COMparison Between Anakinra and Tocilizumab in NORSE - "COMBAT-NORSE"

NCT ID: NCT07281027

Last Updated: 2025-12-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

438 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-03-01

Study Completion Date

2030-09-30

Brief Summary

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The goal of this clinical trial is to find out whether two existing medications-anakinra and tocilizumab-can effectively treat a rare and life-threatening brain condition called NORSE (New-Onset Refractory Status Epilepticus). NORSE causes continuous seizures in previously healthy children and adults and does not respond to standard treatments. It often leads to long-term disability or death.

Doctors currently use anakinra and tocilizumab as second-line treatments when first-line therapies fail, but there is no clear evidence showing which drug works better or when it should be given. This study aims to answer those questions.

The study will enroll patients across 33 hospitals in the United States, Canada, Europe, and Asia.

It includes two groups:

1. Randomized Cohort Patients will be randomly assigned to receive either anakinra or tocilizumab within the first 7 days of their illness. Only patients whose doctors were already planning to use one of these medications as part of standard care will be eligible for randomization. Researchers will monitor their recovery and compare outcomes between the two treatments.
2. Observational Cohort Patients who cannot be randomized-usually because they were diagnosed too late-will still be followed to study how the timing of treatment affects recovery.

Participants will:

* Receive one of the two medications (depending on their group assignment).
* Take part in follow-up assessments over the course of one year, including medical evaluations and surveys. Some participants may be followed annually beyond one year.
* Optionally participate in a 60-minute interview to share their or their caregiver's experience with NORSE.

Detailed Description

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Conditions

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New Onset Refractory Status Epilepticus New-Onset Refractory Status Epilepticus Febrile Infection-Related Epilepsy Syndrome (FIRES)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Randomized Controlled Trial (RCT) Cohort

A randomized controlled cohort (RCT) of anakinra vs. tocilizumab (targeted immunotherapies) started up to and including 7 days after the onset of status epilepticus (SE)

Group Type ACTIVE_COMPARATOR

Anakinra

Intervention Type DRUG

SOC will be followed , Suggested Dose:

10 mg/kg/day IV, divided into 4 daily doses (q6h) Maximum dose: 400 mg/day

Tocilizumab

Intervention Type DRUG

SOC will be followed,

Suggested Dose:

If \<30 kg: 12 mg/kg IV once every 2 weeks If ≥30 kg: 8 mg/kg IV once every 2 weeks Maximum dose: 800 mg per dose

Observational Cohort

An observational cohort enrolling patients with acute cryptogenic NORSE who cannot be randomized or who are identified too late to be randomized by the end of day 7 .

Group Type OTHER

Standard medical treatment

Intervention Type OTHER

For patients who could not be randomized by day 7, standard clinical care will be followed and patients will be followed prospectively and observationally.

Interventions

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Anakinra

SOC will be followed , Suggested Dose:

10 mg/kg/day IV, divided into 4 daily doses (q6h) Maximum dose: 400 mg/day

Intervention Type DRUG

Tocilizumab

SOC will be followed,

Suggested Dose:

If \<30 kg: 12 mg/kg IV once every 2 weeks If ≥30 kg: 8 mg/kg IV once every 2 weeks Maximum dose: 800 mg per dose

Intervention Type DRUG

Standard medical treatment

For patients who could not be randomized by day 7, standard clinical care will be followed and patients will be followed prospectively and observationally.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Age 2 and older.
* In their usual state of health prior to their onset of SE.
* Presenting with NORSE as defined in the consensus criteria:

1. Refractory SE (failed 2 appropriately used anti-seizure medications) in a patient without active epilepsy or other pre-existing relevant neurological disorder and without an acute or active structural, toxic, or metabolic cause found in the first 72 hours.
2. Includes patients with any RSE, not just super-refractory SE.
3. Includes patients who ultimately are discovered to have a known etiology (infectious, autoimmune, genetic, etc.), as well as those who remain cryptogenic.

* Anakinra and/or tocilizumab are being planned or considered as part of standard clinical care.
* The onset of SE was in the prior 7 days at the time of enrollment.

