System

123 studies on the registry are indexed under Autoimmune Diseases of the Nervous System; 59 are open to participants now.

This study's planned enrollment of 116 is above the median of 40 across 63 interventional studies indexed under Autoimmune Diseases of the Nervous System.

Browse Autoimmune Diseases of the Nervous System studies →

Lead sponsor

University of Utah is the lead sponsor of 994 studies on the registry; 175 are open to participants now.

Of its 114 completed or terminated interventional studies of FDA-regulated products, 69 (61%) have results posted.

Browse University of Utah studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
12 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  1. Diagnosis of NMDAR encephalitis, defined by both a and b:

    1. A subacute onset of change in mental status consistent with encephalitis,
    2. A positive cell-based assay for anti-NMDA receptor IgG antibody in the CSF confirmed in study-specified laboratories.
  2. Participants, ≥ 12 years of age at the time of . Participants under 18 years of age must weigh ≥40 kilograms.
  3. 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.

  4. Non-sterilized participants who are sexually active with a partner capable of becoming pregnant must use a condom with spermicide from Day 1 through to the end of the study and must agree to continue using such precautions for at least 6 months after the final dose of IP. A recommendation will be made that the partners (capable of becoming pregnant) of study participants (capable of getting their partner pregnant) should use a highly effective method of other than a physical method.

    Participants of who are sexually active with a non-sterilized partner capable of getting their partner pregnant must agree to use a highly effective method of contraception beginning at screening or upon discharge from hospitalization/inpatient rehabilitation (for participants who were incapacitated at the time of screening), and to continue precautions for 12 months after the final dose of IP.

    1. Participants of childbearing potential are defined as those who are not surgically sterile (e.g., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or those who are not (per ICH M3 (R2) 11.2: defined as 12 months with no menses without an alternative medical cause).

    2. A highly effective method of contraception is defined as one that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly. Periodic abstinence, the rhythm method, and the withdrawal method do not qualify as "highly effective" or acceptable methods of contraception for study purposes. Acceptable methods of contraception are listed in the table below:

      Physical Methods Hormonal Methods e

      • Intrauterine device (IUD)
      • Intrauterine hormone-releasing system, also known as drug-eluting IUD a
      • Bilateral tubal occlusion
      • Vasectomized partner b
      • Sexual abstinence c • Combined (estrogen and progestogen-containing hormonal contraception)
      • Oral (combined pill)
      • Injectable
      • Transdermal (patch)
      • Progestogen-only hormonal contraception associated with inhibition of ovulation d
      • Implantable
      • Intravaginal a This is also considered to be a hormonal method. b With appropriate post-vasectomy documentation of surgical success (absence of sperm in ejaculate).

      c Sexual abstinence is considered to be a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of the study and if it is the preferred and usual lifestyle of the participant.

      d Progestogen-only hormonal contraception, where inhibition of ovulation is not the primary mode of action (minipill) is not accepted as a highly effective method.

      e These methods are only considered highly effective and therefore acceptable when used in conjunction with a barrier method (i.e., diaphragm with spermicide, sponge with spermicide, cervical cap with spermicide, condoms, spermicide alone.)

  5. Willing to forgo other immunomodulatory therapies ( or otherwise) for NMDAR encephalitis during the study.

  6. Participant must have received at least 3 days of methylprednisolone 1000 mg IV or equivalent within 90 days prior to randomization (Day 1). In addition, participants must have received EITHER of the following treatments within 90 days before randomization.

    1. IVIg, at a dose range between 1.2 and 2 g/kg
    2. Plasma exchange or plasmapheresis, (defined as 5 to 6 exchanges).

    NOTE: These treatments may be provided during the screening period but must be completed prior to randomization. Participants who receive methylprednisolone and BOTH IVIg and plasma exchange are not excluded from participating in the trial, however, this treatment course with both IVIg and plasma exchange is not encouraged, and enrollment and randomization should not be delayed in order to complete additional treatments.

