- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04912856
An Open-Label Extension of the Study XEN496 (Ezogabine) in Children With KCNQ2-DEE (EPIK-OLE)
An Open-Label Extension of the Study XEN496 in Children With KCNQ2 Developmental and Epileptic Encephalopathy
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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New South Wales
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Sydney, New South Wales, Australia, 2031
- Sydney Children's Hospital
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Antwerpen
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Edegem, Antwerpen, Belgium, 2650
- Universitair Ziekenhuis Antwerpen - Dienst Kinderneurologie
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- Children's Hospital of Philadelphia
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Washington
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Tacoma, Washington, United States, 98405
- MultiCare Health System - Mary Bridge Pediatrics - Tacoma
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Subject completed participation in the primary study, XPF-009-301. A subject who withdraws from the primary study due to meeting protocol-specified worsening criteria will be considered as having completed participation in the primary study.
- The caregiver is willing and able to be compliant with diary completion, visit schedule, and study drug administration.
- Subject's caregiver achieved a minimum of 85% compliance with daily diary completion during both baseline and the double-blind period of the primary study.
Exclusion Criteria:
- Any adverse event(s) or serious adverse event(s) during the primary study XPF-009-301, which in the opinion of the investigator and sponsor's medical monitor, would preclude the subject's entry into the OLE study.
- A clinically significant condition or illness, or symptoms other than those resulting from KCNQ2-DEE, present at screening/baseline that, in the opinion of the investigator, would pose a risk to the subject if s/he were to enter the study.
- Any conditions that were specified as exclusion criteria in the primary study, XPF-009-301.
- It is anticipated that the subject will require treatment with at least 1 of the disallowed medications during the study.
- Any change in cardiac rhythm or atrioventricular conduction in the primary study that, in the investigator's opinion, is a significant risk to subject safety.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Stage 1: Blinded Dose Transition/Titration
24-day blinded transition/titration period. Subjects who received XEN496 in the preceding study will continue to receive XEN496 at the same dose, in a blinded manner, without any further titration. Subjects, who were allocated to placebo in the preceding study, will be titrated to a tolerated dose up to a maximum dose of 21 mg/kg/day, with a maximum daily dose of 672 mg/day. To maintain the blinded aspect of the study, placebo will be dispensed to all subjects during the transition/titration period to ensure the total number of capsules are consistent across all subjects. Subjects who discontinue will be required to taper off study drug over a period of up to 15 days |
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 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.
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Experimental: Stage 2: Open-Label Treatment
Optimally-tolerated dose level established during the transition/titration period will be maintained throughout the duration of open-label period unless dose adjustment is required. Subjects who discontinue or complete the study treatment will be required to taper off study drug over a period of up to 15 days. |
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:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) related to intervention
Time Frame: From Screening/Baseline through to 4 weeks post last dose
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Safety and tolerability of XEN496 as assessed by incidence and severity of AEs and SAEs
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From Screening/Baseline through to 4 weeks post last dose
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in monthly countable motor seizure frequency
Time Frame: Screening/Baseline to first 15 weeks (up to Visit 10)
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Comparing the first 15 weeks of XEN496 treatment in the OLE study to the seizure frequency reported during treatment in the preceding primary study, XPF-009-301, among only those subjects who were randomized to the placebo arm in the primary study, XPF-009-301
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Screening/Baseline to first 15 weeks (up to Visit 10)
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Change from pre-randomization baseline in the previous study over time based on response categories (<25%, 25 to <50%, 50 to <75%, 75 to <100%, 100%), based on estimated seizure frequency every 3 months during the OLE period
Time Frame: Every three months from screening/baseline through to study completion, up to 162 weeks
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Caregivers will be instructed on how to complete the diary and will be asked to record information daily in the diary.
Information on the number and type of countable motor seizures will be collected daily.
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Every three months from screening/baseline through to study completion, up to 162 weeks
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Percent change from baseline in countable motor seizure frequency, relative to pre-randomization baseline of the primary study, XPF-009-301, assessed over time every 3 months during the OLE
Time Frame: Every three months from screening/baseline through to study completion, up to 162 weeks
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Caregivers will be instructed on how to complete the diary and will be asked to record information daily in the diary.
Information on the number and type of countable motor seizures will be collected daily.
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Every three months from screening/baseline through to study completion, up to 162 weeks
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Percent change from baseline in countable motor seizure frequency, relative to pre-randomization baseline of the primary study, XPF-009-301, every 3 months based on combined data from both primary and OLE studies, by treatment group in the primary study
Time Frame: Every three months from screening/baseline through to study completion, up to 162 weeks
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Caregivers will be instructed on how to complete the diary and will be asked to record information daily in the diary.
