A Study to Evaluate XEN1101 as Adjunctive Therapy in Primary Generalized Tonic-Clonic Seizures
- Conditions
- Primary Generalized Tonic-Clonic Seizures
- Interventions
- Drug: Placebo
- Registration Number
- NCT05667142
- Lead Sponsor
- Xenon Pharmaceuticals Inc.
- Brief Summary
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate the clinical efficacy, safety, and tolerability of XEN1101 administered as adjunctive treatment in primary generalized tonic-clonic seizures (PGTCS).
- Detailed Description
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate the clinical efficacy, safety, and tolerability of XEN1101 administered as adjunctive treatment in subjects diagnosed with generalized epilepsy and experiencing probable or possible PGTCS (with or without other subtypes of generalized seizures), and taking 1 to 3 anti-seizure medications (ASMs). Eligible subjects will be randomly assigned 1:1 to XEN1101 or placebo: subjects aged ≥ 18 years will receive XEN1101 25 mg or placebo, and subjects aged ≥12 years and \<18 years will receive either XEN1101 15 mg, 25 mg, or placebo. Randomization will be stratified based on region, age group, and background use of CYP3A4-inducer ASMs. Eligible subjects will have up to 9.5 weeks durations to assess the baseline frequency of seizures, followed by a double-blind treatment period (DBP) where subjects will receive 12 weeks of blinded treatment. 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 enroll in a separate open-label-extension (OLE) study for continued treatment with XEN1101. Subjects who do not enroll in the OLE will enter an 8 week post-treatment follow-up period.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 160
- Subject is properly informed of the nature and risks of the study and gives informed consent in writing prior to entering the study (for adult subjects) and for adolescent subjects parent/legal guardian and subject gives informed consent or assent in writing prior to entering the study.
- Subject is ≥12 years of age with a BMI ≤40 kg/m2 at Visit 1.
- 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.
- Subject has probable or possible PGTCS (with or without other subtypes of generalized seizures) for ≥1 year, in the setting of generalized epilepsy according to the International League Against Epilepsy 2017 classification criteria, and subject is approved by The Epilepsy Study Consortium (TESC).
- Subject is on a stable dose of 1 to 3 allowable current ASMs for at least 1 month prior to screening (Visit 1), during screening/baseline, and throughout the DBP.
- Subject is able to keep accurate seizure diaries.
-
Subject has had status epilepticus within the 12 months prior to Visit 1.
-
Subject has history of repetitive seizures within the 12-month period preceding Visit 1 where the individual seizures cannot be counted.
-
Subject has a history of non-epileptic psychogenic seizures.
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Subject has a concomitant diagnosis of focal-onset seizures (FOS).
-
Subject has presence or history of a developmental and epileptic encephalopathy, including Lennox-Gastaut syndrome.
-
Subject has 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.
-
Subject has history of neurosurgery for seizures <1 year prior to Visit 1, or radiosurgery <2 years prior to Visit 1.
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Subject has schizophrenia and other psychotic disorders (eg, schizophreniform disorder, schizoaffective disorder, psychosis not otherwise specified), bipolar disorder, obsessive-compulsive disorder, or another serious mental health disorder. Subject has uncontrolled unipolar major depression where changes in pharmacotherapy are needed or anticipated during the study.
-
Subject has any clinically significant laboratory abnormalities or clinically significant abnormalities on prestudy physical examination, vital signs, or ECG that, in the judgment of the investigator, indicate a medical problem that would preclude study participation, including but not limited to:
a. History or presence of long QT syndrome; QTcF >450 msec at baseline; family history of sudden death of unknown cause.
-
Any personal circumstance that, in the opinion of the investigator, prevents adherence to the protocol.
The criteria to be eligible for randomization are:
- During the last 56 days of the baseline period that preceded the randomization visit (Visit 2), subject must have had a sufficient documented seizure frequency of PGTCS, including ≥1 PGTCS during each of the first and second 4-week periods preceding randomization.
- Seizure diary was completed a minimum of 80% of all days (ie, ≥45 days) during the last 56 days of the baseline period that preceded randomization as evidence of adequate compliance.
- Subject did not change dose of, stop, or initiate any new ASM(s) during the baseline period and plans on maintaining a stable dose of ASM(s) during the DBP.
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) PGTCS frequency Baseline through DBP (Week 12) Median percent change (MPC) in monthly (28 days) PGTCS frequency from baseline through the DBP for XEN1101 versus placebo.
- Secondary Outcome Measures
Name Time Method Proportion of subjects Baseline through Week 12 Proportion of subjects experiencing PGTCS freedom from baseline through the DBP for XEN1101 versus placebo.
Trial Locations
- Locations (129)
MHATNP 'Sveti Naum' EAD
🇧🇬Sofia, Bulgaria
University Hospital Center Zagreb
🇭🇷Zagreb, Croatia
Neurociencias Estudios Clínicos S.C
🇲🇽Sinaloa, Mexico
Kempenhaeghe
🇳🇱Heeze, Netherlands
Centrum Medyczne Neuromed
🇵🇱Bydgoszcz, Poland
COPERNICUS Podmiot Leczniczy Sp. z o.o.
