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

Xenon Pharmaceuticals

Status and phase: Terminated; Phase 3

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

Treatments: Drug: XEN496

Study type: Interventional

Funder types: Industry

Identifiers

NCT04912856

2020-003447-28 (EudraCT Number)

XPF-009-302

Details and patient eligibility

About

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).

Full 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.

Enrollment: 8 patients

Sex: All

Ages: 1 month to 6 years old

Volunteers: No Healthy Volunteers

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 exclusion criteria in the primary study, XPF-009-301.
• 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

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8 participants in 2 patient groups

Group 1: XEN496 only

Experimental group

Description:

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

Treatment:

Drug: XEN496

Group 2: Placebo to XEN496

Experimental group

Description:

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.

Treatment:

Drug: XEN496