Clinical trial NCT05716100: A Randomized Study of XEN1101 Versus Placebo in Focal-Onset Seizures (X-TOLE3)
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Focal Onset Seizures
Keywords: Epilepsy
Lead sponsor: Xenon Pharmaceuticals Inc.
Sponsor class: INDUSTRY
Collaborators: name: Worldwide Clinical Trials
First posted: 2023-02-08
Enrollment: 360
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

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.

Primary outcomes:
measure: Median percent change (MPC) in focal seizure frequency from baseline to DBP for XEN1101 versus placebo.
timeFrame: From baseline through to the double blind period (week 12).
Secondary outcomes:
measure: Proportion of subjects experiencing ≥50% reduction in focal seizure frequency from baseline through the DBP for XEN1101 versus placebo.
timeFrame: From baseline through to the double blind period (week 12).
measure: MPC in weekly (7 days) focal seizure frequency from baseline to Week 1 for XEN1101 versus placebo.
timeFrame: From baseline through to the week 1.
measure: Proportion of subjects experiencing "at least much improved" (including "much" and "very much improved") in Patient Global Impression of Change (PGI-C).
timeFrame: From baseline through to the double blind period (week 12).
measure: To assess adverse events as criteria for safety and tolerability of XEN1101.
timeFrame: From screening through to 56 days post-final dose
Other outcomes:
Locations:
city: Downey
country: United States
facility: Rancho Research Institute
state: California
city: Orange
country: United States
facility: University of California Irvine Health
state: California
city: Springfield
country: United States
facility: Southern Illinois University School of Medicine
state: Illinois
city: Detroit
country: United States
facility: 9D University Health Center
state: Michigan
city: Woodmere
country: United States
facility: Five Towns Neuroscience Research
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: OhioHealth
state: Ohio
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Salt Lake City
country: United States
facility: University of Utah Clinical Neurosciences Center
state: Utah
city: Buenos Aires
country: Argentina
facility: Hospital Ramos Mejia
city: Buenos Aires
country: Argentina
facility: Hospital De Alta Complejidad en Red el Cruce
city: Buenos Aires
country: Argentina
facility: Policlinico Lomas
city: Buenos Aires
country: Argentina
facility: Hospital Italiano
city: Buenos Aires
country: Argentina
facility: STAT Resarch S.A.
city: C.a.b.a.
country: Argentina
facility: CENyR Centro de Especialidades Neurologicas y Rehabilitacion
city: C.a.b.a.
country: Argentina
facility: FLENI
city: San Miguel De Tucumán
country: Argentina
facility: Sanatori del Sur S.A.
city: Innsbruck
country: Austria
facility: University Hospital Innsbruck
city: Salzburg
country: Austria
facility: Universitätsklinik für Neurologie
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc (UCL)
city: Ghent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Sofia
country: Bulgaria
facility: MHATNPsy Sveti Naum EAD
city: Sofia
country: Bulgaria
facility: Medical center OPHTHA-NEURO
city: Santiago
country: Chile
facility: Clinica Universidad de Los Andes
city: Santiago
country: Chile
facility: Centro de Investigacion Clinica UC
city: Santiago
country: Chile
facility: CINSAN
city: Viña Del Mar
country: Chile
facility: Hospital Clínico Viña del Mar
city: Osijek
country: Croatia
facility: University Hospital Center Osijek
city: Rijeka
country: Croatia
facility: Clinical Hospital Center Rijeka, Klinika za Neurologiju
city: Zagreb
country: Croatia
facility: Poliklinika Bonifarm
city: Zagreb
country: Croatia
facility: University Hospital Center Zagreb
city: Zagreb
country: Croatia
facility: Poliklinika LF MEDICAL
city: Hradec Králové
country: Czechia
facility: EUC Hradec Kralove Clinic
city: Prague
country: Czechia
facility: Nemocnicni lekarna FN Motol / Motol University Hospital
city: Prague
country: Czechia
facility: Forbeli s.r.o.
city: Bron
country: France
facility: Hopital Neurologique Pierre Wertheimer
city: Lille
country: France
facility: Centre Hospitalier Universitaire de Lille (CHU de Lille)
city: Paris
country: France
facility: Hôpital de la Pitié Salpêtrière
city: Paris
country: France
facility: Hôpital Fondation A. de Rothschild
city: Rennes
country: France
facility: Chu de Rennes Hôpital Pontchaillou
city: Strasbourg
country: France
facility: Hôpital de Hautepierre
city: Aachen
country: Germany
facility: Universitätsklinikum Aachen
city: Budapest
country: Hungary
facility: Semmelweis Egyetem, Idegsebészeti és Neurointervenciós Klinika
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center
city: Reẖovot
country: Israel
facility: Kaplan Medical Center
city: Tel Aviv
country: Israel
facility: The Tel Aviv Sourasky Medical Center
city: Ancona
country: Italy
facility: Ospedali Riuniti di Ancona
city: Bari
country: Italy
facility: Università degli studi di Bari Aldo Moro
city: Benito Juárez
country: Mexico
facility: Grupo Medico Camino
city: Mexico City
country: Mexico
facility: Human Science Research Trials
city: Sinaloa
country: Mexico
facility: Neurocencias Esudios Clinicos S.C.
city: Heeze
country: Netherlands
facility: Kempenhaeghe
city: Gdańsk
country: Poland
facility: COPERNICUS Podmiot Leczniczy
city: Lublin
country: Poland
facility: NZOZ Neuromed M. i M. Nastaj Sp. P.
city: Nowa Sól
country: Poland
facility: Twoja Przychodnia Nowosolskie Centrum Medyczne
city: Warsaw
country: Poland
facility: MTZ Clinical Research Powered by Pratia
city: Coimbra
country: Portugal
facility: Centro Hospitalar Universitário de Coimbra - CHUC
city: Guimarães
country: Portugal
facility: Hospital da Senhora da Oliveira
city: Lisbon
country: Portugal
facility: Centro Hospitalar de Lisboa Norte
city: Lisbon
country: Portugal
facility: Centro Hospitalar Lisboa Ocidental
city: Porto
country: Portugal
facility: Centro Hospitalar Universitário de Santo António
city: Porto
country: Portugal
facility: Hospital Pedro Hispano
city: Santa Maria Da Feira
country: Portugal
facility: Centro Hospitalar de Entre o Douro e Vouga
city: Barakaldo
country: Spain
facility: Hospital Universitario Cruces
Study officials:
affiliation: Xenon Pharmaceuticals Inc.
name: Xenon Medical Director
role: STUDY_DIRECTOR
References: