- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04639310
XEN496 (Ezogabine) in Children With KCNQ2 Developmental and Epileptic Encephalopathy (EPIK)
June 26, 2023 updated by: Xenon Pharmaceuticals Inc.
A Phase 3 Study of Adjunctive XEN496 in Pediatric Subjects With KCNQ2 Developmental and Epileptic Encephalopathy
To investigate the potential antiseizure effects of adjunctive XEN496 (ezogabine) compared with placebo in children with KCNQ2 Developmental and Epileptic Encephalopathy (KCNQ2-DEE).
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
Detailed 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.
Study Type
Interventional
Enrollment (Actual)
8
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
New South Wales
-
Sydney, New South Wales, Australia, 2031
- Sydney Children's Hospital
-
-
Queensland
-
South Brisbane, Queensland, Australia, 4101
- Children's Health Queensland Hospital and Health Service
-
-
Victoria
-
Heidelberg, Victoria, Australia, 3084
- Austin Health
-
-
-
-
Antwerpen
-
Edegem, Antwerpen, Belgium, 2650
- Universitaire Ziekenhuis Anterpen - Dienst Kinderneurologie
-
-
-
-
-
Genova, Italy, 16147
- Istituto Giannina Gaslini - Ospedale Pediatrico
-
Milan, Italy, 20154
- U.O. Neurologia Pediatrica Ospedale dei Bambini "Vittore Buzzi"- ASST Fatebenefratelli Sacco
-
Verona, Italy, 37126
- UOC Neuropsichiatria Infantile Azienda Ospedaliera Universitaria Integrata Verona Ospedale Donna e Bambino
-
-
-
-
-
Madrid, Spain, 28009
- Hospital Niño Jesús
-
-
Barcelona
-
Esplugues de Llobregat, Barcelona, Spain, 08950
- Hospital Sant Joan de Deu
-
-
-
-
California
-
Orange, California, United States, 92868
- Children's Hospital of Orange County
-
San Francisco, California, United States, 94158
- UCSF Beniof Children's Hospital
-
-
Colorado
-
Aurora, Colorado, United States, 80045
- Children's Hospital of Colorado
-
-
District of Columbia
-
Washington, District of Columbia, United States, 20010
- Children's National Medical Center
-
-
Florida
-
Gulf Breeze, Florida, United States, 32561
- Northwest Florida Clinical Research Group
-
-
Illinois
-
Chicago, Illinois, United States, 60611
- Ann & Robert H. Lurie Children's Hospital of Chicago
-
-
New York
-
New York, New York, United States, 10032
- Columbia University Irving Medical Center
-
-
Ohio
-
Cleveland, Ohio, United States, 44195
- The Cleveland Clinic Foundation
-
-
Oregon
-
Portland, Oregon, United States, 97239
- Oregon Health and Science University
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, United States, 19104-4318
- Children's Hpspital of Philadelphia
-
-
Washington
-
Tacoma, Washington, United States, 98405
- MultiCare Health System - Mary Bridge Pediatrics - Tacoma
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
1 month to 6 years (Child)
Accepts Healthy Volunteers
No
Description
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.
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: XEN496
24-day dose titration period to a top dose of 21 mg/kg/day.
Subjects continue at the top dose, or the highest tolerated dose up to the top dose, for 12-week maintenance period.
If the subject does not immediately enter into the separate open-label extension (OLE) study, the maintenance period will be followed by a 15-day taper period.
|
XEN496 sprinkle capsules.
Parents / caregivers will be instructed to sprinkle and mix the contents of the capsules into soft foods or liquids and feed it to the child.
Other Names:
|
Placebo Comparator: Placebo
To maintain the blinded aspect of the study, subjects will be titrated on placebo over the 24-day period and remain at this dose for the 12-week maintenance period.
If the subject does not immediately enter into the separate OLE study, the maintenance period will be followed by a 15-day taper period.
|
Placebo sprinkle capsules.
Parents / caregivers will be instructed to sprinkle and mix the contents of the capsules into soft foods or liquids and feed it to the child.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percent change from baseline in monthly (28 day) countable motor seizure frequency during the blinded treatment period
Time Frame: From baseline to the end of the double-blind, 12 week treatment period (maintenance)
|
Parent/caregiver seizure diary record will be used to assess frequency, type and duration of seizure activity
|
From baseline to the end of the double-blind, 12 week treatment period (maintenance)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Proportion of subjects with ≥50 percent reduction in monthly (28 day) seizure frequency
Time Frame: From baseline to the end of the double-blind, 12 week treatment period (maintenance)
|
Parent/caregiver seizure diary record will be used to assess frequency, type and duration
|
From baseline to the end of the double-blind, 12 week treatment period (maintenance)
|
Caregiver Global Impression of Change (CaGI-C) scores for the subject's overall condition and for seizures
Time Frame: Study Days 24, 67, 88 and 109
|
CaGI-C scale is a caregiver-reported assessment for the subject's overall condition and for seizures.
Responses to the CaGI-C questionnaire are to be rated on a 7 item Likert scale ranging from very much improved to very much worse.
|
Study Days 24, 67, 88 and 109
|
Change from baseline in the Caregiver Global Impression of Severity (CaGI-S) for the subject's overall condition and for seizures
Time Frame: Study Days 1, 24, 67, 88 and 109
|
CaGI-S scale is Caregiver-reported assessment of the severity of the subject's seizures and overall condition over the previous 7 days.
Responses to the CaGI-S questionnaire are to be rated on a 5 item Likert scale ranging from none to very severe.
|
Study Days 1, 24, 67, 88 and 109
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Assess the safety and tolerability of XEN496 (e.g., adverse events) in pediatric subjects with KCNQ2-DEE
Time Frame: From screening through to the end of the study (maintenance phase for those continuing into the OLE) or Day 151 for those exiting the study
|
To assess adverse events as criteria for safety and tolerability
|
From screening through to the end of the study (maintenance phase for those continuing into the OLE) or Day 151 for those exiting the study
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Study Director, Xenon Pharmaceuticals Inc.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 29, 2021
Primary Completion (Actual)
May 16, 2023
Study Completion (Actual)
May 16, 2023
Study Registration Dates
First Submitted
November 4, 2020
First Submitted That Met QC Criteria
November 19, 2020
First Posted (Actual)
November 20, 2020
Study Record Updates
Last Update Posted (Actual)
June 28, 2023
Last Update Submitted That Met QC Criteria
June 26, 2023
Last Verified
June 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- XPF-009-301
- 2020-002396-35 (EudraCT Number)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Brain Diseases
-
Brent MaselThe Moody FoundationCompletedChronic Traumatic Brain InjuryUnited States
-
Center for Vision Development, New Market, MarylandUnknownBrain Injuries | Brain Injuries, Traumatic | Traumatic Brain Injury | Brain Injury, Chronic | Injury, Brain, TraumaticUnited States
-
Toronto Rehabilitation InstituteCentre for Aging and Brain Health Innovation; Ontario Neurotrauma FoundationUnknownBrain Injuries, Traumatic | Brain Injury, Chronic | Brain Injury Traumatic Severe | Brain Injury Traumatic ModerateCanada
-
Duke UniversityNational Institute of Neurological Disorders and Stroke (NINDS); National Institutes...Enrolling by invitationMild Traumatic Brain Injury | Concussion, BrainUnited States
-
Oculogica, Inc.CompletedMild Traumatic Brain Injury | Concussion, BrainUnited States
-
Oculogica, Inc.Completed
-
Virginia Commonwealth UniversityU.S. Department of EducationCompletedTraumatic Brain Injury | Brain Injury, ChronicUnited States
-
University of TurkuTurku University Hospital; The Finnish Funding Agency for Technology and Innovation... and other collaboratorsCompletedBrain Injuries | TBI (Traumatic Brain Injury) | Brain Injuries, Traumatic | Traumatic Brain Injury | Injury, Brain, TraumaticFinland
-
University of Sao Paulo General HospitalUnknownTraumatic Brain Injury | Severe Brain Injury | Closed Traumatic Brain InjuryBrazil
-
Indiana UniversityRecruitingMild Traumatic Brain Injury | Concussion, BrainUnited States
Clinical Trials on XEN496
-
Xenon Pharmaceuticals Inc.TerminatedBrain Diseases | Central Nervous System Diseases | Nervous System Diseases | Epilepsy | Epileptic Syndromes | Disease | Epilepsy; Seizure | Epilepsy in ChildrenUnited States, Australia, Belgium