  7. Modified Rankin Score of ≥3 at the screening visit, indicating at least moderate disability. The baseline mRS must be confirmed by Site Investigators at screening and confirmed / adjudicated before randomization.
  8. Ability and willingness to attend study visits and complete the study. *All inclusion criteria must be met during the screening period, prior to randomization, except where noted.

Exclusion criteria

Exclusion Criteria

Any of the following excludes an individual from participation in the study:

  1. 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).
  2. Presence of an active or chronic infection that is serious in the opinion of the Investigator.
  3. History of solid organ or cell-based transplantation.

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  1. Concurrent/previous enrollment in another clinical study involving an treatment within 4 weeks or 5 published half-lives of the investigational treatment, whichever is longer, prior to randomization.
  2. Lactating or pregnant individuals, or individuals who intend to become pregnant anytime from study enrollment to 12 months following last dose of investigational agent.
  3. Known history of allergy or reaction to any component of the investigational agent formulation or history of anaphylaxis following any biologic therapy.

  4. Receipt of the following at any time prior to randomization:

    a. Alemtuzumab b. Total lymphoid irradiation c. Bone marrow transplant d. T-cell vaccination therapy

  5. Receipt of any biologic B cell-depleting therapy (e.g., rituximab, ocrelizumab, obinutuzumab, ofatumumab, inebilizumab) in the 6 months prior to screening. Receipt of such a B cell-depleting agent in the period 6-12 months prior to screening is exclusionary unless B cell counts have returned to ≥ age-based LLN by central laboratory. For EU participants, B cell counts at screening will be determined by the laboratories of the participating sites. Receipt of non-depleting B cell-directed therapy (e.g., belimumab), abatacept, or other biologic immunomodulatory agent within 6 months prior screening.

  6. Treatment at therapeutic doses/durations with any of the following within 3 months prior to randomization

    a. Natalizumab (Tysabri®) b. Cyclosporine c. Methotrexate d. Mitoxantrone e. Cyclophosphamide* f. Azathioprine g. Mycophenolate mofetil

    *Cyclophosphamide is only permitted as rescue therapy to be administered as outlined in Section 5.4.1 no earlier than the week 6 visit.

  7. Severe drug allergic history or anaphylaxis to two or more food products or medicines (including known sensitivity to acetaminophen/paracetamol, diphenhydramine (cetirizine in EU) or equivalent antihistamine, and methylprednisolone or equivalent ).
  8. Known history of a primary immunodeficiency (congenital or acquired) or an underlying condition such as (HIV) infection or splenectomy that predisposes the participant to infection.
  9. Active or history of malignancy that was active within the last 10 years, apart from ovarian or extra-ovarian teratoma (also known as a dermoid cyst) or germ cell tumor, or squamous cell carcinoma of the skin or basal cell carcinoma of the skin, that in the opinion of the Medical Safety Monitor (MSM) would preclude enrollment due to safety concerns. Squamous cell and basal cell carcinomas should be treated with documented success of curative therapy > 3 months prior to randomization.

  10. At screening (repeat testing may be conducted to confirm results within the same screening period, prior to randomization), any of the following:

    a. Total white blood count \<2,500 cells/mm3 (or \< 2.5 × 109/L) b. Total immunoglobulin \< 600 mg/dL (or 6 µmol/L; 400 mg/dL for participants \<18 years)* c. \< 1200 cells/μL (or \< 1.2 × 109/L) d. \< 300 cells/µL (or \< 0.3 × 109/L)

    *Baseline levels of IgG prior to treatments (methylprednisolone, plasmapheresis/plasma exchange) should be used to determine eligibility.

