An Open-label Study of XEN1101 in Epilepsy

Focal Epilepsy Clinical Trial

— X-TOLE4  

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05718817
• Other study ID #: XPF-010-304
• Status: Enrolling by invitation
• Phase: Phase 3
• Start date: April 25, 2023
• Est. completion date: September 2028

Study information

• Verified date: March 2024
• Source: Xenon Pharmaceuticals Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 880
• Est. completion date: September 2028
• Est. primary completion date: July 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Epilepsies, Partial
• Epilepsy
• Focal Epilepsy
• Seizures

Intervention

Drug:
• XEN1101
XEN1101 capsules

Locations

Country	Name	City	State
Canada	Center for Neurologic Research	Lethbridge	Alberta
Poland	NZOZ Neuromed M. i M.	Lublin
Spain	Hospital Clinico San Carlos	Madrid
United States	Mid-Atlantic Epilepsy and Sleep Center	Bethesda	Maryland
United States	Dent Neurosciences Research Center	Buffalo	New York
United States	Michigan State University	East Lansing	Michigan
United States	Northeast Epilepsy Group	Hackensack	New Jersey
United States	Hawaii Pacific Neuroscience	Honolulu	Hawaii
United States	Kentucky Clinic	Lexington	Kentucky
United States	Clinical Trials, Inc	Little Rock	Arkansas
United States	New York University Comprehensive Epilepsy Center	New York	New York
United States	Research Institute of Orlando, LLC	Orlando	Florida
United States	Panhandle Research & Medical Clinic	Pensacola	Florida
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	University of Utah Clinical Neurosciences Center	Salt Lake City	Utah
United States	MMP Neurology	Scarborough	Maine
United States	University of Washington Main Hospital	Seattle	Washington
United States	SUNY Upstate Medical University	Syracuse	New York

Sponsors (2)

Lead Sponsor	Collaborator
Xenon Pharmaceuticals Inc.	Worldwide Clinical Trials

Countries where clinical trial is conducted

United States,  Canada,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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).
Secondary	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).
Secondary	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).
Secondary	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).
Secondary	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).