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AzTrials

Autoimmune EncephalitisPhase 2ExTINGUISHNCT04372615

The ExTINGUISH Trial of Inebilizumab in NMDAR Encephalitis

A Phase 2 study testing Inebilizumab in people with Autoimmune Encephalitis and Encephalitis, run by University of Utah at 39 sites in 3 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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 more about this study

Who is it for?
Ages 12 years and older
Conditions the study is for
Autoimmune Encephalitis, Encephalitis
What is being tested?
Inebilizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
116 participants
Where
39 sitesin 3 countries
Study dates
30 Mar 2022to 30 Sep 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Diagnosis of NMDAR encephalitis, defined by both a and b:
  • 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.
  • 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 contraception other than a physical method.
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  • Participants of childbearing potential 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.
  • 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 postmenopausal (per ICH M3 (R2) 11.2: defined as 12 months with no menses without an alternative medical cause).
  • 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.)
  • Willing to forgo other immunomodulatory therapies (investigational or otherwise) for NMDAR encephalitis during the study.
  • Participant must have received at least 3 days of methylprednisolone 1000 mg IV or equivalent corticosteroid within 90 days prior to randomization (Day 1). In addition, participants must have received EITHER of the following treatments within 90 days before randomization.
  • IVIg, at a dose range between 1.2 and 2 g/kg
  • 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 first line treatments.
  • 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.
  • 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.

Who cannot join

  • Any of the following excludes an individual from participation in the study:
  • 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.
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  • 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.
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  • Lactating or pregnant individuals, or individuals who intend to become pregnant anytime from study enrollment to 12 months following last dose of investigational agent.
  • Known history of allergy or reaction to any component of the investigational agent formulation or history of anaphylaxis following any biologic therapy.
  • Receipt of the following at any time prior to randomization:
  • Alemtuzumab b. Total lymphoid irradiation c. Bone marrow transplant d. T-cell vaccination therapy
  • 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.
  • Treatment at therapeutic doses/durations with any of the following within 3 months prior to randomization
  • 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.
  • 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 glucocorticoid).
  • Known history of a primary immunodeficiency (congenital or acquired) or an underlying condition such as human immunodeficiency virus (HIV) infection or splenectomy that predisposes the participant to infection.
  • Active malignancy 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.
  • At screening (repeat testing may be conducted to confirm results within the same screening period, prior to randomization), any of the following:
  • 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. Absolute neutrophil count < 1200 cells/μL (or < 1.2 × 109/L) d. CD4 T lymphocyte count < 300 cells/µL (or < 0.3 × 109/L)
  • Baseline levels of IgG prior to first line treatments (methylprednisolone, plasmapheresis/plasma exchange) should be used to determine eligibility.
  • Active hepatitis B or C established with positive hepatitis B serology (hepatitis B surface antigen and core antigen) and/or positive hepatitis C PCR testing and confirmed by the MSM
  • Any live or attenuated vaccine within 4 weeks prior to Day 1 (administration of killed vaccines is acceptable).
  • Bacillus of Calmette and Guérin (BCG) vaccine within 1 year of enrollment.
  • 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.
  • 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.
  • Evidence of active tuberculosis* (TB) or being at high risk for TB based on:
  • 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.
  • 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).
  • Signs or symptoms that could represent active TB by medical history or physical examination.
  • 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.
  • 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.
  • Active, clinically significant (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:
  • 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:
  • Aspartate transaminase (AST) > 2.5 × age-based upper limit of normal (ULN)
  • Alanine transaminase (ALT) > 2.5 × age-based ULN
  • Total bilirubin > 1.5 × age-based ULN (unless due to Gilbert's syndrome)
  • Platelet count < 75,000/μL (or < 75 × 109/L)
  • Hemoglobin < 8 g/dL (or < 80 g/L or 5 mmol/L)
  • 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.
  • Patients with coexistent autoantibodies should not immediately be excluded but should be reviewed with the MSM to determine eligibility.

