EpilepsyPhase 3EPIKNCT04639310
XEN496 (Ezogabine) in Children With KCNQ2 Developmental and Epileptic Encephalopathy
A Phase 3 study testing XEN496 in people with Epilepsy and Epilepsy in Children, run by Xenon Pharmaceuticals Inc. at 20 sites in 5 countries.
Trial summary
To investigate the potential antiseizure effects of adjunctive XEN496 (ezogabine) compared with placebo in children with KCNQ2 Developmental and Epileptic Encephalopathy (KCNQ2-DEE). Read more about this study
- Who is it for?
- Ages 1 month to 6 years
- Conditions the study is for
- Epilepsy, Epilepsy in Children, Epilepsy; Seizure
- What is being tested?
- XEN496
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 8 participants
- Where
- 20 sitesin 5 countries
- Study dates
- 29 Mar 2021to 16 May 2023
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 month to 6 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
20 sites in 5 countries.
20 sites in 5 countries
United States11 sites
Children's Hospital of Colorado
Aurora, Colorado, 80045
Anne & Robert H. Lurie Children's Hospital
Chicago, Illinois, 60611
The Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Northwest Florida Clinical Research Group
Gulf Breeze, Florida, 32561
Columbia University Irving Medical Center
New York, New York, 10032
Children's Hospital of Orange County
Orange, California, 92868
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104-4318
Oregon Health and Science University
Portland, Oregon, 97239
UCSF Medical Center
San Francisco, California, 94158
MultiCare Medical Center
Tacoma, Washington, 98405
Children's National Health System
Washington D.C., District of Columbia, 20010
Australia3 sites
Austin Health
Heidelberg, Victoria, 3084
Children's Health Queensland Hospital and Health Service
South Brisbane, Queensland, 4101
Sydney Children's Hospital
Sydney, New South Wales, 2031
Italy3 sites
Istituto Giannina Gaslini
Genova, 16147
U.O.C. Neurologia Pediatrica Ospedale dei Bambini V. Buzzi
Milan, 20154
Azienda Ospedaliera Universitaria Integrata di Verona
Verona, 37126
Spain2 sites
Universitat de Barcelona - Hospital Sant Joan de Déu Barcelona (HSJDB)
Esplugues de Llobregat, Barcelona, 08950
Hospital Nino Jesus
Madrid, 28009
Belgium1 site
Universitaire Ziekenhuis Anterpen - Dienst Kinderneurologie
Edegem, Antwerpen, 2650
About this study
Official title: 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).
Read the 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.
- Conditions
- Epilepsy, Epilepsy in Children, Epilepsy; Seizure, Disease, Brain Diseases, Central Nervous System Diseases
- Being tested
- XEN496, Placebo
- Keywords
- XEN496, Ezogabine, Retigabine, Encephalopathy, Seizure, KCNQ2
- Medical subject headings
- Epilepsy, Disease, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Epileptic Syndromes, Seizures
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
XEN496Drug
Also called ezogabine, retigabine
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 TID.
PlaceboDrug
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 TID.
| Study group | Role | What they receive |
|---|---|---|
| XEN496 | Experimental | 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. Receives: Drug: XEN496 |
| Placebo | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change From Baseline in Monthly (28 Day) Countable Motor Seizure Frequency During the Blinded Treatment Period
Parent/caregiver seizure diary record will be used to assess frequency, type and duration of seizure activity
Measured: From baseline to the end of the double-blind, 12 week treatment period (maintenance)
Secondary outcomes (3)
Percentage of Subjects With ≥50 Percent Reduction in Monthly (28 Day) Seizure Frequency
Parent/caregiver seizure diary record will be used to assess frequency, type of seizure with a duration of at least 3 seconds.
Measured: 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
CaGI-C scale is a caregiver-reported assessment of the change from baseline in the subject's overall condition and seizure severity. Responses to the CaGI-C questionnaire are to be rated on a 7-point Likert scale anchored at 1="Very much improved" and 7="Very much worse".
Subjects at least minimally improved compared to baseline (a score of <=3) for overall condition or for seizure severity are reported in the analysis population.
The primary comparison between treatments will be based on the last visit in the double-blind treatment period (or the early termination visit if the patient discontinued the treatment early). The results at Study Day 109 (end of treatment period) are provided.
Measured: Study Day 109
Change From Baseline in the Caregiver Global Impression of Severity (CaGI-S) for the Subject's Overall Condition and for Seizures
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-point Likert scale ranging from none to very severe. The CaGI-S consists of single items relating to each concept and is scored by the caregiver using a 5-point response ranging from 1 to 5, anchored at 1="None" and 5="Very Severe".
Subjects with improvement of at least 1 level compared to baseline for overall condition or for seizure severity are reported in the analysis population.
The results at Study Day 109 (end of treatment period) are provided.
Measured: Study Day 109
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2020
- Study start29 Mar 2021
- Primary completion16 May 2023
- Study completion16 May 2023
Why it stopped: Sponsor decision; Not a safety decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for EpilepsyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Xenon Pharmaceuticals Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Xenon Pharmaceuticals Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04639310
- Sponsor's protocol ID
- XPF-009-301
- Other IDs
- 2020-002396-35
- Acronym
- EPIK
- Status last verified
- Aug 2024
- First submitted
- 4 Nov 2020
- Last updated
- 23 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3 Study of Adjunctive XEN496 in Pediatric Subjects With KCNQ2 Developmental and Epileptic Encephalopathy
- ClinicalTrials.gov ID
- NCT04639310
- Acronym / sponsor ID
- EPIK / XPF-009-301
- Conditions
- Epilepsy, Epilepsy in Children, Epilepsy; Seizure, Disease, Brain Diseases, Central Nervous System Diseases
- Keywords
- XEN496, Ezogabine, Retigabine, Encephalopathy, Seizure, KCNQ2
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision; Not a safety decision
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Xenon Pharmaceuticals Inc.Industry (pharma, biotech, devices)
- Study start
- 29 Mar 2021 (actual)
- Primary completion
- 16 May 2023 (actual)
- Study completion
- 16 May 2023 (actual)
- First posted
- 20 Nov 2020 (actual)
- Results
- Posted 23 Aug 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To investigate the potential antiseizure effects of adjunctive XEN496 (ezogabine) compared with placebo in children with KCNQ2 Developmental and Epileptic Encephalopathy (KCNQ2-DEE).
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| XEN496 | Experimental | Drug: XEN49624-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 | Placebo comparator | Drug: PlaceboTo 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. |
Who may qualify
- Ages
- 1 month to 6 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (20 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| XEN496Also: ezogabine, retigabineXEN496 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 TID. | Drug | XEN496 |
| PlaceboPlacebo 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 TID. | Drug | Placebo |
Primary outcome
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
3 secondary outcomes
Percentage 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)
Caregiver Global Impression of Change (CaGI-C) Scores for the Subject's Overall Condition and for Seizures
Time frame: Study Day 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 Day 109
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Xenon Pharmaceuticals Inc.
20 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing XEN496 in people with Epilepsy and Epilepsy in Children, run by Xenon Pharmaceuticals Inc. at 20 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 23 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in United States, Australia, Italy, Spain, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Aug 2024.