A Randomized Study of XEN1101 Versus Placebo in Focal-Onset Seizures (X-TOLE3)

Study Overview
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Brief Summary
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The X-TOLE3 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.

Detailed Description
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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.

Official Title
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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

Conditions
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Focal Onset Seizures

Intervention / Treatment
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* Drug: XEN1101
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: XEN1101 25 mg/day<br>XEN1101 25 mg/day | Drug: XEN1101<br>* XEN1101 Capsules<br>|
| Experimental: XEN1101 15 mg/day<br>XEN1101 15 mg/day | Drug: XEN1101<br>* XEN1101 Capsules<br>|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Placebo Capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median percent change (MPC) in focal seizure frequency from baseline to DBP for XEN1101 versus placebo. |  | From baseline through to the double blind period (week 12). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects experiencing ≥50% reduction in focal seizure frequency from baseline through the DBP for XEN1101 versus placebo. |  | From baseline through to the double blind period (week 12). | 
| MPC in weekly (7 days) focal seizure frequency from baseline to Week 1 for XEN1101 versus placebo. |  | From baseline through to the week 1. | 
| Proportion of subjects experiencing at least much improved (including much and very much improved) in Patient Global Impression of Change (PGI-C). |  | From baseline through to the double blind period (week 12). | 
| To assess adverse events as criteria for safety and tolerability of XEN1101. |  | From screening through to 56 days post-final dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epilepsy