An Open-Label Extension of the Study XEN496 (Ezogabine) in Children With KCNQ2-DEE

NCT04912856 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: XPF-009-3022020-003447-28
• Study Type: interventional
• Target: 8
• Locations: 3 countries
• Sites: 4

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).

Conditions

Epilepsy; Epilepsy in Children; Epilepsy; Seizure; Disease; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes

Keywords

XEN496; Ezogabine; Retigabine; Encephalopathy; Seizure; KCNQ2; EPIK

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

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

Drug: XEN496

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.

Drug: XEN496

Interventions

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.

Also known as: ezogabine, retigabine

Group 1: XEN496 only; Group 2: Placebo to XEN496

Eligibility Criteria

• Age: 1 Month - 6 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• It is anticipated that the subject will require treatment with at least 1 of the disallowed medications during the study.
• Any change in cardiac rhythm or atrioventricular conduction in the primary study that, in the investigator's opinion, is a significant risk to subject safety.

Sponsors & Collaborators

• Xenon Pharmaceuticals Inc.: lead

Study Sites (4)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

MultiCare Health System - Mary Bridge Pediatrics - Tacoma

Tacoma, Washington, 98405, United States

Location

Sydney Children's Hospital

Sydney, New South Wales, 2031, Australia

Location

Universitair Ziekenhuis Antwerpen - Dienst Kinderneurologie

Edegem, Antwerpen, 2650, Belgium

Location

Related Links

• XPF-009-301 Study (EPIK)

MeSH Terms

Conditions

Epilepsy; Disease; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes; Seizures

Interventions

ezogabine

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neurologic Manifestations; Signs and Symptoms

Limitations and Caveats

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.

Results Point of Contact

• Title: Dr. Noam Butterfield
• Organization: Xenon Pharmaceuticals

nbutterfield@xenon-pharma.com

604 484 3300

Study Officials

• Study Director

  Xenon Pharmaceuticals Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Patients will enter a blinded titration period (24 days) before moving to the open label treatment period for the remaining 35 months.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2021
• First Posted: June 3, 2021
• Study Start: August 17, 2021
• Primary Completion: November 17, 2023
• Study Completion: November 17, 2023
• Last Updated: February 14, 2025
• Results First Posted: February 14, 2025

Record last verified: 2024-12

Locations

US (2); BE (1); AU (1)