A Randomized Study of XEN1101 Versus Placebo in Focal-Onset Seizures
- Registration Number
- NCT05614063
- Lead Sponsor
- Xenon Pharmaceuticals Inc.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 360
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description XEN1101 25 mg/day XEN1101 XEN1101 25 mg/day XEN1101 15 mg/day XEN1101 XEN1101 15 mg/day Placebo Placebo Placebo
- Primary Outcome Measures
Name Time Method Median percent change (MPC) in monthly (28 days) focal seizure frequency from baseline to DBP for XEN1101 versus placebo. From baseline through to the double blind period (week 12)
- Secondary Outcome Measures
Name Time Method Proportion of subjects experiencing ≥50% reduction in monthly (28 days) 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.
Trial Locations
- Locations (130)
Universitatsklinikum Bonn
🇩🇪Bonn, Germany
Hospital Ramón y Cajal
🇪🇸Madrid, Spain
Hospital Ruber Internacional
🇪🇸Madrid, Spain
Hospital Vithas La Milagrosa
🇪🇸Madrid, Spain
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
IIS-Fundacion Jimenez Diaz/Farmacia
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Regional De Malaga
🇪🇸Málaga, Spain
Epilepsy Center Bethel
🇩🇪Bielefeld, Germany
American Hospital Network LLC
🇬🇪Tbilisi, Georgia
Institute of Neurology and Neuropsychology
🇬🇪Tbilisi, Georgia
Vivantes Humboldt Klinikum
🇩🇪Berlin, Germany
Strada Patient Care Center
🇺🇸Mobile, Alabama, United States
Xenoscience
🇺🇸Phoenix, Arizona, United States
St. Joseph's Hospital
🇺🇸Phoenix, Arizona, United States
University of Arizona, Health Sciences Center
🇺🇸Tucson, Arizona, United States
Clinical Trials, Inc
🇺🇸Little Rock, Arkansas, United States
Brain Science Research Institute
🇺🇸Los Angeles, California, United States
University of California, David Clinical & Translational Science Center Clinical Research (CCRC)
🇺🇸Sacramento, California, United States
California Pacific Medical Center (CPMC)
🇺🇸San Francisco, California, United States
Anschutz Health Sciences
🇺🇸Aurora, Colorado, United States
Floridian Community Research Center
🇺🇸Coral Gables, Florida, United States
Serenity Research
🇺🇸Miami, Florida, United States
Research Institute of Orlando, LLC
🇺🇸Orlando, Florida, United States
Panhandle Research & Medical Clinic
🇺🇸Pensacola, Florida, United States
Medsol Clinical Research Center
🇺🇸Port Charlotte, Florida, United States
University of South Florida
🇺🇸Tampa, Florida, United States
Encore Medical Research of Weston, LLC
🇺🇸Weston, Florida, United States
Emory Brain Health Center
🇺🇸Atlanta, Georgia, United States
Georgia Neurology and Sleep Medicine Associates
🇺🇸Suwanee, Georgia, United States
Hawaii Pacific Neuroscience
🇺🇸Honolulu, Hawaii, United States
Consultants in Epilepsy and Neurology
🇺🇸Boise, Idaho, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Indiana University, IU Health Partners, Adult Neurology Clinic
🇺🇸Indianapolis, Indiana, United States
The University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
Bluegrass Epilepsy Research, LLC
🇺🇸Lexington, Kentucky, United States
University of Kentucky, Dept. of Neurology
🇺🇸Lexington, Kentucky, United States
MaineHealth Neurology - Scarborough
🇺🇸Scarborough, Maine, United States
University of Maryland Medical Center
🇺🇸Baltimore, Maryland, United States
Mid-Atlantic Epilepsy and Sleep Center
🇺🇸Bethesda, Maryland, United States
MedStar Health Research Institute
🇺🇸Clinton, Maryland, United States
Medstar Health Research Institute
🇺🇸Hyattsville, Maryland, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
UMass Memorial Medical Center
🇺🇸Worcester, Massachusetts, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Michigan State University
🇺🇸East Lansing, Michigan, United States
Cornwell Health
🇺🇸Grand Rapids, Michigan, United States
Minneapolis Clinic of Neurology
🇺🇸Burnsville, Minnesota, United States
Saint Louis University Medical School - Neurosciences Clinical Research Unit
🇺🇸Saint Louis, Missouri, United States
Washington University, St. Louis
🇺🇸Saint Louis, Missouri, United States
Northeast Epilepsy Group
🇺🇸Hackensack, New Jersey, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States
Dent Neurosciences Research Center
🇺🇸Buffalo, New York, United States
NYU Comprehensive Epilepsy Center (CEC)
🇺🇸New York, New York, United States
Weill Cornell Medicine/ New York-Presbyterian Hospital
🇺🇸New York, New York, United States
Mount Sinai Medical Center
🇺🇸New York, New York, United States
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
Onsite Clinical Solutions, LLC
🇺🇸Charlotte, North Carolina, United States
Duke Neurology
🇺🇸Durham, North Carolina, United States
Meridian Clinical Research, LLC
🇺🇸Raleigh, North Carolina, United States
Wake Forest Baptist Health
🇺🇸Winston-Salem, North Carolina, United States
Summa Health
🇺🇸Akron, Ohio, United States
University of Toledo Medical Center
🇺🇸Toledo, Ohio, United States
Providence Brain & Spine Institute
🇺🇸Portland, Oregon, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States
Temple University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Austin Epilepsy Care Center (AECC)
🇺🇸Austin, Texas, United States
ANESC Research
🇺🇸El Paso, Texas, United States
UT Physicians Epilepsy Clinic
🇺🇸Houston, Texas, United States
UT Health San Antonio
🇺🇸San Antonio, Texas, United States
Carilion Clinic - Neurology
🇺🇸Roanoke, Virginia, United States
Sentara Neurology Specialists
🇺🇸Virginia Beach, Virginia, United States
University of Washington Main Hospital
🇺🇸Seattle, Washington, United States
Aurora St. Luke's Medical Center
🇺🇸Milwaukee, Wisconsin, United States
Hospital General de Agudos J.M. Ramos Mejia
🇦🇷Buenos Aires, Argentina
STAT Research S.A.
