Brain Diseases, Central Nervous System Diseases, Disease, Epilepsy, Epilepsy in Children, Epilepsy; Seizure, Epileptic Syndromes, Nervous System Diseases
Conditions
Keywords
XEN496, Ezogabine, Retigabine, Encephalopathy, Seizure, KCNQ2, EPIK
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).
Detailed description
This is an open-label, long-term extension study of XEN496 for the treatment of seizures in subjects with KCNQ2-DEE, that will be open to eligible subjects who participated in the primary study, XPF-009-301. The primary objective is to assess the long-term safety of XEN496. A double-blind transition/titration period will be used to maintain blinding to the treatment allocation in the primary study (XPF-009-301). After completion of the blinded transition/titration period, subjects will receive the open label study drug at their optimal dose for approximately 35 months.
Interventions
DRUGXEN496
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.
Sponsors
Xenon Pharmaceuticals Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Patients will enter a blinded titration period (24 days) before moving to the open label treatment period for the remaining 35 months.
Eligibility
Sex/Gender
ALL
Age
1 Months to 6 Years
Healthy volunteers
No
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.
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) Related to Intervention | From Screening/Baseline through to 4 weeks post last dose | Safety and tolerability of XEN496 as assessed by incidence and severity of AEs and SAEs |
Countries
Australia, Belgium, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1: XEN496 Treatment in Preceding Study 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. 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
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. | 5 |
| Group 2: Placebo Treatment in Preceding Study 24-day blinded transition/titration period. 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.
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.
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. | 3 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Not reported in synoptic CSR. | 0 | 1 |
| Overall Study | Sponsor Decision; not due to safety reasons | 4 | 2 |
Baseline characteristics
| Characteristic | Group 1: XEN496 Treatment in Preceding Study | Total | Group 2: Placebo Treatment in Preceding Study |
|---|---|---|---|
| Age, Categorical <=18 years | 5 Participants | 8 Participants | 3 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 8 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 6 Participants | 3 Participants |
| Region of Enrollment Australia | 1 participants | 0 participants | 0 participants |
| Region of Enrollment Belgium | 1 participants | 3 participants | 2 participants |
| Region of Enrollment United States | 3 participants | 4 participants | 1 participants |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 2 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 3 |
| other Total, other adverse events | 5 / 5 | 3 / 3 |
| serious Total, serious adverse events | 2 / 5 | 1 / 3 |
Outcome results
Primary
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) Related to Intervention
Safety and tolerability of XEN496 as assessed by incidence and severity of AEs and SAEs
Time frame: From Screening/Baseline through to 4 weeks post last dose
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1: XEN496 Treatment in Preceding Study | Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) Related to Intervention | Number of participants with any TEAE | 5 Participants |
| Group 1: XEN496 Treatment in Preceding Study | Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) Related to Intervention | Number of participants with any AEs | 5 Participants |
| Group 1: XEN496 Treatment in Preceding Study | Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) Related to Intervention | Participants with any treatment related TEAE | 1 Participants |
| Group 1: XEN496 Treatment in Preceding Study | Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) Related to Intervention | Participants with any TEAE leading to discontinuation of study drug | 0 Participants |
| Group 1: XEN496 Treatment in Preceding Study | Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) Related to Intervention | Participants with any TEAE leading to a dose reduction or treatment interruption | 1 Participants |
| Group 1: XEN496 Treatment in Preceding Study | Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) Related to Intervention | Participants with any Severe TEAE | 1 Participants |
| Group 1: XEN496 Treatment in Preceding Study | Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) Related to Intervention | Participants with any Serious TEAE | 2 Participants |
| Group 1: XEN496 Treatment in Preceding Study | Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) Related to Intervention | Participants with any TEAE leading to death | 0 Participants |
| Group 2: Placebo Treatment in Preceding Study | Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) Related to Intervention | Participants with any TEAE leading to death | 0 Participants |
| Group 2: Placebo Treatment in Preceding Study | Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) Related to Intervention | Participants with any TEAE leading to a dose reduction or treatment interruption | 1 Participants |
| Group 2: Placebo Treatment in Preceding Study | Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) Related to Intervention | Number of participants with any AEs | 3 Participants |
| Group 2: Placebo Treatment in Preceding Study | Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) Related to Intervention | Number of participants with any TEAE | 3 Participants |
| Group 2: Placebo Treatment in Preceding Study | Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) Related to Intervention | Participants with any Serious TEAE | 1 Participants |
| Group 2: Placebo Treatment in Preceding Study | Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) Related to Intervention | Participants with any treatment related TEAE | 2 Participants |
| Group 2: Placebo Treatment in Preceding Study | Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) Related to Intervention | Participants with any Severe TEAE | 0 Participants |
| Group 2: Placebo Treatment in Preceding Study | Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) Related to Intervention | Participants with any TEAE leading to discontinuation of study drug | 0 Participants |