An Open-label Study of XEN1101 in Epilepsy
- Registration Number
- NCT05718817
- Lead Sponsor
- Xenon Pharmaceuticals Inc.
- Brief Summary
This study will evaluate the long term safety, tolerability, pharmacokinetics (PK), and efficacy of XEN1101 in subjects with Focal Onset Seizures (FOS) or Primary Generalized Tonic-Clonic Seizures (PGTCS) for the treatment of seizures for up to 3 years.
- Detailed Description
This is an Open Label Extension study of the following Phase 3 clinical studies: XPF-010-301 (X-TOLE2), XPF-010-302 (X-TOLE3), and XPF-010-303 (X-ACKT). This study will evaluate the long-term safety, tolerability, PK, and efficacy of XEN1101 in subjects with FOS or PGTCS for the treatment of seizures for up to 3 years. Subjects who successfully completed and did not terminate early from one of the antecedent studies (X-TOLE2, X-TOLE3, or X-ACKT) are eligible to participate in X-TOLE4.
Following enrollment into X-TOLE4, subjects will undergo a treatment period of up to 3 years, during which there will be a visit at 2-, 4-, and 13-weeks post-entry, with subsequent visits occurring at 13-week intervals during the first year, and then at 26-week intervals (with a telephone call in between) until dosing is completed.
Subjects will be initially assigned to XEN1101 as follows:
* 25 mg QD for subjects aged ≥18 years
* For subjects aged ≥12 and \<18 years
* 15 mg QD for those
* who weigh \<45 kg at the start of the X-TOLE4 study
* who weighed \<45 kg during the X-ACKT study
* who weighed ≥45 kg at randomization in the X-ACKT study and had dose reduction(s) for intolerability
* 25 mg QD for all others
Subjects will be instructed to orally take XEN1101 once daily (QD) with an evening meal. Subjects will be expected to keep a daily seizure eDiary with a minimum of 80% compliance for the duration of the extension study (reporting on ≥80% of days between visits).
Upon completion of dosing at the end of the treatment period, there will be an 8-week follow up period.
Recruitment & Eligibility
- Status
- ENROLLING_BY_INVITATION
- Sex
- All
- Target Recruitment
- 880
- Subject must be properly informed of the nature and risks of the study and give informed consent in writing prior to entering the study (for adult subjects) and for adolescent subject's parent/legal guardian and subject gives informed consent or assent in writing prior to entering the study.
- Subject must have successfully completed the double-blind treatment period (DBP) and have not terminated early from Study X-TOLE2, X-TOLE3, or X-ACKT, met all eligibility requirements, and had no important protocol deviations (in the opinion of the sponsor) or adverse events (AEs) (in the opinion of the investigator) that would preclude the subject's entry into the long-term extension study.
- In the opinion of the investigator, the subject is able to understand verbal and written instructions and will adhere to all study schedules and requirements.
- Subject is able to keep accurate seizure diaries.
- Subject met any of the withdrawal criteria while in Study X-TOLE2, X-TOLE3, or X-ACKT.
- Subject has any medical condition, personal circumstance, or ongoing AE (from Study X-TOLE2, X-TOLE3, or X-ACKT) that, in the opinion of the investigator, exposes the subject to unacceptable risk by participating in the study, or prevents adherence to the protocol.
- Subject is planning to enter a clinical study with a different investigational drug or planning to use any experimental device for treatment of epilepsy or any other medical condition during the study and until 28 days after completion of this study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description XEN1101 15 or 25 mg/day XEN1101 XEN1101 15 or 25 mg/day
- Primary Outcome Measures
Name Time Method The adverse events From the start of treatment in the open-label extension (OLE) study through 8 weeks after the last dose. To assess the safety and tolerability of XEN1101
- Secondary Outcome Measures
Name Time Method Change in Clinical Global Impression of Severity (CGI-S) From baseline through the active extension treatment (Week 156). Improvement in Clinical Global Impression of Severity (CGI-S) scores over time.
Change in monthly seizure rate From baseline through the active extension treatment (Week 156). Percent change in monthly seizure rate recorded at baseline (in the antecedent studies) compared to each 4-week assessment period in the treatment period in X-TOLE4.
