Trial Review

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/ct2/show/NCT04639310




Registration number
NCT04639310
Ethics application status
Date submitted
4/11/2020
Date registered
20/11/2020
Date last updated
28/06/2023

Titles & IDs
Public title
XEN496 (Ezogabine) in Children With KCNQ2 Developmental and Epileptic Encephalopathy
Scientific title
A Phase 3 Study of Adjunctive XEN496 in Pediatric Subjects With KCNQ2 Developmental and Epileptic Encephalopathy
Secondary ID [1] 0 0
2020-002396-35
Secondary ID [2] 0 0
XPF-009-301
Universal Trial Number (UTN)
Trial acronym
EPIK
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: 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.

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.


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
Percent change from baseline in monthly (28 day) countable motor seizure frequency during the blinded treatment period
Timepoint [1] 0 0
From baseline to the end of the double-blind, 12 week treatment period (maintenance)
Secondary outcome [1] 0 0
Proportion of subjects with =50 percent reduction in monthly (28 day) seizure frequency
Timepoint [1] 0 0
From baseline to the end of the double-blind, 12 week treatment period (maintenance)
Secondary outcome [2] 0 0
Caregiver Global Impression of Change (CaGI-C) scores for the subject's overall condition and for seizures
Timepoint [2] 0 0
Study Days 24, 67, 88 and 109
Secondary outcome [3] 0 0
Change from baseline in the Caregiver Global Impression of Severity (CaGI-S) for the subject's overall condition and for seizures
Timepoint [3] 0 0
Study Days 1, 24, 67, 88 and 109

Eligibility
Key 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.
Minimum age
1 Month
Maximum age
6 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
29/03/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
16/05/2023
Sample size
Target
Accrual to date
Final
8
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Sydney Children's Hospital - Sydney
Recruitment hospital [2] 0 0
Children's Health Queensland Hospital and Health Service - South Brisbane
Recruitment hospital [3] 0 0
Austin Health - Heidelberg
Recruitment postcode(s) [1] 0 0
2031 - Sydney
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Oregon
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
Washington
Country [11] 0 0
Belgium
State/province [11] 0 0
Antwerpen
Country [12] 0 0
Italy
State/province [12] 0 0
Genova
Country [13] 0 0
Italy
State/province [13] 0 0
Milan
Country [14] 0 0
Italy
State/province [14] 0 0
Verona
Country [15] 0 0
Spain
State/province [15] 0 0
Barcelona
Country [16] 0 0
Spain
State/province [16] 0 0
Madrid

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

Ethics approval
Ethics application status

Summary
Brief summary
To investigate the potential antiseizure effects of adjunctive XEN496 (ezogabine) compared
with placebo in children with KCNQ2 Developmental and Epileptic Encephalopathy (KCNQ2-DEE).
Trial website
https://clinicaltrials.gov/ct2/show/NCT04639310
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/ct2/show/NCT04639310