  11. Active or C established with positive hepatitis B serology (hepatitis B surface antigen and core antigen) and/or positive PCR testing and confirmed by the MSM
  12. Any live or attenuated vaccine within 4 weeks prior to Day 1 (administration of killed vaccines is acceptable).
  13. Bacillus of Calmette and Guérin (BCG) vaccine within 1 year of enrollment.
  14. History of alcohol or drug abuse that, in the opinion of the Investigator, might affect participant safety or compliance with visits or interfere with safety or other study assessments.
  15. Recurrence of previously treated NMDAR encephalitis within the last 5 years, or suspicion of symptomatic untreated NMDAR encephalitis of greater than 3 months duration at the time of screening.

  16. Evidence of active tuberculosis* (TB) or being at high risk for TB based on:

    a. History of active TB or untreated/incompletely treated latent TB. Participants with a history of active or latent TB who have documentation of completion of treatment according to local guidelines may be enrolled.

    b. History of recent (≤ 12 weeks of screening) close contact with someone with active TB (close contact is defined as ≥ 4 hours/week OR living in the same household OR in a house where a person with active TB is a frequent visitor).

    c. Signs or symptoms that could represent active TB by medical history or physical examination.

    d. Positive, indeterminate, or invalid interferon-gamma release assay test result at screening, unless previously treated for TB. Participants with an indeterminate test result can repeat the test once, but if the repeat test is also indeterminate, the participant is excluded.

    e. Chest radiograph, chest computed tomography or MRI scan that suggests a possible diagnosis of TB or suggests that a work-up for TB should be considered; all participants must have had lung imaging with an acceptable reading within 6 months prior to consent, or during screening.

  17. Active, (CS) infection at the time of randomization (IP administration may be delayed until recovery, if within 14-day screening window, otherwise participant may be rescreened).

Exclusion criteria are applied at time of screening and are applicable throughout the study.

  • Participants will undergo QuantiFERON®-TB Gold testing or equivalent TB testing during screening as standard of care. A positive result will not exclude patients from participation; thus, enrollment should not be delayed awaiting this result. If positive, an appropriate course of anti-TB treatment will need to be documented. If results are in indeterminate, participants may still be eligible for randomization if history is not suggestive of active / latent TB and a chest x-ray shows no evidence of active or latent TB.

1.1 Additional Eligibility Considerations

The following criteria are not necessarily exclusionary but require review from the MSM to determine if a participant should be excluded due to safety concerns:

  1. At screening (out of range lab values may be reviewed with the MSM to determine whether a potential participant should be excluded for safety reasons; repeat testing may be conducted to confirm results within the same screening period, prior to randomization), any of the following:

    1. (AST) > 2.5 × age-based (ULN)
    2. Alanine transaminase (ALT) > 2.5 × age-based ULN
    3. Total > 1.5 × age-based ULN (unless due to Gilbert's syndrome)
    4. count \< 75,000/μL (or \< 75 × 109/L)
    5. \< 8 g/dL (or \< 80 g/L or 5 mmol/L)
  2. History of untreated hepatitis C infection. Participants who are considered cured following antiviral therapy with an HCV load below the limit of detection may be enrolled pending confirmation from the MSM that there are no safety concerns for inclusion.
  3. Patients with coexistent autoantibodies should not immediately be excluded but should be reviewed with the MSM to determine eligibility.
Terms in these criteria, in plain language(20)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Autoimmune disease

A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.

Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

Postmenopausal

Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).

Investigational drug or device

A drug or device being studied in a clinical trial.

It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.

Corticosteroids (steroids)

Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.

Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.

Line of therapy

A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.

“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

Absolute neutrophil count (ANC)

The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.

It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.

CD4 count

The number of CD4 cells, a type of white blood cell, in a given amount of blood. It is used to follow how well the immune system is doing in HIV.

Hepatitis B tests

Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.

Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.

Hepatitis C tests

Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.

After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.

Clinically significant

Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.

ALT and AST (liver enzymes)

Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.

Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.

ULN (upper limit of normal)

The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.

“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.

Bilirubin

A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.

Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.

Platelets

Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.

Hemoglobin (Hb)

The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
116 participants (estimated)

Study arms

  • Active comparator
    Inebilizumab

    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.