Proportion of responders From baseline through the active extension treatment (Week 156). Proportion of responders (subjects experiencing ≥50% reduction in seizure frequency from baseline) in each consecutive 4-week assessment period of the treatment period of the OLE study.
Change in Quality of Life in Epilepsy Inventory (QOLIE-31) From baseline through the active extension treatment (Week 156). Change in the 31-Item Quality of Life in Epilepsy Inventory (QOLIE-31) over time.
Change in Patient Global Impression of Severity (PGI-S) From baseline through the active extension treatment (Week 156). Improvement in Patient Global Impression of Severity (PGI-S) scores over time.
Trial Locations
- Locations (97)
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
Hospital Universitario Fundación Jiménez Díaz
🇪🇸Madrid, Spain
Hospital Regional De Malaga
🇪🇸Málaga, Spain
Hospital La Fe
🇪🇸Valencia, Spain
St George's Hospital NHS Foundation Trust
🇬🇧London, United Kingdom
University College London
🇬🇧London, United Kingdom
STAT Research S.A.
🇦🇷Buenos Aires, Argentina
FLENI (Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia)
🇦🇷Buenos Aires, Argentina
MHATNP St. Naum
🇧🇬Sofia, Bulgaria
Motol University Hospital
🇨🇿Prague, Czechia
Forbeli s.r.o.
🇨🇿Prague, Czechia
Hopital Neurologique Pierre Wertheimer, Hospices Civils de Lyon
🇫🇷Lyon, France
Hôpital Fondation Adolphe de Rothschild
🇫🇷Paris, France
Krankenhaus Mara gGmbH
🇩🇪Bielefeld, Germany
Vall d'Hebron Hospital
🇪🇸Barcelona, Spain
Hospital Vithas La Milagrosa
🇪🇸Madrid, Spain
Cardiff and Vale UHB
🇬🇧Cardiff, Wales, United Kingdom
Hospital Ramón Y Cajal
🇪🇸Madrid, Spain
Hospital Ruber Internacional
🇪🇸Madrid, Spain
Mater Misericordiae Ltd South Brisbane
🇦🇺South Brisbane, Australia
Providence Neurological Specialities
🇺🇸Portland, Oregon, United States
Clinical Trials, Inc
🇺🇸Little Rock, Arkansas, United States
Brain Science Research Institute
🇺🇸Los Angeles, California, United States
UC Irvine Health
🇺🇸Orange, California, United States
University of Colorado Hospital Anschutz Outpatient Pavilion
🇺🇸Aurora, Colorado, United States
Research Institute of Orlando, LLC
🇺🇸Orlando, Florida, United States
Panhandle Research & Medical Clinic
🇺🇸Pensacola, Florida, United States
Hawaii Pacific Neuroscience
🇺🇸Honolulu, Hawaii, United States
Consultants in Epilepsy and Neurology
🇺🇸Boise, Idaho, United States
Indiana University School of Medicine
🇺🇸Indianapolis, Indiana, United States
The University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
Bluegrass Epilepsy Research, LLC
🇺🇸Lexington, Kentucky, United States
Kentucky Clinic
🇺🇸Lexington, Kentucky, United States
MMP Neurology
🇺🇸Scarborough, Maine, United States
Mid-Atlantic Epilepsy and Sleep Center
🇺🇸Bethesda, Maryland, United States
University of Michigan Hospitals
🇺🇸Ann Arbor, Michigan, United States
Michigan State University
🇺🇸East Lansing, Michigan, United States
Cornwell Health (Spectrum Health Hospitals)
🇺🇸Grand Rapids, Michigan, United States
Northeast Epilepsy Group
🇺🇸Hackensack, New Jersey, United States
Montefiiore Medical Center
🇺🇸Bronx, New York, United States
Dent Neurosciences Research Center
🇺🇸Buffalo, New York, United States
New York University Comprehensive Epilepsy Center
🇺🇸New York, New York, United States
Mount Sinai Health
🇺🇸New York, New York, United States
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
Duke University
🇺🇸Durham, North Carolina, United States
Meridian Clinical Research, LLC
🇺🇸Raleigh, North Carolina, United States
Summa Health
🇺🇸Akron, Ohio, United States
Queen Elizabeth Hospital Birmingham
🇬🇧Birmingham, United Kingdom
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States
Hospital Clinico Universitario de Valladolid
🇪🇸Valladolid, Spain
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Austin Epilepsy Care Center
🇺🇸Austin, Texas, United States
ANESC Research
🇺🇸El Paso, Texas, United States
University of Utah Clinical Neurosciences Center
🇺🇸Salt Lake City, Utah, United States
Carilion Clinic
🇺🇸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 "José M. Ramos Mejía"
🇦🇷Buenos Aires, Argentina
Hospital De Alta Complejidad en Red El Cruce - Dr Nester Carlos Kirchner Servicio de Atencion Medica Integral Para la Communidad
🇦🇷Florencio Varela, Argentina
Sanatorio del SUR S.A.