🇦🇷Buenos Aires, Argentina
CENyR
🇦🇷Caba, Argentina
Hospital Córdoba
🇦🇷Córdoba, Argentina
Sanatorio del Sur S.A.
🇦🇷Tucumán, Argentina
St Vincent's Hospital Melbourne
🇦🇺Fitzroy, Melbourne, Australia
Royal Prince Alfred Hospital (RAPH)
🇦🇺Camperdown, New South Wales, Australia
Prince of Wales Hospital
🇦🇺Sydney, New South Wales, Australia
Southern Neurology
🇦🇺Sydney, New South Wales, Australia
Westmead Hospital
🇦🇺Westmead, New South Wales, Australia
The University of Queensland (UQ) - Mater Research Institute (MRI)
🇦🇺Brisbane, Queensland, Australia
Austin Health Pharmacy Clinical Trials
🇦🇺Heidelberg, Victoria, Australia
The Alfred Hospital (Alfred Health)
🇦🇺Melbourne, Victoria, Australia
The Royal Melbourne Hospital
🇦🇺Melbourne, Australia
MHAT Puls AD
🇧🇬Blagoevgrad, Bulgaria
First Multiprofile Hospital for Active Treatment
🇧🇬Sofia, Bulgaria
Center For Neurologic Research
🇨🇦Lethbridge, Alberta, Canada
London Health Sciences Centre
🇨🇦London, Ontario, Canada
Le Centre Hospitalier de l'Universite' de Montreal (CHUM)
🇨🇦Montréal, Quebec, Canada
FORBELI s.r.o., Neurologicka ambulance
🇨🇿Prague, Czechia
Epilepsiezentrum Frankfurt Rhein-Main
🇩🇪Frankfurt, Germany
University Medical Center Freiburg
🇩🇪Freiburg im Breisgau, Germany
Philipps-Universität Marburg
🇩🇪Marburg, Germany
LMU Munich, Department of Neurology
🇩🇪Munich, Germany
Epilepsiezentrum Kleinwachau Gemeinnutzige eGmbH
🇩🇪Radeberg, Germany
Universitätsklinikum Tübingen
🇩🇪Tübingen, Germany
Universitatsklinik fur neurologie, universitats - und Rehabilitationskliniken Ulm
🇩🇪Ulm, Germany
Beaumont Hospital
🇮🇪Dublin, Ireland
Istituto delle Scienze Neurologiche di Bologna
🇮🇹Bologna, Italy
Università Degli Studi Gabriele d'Annunzio Di Chieti
🇮🇹Pescara, Italy
Azienda Ospedaliero Universitaria Pisana
🇮🇹Pisa, Italy
Ospedale Pediatrico Bambino Gesu
🇮🇹Roma, Italy
Azienda Ospedaliero-Universitaria Policlinico Umberto I
🇮🇹Rome, Italy
Pauls Stradina Clinical university hospital
🇱🇻Riga, Latvia
Riga East University Hospital
🇱🇻Riga, Latvia
University of Auckland
🇳🇿Auckland, New Zealand
Waikato Hospital
🇳🇿Hamilton, New Zealand
Centrum Medyczne Neuromed
🇵🇱Bydgoszcz, Poland
NZOZ Novo-Med
🇵🇱Katowice, Poland
Clinical Best Solutions
🇵🇱Lublin, Poland
Twoja Przychodnia NCM
🇵🇱Nowa Sól, Poland
Neurosphera Sp. z o.o.
🇵🇱Warszawa, Poland
Unidade Local de Saúde de São João
🇵🇹Porto, Portugal
Hospital Pedro Hispano
🇵🇹Porto, Portugal
Unitat d'Assaigs Clínics. Servei de Farmàcia
🇪🇸Barcelona, Spain
Hospital Universitario y Politecnico La Fe
🇪🇸Valencia, Spain
Hospital Clínico Universitario Valladolid
🇪🇸Valladolid, Spain
Mid Yorkshire Hospitals NHS Trust
🇬🇧Wakefield, West Yorkshire, United Kingdom
University Hospitals Birmingham NHS Foundation Trust
🇬🇧Birmingham, United Kingdom
University Hospital of Wales
🇬🇧Cardiff, United Kingdom
Ninewells Hospital and Medical School
🇬🇧Dundee, United Kingdom
Leeds Teaching Hospitals NHS Trust
🇬🇧Leeds, United Kingdom
St. George's Hospital NHS Foundation Trust
🇬🇧London, United Kingdom
Royal London Hospital for Integrated Medicine
🇬🇧London, United Kingdom
John Radcliffe Hospital
🇬🇧Oxford, United Kingdom
Northern Care Alliance NHS Foundation Trust, Salford Care Organisation
🇬🇧Salford, United Kingdom