Clinical trial NCT05614063: A Randomized Study of XEN1101 Versus Placebo in Focal-Onset Seizures
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: 2022-11-14
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-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.

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 monthly (28 days) 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 monthly (28 days) 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: Mobile
country: United States
facility: Strada Patient Care Center
state: Alabama
city: Phoenix
country: United States
facility: Xenoscience
state: Arizona
city: Phoenix
country: United States
facility: St. Joseph's Hospital
state: Arizona
city: Tucson
country: United States
facility: University of Arizona, Health Sciences Center
state: Arizona
city: Little Rock
country: United States
facility: Clinical Trials, Inc
state: Arkansas
city: Los Angeles
country: United States
facility: Brain Science Research Institute
state: California
city: Sacramento
country: United States
facility: University of California, David Clinical & Translational Science Center Clinical Research (CCRC)
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center (CPMC)
state: California
city: Aurora
country: United States
facility: Anschutz Health Sciences
state: Colorado
city: Coral Gables
country: United States
facility: Floridian Community Research Center
state: Florida
city: Miami
country: United States
facility: Serenity Research
state: Florida
city: Orlando
country: United States
facility: Research Institute of Orlando, LLC
state: Florida
city: Pensacola
country: United States
facility: Panhandle Research & Medical Clinic
state: Florida
city: Port Charlotte
country: United States
facility: Medsol Clinical Research Center
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Weston
country: United States
facility: Encore Medical Research of Weston, LLC
state: Florida
city: Atlanta
country: United States
facility: Emory Brain Health Center
state: Georgia
city: Suwanee
country: United States
facility: Georgia Neurology and Sleep Medicine Associates
state: Georgia
city: Honolulu
country: United States
facility: Hawaii Pacific Neuroscience
state: Hawaii
city: Boise
country: United States
facility: Consultants in Epilepsy and Neurology
state: Idaho
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University, IU Health Partners, Adult Neurology Clinic
state: Indiana
city: Kansas City
country: United States
facility: The University of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: Bluegrass Epilepsy Research, LLC
state: Kentucky
city: Lexington
country: United States
facility: University of Kentucky, Dept. of Neurology
state: Kentucky
city: Scarborough
country: United States
facility: MaineHealth Neurology - Scarborough
state: Maine
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Bethesda
country: United States
facility: Mid-Atlantic Epilepsy and Sleep Center
state: Maryland
city: Clinton
country: United States
facility: MedStar Health Research Institute
state: Maryland
city: Hyattsville
country: United States
facility: Medstar Health Research Institute
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Worcester
country: United States
facility: UMass Memorial Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: East Lansing
country: United States
facility: Michigan State University
state: Michigan
city: Grand Rapids
country: United States
facility: Cornwell Health
state: Michigan
city: Burnsville
country: United States
facility: Minneapolis Clinic of Neurology
state: Minnesota
city: Saint Louis
country: United States
facility: Saint Louis University Medical School - Neurosciences Clinical Research Unit
state: Missouri
city: Saint Louis
country: United States
facility: Washington University, St. Louis
state: Missouri
city: Hackensack
country: United States
facility: Northeast Epilepsy Group
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Buffalo
country: United States
facility: Dent Neurosciences Research Center
state: New York
city: New York
country: United States
facility: NYU Comprehensive Epilepsy Center (CEC)
state: New York
city: New York
country: United States
facility: Weill Cornell Medicine/ New York-Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Charlotte
country: United States
facility: Onsite Clinical Solutions, LLC
state: North Carolina
city: Durham
country: United States
facility: Duke Neurology
state: North Carolina
city: Raleigh
country: United States
facility: Meridian Clinical Research, LLC
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Akron
country: United States
facility: Summa Health
state: Ohio
city: Toledo
country: United States
facility: University of Toledo Medical Center
state: Ohio
city: Portland
country: United States
facility: Providence Brain & Spine Institute
state: Oregon
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Austin
country: United States
facility: Austin Epilepsy Care Center (AECC)
state: Texas
city: El Paso
country: United States
facility: ANESC Research
state: Texas
city: Houston
country: United States
facility: UT Physicians Epilepsy Clinic
state: Texas
city: San Antonio
country: United States
facility: UT Health San Antonio
state: Texas
city: Roanoke
country: United States
facility: Carilion Clinic - Neurology
state: Virginia
city: Virginia Beach
country: United States
facility: Sentara Neurology Specialists
state: Virginia
city: Seattle
country: United States
facility: University of Washington Main Hospital
state: Washington
city: Milwaukee
country: United States
facility: Aurora St. Luke's Medical Center
state: Wisconsin
city: Buenos Aires
country: Argentina
facility: INECO and Favoloro Fundation
city: Buenos Aires
country: Argentina
facility: Hospital General de Agudos J.M. Ramos Mejia
city: Buenos Aires
country: Argentina
facility: STAT Research S.A.
