Trial Outcomes & Findings for XEN496 (Ezogabine) in Children With KCNQ2 Developmental and Epileptic Encephalopathy (NCT NCT04639310)
NCT ID: NCT04639310
Last Updated: 2024-08-23
Results Overview
Parent/caregiver seizure diary record will be used to assess frequency, type and duration of seizure activity
Recruitment status
TERMINATED
Study phase
PHASE3
Target enrollment
8 participants
Primary outcome timeframe
From baseline to the end of the double-blind, 12 week treatment period (maintenance)
Results posted on
2024-08-23
Participant Flow
Participants entered a 2 or 4 week baseline period based upon seizure frequency prior to enrollment. Baseline period was extended by an additional 2 weeks to ensure adequate establishment of baseline seizure frequency, at the discretion of the investigator.
Participant milestones
| Measure |
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.
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 TID.
|
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.
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 TID.
|
|---|---|---|
|
Overall Study
STARTED
|
5
|
3
|
|
Overall Study
COMPLETED
|
5
|
2
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
| Measure |
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.
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 TID.
|
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.
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 TID.
|
|---|---|---|
|
Overall Study
Subject qualified to rollover to open label extension due to meeting disease worsening criteria
|
0
|
1
|
Baseline Characteristics
XEN496 (Ezogabine) in Children With KCNQ2 Developmental and Epileptic Encephalopathy
Baseline characteristics by cohort
| Measure |
XEN496
n=5 Participants
XEN496 capsules: immediate-release, multiparticulate sprinkle capsule formulation of ezogabine administered orally TID for up to approximately 15 weeks (titration and maintenance).
|
Placebo
n=3 Participants
Placebo capsules: matching XEN496 in appearance containing only inactive ingredients.
|
Total
n=8 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
age < 2 years · Age < 2 years
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Age, Customized
age < 2 years · Age >= 2 years
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
Belgium
|
1 participants
n=5 Participants
|
2 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
3 participants
n=5 Participants
|
1 participants
n=7 Participants
|
4 participants
n=5 Participants
|
|
Region of Enrollment
Australia
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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
Outcome measures
| Measure |
XEN496
n=5 Participants
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.
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 TID.
|
Placebo
n=3 Participants
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.
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 TID.
|
|---|---|---|
|
Percent Change From Baseline in Monthly (28 Day) Countable Motor Seizure Frequency During the Blinded Treatment Period
|
-46.0 percentage change from baseline
Standard Deviation 23.49
|
25.6 percentage change from baseline
Standard Deviation 46.84
|
SECONDARY outcome
Timeframe: 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 of seizure with a duration of at least 3 seconds.
Outcome measures
| Measure |
XEN496
n=5 Participants
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.
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 TID.
|
Placebo
n=3 Participants
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.
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 TID.
|
|---|---|---|
|
Percentage of Subjects With ≥50 Percent Reduction in Monthly (28 Day) Seizure Frequency
|
2 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Study Day 109Population: Subjects at least minimally improved (a score of \<=3) compared to baseline.
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.
Outcome measures
| Measure |
XEN496
n=5 Participants
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.
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 TID.
|
Placebo
n=3 Participants
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.
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 TID.
|
|---|---|---|
|
Caregiver Global Impression of Change (CaGI-C) Scores for the Subject's Overall Condition and for Seizures
Overall Condition
|
1 Participants
|
1 Participants
|
|
Caregiver Global Impression of Change (CaGI-C) Scores for the Subject's Overall Condition and for Seizures
Seizure Severity
|
1 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Study Day 109Population: Subjects with improvement of at least 1 level compared to baseline
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.
Outcome measures
| Measure |
XEN496
n=5 Participants
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.
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 TID.
|
Placebo
n=3 Participants
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.
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 TID.
|
|---|---|---|
|
Change From Baseline in the Caregiver Global Impression of Severity (CaGI-S) for the Subject's Overall Condition and for Seizures
Overall Condition
|
0 Participants
|
1 Participants
|
|
Change From Baseline in the Caregiver Global Impression of Severity (CaGI-S) for the Subject's Overall Condition and for Seizures
Seizure Severity
|
1 Participants
|
0 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From screening through study completion (Day 109) or Day 151 for those not entering the OLETo assess adverse events as criteria for safety and tolerability
Outcome measures
| Measure |
XEN496
n=5 Participants
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.
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 TID.
|
Placebo
n=3 Participants
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.