    Drug: Inebilizumab

  • Placebo comparator
    Placebo

    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.

    Drug: Placebo

Interventions

  • DrugInebilizumab

    RCP: 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).

    Also known as: UPLIZNA

  • DrugPlacebo

    The placebo group will receive IV matching placebo on Day 1 and Day 15,

06

What researchers measure

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 weeks

  2. 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 weeks

Secondary outcomes

  1. Time to mRS ≤ 2, corrected for baseline value.

    Time to mRS ≤ 2, corrected for baseline value.

    Time frame: 96 weeks

  2. 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 weeks

  3. 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 weeks

  4. 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 weeks

  5. 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).

    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).

    Time frame: 24 weeks

  6. Survival as measured by a Kaplan-Meier analysis.

    Survival as measured by a Kaplan-Meier analysis.

    Time frame: 96 weeks

07

Study locations

39 of 39 sites recruiting
08

References and documents

Publications

  • Titulaer MJ, McCracken L, Gabilondo I, Armangue T, Glaser C, Iizuka T, Honig LS, Benseler SM, Kawachi I, Martinez-Hernandez E, Aguilar E, Gresa-Arribas N, Ryan-Florance N, Torrents A, Saiz A, Rosenfeld MR, Balice-Gordon R, Graus F, Dalmau J. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol. 2013 Feb;12(2):157-65. doi: 10.1016/S1474-4422(12)70310-1. Epub 2013 Jan 3. PubMed 23290630 ↗
  • Gabilondo I, Saiz A, Galan L, Gonzalez V, Jadraque R, Sabater L, Sans A, Sempere A, Vela A, Villalobos F, Vinals M, Villoslada P, Graus F. Analysis of relapses in anti-NMDAR encephalitis. Neurology. 2011 Sep 6;77(10):996-9. doi: 10.1212/WNL.0b013e31822cfc6b. Epub 2011 Aug 24. PubMed 21865579 ↗
  • Dalmau J, Tuzun E, Wu HY, Masjuan J, Rossi JE, Voloschin A, Baehring JM, Shimazaki H, Koide R, King D, Mason W, Sansing LH, Dichter MA, Rosenfeld MR, Lynch DR. Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol. 2007 Jan;61(1):25-36. doi: 10.1002/ana.21050. PubMed 17262855 ↗
  • Dubey D, Pittock SJ, Kelly CR, McKeon A, Lopez-Chiriboga AS, Lennon VA, Gadoth A, Smith CY, Bryant SC, Klein CJ, Aksamit AJ, Toledano M, Boeve BF, Tillema JM, Flanagan EP. Autoimmune encephalitis epidemiology and a comparison to infectious encephalitis. Ann Neurol. 2018 Jan;83(1):166-177. doi: 10.1002/ana.25131. PubMed 29293273 ↗
  • Dalmau J, Gleichman AJ, Hughes EG, Rossi JE, Peng X, Lai M, Dessain SK, Rosenfeld MR, Balice-Gordon R, Lynch DR. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol. 2008 Dec;7(12):1091-8. doi: 10.1016/S1474-4422(08)70224-2. Epub 2008 Oct 11. PubMed 18851928 ↗
  • Gresa-Arribas N, Titulaer MJ, Torrents A, Aguilar E, McCracken L, Leypoldt F, Gleichman AJ, Balice-Gordon R, Rosenfeld MR, Lynch D, Graus F, Dalmau J. Antibody titres at diagnosis and during follow-up of anti-NMDA receptor encephalitis: a retrospective study. Lancet Neurol. 2014 Feb;13(2):167-77. doi: 10.1016/S1474-4422(13)70282-5. Epub 2013 Dec 18. PubMed 24360484 ↗