Information on the number and type of countable motor seizures will be collected daily.
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Every three months from screening/baseline through to study completion, up to 162 weeks
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Change over time in Caregiver Global Impression of Severity (CaGI-S) scores for the subject's overall condition and for seizures.
Time Frame: Study days: 1, 24, 67, 109, 182, 273, 364, 455, 546, 637, 728, 819, 910, 1001 and 1092
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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.
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Study days: 1, 24, 67, 109, 182, 273, 364, 455, 546, 637, 728, 819, 910, 1001 and 1092
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Change over time in Caregiver Global Impression of Change (CaGI-C) scores for the subject
Time Frame: Study days: 24, 67, 109, 182, 273, 364, 455, 546, 637, 728, 819, 910, 1001 and 1092
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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.
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Study days: 24, 67, 109, 182, 273, 364, 455, 546, 637, 728, 819, 910, 1001 and 1092
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Change over time in neurocognitive development based on the Bayley Scales of Infant and Toddler Development III (BSID-III)
Time Frame: Study days: 1, 109, 364, 728 and 1092
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The BSID-III is designed to identify young children with development delays, and assesses developmental function across 5 domains: cognition; language (expressive and receptive); motor (fine and gross motor functioning); social-emotional, and adaptive behavior.
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Study days: 1, 109, 364, 728 and 1092
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Change over time in adaptive behavior based on the Adaptive Behavior Assessment System, Third Edition (ABAS-3)
Time Frame: Study days: 1, 109, 182, 364, 546, 728, 910 and 1092
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On a 4-point response scale, raters indicate whether, and how frequently, the individual performs each activity.
The ABAS-3 assesses up to 11 skill areas: communication, community use, functional academics, health and safety, home or school living, leisure, motor, self-care, self-direction, social, and work.
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Study days: 1, 109, 182, 364, 546, 728, 910 and 1092
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Change over time in the Investigator's Clinical Global Impression of Change scale (CGI-C) scores for the subject's seizures and overall condition
Time Frame: Study days: 67, 109, 182, 364, 546, 728, 910 and 1092
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The CGI-C consists of single items relating to each concept and is scored by the investigator using a 7-point Likert scale ranging from 1 to 7, anchored at 1 = "Very much improved" and 7 = "Very much worse".
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Study days: 67, 109, 182, 364, 546, 728, 910 and 1092
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Use of rescue medication
Time Frame: From screening/baseline through to study completion, up to 162 weeks
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Caregivers will be instructed on how to complete the diary and will be asked to record information daily in the diary.
Information on the number and type of rescue medications will be collected daily.
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From screening/baseline through to study completion, up to 162 weeks
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Use of all concomitant medications including treatments used for seizure control
Time Frame: From screening/baseline through to 162 weeks
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Caregivers will be instructed on how to complete the diary and will be asked to record information daily in the diary.
Information on the number and type of concomitant medications will be collected daily.
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From screening/baseline through to 162 weeks
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Change in the Pediatric Quality of Life Inventory scale in subjects with KCNQ2-DEE
Time Frame: Study days: 1, 67, 109, 182, 546, 728, 910 and 1092
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A modular instrument designed to measure health-related quality of life in both healthy and chronically ill children.
The scales include parent-reported measures of the child's physical functioning, physical symptoms, emotional functioning, social functioning, and cognitive functioning
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Study days: 1, 67, 109, 182, 546, 728, 910 and 1092
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Change in Pediatric Quality of Life Inventory, Family Impact scale in subjects with KCNQ2-DEE
Time Frame: Study days: 1, 67, 109, 182, 546, 728, 910 and 1092
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To evaluate the impact of pediatric chronic health conditions on parents and the family including measures of parent self-reported physical, emotional, social and cognitive function, communication and worry, in addition to family daily activities and family relationships
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Study days: 1, 67, 109, 182, 546, 728, 910 and 1092
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Plasma concentrations of ezogabine and N-acetyl metabolite of ezogabine (NAMR)
Time Frame: Study days: 1, 16, 32, 67, 109, 182, 546, 728, 910 and 1092
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Blood samples will be taken at predefined visit dates to analyze the plasma concentrations.
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Study days: 1, 16, 32, 67, 109, 182, 546, 728, 910 and 1092
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Study Director, Xenon Pharmaceuticals Inc.
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- XPF-009-302
- 2020-003447-28 (EudraCT Number)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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.
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