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 TID.
|
|---|---|---|
|
Safety and Tolerability of XEN496 (e.g., Adverse Events) in Pediatric Subjects With KCNQ2-DEE
No. of Subject with any AE
|
5 Participants
|
3 Participants
|
|
Safety and Tolerability of XEN496 (e.g., Adverse Events) in Pediatric Subjects With KCNQ2-DEE
No. of Subjects with any TEAE
|
5 Participants
|
3 Participants
|
|
Safety and Tolerability of XEN496 (e.g., Adverse Events) in Pediatric Subjects With KCNQ2-DEE
No. of Subjects with any Treatment Related TEAE
|
1 Participants
|
0 Participants
|
|
Safety and Tolerability of XEN496 (e.g., Adverse Events) in Pediatric Subjects With KCNQ2-DEE
No. of Subjects with any TEAE leading to discontinuation of study drug
|
0 Participants
|
0 Participants
|
|
Safety and Tolerability of XEN496 (e.g., Adverse Events) in Pediatric Subjects With KCNQ2-DEE
No. of Subjects with any TEAE leading to dose reduction of treatment interruption
|
1 Participants
|
0 Participants
|
|
Safety and Tolerability of XEN496 (e.g., Adverse Events) in Pediatric Subjects With KCNQ2-DEE
No. of Subjects with any Severe TEAE
|
1 Participants
|
1 Participants
|
|
Safety and Tolerability of XEN496 (e.g., Adverse Events) in Pediatric Subjects With KCNQ2-DEE
No. of Subjects with any TEAE by relationship to study drug
|
5 Participants
|
3 Participants
|
|
Safety and Tolerability of XEN496 (e.g., Adverse Events) in Pediatric Subjects With KCNQ2-DEE
No. of Subjects with any Serious TEAE
|
1 Participants
|
1 Participants
|
|
Safety and Tolerability of XEN496 (e.g., Adverse Events) in Pediatric Subjects With KCNQ2-DEE
No. of Subjects with any TEAE of Special Interest
|
0 Participants
|
0 Participants
|
|
Safety and Tolerability of XEN496 (e.g., Adverse Events) in Pediatric Subjects With KCNQ2-DEE
No. of Subjects with any TEAE leading to death
|
0 Participants
|
0 Participants
|
Adverse Events
XEN496
Serious events: 1 serious events
Other events: 5 other events
Deaths: 0 deaths
Placebo
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
XEN496
n=5 participants at risk
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.
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 TID.
|
Placebo
n=3 participants at risk
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.
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 TID.
|
|---|---|---|
|
Infections and infestations
Metapneumovirus pneumonia
|
20.0%
1/5 • Number of events 1 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
0.00%
0/3 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
|
Nervous system disorders
Status epilepticus
|
0.00%
0/5 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
33.3%
1/3 • Number of events 1 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
|
Infections and infestations
Pneumonia viral
|
20.0%
1/5 • Number of events 1 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
0.00%
0/3 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
Other adverse events
| Measure |
XEN496
n=5 participants at risk
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.
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 TID.
|
Placebo
n=3 participants at risk
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.
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 TID.
|
|---|---|---|
|
Infections and infestations
COVID-19
|
0.00%
0/5 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
66.7%
2/3 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
|
Infections and infestations
Upper respiratory tract infection
|
20.0%
1/5 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
33.3%
1/3 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
|
Infections and infestations
Viral infection
|
40.0%
2/5 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
0.00%
0/3 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
|
Infections and infestations
Bronchitis
|
0.00%
0/5 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
33.3%
1/3 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
|
Infections and infestations
Nasopharyngitis
|
20.0%
1/5 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
0.00%
0/3 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
|
Infections and infestations
Otitis media
|
20.0%
1/5 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
0.00%
0/3 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
|
Infections and infestations
Pneumonia
|
40.0%
2/5 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
0.00%
0/3 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
|
Gastrointestinal disorders
Constipation
|
20.0%
1/5 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
0.00%
0/3 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
|
Gastrointestinal disorders
Diarrhoea
|
40.0%
2/5 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
33.3%
1/3 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
|
Gastrointestinal disorders
Hemotochemia
|
0.00%
0/5 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
33.3%
1/3 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
|
Gastrointestinal disorders
Teething
|
20.0%
1/5 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
0.00%
0/3 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
|
Gastrointestinal disorders
Vomiting
|
20.0%
1/5 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
0.00%
0/3 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
|
Nervous system disorders
Lethargy
|
20.0%
1/5 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
0.00%
0/3 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
|
Nervous system disorders
Somnolence
|
20.0%
1/5 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
0.00%
0/3 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
|
General disorders
Pyrexia
|
40.0%
2/5 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
0.00%
0/3 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
|
Investigations
Gamma-glutamyltransferase increased
|
20.0%
1/5 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
0.00%
0/3 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
|
Investigations
Weight decreased
|
0.00%
0/5 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
33.3%
1/3 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
|
Psychiatric disorders
Poor quality sleep
|
0.00%
0/5 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
33.3%
1/3 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
|
Psychiatric disorders
Sleep disorder
|
20.0%
1/5 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
0.00%
0/3 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
|
Eye disorders
Conjunctival hyperemia
|
20.0%
1/5 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
0.00%
0/3 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/5 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
33.3%
1/3 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
|
Renal and urinary disorders
Chromaturia
|
20.0%
1/5 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
0.00%
0/3 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary congestion
|
20.0%
1/5 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
0.00%
0/3 • From screening through study completion (Day 109) or Day 151 for those not entering the OLE
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60