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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04912856




Registration number
NCT04912856
Ethics application status
Date submitted
3/05/2021
Date registered
3/06/2021
Date last updated
26/12/2023

Titles & IDs
Public title
An Open-Label Extension of the Study XEN496 (Ezogabine) in Children With KCNQ2-DEE
Scientific title
An Open-Label Extension of the Study XEN496 in Children With KCNQ2 Developmental and Epileptic Encephalopathy
Secondary ID [1] 0 0
2020-003447-28
Secondary ID [2] 0 0
XPF-009-302
Universal Trial Number (UTN)
Trial acronym
EPIK-OLE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Epilepsy 0 0
Epilepsy in Children 0 0
Epilepsy; Seizure 0 0
Disease 0 0
Brain Diseases 0 0
Central Nervous System Diseases 0 0
Nervous System Diseases 0 0
Epileptic Syndromes 0 0
Condition category
Condition code
Neurological 0 0 0 0
Epilepsy
Neurological 0 0 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - XEN496
Treatment: Drugs - Placebo

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

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.


Treatment: Drugs: XEN496
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.

Treatment: Drugs: Placebo
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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) related to intervention
Timepoint [1] 0 0
From Screening/Baseline through to 4 weeks post last dose
Secondary outcome [1] 0 0
Change in monthly countable motor seizure frequency
Timepoint [1] 0 0
Screening/Baseline to first 15 weeks (up to Visit 10)
Secondary outcome [2] 0 0
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
Timepoint [2] 0 0
Every three months from screening/baseline through to study completion, up to 162 weeks
Secondary outcome [3] 0 0
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
Timepoint [3] 0 0
Every three months from screening/baseline through to study completion, up to 162 weeks
Secondary outcome [4] 0 0
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
Timepoint [4] 0 0
Every three months from screening/baseline through to study completion, up to 162 weeks
Secondary outcome [5] 0 0
Change over time in Caregiver Global Impression of Severity (CaGI-S) scores for the subject's overall condition and for seizures.
Timepoint [5] 0 0
Study days: 1, 24, 67, 109, 182, 273, 364, 455, 546, 637, 728, 819, 910, 1001 and 1092
Secondary outcome [6] 0 0
Change over time in Caregiver Global Impression of Change (CaGI-C) scores for the subject
Timepoint [6] 0 0
Study days: 24, 67, 109, 182, 273, 364, 455, 546, 637, 728, 819, 910, 1001 and 1092
Secondary outcome [7] 0 0
Change over time in neurocognitive development based on the Bayley Scales of Infant and Toddler Development III (BSID-III)
Timepoint [7] 0 0
Study days: 1, 109, 364, 728 and 1092
Secondary outcome [8] 0 0
Change over time in adaptive behavior based on the Adaptive Behavior Assessment System, Third Edition (ABAS-3)
Timepoint [8] 0 0
Study days: 1, 109, 182, 364, 546, 728, 910 and 1092
Secondary outcome [9] 0 0
Change over time in the Investigator's Clinical Global Impression of Change scale (CGI-C) scores for the subject's seizures and overall condition
Timepoint [9] 0 0
Study days: 67, 109, 182, 364, 546, 728, 910 and 1092
Secondary outcome [10] 0 0
Use of rescue medication
Timepoint [10] 0 0
From screening/baseline through to study completion, up to 162 weeks
Secondary outcome [11] 0 0
Use of all concomitant medications including treatments used for seizure control
Timepoint [11] 0 0
From screening/baseline through to 162 weeks
Secondary outcome [12] 0 0
Change in the Pediatric Quality of Life Inventory scale in subjects with KCNQ2-DEE
Timepoint [12] 0 0
Study days: 1, 67, 109, 182, 546, 728, 910 and 1092
Secondary outcome [13] 0 0
Change in Pediatric Quality of Life Inventory, Family Impact scale in subjects with KCNQ2-DEE
Timepoint [13] 0 0
Study days: 1, 67, 109, 182, 546, 728, 910 and 1092
Secondary outcome [14] 0 0
Plasma concentrations of ezogabine and N-acetyl metabolite of ezogabine (NAMR)
Timepoint [14] 0 0
Study days: 1, 16, 32, 67, 109, 182, 546, 728, 910 and 1092

Eligibility
Key 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.
Minimum age
1 Month
Maximum age
6 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
17/08/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
17/11/2023
Sample size
Target
Accrual to date
Final
8
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Sydney Children's Hospital - Sydney
Recruitment postcode(s) [1] 0 0
2031 - Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Pennsylvania
Country [2] 0 0
United States of America
State/province [2] 0 0
Washington
Country [3] 0 0
Belgium
State/province [3] 0 0
Antwerpen

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Xenon Pharmaceuticals Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
To assess the long-term safety and tolerability of XEN496 in pediatric subjects with KCNQ2 developmental and epileptic encephalopathy (KCNQ2-DEE) who had participated in the primary study (XPF-009-301).
Trial website
https://clinicaltrials.gov/study/NCT04912856
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Study Director
Address 0 0
Xenon Pharmaceuticals Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04912856