Trial locations and contacts

39 sites in 3 countries. Contact the study team or a site near you to ask about taking part.

Stacey L Clardy, MD, PhD contact

8015857575

stacey.clardy@hsc.utah.edu

Ka-Ho Wong, MBA contact

8015857575

ka-ho.wong@hsc.utah.edu

39 sites in 3 countries

United States35 sites, 35 recruiting

  • University of Michigan Health System

    Ann Arbor, Michigan, 48109

    Amanda Rasnake, 734-232-2452, arasnake@med.umich.edu

    Craig Williamson, MD

    Recruiting

  • Emory University

    Atlanta, Georgia, 30322

    Connor McMillan, 404-727-3818, connor.logan.mcmillan@emory.edu

    Erika Sigman

    Recruiting

  • Children's Hospital Colorado Main Campus

    Aurora, Colorado, 80045

    Diana Rodriguez, 720-777-9214, Diana.Rodriguez@childrenscolorado.org

    Ryan Kammeyer, MD

    Recruiting

  • University of Colorado

    Aurora, Colorado, 80045

    Jordan Hood, 720-240-1329, jordan.j.hood@cuanschutz.edu

    Amanda Piquet

    Recruiting

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35233

    Melanie Benge, melaniebenge@uabmc.edu

    Louis Nabors

    Recruiting

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

    Rina Dhawlikar, 908-601-8967, rdhawlikar@mgh.harvard.edu

    Santiago Pardo, 410-926-6248, SPARDO1@mgh.harvard.edu

    Recruiting

  • SUNY Downstate

    Brooklyn, New York, 11203

    Nadege Gilles, 718-270-7786, Nadege.Gilles@Downstate.edu

    Sofya Glazman, Sofya.Glazman@downstate.edu

    Recruiting

  • University of Virginia

    Charlottesville, Virginia, 22903

    Kay Maupin, 434-982-6961, klm8a@hscmail.mcc.virginia.edu

    Meena Kannan, MD

    Recruiting

  • Ann and Robert H. Lurie Childrens Hospital of Chicago

    Chicago, Illinois, 60611

    Alexandra Byrd, 312-227-4000, albyrd@luriechildrens.org

    Kavita Thakkar, MD

    Recruiting

  • Northwestern University Feinberg School of Medicine

    Chicago, Illinois, 60611

    Monika Szela, monika.szela@northwestern.edu

    Elena Grebenciucova, MD

    Recruiting

  • University of Cincinnati

    Cincinnati, Ohio, 45219

    Tiffany Rupert, 513-558-0269, rupertts@ucmail.uc.edu

    Angela Molloy, 513-558-7118, angela.molloy@uc.edu

    Recruiting

  • Ohio State University

    Columbus, Ohio, 43210

    Casey Mitchell, 614-685-9906, casey.mitchell@osumc.edu

    Marina Rodriguez, 614-366-2840, marina.rodriguez@osumc.edu

    Recruiting

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

    Amy Conger, 214-645-8208, amy.conger@utsouthwestern.edu

    Kyle Blackburn, MD

    Recruiting

  • Texas Children's Hospital

    Houston, Texas, 77030

    Navjot Sandhu, 832-824-1000, Navjot.Sandhu@bcm.edu

    Kristen Fisher

    Recruiting

  • University of Iowa

    Iowa City, Iowa, 52242

    Loraine Brenner, 319-356-4361, loraine-brenner@uiowa.edu

    Tracey Cho, MD

    Recruiting

  • Mayo Clinic Jacksonville

    Jacksonville, Florida, 32224

    Pamela Desaro, 904-953-7720, Desaro.Pamela@mayo.edu

    Gregory Day, MD

    Recruiting

  • University of Miami

    Miami, Florida, 33136

    Julie Steele, 305-775-9502, jsteele@med.miami.edu

    Danielle Bass, 305-243-6320, dhb55@med.miami.edu

    Recruiting

  • Vanderbilt University

    Nashville, Tennessee, 37212

    Ryann Gardner, 615-322-4085, ryann.gardner@vumc.org

    Kehaunani Hubbard, 615-322-4322, kehaunani.m.hubbard@vumc.org

    Recruiting

  • Yale University

    New Haven, Connecticut, 06510

    Danielle Paquette, danielle.paquette@yale.edu

    Erin Longbrake, MD

    Recruiting

  • Mount Sinai

    New York, New York, 10029

    Kevin Van Geem, 347-804-3699, kevin.vangeem@mssm.edu