Exclusion Criteria

* Any acute or active systemic medical illness such as metastatic cancer, renal failure, hepatic failure, poorly controlled diabetes, etc., in the opinion of the investigators. If this is unclear, the study PI Dr. Hirsch will determine if this criterion is met.


* Contraindication to either anakinra or tocilizumab as listed in the prescribing information:

1. Known hypersensitivity to E. Coli-derived proteins, anakinra, tocilizumab, or any component of the products
2. Active serious infection at the time of initiation
3. Concomitant use of TNF blocking agents; absolute neutrophil count \< 2000; platelet count \< 100,000 per mm³; or ALT or AST \> 1.5 X the upper limit of normal
4. Elevated risk of GI perforation.
Minimum Eligible Age

2 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Patient-Centered Outcomes Research Institute

OTHER

Sponsor Role collaborator

Yale University

OTHER

Sponsor Role lead

Responsible Party

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Lawrence Hirsch

Professor of Neurology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Lawrence Hirsch, MD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

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Barrow Institute

Phoenix, Arizona, United States

Site Status

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status

Yale New Haven Hospital

New Haven, Connecticut, United States

Site Status

Children's National (DC)

Washington D.C., District of Columbia, United States

Site Status

University of Florida

Gainesville, Florida, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

Northwestern University

Evanston, Illinois, United States

Site Status

Mass General (MGH)

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess

Boston, Massachusetts, United States

Site Status

Boston Children's Hospital

Boston, Massachusetts, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

University of Nebraska

Lincoln, Nebraska, United States

Site Status

New York University

New York, New York, United States

Site Status

Columbia University

New York, New York, United States

Site Status

Mount Sinai (NY)

New York, New York, United States

Site Status

University of Cincinnati

Cincinnati, Ohio, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Oregon Health and Science University

Portland, Oregon, United States

Site Status

Children's Hospital Philadelphia (CHOP)

Philadelphia, Pennsylvania, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

UT Southwestern Medical Center

Dallas, Texas, United States

Site Status

Baylor/Texas Children's

Houston, Texas, United States

Site Status

Seattle Children's Hospital

Seattle, Washington, United States

Site Status

University of Wisconsin

Madison, Wisconsin, United States

Site Status

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Western University

London, , Canada

Site Status

Hospital for Sick Children

Toronto, , Canada

Site Status

Salpêtrière

Paris, , France

Site Status

University of Modena

Modena, , Italy

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Karolinska Institute

Stockholm, , Sweden

Site Status

Great Ormond Street Hospital

London, , United Kingdom

Site Status

King's College

London, , United Kingdom

Site Status

Countries

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United States Canada France Italy South Korea Sweden United Kingdom

Central Contacts

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Camalene Chrysostoum

Role: CONTACT

2037375851

Tara McPartland

Role: CONTACT

2037375851

Facility Contacts

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Susan Herman

Role: primary

Krista Eschbach

Role: primary

Lawrence Hirsch

Role: primary

Elizabeth Wells

Role: primary

Carolina Maciel

Role: primary

Hiba Haider

Role: primary

Stephen vanHaerents

Role: primary

Sahar Zafar

Role: primary

Brandon Westover

Role: primary

Coral Stredny

Role: primary

Kelsey Smith

Role: primary

Olga Taraschenko

Role: primary

Claude Steriade

Role: primary

Jan Claassen

Role: primary

Ji Yeoun Yoo

Role: primary

Brandon Foreman

Role: primary

Vineet Punia

Role: primary

Marissa Kellogg

Role: primary

Danielle Decampo

Role: primary

Catherine Kulick

Role: primary

Rana Said

Role: primary

Yichen Lai

Role: primary

Mark Wainwright

Role: primary

Aaron Struck

Role: primary

Raquel Farias-Moeller

Role: primary

Teneille Gofton

Role: primary

Cecil Hahn

Role: primary

Vincent Navarro

Role: primary

Stefano Meletti

Role: primary

Soon-Tae Lee

Role: primary

Ronny Wickstrom

Role: primary

Marios Kaliakatsos

Role: primary

Laura Mantoan

Role: primary

Other Identifiers

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RD-2024C2-39648

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

2000041289

Identifier Type: -

Identifier Source: org_study_id

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