Trial Review

The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
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
Trial website
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT04912856