🇦🇷Tucumán, Argentina
Royal Prince Alfred Hospital
🇦🇺Camperdown, Australia
Austin Health Pharmacy Clinical Trials
🇦🇺Heidelberg, Australia
Southern Neurology
🇦🇺Kogarah, Australia
Alfred Hospital Neurology CT Dept of Neuroscience
🇦🇺Melbourne, Australia
The Royal Melbourne Hospital
🇦🇺Parkville, Australia
Westmead Hospital Dept. of Neurology Epilepsy Unit
🇦🇺Westmead, Australia
University Hospital Innsbruck
🇦🇹Innsbruck, Austria
Hospital for active treatmnt Puls AD Neurology Dpt
🇧🇬Blagoevgrad, Bulgaria
Center for Neurologic Research
🇨🇦Lethbridge, Alberta, Canada
Centro de investigación Clinica UC
🇨🇱Santiago, Chile
Altavita Centar j.d.o.o.
🇭🇷Zagreb, Croatia
University Hospital Centre Zagreb
🇭🇷Zagreb, Croatia
Universitätsklinikum, ZNN - Epilepsiezentrum Frankfurt Rhein-Main
🇩🇪Frankfurt, Germany
Klinikum der Universität München
🇩🇪München, Germany
Universitaets-Und Rehabilitations Ulm (RKU)
🇩🇪Ulm, Germany
Semmelweis Egyetem, Idegsebeszeti es Neurointervencios Klinika
🇭🇺Budapest, Hungary
Hadassah Medical Center (HMC)
🇮🇱Jerusalem, Israel
Kaplan Medical Center (KMC)
🇮🇱Reẖovot, Israel
The Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
IRCCS Istituto delle Scienze Neurologiche Bologna
🇮🇹Bologna, Italy
Universita' Degli Studi Gabriele d'Annunzio Di Chieti
🇮🇹Chieti, Italy
Azienda Ospedaliero Universitaria Pisana
🇮🇹Pisa, Italy
Grupo Medico Camino SC
🇲🇽Ciudad de México, Mexico
Human Science Research Trials
🇲🇽Mexico City, Mexico
Centrum Medyczne Neuromed
🇵🇱Bydgoszcz, Poland
COPERNICUS Podmiot Leczniczy Sp. z o.o.
🇵🇱Gdańsk, Poland
NZOZ Neuromed M. i M.
🇵🇱Lublin, Poland
Twoja Przychodnia Nowosolskie Centrum Medyczne
🇵🇱Nowa Sól, Poland
MTZ Clinical Research Powered by Pratia
🇵🇱Warsaw, Poland
Centro Hospitalar Universitário de Coimbra (CHUC)
🇵🇹Coimbra, Portugal
Hospital Senhora da Oliviera de Guimaraes
🇵🇹Guimarães, Portugal
Centro Hospitalar Lisboa Ocidental, EPE - Hospital Egas Moniz
🇵🇹Lisboa, Portugal
Centro Hospitalar Universitario de Santo António, E.P.E
🇵🇹Porto, Portugal
Unidade Local Saúde Matosinhos
🇵🇹Porto, Portugal
Centro Hospitalar de Entre o Douro e Vouga
🇵🇹Santa Maria Da Feira, Portugal
Hospital Universitario Cruces
🇪🇸Baracaldo, Spain