XEN496 for Childhood Epilepsy

(EPIK-OLE Trial)

No longer recruiting at 12 trial locations

Overseen By Xenon Pharmaceuticals Inc.

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Xenon Pharmaceuticals Inc.

Disqualifiers: Adverse events, Cardiac issues, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial evaluates the long-term safety and tolerability of XEN496, an experimental treatment for children with KCNQ2 developmental and epileptic encephalopathy (KCNQ2-DEE). It includes children who participated in an earlier study, either continuing with XEN496 or switching from a placebo to XEN496. Eligible participants must have completed the initial study, and their caregivers must reliably keep records and administer the medication. As a Phase 3 trial, this is the final step before FDA approval, offering a chance to contribute to a potentially groundbreaking treatment for KCNQ2-DEE.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications, but it mentions that you cannot participate if you need to take any disallowed medications during the study.

Is there any evidence suggesting that XEN496 is likely to be safe for humans?

Research has shown that XEN496 is generally safe and well-tolerated. Studies found no major safety concerns during physical or neurological exams, and no issues arose with heart, lab, or urine tests.

In healthy adults, XEN496 demonstrated a safety profile similar to Potiga®, an already approved medication, indicating a known and acceptable level of safety.

While these findings are promising, they come from earlier studies. Individual experiences may vary, so discussing any concerns with a doctor is advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Ezogabine, marketed as XEN496, is unique because it targets the KCNQ2 potassium channels, which play a crucial role in brain activity. Unlike typical treatments for KCNQ2 developmental and epileptic encephalopathy (DEE) that focus on general seizure suppression with medications like valproic acid or levetiracetam, XEN496 directly addresses the genetic mutation at the root of the condition. This targeted approach could offer more effective management of seizures with potentially fewer side effects. Researchers are excited because this precision-targeting method may improve quality of life for children affected by this rare and challenging form of epilepsy.

What evidence suggests that XEN496 might be an effective treatment for KCNQ2-DEE?

Research shows that XEN496, a new version of the drug ezogabine, may help treat KCNQ2 developmental and epileptic encephalopathy (KCNQ2-DEE). Studies have found that XEN496 dissolves better in the body, leading to more even absorption compared to older versions like Potiga®. This can result in more consistent treatment effects and possibly better outcomes. Additionally, XEN496 has demonstrated similar safety and effectiveness to Potiga®, which is reassuring since Potiga® has been used to treat epilepsy before. In this trial, participants will join one of two groups: one group will receive XEN496 only, while the other will transition from placebo to XEN496. The goal is for XEN496 to reduce seizures and improve other outcomes for children with KCNQ2-DEE. ^{1 4 6 7 8}

Who Is on the Research Team?

Study Director

Principal Investigator

Xenon Pharmaceuticals Inc.

Are You a Good Fit for This Trial?

Inclusion Criteria

The caregiver is willing and able to be compliant with diary completion, visit schedule, and study drug administration.

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.

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 conditions that were specified as exclusion criteria in the primary study, XPF-009-301.

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 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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Blinded Transition/Titration

A 24-day blinded transition/titration period where subjects transition from the primary study to the open-label extension, maintaining blinding to treatment allocation.

24 days

1 visit (in-person)

Open-label Treatment

Participants receive the open-label study drug at their optimal dose for long-term safety and tolerability assessment.

35 months

Regular visits every 3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• XEN496

How Is the Trial Designed?

Group I: Group 2: Placebo to XEN496 Experimental Treatment 1 Intervention

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.

Group II: Group 1: XEN496 only Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

Xenon Pharmaceuticals Inc.

Lead Sponsor

Trials

19

Recruited

3,400+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9095778/

Pharmacokinetics of XEN496, a Novel Pediatric Formulation ... Furthermore, these data suggest that XEN496 likely has a better dissolution profile, resulting in more uniform absorption of ezogabine and a smoother PK ...

2. xenon-pharma.com xenon-pharma.com/wp-content/uploads/2022/12/Butterfield2FinalWeb.pdf

Design of a Clinical Trial to Determine the Efficacy of ... improve outcomes beyond seizure reduction ... ▫ The electronic seizure diary facilitates data capture, allows remote monitoring, and provides a.

3. aesnet.org aesnet.org/abstractslisting/pharmacokinetic-(pk)-and-food-effect-assessment-of-xen496--a-pediatric-formulation-of-ezogabine--in-healthy-adults-and-retrospective-pk-and-safety-comparison-with-potiga%C2%AE

a-Pediatric-Formulation-of-Ezogabine--in-Healthy-Adults-and ... When compared to historical Potiga® data, XEN496 exhibited comparable biopharmaceutical and safety performance, suggesting that no ...

4. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/56/NCT04912856/Prot_SAP_001.pdf

protocol An international, multicenter, open-label extension (OLE) study to assess the long-term safety, tolerability, and efficacy of XEN496 in pediatric subjects ...

5. neurology.org neurology.org/doi/10.1212/WNL.94.15_supplement.4918

Pharmacokinetic and Food Effect Assessment of XEN496 ... The results from this study are expected to provide guidance and facilitate dose selection for a planned XEN496 pediatric study in KCNQ2-DEE.

6. xenon-pharma.com xenon-pharma.com/wp-content/uploads/2022/06/EILAT2022_XEN1101-496_5-18-22_CK_JR_Final.pdf

XEN1101 and XEN496 ▫ There were no safety signals of concern from physical or neurologic exams. ▫ No signals of concern from ECGs, safety labs or urinalysis. ▫ There was no ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04912856

An Open-Label Extension of the Study XEN496 ... To assess the long-term safety and tolerability of XEN496 in pediatric subjects with KCNQ2 developmental and epileptic encephalopathy (KCNQ2-DEE) who had ...

8. xenon-pharma.com xenon-pharma.com/wp-content/uploads/2020/05/Cadieux_AAN-Poster-FINAL.pdf

Pharmacokinetic and Food Effect Assessment of XEN496 In this Phase 1 PK and safety study in healthy adult volunteers, XEN496 was generally safe and well-tolerated. • Overall, XEN496's safety profile was comparable ...