Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2020-003447-28 | EudraCT Number |
Not provided
Not provided
Sponsor decision; not a safety decision
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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).
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1: XEN496 only | Experimental | 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 |
|
| Group 2: Placebo to XEN496 | Experimental | 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 Subjects who discontinue or complete the study treatment will be required to taper off study drug over a period of up to 15 days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| XEN496 | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | From Screening/Baseline through to 4 weeks post last dose |
Not provided
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Study Director | Xenon Pharmaceuticals Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States | ||
| MultiCare Health System - Mary Bridge Pediatrics - Tacoma |
Not provided
| Label | URL |
|---|---|
| XPF-009-301 Study (EPIK) | View source |
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 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. 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 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. 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan: Study Protocol | May 9, 2022 |
Not provided
Not provided
Not provided
Not provided
Patients will enter a blinded titration period (24 days) before moving to the open label treatment period for the remaining 35 months.
|
| Tacoma |
| Washington |
| 98405 |
| United States |
| Sydney Children's Hospital | Sydney | New South Wales | 2031 | Australia |
| Universitair Ziekenhuis Antwerpen - Dienst Kinderneurologie | Edegem | Antwerpen | 2650 | Belgium |
| FG001 | 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 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. 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. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | Posted | Count of Participants | Participants | From Screening/Baseline through to 4 weeks post last dose |
|
|
|
Collection of adverse event data began at Visit 1 when consent was obtained and continued throughout the course subject's participation in the study. The intended duration of the collection period was 3 years. Following the termination of the study, the collection period was up to 2 years and 3 months.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. | 0 | 5 | 2 | 5 | 5 | 5 |
| EG001 | 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. | 0 | 3 | 1 | 3 | 3 | 3 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastroenteritis | Gastrointestinal disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Pneumonia | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Seizure cluster | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Intestinal malrotation | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Urinary retention | Renal and urinary disorders | MedDRA 26.0 | Non-systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 26.0 | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA 26.0 | Systematic Assessment |
| |
| Retinal Pigmentation | Eye disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Blood pressure systolic increased | Investigations | MedDRA 26.0 | Systematic Assessment |
| |
| Salivary gland enlargement | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
| |
| Peripheral swelling | General disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Swelling face | General disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Viral upper respiratory tract infection | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Otitis Media | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Respiratory synctial virus test positive | Investigations | MedDRA 26.0 | Systematic Assessment |
| |
| Intestinal malrotation | Congenital, familial and genetic disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Gastrointestinal bacterial overgrowth | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
| |
| Blood in the stool | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
| |
| Urinary hesitation | Renal and urinary disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Initial Insomnia | Psychiatric disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Ear Swelling | Ear and labyrinth disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Dermatitis allergic | Skin and subcutaneous tissue disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Bronchitis viral | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
| |
| Blister | Skin and subcutaneous tissue disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Abnormal behaviour | Psychiatric disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Epilepsy | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
|
Due to the early termination of the study (not due to safety reasons or futility) and the limited number of subjects enrolled in this OLE, the full analysis was not completed, and no efficacy data were assessed.
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Noam Butterfield | Xenon Pharmaceuticals | 604 484 3300 | nbutterfield@xenon-pharma.com |
| Dec 18, 2024 |
| Prot_SAP_001.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan: Statistical Analysis Plan | May 4, 2023 | Feb 11, 2025 | SAP_002.pdf |
Not provided
| ID | Term |
|---|---|
| D004827 | Epilepsy |
| D004194 | Disease |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D000073376 | Epileptic Syndromes |
| D012640 | Seizures |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| C101866 | ezogabine |
Not provided
Not provided
Not provided
| >=65 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| United States |
|
| Australia |
|
| Participants with any treatment related TEAE |
|
| Participants with any TEAE leading to discontinuation of study drug |
|
| Participants with any TEAE leading to a dose reduction or treatment interruption |
|
| Participants with any Severe TEAE |
|
| Participants with any Serious TEAE |
|
| Participants with any TEAE leading to death |
|