  • Guasp M, Modena Y, Armangue T, Dalmau J, Graus F. Clinical features of seronegative, but CSF antibody-positive, anti-NMDA receptor encephalitis. Neurol Neuroimmunol Neuroinflamm. 2020 Jan 3;7(2):e659. doi: 10.1212/NXI.0000000000000659. Print 2020 Mar. PubMed 31900318 ↗
  • Dalmau J, Lancaster E, Martinez-Hernandez E, Rosenfeld MR, Balice-Gordon R. Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurol. 2011 Jan;10(1):63-74. doi: 10.1016/S1474-4422(10)70253-2. PubMed 21163445 ↗
  • Cree BAC, Bennett JL, Kim HJ, Weinshenker BG, Pittock SJ, Wingerchuk DM, Fujihara K, Paul F, Cutter GR, Marignier R, Green AJ, Aktas O, Hartung HP, Lublin FD, Drappa J, Barron G, Madani S, Ratchford JN, She D, Cimbora D, Katz E; N-MOmentum study investigators. Inebilizumab for the treatment of neuromyelitis optica spectrum disorder (N-MOmentum): a double-blind, randomised placebo-controlled phase 2/3 trial. Lancet. 2019 Oct 12;394(10206):1352-1363. doi: 10.1016/S0140-6736(19)31817-3. Epub 2019 Sep 5. PubMed 31495497 ↗
  • Hara M, Martinez-Hernandez E, Arino H, Armangue T, Spatola M, Petit-Pedrol M, Saiz A, Rosenfeld MR, Graus F, Dalmau J. Clinical and pathogenic significance of IgG, IgA, and IgM antibodies against the NMDA receptor. Neurology. 2018 Apr 17;90(16):e1386-e1394. doi: 10.1212/WNL.0000000000005329. Epub 2018 Mar 16. PubMed 29549218 ↗
  • Warikoo N, Brunwasser SJ, Benz A, Shu HJ, Paul SM, Lewis M, Doherty J, Quirk M, Piccio L, Zorumski CF, Day GS, Mennerick S. Positive Allosteric Modulation as a Potential Therapeutic Strategy in Anti-NMDA Receptor Encephalitis. J Neurosci. 2018 Mar 28;38(13):3218-3229. doi: 10.1523/JNEUROSCI.3377-17.2018. Epub 2018 Feb 23. PubMed 29476014 ↗
  • Hughes EG, Peng X, Gleichman AJ, Lai M, Zhou L, Tsou R, Parsons TD, Lynch DR, Dalmau J, Balice-Gordon RJ. Cellular and synaptic mechanisms of anti-NMDA receptor encephalitis. J Neurosci. 2010 Apr 28;30(17):5866-75. doi: 10.1523/JNEUROSCI.0167-10.2010. PubMed 20427647 ↗
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Individual participant data

Plan to share: No — Data from this study will only be shared with the researchers and organizations listed in the application and consent form. Participants can opt to have their excess biosamples banked as part of an optional substudy. Any samples shared in the future will be deidentified.

09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Started Mar 2022 (actual). Primary completion is estimated for Sep 2028, 78 months after the start.

How these figures are worked out, and which studies are left out of them.

Registered
Apr 30, 2020
First posted
May 4, 2020
StartActual
Mar 30, 2022
Primary completionEst.
Sep 30, 2028
CompletionEst.
Sep 30, 2028
Last update
Jul 1, 2025
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Jul 1, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT04372615
Lead sponsor
University of Utah
Responsible party
Stacey Clardy MD PhD (Associate Professor, University of Utah) — Principal investigator
First posted
May 4, 2020
Start date
Mar 30, 2022
Primary completion
Sep 30, 2028 (estimated)
Completion
Sep 30, 2028 (estimated)
Last update
Jul 1, 2025

Study contacts

Stacey L Clardy, MD, PhD
Contact
stacey.clardy@hsc.utah.edu
8015857575
Ka-Ho Wong, MBA
Contact
ka-ho.wong@hsc.utah.edu
8015857575
Stacey L Clardy, MD, PhD
principal investigator · University of Utah

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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