    Pojen Deng

    Recruiting

  • Columbia University Medical Center

    New York, New York, 10033

    Jennie Mata, jmm2220@cumc.columbia.edu

    Sarah Wesley, MD

    Recruiting

  • Children's Hospital of Orange County

    Orange, California, 92868

    Linda Do, 714-997-3000, Linh.Do@choc.org

    Janetta Arellano, MD

    Recruiting

  • UC Irvine

    Orange, California, 92868

    Isela Hernandez, 714-509-2664, iselah@uci.edu

    Xiao-Tang Kong, MD

    Recruiting

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

    Priyanka Kalyani, 215-820-2726, priyanka.kalyani@pennmedicine.upenn.edu

    Eric Lancaster, MD

    Recruiting

  • St. Joseph Hospital and Medical Center Barrow Neurological Institute

    Phoenix, Arizona, 85013

    Mary Thornton, 602-406-6287, mary.thornton@dignityhealth.org

    Michael Robers, MD

    Recruiting

  • University of Pittsburgh

    Pittsburgh, Pennsylvania, 15213

    Kerry Oddis, 412-692-4918, kmoddis@upmc.edu

    Dane Prince, 262-490-6818, princede2@upmc.edu

    Recruiting

  • Mayo Clinic Rochester

    Rochester, Minnesota, 55905

    Morgan Mohler, 507-284-2511, mohler.morgan@mayo.edu

    Anastasia Zekeridou

    Recruiting

  • University of Rochester

    Rochester, New York, 14618

    Christine Anne, 585-276-3037, Christine_annis@urmc.rochester.edu

    Andrew Goodman, MD

    Recruiting

  • UC Davis

    Sacramento, California, 95816

    Lynea Kaethler, 916-734-3993, lbkaethler@ucdavis.edu

    Erica Goude, 916-734-0384, emgoude@ucdavis.edu

    Recruiting

  • University of Utah

    Salt Lake City, Utah, 84108

    Stacey L Clardy, MD, PhD, 801-585-7575, stacey.clardy@hsc.utah.edu

    Ka-Ho Wong, MBA, 8015857575, ka-ho.wong@hsc.utah.edu

    Recruiting

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

    Erica Boyd, 480-301-8000, Boyd.Erica@mayo.edu

    Marie Grill

    Recruiting

  • University of Washington

    Seattle, Washington, 98195

    Ashtyn Winter, 206-598-7688, ashtynw@uw.edu

    Yujie Wang, MD

    Recruiting

  • Washington University in St. Louis School of Medicine

    St Louis, Missouri, 63110

    Mengesha Teshome, 314-747-8420, teshomem@wustl.edu

    Steven Dunham, MD

    Recruiting

  • SUNY Buffalo

    Williamsville, New York, 14221

    Annemarie Crumlish, 716-829-5046, ac35@buffalo.edu

    Kara Patrick, 716-829-5037, KPatrick@buffalo.edu

    Recruiting

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27101

    Carolina Burgos, caguilar@wakehealth.edu

    Roy Strowd, MD

    Recruiting

Other trials in United States

Netherlands2 sites, 2 recruiting

  • Erasmus Medical University Center

    Rotterdam

    Wendy Hamerslag-de Groot, 29066799230, w.degroot.1@erasmusmc.nl

    Maarten Titulaer, MD

    Recruiting

  • Erasmus University Rotterdam

    Rotterdam

    Anne-Marieke Vegter, +31 10 704 01 30, a.vegter@erasmusmc.nl

    Maarten Titulaer

    Recruiting

Other trials in Netherlands

Spain2 sites, 2 recruiting

  • Hospital Clínic Barcelona

    Barcelona

    Montse Artola, +34 93 227 54 00 (Ext. 3271), martola@clinic.cat

    Mar Guasp

    Recruiting

  • Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona

    Barcelona

    Dalmau Josep, 93 227 99 51, ope@clinic.cat

    Josep Dalmau

    Recruiting

Other trials in Spain

About this study

Official title: A Phase-2b, Double-Blind, Randomized Controlled Trial to Evaluate the Activity and Safety of Inebilizumab in Anti-Nmda Receptor Encephalitis and Assess Markers of Disease

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.

Being tested
Inebilizumab, Placebo
Keywords
Inebilizumab, NMDAR encephalitis, Autoimmune Encephalitis, Rare Disease
