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

  • STATUS
    Recruiting
  • End date
    Dec 16, 2023
  • participants needed
    40
  • sponsor
    Xenon Pharmaceuticals Inc.
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Updated on 4 October 2022
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stroke
seizure
electroencephalogram
tonic
ketogenic diet
ezogabine

Summary

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

Description

The EPIK Phase 3 clinical trial is designed as a randomized, double-blind, placebo-controlled, multicenter study targeting to enroll approximately 40 pediatric subjects (aged from 1 month to less than 6 years) with documented genetic evidence consistent with a diagnosis of KCNQ2 Developmental and Epileptic Encephalopathy (KCNQ2-DEE). After screening, subjects will enter a baseline period before being randomized to receive either XEN496 (ezogabine) or placebo, added to their existing antiseizure medications (ASMs), for 12 weeks (maintenance), once a titration period of up to 24 days is complete. At the end of the maintenance phase, eligible subjects will have the opportunity to qualify for and participate in the separate open-label extension (OLE) study and receive XEN496 or, should they choose to exit the study, will undergo a dose taper period of up to 15 days and 4-week follow-up.

Details
Condition Epilepsy, Epilepsy in Children, Epilepsy; Seizure, Disease, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Epileptic Syndromes
Treatment Placebo, XEN496
Clinical Study IdentifierNCT04639310
SponsorXenon Pharmaceuticals Inc.
Last Modified on4 October 2022

Eligibility

 Yes No Not Sure

Inclusion Criteria

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

Exclusion Criteria

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
Other exclusion criteria apply, and will be assessed by the study team
Subjects with a known hypersensitivity to ezogabine or any of the excipients in the study drug
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