Brief Summary
This study will evaluate the long term safety, tolerability, pharmacokinetics (PK), and efficacy of XEN1101 in subjects with Focal Onset Seizures (FOS) or Primary Generalized Tonic-Clonic Seizures (PGTCS) for the treatment of seizures for up to 3 years.
Brief Title
An Open-label Study of XEN1101 in Epilepsy
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 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.
Subjects will be initially assigned to XEN1101 as follows:
* 25 mg QD for subjects aged ≥18 years
* For subjects aged ≥12 and \<18 years
* 15 mg QD for those
* who weigh \<45 kg at the start of the X-TOLE4 study
* who weighed \<45 kg during the X-ACKT study
* who weighed ≥45 kg at randomization in the X-ACKT study and had dose reduction(s) for intolerability
* 25 mg QD for all others
Subjects will be instructed to orally take XEN1101 once daily (QD) 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.
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.
Subjects will be initially assigned to XEN1101 as follows:
* 25 mg QD for subjects aged ≥18 years
* For subjects aged ≥12 and \<18 years
* 15 mg QD for those
* who weigh \<45 kg at the start of the X-TOLE4 study
* who weighed \<45 kg during the X-ACKT study
* who weighed ≥45 kg at randomization in the X-ACKT study and had dose reduction(s) for intolerability
* 25 mg QD for all others
Subjects will be instructed to orally take XEN1101 once daily (QD) 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.
Categories
Completion Date
Completion Date Type
Estimated
Conditions
Focal Epilepsy
Tonic-Clonic Seizures
Eligibility Criteria
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 (for adult subjects) and for adolescent subject's parent/legal guardian and subject gives informed consent or assent in writing prior to entering the study.
2. Subject must have successfully completed the double-blind treatment period (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 adverse events (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.
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 (for adult subjects) and for adolescent subject's parent/legal guardian and subject gives informed consent or assent in writing prior to entering the study.
2. Subject must have successfully completed the double-blind treatment period (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 adverse events (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.
Inclusion Criteria
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 (for adult subjects) and for adolescent subject's parent/legal guardian and subject gives informed consent or assent in writing prior to entering the study.
2. Subject must have successfully completed the double-blind treatment period (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 adverse events (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.
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 (for adult subjects) and for adolescent subject's parent/legal guardian and subject gives informed consent or assent in writing prior to entering the study.
2. Subject must have successfully completed the double-blind treatment period (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 adverse events (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.
Gender
All
Gender Based
false
Keywords
Epilepsy
Seizures
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
12 Years
NCT Id
NCT05718817
Org Class
Industry
Org Full Name
Xenon Pharmaceuticals Inc.
Org Study Id
XPF-010-304
Overall Status
Enrolling by invitation
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Multicenter, Open-label, Long-term, Safety, Tolerability, and Efficacy Study of XEN1101 in Subjects Diagnosed With Epilepsy
Primary Outcomes
Outcome Description
To assess the safety and tolerability of XEN1101
Outcome Measure
The adverse events
Outcome Time Frame
From the start of treatment in the open-label extension (OLE) study through 8 weeks after the last dose.
Secondary Ids
Secondary Id
2022-502282-24-00
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
From baseline through the active extension treatment (Week 156).
Outcome Measure
Change in monthly seizure rate
Outcome Description
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.
Outcome Time Frame
From baseline through the active extension treatment (Week 156).
Outcome Measure
Proportion of responders
Outcome Description
Improvement in Clinical Global Impression of Severity (CGI-S) scores over time.
Outcome Time Frame
From baseline through the active extension treatment (Week 156).
Outcome Measure
Change in Clinical Global Impression of Severity (CGI-S)
Outcome Description
Improvement in Patient Global Impression of Severity (PGI-S) scores over time.
Outcome Time Frame
From baseline through the active extension treatment (Week 156).
Outcome Measure
Change in Patient Global Impression of Severity (PGI-S)
Outcome Description
Change in the 31-Item Quality of Life in Epilepsy Inventory (QOLIE-31) over time.
Outcome Time Frame
From baseline through the active extension treatment (Week 156).
Outcome Measure
Change in Quality of Life in Epilepsy Inventory (QOLIE-31)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Child
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
12
Investigators
Investigator Type
Principal Investigator
Investigator Name
Jonathan Gursky
Investigator Email
jgursky@montefiore.org