Medical subject headings
Autoimmune Diseases of the Nervous System, Encephalitis, Rare Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • InebilizumabDrug

    Also called UPLIZNA

    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).

  • PlaceboDrug

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

Study groups in NCT04372615
Study groupRoleWhat they receive
InebilizumabActive comparatorApproximately 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.
Receives: Drug: Inebilizumab
PlaceboPlacebo comparatorApproximately 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.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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)

    Measured: 96 weeks

Secondary outcomes (6)

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

    Time to mRS ≤ 2, corrected for baseline value.

    Measured: 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).

    Measured: 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.

    Measured: 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.

    Measured: 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).

    Measured: 24 weeks

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

    Survival as measured by a Kaplan-Meier analysis.

    Measured: 96 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 May 2020
  2. Study start30 Mar 2022
  3. Primary completion30 Sep 2028 (estimated)
  4. Study completion30 Sep 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
116 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04372615
Sponsor's protocol ID
143461
Acronym
ExTINGUISH
Status last verified
Jun 2025
First submitted
30 Apr 2020
Last updated
1 Jul 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
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.

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

  • Tuzun E, Zhou L, Baehring JM, Bannykh S, Rosenfeld MR, Dalmau J. Evidence for antibody-mediated pathogenesis in anti-NMDAR encephalitis associated with ovarian teratoma. Acta Neuropathol. 2009 Dec;118(6):737-43. doi: 10.1007/s00401-009-0582-4.

    PubMed 19680671

  • Matute C, Palma A, Serrano-Regal MP, Maudes E, Barman S, Sanchez-Gomez MV, Domercq M, Goebels N, Dalmau J. N-Methyl-D-Aspartate Receptor Antibodies in Autoimmune Encephalopathy Alter Oligodendrocyte Function. Ann Neurol. 2020 May;87(5):670-676. doi: 10.1002/ana.25699. Epub 2020 Feb 24.

    PubMed 32052483

  • Planaguma J, Leypoldt F, Mannara F, Gutierrez-Cuesta J, Martin-Garcia E, Aguilar E, Titulaer MJ, Petit-Pedrol M, Jain A, Balice-Gordon R, Lakadamyali M, Graus F, Maldonado R, Dalmau J. Human N-methyl D-aspartate receptor antibodies alter memory and behaviour in mice. Brain. 2015 Jan;138(Pt 1):94-109. doi: 10.1093/brain/awu310. Epub 2014 Nov 11.

    PubMed 25392198

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Inebilizumab in people with Autoimmune Encephalitis and Encephalitis, run by University of Utah at 39 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 31 inclusion and 44 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 1 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 39 sites in United States, Netherlands, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Stacey L Clardy, MD, PhD (8015857575, stacey.clardy@hsc.utah.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change of modified Rankin score at 16 weeks (time frame: 16 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04372615, which also lists 39 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2025.

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