city: Buenos Aires
country: Argentina
facility: Hospital Italiano
city: Caba
country: Argentina
facility: CENyR
city: Córdoba
country: Argentina
facility: Hospital Córdoba
city: Tucumán
country: Argentina
facility: Sanatorio del Sur S.A.
city: Fitzroy
country: Australia
facility: St Vincent's Hospital Melbourne
state: Melbourne
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital (RAPH)
state: New South Wales
city: Sydney
country: Australia
facility: Prince of Wales Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Southern Neurology
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: The University of Queensland (UQ) - Mater Research Institute (MRI)
state: Queensland
city: Heidelberg
country: Australia
facility: Austin Health Pharmacy Clinical Trials
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital (Alfred Health)
state: Victoria
city: Melbourne
country: Australia
facility: The Royal Melbourne Hospital
city: Blagoevgrad
country: Bulgaria
facility: MHAT Puls AD
city: Sofia
country: Bulgaria
facility: First Multiprofile Hospital for Active Treatment
city: Lethbridge
country: Canada
facility: Center For Neurologic Research
state: Alberta
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Montréal
country: Canada
facility: Le Centre Hospitalier de l'Universite' de Montreal (CHUM)
state: Quebec
city: Santiago
country: Chile
facility: Centro de investigación Clinica UC
city: Viña Del Mar
country: Chile
facility: Hospital Clínico Vina del Mar
city: Prague
country: Czechia
facility: FORBELI s.r.o., Neurologicka ambulance
city: Tbilisi
country: Georgia
facility: American Hospital Network LLC
city: Tbilisi
country: Georgia
facility: Institute of Neurology and Neuropsychology
city: Berlin
country: Germany
facility: Vivantes Humboldt Klinikum
city: Bielefeld
country: Germany
facility: Epilepsy Center Bethel
city: Bonn
country: Germany
facility: Universitatsklinikum Bonn
city: Frankfurt
country: Germany
facility: Epilepsiezentrum Frankfurt Rhein-Main
city: Freiburg im Breisgau
country: Germany
facility: University Medical Center Freiburg
city: Marburg
country: Germany
facility: Philipps-Universität Marburg
city: Munich
country: Germany
facility: LMU Munich, Department of Neurology
city: Radeberg
country: Germany
facility: Epilepsiezentrum Kleinwachau Gemeinnutzige eGmbH
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Ulm
country: Germany
facility: Universitatsklinik fur neurologie, universitats - und Rehabilitationskliniken Ulm
city: Dublin
country: Ireland
facility: Beaumont Hospital
city: Bologna
country: Italy
facility: Istituto delle Scienze Neurologiche di Bologna
city: Pescara
country: Italy
facility: Università Degli Studi Gabriele d'Annunzio Di Chieti
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
city: Roma
country: Italy
facility: Ospedale Pediatrico Bambino Gesu
city: Rome
country: Italy
facility: Azienda Ospedaliero-Universitaria Policlinico Umberto I
city: Riga
country: Latvia
facility: Pauls Stradina Clinical university hospital
city: Riga
country: Latvia
facility: Riga East University Hospital
city: Sinaloa
country: Mexico
facility: Neurocencias Esudios Clinicos SC
city: Auckland
country: New Zealand
facility: University of Auckland
city: Hamilton
country: New Zealand
facility: Waikato Hospital
city: Bydgoszcz
country: Poland
facility: Centrum Medyczne Neuromed
city: Katowice
country: Poland
facility: NZOZ Novo-Med
city: Lublin
country: Poland
facility: Clinical Best Solutions
city: Nowa Sól
country: Poland
facility: Twoja Przychodnia NCM
city: Warszawa
country: Poland
facility: Neurosphera Sp. z o.o.
city: Porto
country: Portugal
facility: Unidade Local de Saúde de São João
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: Barcelona
country: Spain
facility: Unitat d'Assaigs Clínics. Servei de Farmàcia
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Ruber Internacional
city: Madrid
country: Spain
facility: Hospital Vithas La Milagrosa
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: IIS-Fundacion Jimenez Diaz/Farmacia
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Málaga
country: Spain
facility: Hospital Regional De Malaga
city: Valencia
country: Spain
facility: Hospital Universitario y Politecnico La Fe
city: Valladolid
country: Spain
facility: Hospital Clínico Universitario Valladolid
city: Wakefield
country: United Kingdom
facility: Mid Yorkshire Hospitals NHS Trust
state: West Yorkshire
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
city: Dundee
country: United Kingdom
facility: Ninewells Hospital and Medical School
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust
city: London
country: United Kingdom
facility: St. George's Hospital NHS Foundation Trust
city: London
country: United Kingdom
facility: Royal London Hospital for Integrated Medicine
city: Oxford
country: United Kingdom
facility: John Radcliffe Hospital
city: Salford
country: United Kingdom
facility: Northern Care Alliance NHS Foundation Trust, Salford Care Organisation
Study officials:
affiliation: Xenon Pharmaceuticals Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: