The ExTINGUISH Trial of Inebilizumab in NMDAR Encephalitis

Recruiting now · Phase 2 · Has a placebo group

Conditions studied: Autoimmune Encephalitis, Encephalitis

In brief

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.

Key facts

Study ID

NCT04372615

Run by

University of Utah

People needed

116

Starts

2022-03-30

Expected to finish

2028-09-30

Last updated by the study team

2025-07-01

Who can join

Age: 12 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.
• 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.

You may not qualify if…

• 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.
• 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:
• a. 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
• 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.
• 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:
• 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. 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.

Where it is running

• University of Alabama at Birmingham — Birmingham, Alabama, United States (enrolling)
• St. Joseph Hospital and Medical Center Barrow Neurological Institute — Phoenix, Arizona, United States (enrolling)
• Mayo Clinic in Arizona — Scottsdale, Arizona, United States (enrolling)
• Children's Hospital of Orange County — Orange, California, United States (enrolling)
• UC Irvine — Orange, California, United States (enrolling)
• UC Davis — Sacramento, California, United States (enrolling)
• Children's Hospital Colorado Main Campus — Aurora, Colorado, United States (enrolling)
• University of Colorado — Aurora, Colorado, United States (enrolling)
• Yale University — New Haven, Connecticut, United States (enrolling)
• Mayo Clinic Jacksonville — Jacksonville, Florida, United States (enrolling)
• University of Miami — Miami, Florida, United States (enrolling)
• Emory University — Atlanta, Georgia, United States (enrolling)
• Ann and Robert H. Lurie Childrens Hospital of Chicago — Chicago, Illinois, United States (enrolling)
• Northwestern University Feinberg School of Medicine — Chicago, Illinois, United States (enrolling)
• University of Iowa — Iowa City, Iowa, United States (enrolling)
• Massachusetts General Hospital — Boston, Massachusetts, United States (enrolling)
• University of Michigan Health System — Ann Arbor, Michigan, United States (enrolling)
• Mayo Clinic Rochester — Rochester, Minnesota, United States (enrolling)
• Washington University in St. Louis School of Medicine — St Louis, Missouri, United States (enrolling)
• SUNY Downstate — Brooklyn, New York, United States (enrolling)
• Mount Sinai — New York, New York, United States (enrolling)
• Columbia University Medical Center — New York, New York, United States (enrolling)
• University of Rochester — Rochester, New York, United States (enrolling)
• SUNY Buffalo — Williamsville, New York, United States (enrolling)
• Wake Forest University Health Sciences — Winston-Salem, North Carolina, United States (enrolling)

Full record on ClinicalTrials.gov

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