🇵🇱Gdańsk, Poland
Novo-Med Zielinski I Wspolnicy Sp. J.
🇵🇱Katowice, Poland
NZOZ Neuromed M. i M.
🇵🇱Lublin, Poland
Twoja Przychodnia Nowosolskie Centrum Medyczne
🇵🇱Nowa Sól, Poland
Centro Hospitalar Universitário de Coimbra (CHUC)
🇵🇹Coimbra, Portugal
Hospital da Senhora da Oliveira
🇵🇹Guimarães, Portugal
Centro Hospitalar Lisboa Ocidental, Hospital Egas Moniz
🇵🇹Lisboa, Portugal
Centre Hospitalar Universitario de Lisboa Norte (CHULN)
🇵🇹Lisboa, Portugal
Hospital Clinico Viña del Mar
🇪🇸Valparaiso, Spain
Azienda Ospedaliero Universitaria Pisana
🇮🇹Pisa, Italy
Ospedalo Pediatrico Bambino Gesu
🇮🇹Roma, Italy
University of Alabama - Strada Patient Care Center, Neurology
🇺🇸Mobile, Alabama, United States
Xenoscience
🇺🇸Phoenix, Arizona, United States
University of Arizona - Health Science Center
🇺🇸Tucson, Arizona, United States
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
Brain Science Research Institute
🇺🇸Los Angeles, California, United States
University of California, Irvine - Health Neurology Services
🇺🇸Orange, California, United States
University California, Davis Clinical & Translation Science Center Clinical Research (CCRC)
🇺🇸Sacramento, California, United States
University of Colorado Anschutz Medical Campus
🇺🇸Aurora, Colorado, United States
Serenity Research Center, LLC
🇺🇸Miami, Florida, United States
Research Institute of Orlando, LLC
🇺🇸Orlando, Florida, United States
Panhandle Research and Medical Clinic
🇺🇸Pensacola, Florida, United States
Medsol Clinical Research Center Harbor Professional Centre
🇺🇸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
Children's Healthcare of Atlanta
🇺🇸Atlanta, Georgia, United States
Georgia Neurology & Sleep Medicine Associates
🇺🇸Suwanee, Georgia, United States
Hawaii Pacific Neuroscience, Comprehensive Epilepsy Center
🇺🇸Honolulu, Hawaii, United States
Consultants in Epilepsy and Neurology, PLLC
🇺🇸Boise, Idaho, United States
Universitätsklinik für Neurologie, Medizinische Universität Wien
🇦🇹Vienna, Austria
Southern Illinois University School of Medicine
🇺🇸Springfield, Illinois, United States
Indiana University School of Medicine
🇺🇸Indianapolis, Indiana, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
Bluegrass Epilepsy Research, LLC
🇺🇸Lexington, Kentucky, United States
University of Kentucky Albert B. Chandler Hospital (UK Healthcare)
🇺🇸Lexington, Kentucky, United States
University of Maryland Medical Center
🇺🇸Baltimore, Maryland, United States
MedStar Franklin Square Medical Center
🇺🇸Baltimore, Maryland, United States
Mid-Atlantic Epilepsy and Sleep Center
🇺🇸Bethesda, Maryland, United States
Medstar Georgetown University Hospital
🇺🇸Clinton, Maryland, United States
Brigham and Women's Hospital
🇺🇸Chestnut Hill, Massachusetts, United States
UMass Memorial Medical Center
🇺🇸Worcester, Massachusetts, United States
University of Michigan Hospitals
🇺🇸Ann Arbor, Michigan, United States
Wayne State University
🇺🇸Detroit, Michigan, United States
Michigan State University Department of Neurology
🇺🇸East Lansing, Michigan, United States
Spectrum Health
🇺🇸Grand Rapids, Michigan, United States
Northeast Regional Epilepsy Group
🇺🇸Hackensack, New Jersey, United States
Dent Neurosciences Research Facility
🇺🇸Amherst, New York, United States
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
Five Towns Neurology
🇺🇸Woodmere, New York, United States
Onsite Clinical Solutions, LLC
🇺🇸Charlotte, North Carolina, United States
Wake Forest Baptist Health
🇺🇸Winston-Salem, North Carolina, United States
Summa Health Clinical Research Center
🇺🇸Akron, Ohio, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
The Ohio State University
🇺🇸Columbus, Ohio, United States
OhioHealth Riverside Methodist Hospital
🇺🇸Columbus, Ohio, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Temple University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Medical University of South Carolina (MUSC)
🇺🇸Charleston, South Carolina, United States
ANESC Research
🇺🇸El Paso, Texas, United States
