An Open-label Study of XEN1101 in Epilepsy (X-TOLE4)

A Multicenter, Open-label, Long-term, Safety, Tolerability, and Efficacy Study of XEN1101 in Subjects Diagnosed With Epilepsy

This study will evaluate the long term safety, tolerability, PK, and efficacy of XEN1101 25 mg QD taken orally in subjects with Focal Onset Seizures (FOS) or Primary Generalized Tonic-Clonic Seizures (PGTCS) for the treatment of seizures for up to 3 years.

Study Overview

• Status: Enrolling by invitation
• Conditions: Focal Epilepsy; Tonic-Clonic Seizures
• Intervention / Treatment: Drug: XEN1101

Detailed Description

This is an Open Label Extension study of the following Phase 3 clinical studies: XPF-010-301 (X-TOLE2), XPF-010-302 (X-TOLE3), and XPF-010-303 (X-ACKT). This study will evaluate the long term safety, tolerability, PK, and efficacy of XEN1101 25 mg QD taken orally once daily (QD) in subjects with FOS or PGTCS for the treatment of seizures for up to 3 years. Subjects who successfully completed and did not terminate early from one of the antecedent studies (X-TOLE2, X-TOLE3, or X-ACKT) are eligible to participate in X-TOLE4.

Following enrollment into X-TOLE4, subjects will undergo a treatment period of up to 3 years, during which there will be a visit at 2-, 4-, and 13-weeks post-entry, with subsequent visits occurring at 13 week intervals during the first year, and then at 26-week intervals (with a telephone call in between) until dosing is completed. All subjects will be initially assigned to receive 25 mg QD of XEN1101. Subjects will be instructed to orally take XEN1101 once daily with an evening meal. Subjects will be expected to keep a daily seizure eDiary with a minimum of 80% compliance for the duration of the extension study (reporting on ≥80% of days between visits).

Upon completion of dosing at the end of the treatment period, there will be an 8-week follow up period.

• Study Type: Interventional
• Enrollment (Estimated): 880
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Lethbridge, Alberta, Canada, T1J 0N9
      • Center For Neurologic Research
• Poland
  • Lublin, Poland, 20-064
    • NZOZ Neuromed M. i M.
• Spain
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Clinical Trials, Inc
  • Florida
    • Orlando, Florida, United States, 32806
      • Research Institute of Orlando, LLC
    • Pensacola, Florida, United States, 10021
      • Panhandle Research & Medical Clinic
  • Hawaii
    • Honolulu, Hawaii, United States, 96817
      • Hawaii Pacific Neuroscience
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Kentucky Clinic
  • Maine
    • Scarborough, Maine, United States, 04074
      • MMP Neurology
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Mid-Atlantic Epilepsy and Sleep Center
  • Michigan
    • East Lansing, Michigan, United States, 48824
      • Michigan State University
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Northeast Epilepsy Group
  • New York
    • Buffalo, New York, United States, 14226
      • Dent Neurosciences Research Center
    • New York, New York, United States, 10016
      • New York University Comprehensive Epilepsy Center
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Clinical Neurosciences Center
  • Washington
    • Seattle, Washington, United States, 10012
      • University of Washington Main Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subject must be properly informed of the nature and risks of the study and give informed consent in writing, prior to entering the study.
2. Subject must have successfully completed the DBP and have not terminated early from Study X-TOLE2, X-TOLE3, or X-ACKT, met all eligibility requirements, and had no important protocol deviations (in the opinion of the sponsor) or AEs (in the opinion of the investigator) that would preclude the subject's entry into the long-term extension study.
3. In the opinion of the investigator, the subject is able to understand verbal and written instructions and will adhere to all study schedules and requirements.
4. Subject is able to keep accurate seizure diaries.

Exclusion Criteria:

1. Subject met any of the withdrawal criteria while in Study X-TOLE2, X-TOLE3, or X-ACKT.
2. Subject has any medical condition, personal circumstance, or ongoing AE (from Study X-TOLE2, X-TOLE3, or X-ACKT) that, in the opinion of the investigator, exposes the subject to unacceptable risk by participating in the study, or prevents adherence to the protocol.
3. Subject is planning to enter a clinical study with a different investigational drug or planning to use any experimental device for treatment of epilepsy or any other medical condition during the study and until 28 days after completion of this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: XEN1101 25 mg/day	Drug: XEN1101; XEN1101 capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The adverse events	To assess the safety and tolerability of XEN1101	From the start of treatment in the OLE study through 8 weeks after the last dose.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in monthly seizure rate	Percent change in monthly seizure rate recorded at baseline (in the antecedent studies) compared to each 4-week assessment period in the treatment period in X-TOLE4.	From baseline through the active extension treatment (Week 156).
Proportion of responders	Proportion of responders (subjects experiencing ≥50% reduction in seizure frequency from baseline) in each consecutive 4-week assessment period of the treatment period of the OLE study.	From baseline through the active extension treatment (Week 156).
Change in Clinical Global Impression of Severity (CGI-S)	Improvement in Clinical Global Impression of Severity (CGI-S) scores over time.	From baseline through the active extension treatment (Week 156).
Change in Patient Global Impression of Severity (PGI-S)	Improvement in Patient Global Impression of Severity (PGI-S) scores over time.	From baseline through the active extension treatment (Week 156).
Change in Quality of Life in Epilepsy Inventory (QOLIE-31)	Change in the 31-Item Quality of Life in Epilepsy Inventory (QOLIE-31) over time.	From baseline through the active extension treatment (Week 156).

Collaborators and Investigators

• Sponsor: Xenon Pharmaceuticals Inc.
• Collaborators: Worldwide Clinical Trials
• Investigators: Study Director: Medical Director, Xenon Pharmaceuticals Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 25, 2023
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: January 13, 2023
• First Submitted That Met QC Criteria: February 7, 2023
• First Posted (Actual): February 8, 2023

Study Record Updates

• Last Update Posted (Actual): March 5, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Epilepsy; Seizures
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Epilepsy; Seizures; Epilepsies, Partial
• Other Study ID Numbers: XPF-010-304

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No