XEN496 (Ezogabine) in Children With KCNQ2 Developmental and Epileptic Encephalopathy

Stopped early · Phase 3 · Has a placebo group

Conditions studied: Epilepsy, Epilepsy in Children, Epilepsy; Seizure, Disease, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Epileptic Syndromes

In brief

To investigate the potential antiseizure effects of adjunctive XEN496 (ezogabine) compared with placebo in children with KCNQ2 Developmental and Epileptic Encephalopathy (KCNQ2-DEE).

Key facts

Study ID: NCT04639310
Run by: Xenon Pharmaceuticals Inc.
People needed: 8
Starts: 2021-03-29
Expected to finish: 2023-05-16
Last updated by the study team: 2024-08-23

Who can join

Age: 0 and older, up to 6. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Male or female subjects aged from 1 month to less than 6 years, with a body weight of ≥3.0 kg at screening.
Documented evidence of a genetic test result from an appropriately accredited laboratory, consistent with a diagnosis of KCNQ2-DEE (pathogenic, likely pathogenic, variant of unknown significance, or inconclusive but unlikely to support an alternate diagnosis).
Seizure onset within 2 weeks after birth and EEG and documented clinical history consistent with KCNQ2-DEE.
Magnetic resonance imaging has been performed and is without evidence of structural abnormalities, including but not limited to, hypoxia, hypoxia-ischemia, ischemia (arterial or venous), stroke, sinovenous thrombosis, intracranial hemorrhage, or focal or global brain malformation. Brain MRI changes that are described as being associated with the KCNQ2-DEE and presumed to be secondary to the disease itself, will not be exclusionary.
Must have had focal tonic or other countable motor seizures in the 28 days prior to screening.
Taking 1 and no more than 4 concomitant antiseizure medications (ASMs). All doses must be stable for at least 1 week prior to screening and expected to be maintained throughout the duration of the study.
Vagal nerve stimulation (VNS) is allowed and will not be counted as a concomitant ASM. The VNS device must be implanted for at least 6 months before screening, and the device settings must be stable for at least 6 weeks prior to screening and throughout the duration of the study. Use of the VNS device magnet is allowed.
Ketogenic diet is allowed and will not be counted as a concomitant ASM. Must must be on a stable dietary regimen that produces ketosis for at least 6 weeks prior to screening, and expected to be maintained throughout the study.
Additional inclusion criteria apply, and will be assessed by the study team.

You may not qualify if…

Presence of a pathogenic or likely pathogenic variant in an additional gene associated with other epilepsy syndromes. (Variants in other epilepsy-associated genes that are not known to be pathogenic or are not likely to be pathogenic based upon adjudication review will not be a basis for exclusion.)
Presence of a known gain-of-function variant in the KCNQ2 gene, or clinical characteristics consistent with previously reported pathogenic gain-of-function variants in the KCNQ2 gene.
Seizures secondary to infection, neoplasia, demyelinating disease, degenerative neurological disease, or Central nervous system (CNS) disease deemed progressive, metabolic illness, or progressive degenerative disease.
Confirmed diagnosis of infantile spasms within the past month prior to screening.
History or presence of any significant medical or surgical condition or uncontrolled medical illness at screening including, but not limited to, cardiovascular, gastrointestinal, hematologic, hepatic, ocular, pulmonary, renal, or urogenital systems, or other conditions that would not justify the subject's participation in the study, as determined by the investigator's risk benefit assessment.
QT interval corrected for heart rate by Fridericia's formula (QTcF) of >440 msec. In addition, subjects with a history of arrhythmia, prolonged QT, heart disease or subjects taking medications known to increase the QT interval.
History of hyperbilirubinemia, which lasts longer than 1 week will require exclusion of hepatic disease before entering the study.
History of bilirubin-induced neurological dysfunction.
Current disturbance of micturition or known urinary obstructions or history of bladder or urinary dysfunction including abnormal post-void residual bladder ultrasound, vesicoureteral reflux, urinary retention, or required urinary catheterization in the preceding 6 months.
Known to have a terminal illness.
Any clinically significant laboratory abnormalities or clinically significant abnormalities on pre-study physical examination, vital signs, or ECG that in the judgment of the investigator indicates a medical problem that would preclude study participation.
Planned to begin a ketogenic or other specialized dietary therapy during the study.
Caregiver history of chronic noncompliance with their child's prescribed drug regimens that has not been corrected.
Exposure to any other investigational drug or device within 5 half-lives or 30 days prior to screening, whichever is longer or plans to participate in another drug or device trial at any time during the study.
Concurrent enrollment in any other type of medical research judged by the investigator not to be scientifically or medically compatible with this study.
Using felbamate presenting with clinically significant abnormalities and/or hepatic dysfunction during felbamate treatment, and subjects who have taken felbamate for less than 6 months prior to screening.
Currently taking adrenocorticotropic hormone.
Did not tolerate ezogabine when taken previously.
Subjects with a known hypersensitivity to ezogabine or any of the excipients in the study drug.
Other exclusion criteria apply, and will be assessed by the study team.

Where it is running

Children's Hospital of Orange County — Orange, California, United States
UCSF Medical Center — San Francisco, California, United States
Children's Hospital of Colorado — Aurora, Colorado, United States
Children's National Health System — Washington D.C., District of Columbia, United States
Northwest Florida Clinical Research Group — Gulf Breeze, Florida, United States
Anne & Robert H. Lurie Children's Hospital — Chicago, Illinois, United States
Columbia University Irving Medical Center — New York, New York, United States
The Cleveland Clinic Foundation — Cleveland, Ohio, United States
Oregon Health and Science University — Portland, Oregon, United States
Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States
MultiCare Medical Center — Tacoma, Washington, United States
Sydney Children's Hospital — Sydney, New South Wales, Australia
Children's Health Queensland Hospital and Health Service — South Brisbane, Queensland, Australia
Austin Health — Heidelberg, Victoria, Australia
Universitaire Ziekenhuis Anterpen - Dienst Kinderneurologie — Edegem, Antwerpen, Belgium
Istituto Giannina Gaslini — Genova, Italy
U.O.C. Neurologia Pediatrica Ospedale dei Bambini V. Buzzi — Milan, Italy
Azienda Ospedaliera Universitaria Integrata di Verona — Verona, Italy
Universitat de Barcelona - Hospital Sant Joan de Déu Barcelona (HSJDB) — Esplugues de Llobregat, Barcelona, Spain
Hospital Nino Jesus — Madrid, Spain

Full record on ClinicalTrials.gov

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