UTHealth Science Center at Houston
🇺🇸Houston, Texas, United States
University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
University of Utah Clinical Neurosciences Center
🇺🇸Salt Lake City, Utah, United States
Sentara Neurology Specialists
🇺🇸Virginia Beach, Virginia, United States
University of Washington, Regional Epilepsy Center at Harborview Medical Center
🇺🇸Seattle, Washington, United States
Advocate Aurora Research institute, 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
Hospital Italiano
🇦🇷Buenos Aires, Argentina
Sanatorio del Sur S.A
🇦🇷San Miguel De Tucumán, Argentina
Southern Neurology
🇦🇺Kogarah, New South Wales, Australia
Mater Misericordiae Ltd
🇦🇺South Brisbane, Queensland, Australia
Austin Health Pharmacy Clinical Trials
🇦🇺Heidelberg, Victoria, Australia
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
St Vincent's Hospital Melbourne, Clinical Neurosciences
🇦🇺Melbourne, Victoria, Australia
The Royal Melbourne Hospital
🇦🇺Parkville, Australia
University Hospital Innsbruck
🇦🇹Innsbruck, Austria
Universitaetsklinik fuer Kinder
🇦🇹Linz, Austria
Universitätsklinik für Neurologie
🇦🇹Salzburg, Austria
Multiprofile hospital for active treatment Puls AD
🇧🇬Blagoevgrad, Bulgaria
First University Multiprofile Hospital for Active Treatment Sofia Sv. Joan Krastitel
🇧🇬Sofia, Bulgaria
Center for Neurologic Research
🇨🇦Lethbridge, Alberta, Canada
Children and Women's Health Centre of BC (BC Children's Hospital)
🇨🇦Vancouver, British Columbia, Canada
London Health Sciences Center
🇨🇦London, Ontario, Canada
Le Centre Hospitalier de l'Universite' de Montreal (CHUM)
🇨🇦Montréal, Quebec, Canada
Clinical Hospital Center Osijek
🇭🇷Osijek, Croatia
Clinical Hospital Center Rijeka
🇭🇷Rijeka, Croatia
Fakultni nemocnice v Motole Neurologicka klinika 2. LF UK a FN Motol
🇨🇿Prague, Czechia
CHU de Lille, Hôpital Roger Salengro - Neurophysiologie clinique
🇫🇷Lille, France
Hopital Neurologique Pierre Wertheimer, Hospices Civils de Lyon
🇫🇷Lyon, France
Hôpital Fondation A. de Rothschild
🇫🇷Paris, France
CHU de Rennes - Hôpital Pontchaillou
🇫🇷Rennes, France
CHU de Strasbourg - Hôpital de Hautepierre
🇫🇷Strasbourg, France
Universitätsklinikum Aachen
🇩🇪Aachen, Germany
Vivantes Humboldt Klinikum
🇩🇪Berlin, Germany
Bethel Epilepsy Centre
🇩🇪Bielefeld, Germany
Universitätsklinikum Frankfurt
🇩🇪Frankfurt, Germany
Philipps-Universität Marburg
🇩🇪Marburg, Germany
Klinikum der Universität München
🇩🇪München, Germany
Epilepsiezentrum Kleinwachau gemeinnützige GmbH
🇩🇪Radeberg, Germany
Universitätsklinikum Tübingen
🇩🇪Tuebingen, Germany
Universitätsklinikum Ulm
🇩🇪Ulm, Germany
Hadassah University Medical Center
🇮🇱Jerusalem, Israel
The Chaim Sheba Medical Center
🇮🇱Ramat Gan, Israel
Kaplan Medical Center
🇮🇱Reẖovot, Israel
The Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Azienda Ospedaliero Universitaria Ospedali Riuniti Ancona
🇮🇹Ancona, Italy
Università Degli Studi Gabriele d'Annunzio Di Chieti
🇮🇹Chieti, Italy
Policlinico Umberto I
🇮🇹Roma, Italy
Grupo Medico Camino SC
🇲🇽Ciudad de México, Mexico
Human Science Research Trials S. de R.L. de C.V.
🇲🇽Mexico City, Mexico
Unidade Local de Saúde de Matosinhos
🇵🇹Matosinhos, Portugal
Centro Hospitalar Universitário de Santo António
🇵🇹Porto, Portugal
Centro Hospitalar de Entre o Douro e Vouga
🇵🇹Santa Maria Da Feira, Portugal
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario Vithas Madrid La Milagrosa
🇪🇸Madrid, Spain
Hospital Regional Universitario de Málaga
🇪🇸Málaga, Spain
Hospital Clinico Universitario de Valladolid
🇪🇸Valladolid, Spain
University Hospital of Wales
🇬🇧Cardiff, Wales, United Kingdom
Mid Yorkshire Hospitals NHS Trust
🇬🇧Wakefield, West Yorkshire, United Kingdom
St George's University Hospitals NHS Foundation Trust
🇬🇧London, United Kingdom
University College London Hospitals NHS Foundation Trust
🇬🇧London, United Kingdom
John Radcliffe Hospital
🇬🇧Oxford, United Kingdom
Salford Royal NHS Foundation Trust - Greater Manchester Neuroscience Centre (GMNC)
🇬🇧Salford, United Kingdom