The ExTINGUISH Trial of Inebilizumab in NMDAR Encephalitis

NCT04372615 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 143461
• Study Type: interventional
• Target: 116
• Locations: 3 countries
• Sites: 39

Brief 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.

Conditions

Autoimmune Encephalitis; Encephalitis

Keywords

Inebilizumab; NMDAR encephalitis; Autoimmune Encephalitis; Rare Disease

Outcome Measures

Primary Outcomes (2)

• 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.

  16 weeks

• 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)

  96 weeks

Secondary Outcomes (6)

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

  96 weeks

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

  16 weeks

• mRS at week 6 as measured by proportional odds logistic regression/shift analysis.

  6 weeks

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

  6 weeks

• 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).

  24 weeks

Study Arms (2)

Inebilizumab

ACTIVE COMPARATOR

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

PLACEBO COMPARATOR

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

Inebilizumab DRUG

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

Inebilizumab

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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)

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
• 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.

Sponsors & Collaborators

• University of Utah: lead

Study Sites (39)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

RECRUITING

St. Joseph Hospital and Medical Center Barrow Neurological Institute

Phoenix, Arizona, 85013, United States

RECRUITING

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

RECRUITING

Children's Hospital of Orange County

Orange, California, 92868, United States

RECRUITING

UC Irvine

Orange, California, 92868, United States

RECRUITING

UC Davis

Sacramento, California, 95816, United States

RECRUITING

Children's Hospital Colorado Main Campus

Aurora, Colorado, 80045, United States

RECRUITING

University of Colorado

Aurora, Colorado, 80045, United States

RECRUITING

Yale University

New Haven, Connecticut, 06510, United States

RECRUITING

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

RECRUITING

University of Miami

Miami, Florida, 33136, United States

RECRUITING

Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

Ann and Robert H. Lurie Childrens Hospital of Chicago

Chicago, Illinois, 60611, United States

RECRUITING

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

RECRUITING

University of Iowa

Iowa City, Iowa, 52242, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

RECRUITING

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Washington University in St. Louis School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

SUNY Downstate

Brooklyn, New York, 11203, United States

RECRUITING

Mount Sinai

New York, New York, 10029, United States

RECRUITING

Columbia University Medical Center

New York, New York, 10033, United States

RECRUITING

University of Rochester

Rochester, New York, 14618, United States

RECRUITING

SUNY Buffalo

Williamsville, New York, 14221, United States

RECRUITING

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27101, United States

RECRUITING

University of Cincinnati

Cincinnati, Ohio, 45219, United States

RECRUITING

Ohio State University

Columbus, Ohio, 43210, United States

RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

Vanderbilt University

Nashville, Tennessee, 37212, United States

RECRUITING

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

Texas Children's Hospital

Houston, Texas, 77030, United States

RECRUITING

University of Utah

Salt Lake City, Utah, 84108, United States

RECRUITING

University of Virginia

Charlottesville, Virginia, 22903, United States

RECRUITING

University of Washington

Seattle, Washington, 98195, United States

RECRUITING

Erasmus Medical University Center

Rotterdam, Netherlands

RECRUITING

Erasmus University Rotterdam

Rotterdam, Netherlands

RECRUITING

Hospital Clínic Barcelona

Barcelona, Spain

RECRUITING

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

Barcelona, Spain

RECRUITING

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MeSH Terms

Conditions

Autoimmune Diseases of the Nervous System; Encephalitis; Rare Diseases

Interventions

inebilizumab

Condition Hierarchy (Ancestors)

Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Brain Diseases; Central Nervous System Diseases; Neuroinflammatory Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Stacey L Clardy, MD, PhD

  University of Utah

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stacey L Clardy, MD, PhD

CONTACT

8015857575; stacey.clardy@hsc.utah.edu

Ka-Ho Wong, MBA

CONTACT

8015857575; ka-ho.wong@hsc.utah.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: April 30, 2020
• First Posted: May 4, 2020
• Study Start: March 30, 2022
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): September 30, 2028
• Last Updated: July 1, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (35); ES (2); NL (2)