Brief Summary
The X-TOLE2 Phase 3 clinical trial is a randomized, double-blind, placebo-controlled study that will evaluate the clinical efficacy, safety and tolerability of XEN1101 administered as adjunctive therapy in focal-onset seizures.
Brief Title
A Randomized Study of XEN1101 Versus Placebo in Focal-Onset Seizures
Detailed Description
Approximately 360 subjects will be randomized in a blinded manner to one of two active treatment groups or placebo in a 1:1:1 fashion (XEN1101 25 mg : 15 mg : Placebo). Eligible subjects will have up to 9.5 weeks of baseline to assess frequency of seizures, followed by 12 weeks of blinded treatment. In order to be included in the study, subjects must be treated with a stable dose of 1 to 3 allowable antiseizure medications (ASMs) for at least one month prior to screening, during baseline, and throughout the double-blind treatment period (DBP) of the study. During the DBP, subjects will be instructed to orally take XEN1101 or placebo once daily with an evening meal.
Subjects who complete the 12-week DBP will have the opportunity to qualify and enroll in a separate open-label extension (OLE) study for continued treatment with XEN1101. Subjects who do not enroll in the OLE will enter a 8-week post treatment follow-up period.
Subjects who complete the 12-week DBP will have the opportunity to qualify and enroll in a separate open-label extension (OLE) study for continued treatment with XEN1101. Subjects who do not enroll in the OLE will enter a 8-week post treatment follow-up period.
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
1-604-484-3300
Central Contact Email
XenonCares@xenon-pharma.com
Completion Date
Completion Date Type
Estimated
Conditions
Focal Onset Seizures
Eligibility Criteria
Inclusion Criteria:
* Be properly informed of the nature and risks of the study and give informed consent in writing, prior to entering the study
* Diagnosis (≥2 years) of focal epilepsy according to the International League Against Epilepsy (ILAE) Classification of Epilepsy (2017). Subject must have had adequate trials of at least 2 ASMs, which were given (and tolerated) at adequate therapeutic doses, without achieving sustained seizure freedom.
* Treatment with a stable dose of 1 to 3 allowable current ASMs for at least one month prior to screening, during baseline, and throughout the duration of the DBP
* Able to keep accurate seizure diaries
Exclusion Criteria:
* Previously documented electroencephalogram which shows any pattern not consistent with focal etiology of seizures.
* History of focal aware non-motor seizures only, non-epileptic psychogenic seizure, primary generalized seizure, developmental and epileptic encephalopathy, including Lennox-Gastaut syndrome.
* Seizures secondary to drug or alcohol use, ongoing infection, neoplasia, demyelinating disease, degenerative neurological disease, metabolic illness, progressive structural lesion, encephalopathy, or progressive central nervous system (CNS) disease.
* History of status epilepticus or repetitive seizures within the 12-month period preceding Visit 1 where the individual seizures cannot be counted.
* History of neurosurgery for seizures \<1 year prior to Visit 1, or radiosurgery \<2 years prior to enrollment.
* Any medical condition or personal circumstance that, in the opinion of the investigator, exposes the subject to unacceptable risk by participating in the study or prevents adherence to the protocol.
* Be properly informed of the nature and risks of the study and give informed consent in writing, prior to entering the study
* Diagnosis (≥2 years) of focal epilepsy according to the International League Against Epilepsy (ILAE) Classification of Epilepsy (2017). Subject must have had adequate trials of at least 2 ASMs, which were given (and tolerated) at adequate therapeutic doses, without achieving sustained seizure freedom.
* Treatment with a stable dose of 1 to 3 allowable current ASMs for at least one month prior to screening, during baseline, and throughout the duration of the DBP
* Able to keep accurate seizure diaries
Exclusion Criteria:
* Previously documented electroencephalogram which shows any pattern not consistent with focal etiology of seizures.
* History of focal aware non-motor seizures only, non-epileptic psychogenic seizure, primary generalized seizure, developmental and epileptic encephalopathy, including Lennox-Gastaut syndrome.
* Seizures secondary to drug or alcohol use, ongoing infection, neoplasia, demyelinating disease, degenerative neurological disease, metabolic illness, progressive structural lesion, encephalopathy, or progressive central nervous system (CNS) disease.
* History of status epilepticus or repetitive seizures within the 12-month period preceding Visit 1 where the individual seizures cannot be counted.
* History of neurosurgery for seizures \<1 year prior to Visit 1, or radiosurgery \<2 years prior to enrollment.
* Any medical condition or personal circumstance that, in the opinion of the investigator, exposes the subject to unacceptable risk by participating in the study or prevents adherence to the protocol.
Inclusion Criteria
Inclusion Criteria:
* Be properly informed of the nature and risks of the study and give informed consent in writing, prior to entering the study
* Diagnosis (≥2 years) of focal epilepsy according to the International League Against Epilepsy (ILAE) Classification of Epilepsy (2017). Subject must have had adequate trials of at least 2 ASMs, which were given (and tolerated) at adequate therapeutic doses, without achieving sustained seizure freedom.
* Treatment with a stable dose of 1 to 3 allowable current ASMs for at least one month prior to screening, during baseline, and throughout the duration of the DBP
* Able to keep accurate seizure diaries
* Be properly informed of the nature and risks of the study and give informed consent in writing, prior to entering the study
* Diagnosis (≥2 years) of focal epilepsy according to the International League Against Epilepsy (ILAE) Classification of Epilepsy (2017). Subject must have had adequate trials of at least 2 ASMs, which were given (and tolerated) at adequate therapeutic doses, without achieving sustained seizure freedom.
* Treatment with a stable dose of 1 to 3 allowable current ASMs for at least one month prior to screening, during baseline, and throughout the duration of the DBP
* Able to keep accurate seizure diaries
Gender
All
Gender Based
false
Keywords
Epilepsy
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT05614063
Org Class
Industry
Org Full Name
Xenon Pharmaceuticals Inc.
Org Study Id
XPF-010-301
Overall Status
Recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Randomized, Double-blind, Placebo-Controlled, Multicenter Phase 3 Study to Evaluate the Safety, Tolerability, and Efficacy of XEN1101 as Adjunctive Therapy in Focal-Onset Seizures
Primary Outcomes
Outcome Measure
Median percent change (MPC) in monthly (28 days) focal seizure frequency from baseline to DBP for XEN1101 versus placebo.
Outcome Time Frame
From baseline through to the double blind period (week 12)
Secondary Ids
Secondary Id
2022-502000-73-00
Secondary Outcomes
Outcome Time Frame
From baseline through to the double blind period (week 12)
Outcome Measure
Proportion of subjects experiencing ≥50% reduction in monthly (28 days) focal seizure frequency from baseline through the DBP for XEN1101 versus placebo.
Outcome Time Frame
From baseline through to the week 1
Outcome Measure
MPC in weekly (7 days) focal seizure frequency from baseline to Week 1 for XEN1101 versus placebo.
Outcome Time Frame
From baseline through to the double blind period (week 12)
Outcome Measure
Proportion of subjects experiencing "at least much improved" (including "much" and "very much improved") in Patient Global Impression of Change (PGI-C).
Outcome Time Frame
From screening through to 56 days post-final dose.
Outcome Measure
To assess adverse events as criteria for safety and tolerability of XEN1101
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
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Jonathan Gursky
Investigator Email
jgursky@montefiore.org