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

Inclusion Criteria:

• Male or female subjects aged from 1 month to less than 6 years, with a body weightof ≥3.0 kg at screening.

• Documented evidence of a genetic test result from an appropriately accreditedlaboratory, consistent with a diagnosis of KCNQ2-DEE (pathogenic, likely pathogenic,variant of unknown significance, or inconclusive but unlikely to support analternate diagnosis).

• Seizure onset within 2 weeks after birth and EEG and documented clinical historyconsistent with KCNQ2-DEE.

• Magnetic resonance imaging has been performed and is without evidence of structuralabnormalities, including but not limited to, hypoxia, hypoxia-ischemia, ischemia (arterial or venous), stroke, sinovenous thrombosis, intracranial hemorrhage, orfocal or global brain malformation. Brain MRI changes that are described as beingassociated 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 toscreening.

• Taking 1 and no more than 4 concomitant antiseizure medications (ASMs). All dosesmust be stable for at least 1 week prior to screening and expected to be maintainedthroughout the duration of the study.

• Vagal nerve stimulation (VNS) is allowed and will not be counted as a concomitantASM. The VNS device must be implanted for at least 6 months before screening, andthe device settings must be stable for at least 6 weeks prior to screening andthroughout 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 beon a stable dietary regimen that produces ketosis for at least 6 weeks prior toscreening, 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 geneassociated with other epilepsy syndromes. (Variants in other epilepsy-associatedgenes that are not known to be pathogenic or are not likely to be pathogenic basedupon adjudication review will not be a basis for exclusion.)

• Presence of a known gain-of-function variant in the KCNQ2 gene, or clinicalcharacteristics consistent with previously reported pathogenic gain-of-functionvariants in the KCNQ2 gene.

• Seizures secondary to infection, neoplasia, demyelinating disease, degenerativeneurological 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 uncontrolledmedical illness at screening including, but not limited to, cardiovascular,gastrointestinal, hematologic, hepatic, ocular, pulmonary, renal, or urogenitalsystems, or other conditions that would not justify the subject's participation inthe study, as determined by the investigator's risk benefit assessment.

• QT interval corrected for heart rate by Fridericia's formula (QTcF) of >440 msec. Inaddition, subjects with a history of arrhythmia, prolonged QT, heart disease orsubjects taking medications known to increase the QT interval.

• History of hyperbilirubinemia, which lasts longer than 1 week will require exclusionof hepatic disease before entering the study.

• History of bilirubin-induced neurological dysfunction.

• Current disturbance of micturition or known urinary obstructions or history ofbladder or urinary dysfunction including abnormal post-void residual bladderultrasound, vesicoureteral reflux, urinary retention, or required urinarycatheterization in the preceding 6 months.

• Known to have a terminal illness.

• Any clinically significant laboratory abnormalities or clinically significantabnormalities on pre-study physical examination, vital signs, or ECG that in thejudgment of the investigator indicates a medical problem that would preclude studyparticipation.

• Planned to begin a ketogenic or other specialized dietary therapy during the study.

• Caregiver history of chronic noncompliance with their child's prescribed drugregimens that has not been corrected.

• Exposure to any other investigational drug or device within 5 half-lives or 30 daysprior to screening, whichever is longer or plans to participate in another drug ordevice trial at any time during the study.

• Concurrent enrollment in any other type of medical research judged by theinvestigator not to be scientifically or medically compatible with this study.

• Using felbamate presenting with clinically significant abnormalities and/or hepaticdysfunction during felbamate treatment, and subjects who have taken felbamate forless 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 thestudy drug.

• Other exclusion criteria apply, and will be assessed by the study team.