A Study to Evaluate XEN1101 as Adjunctive Therapy in Focal Epilepsy
- Conditions
- Focal Epilepsy
- Interventions
- Drug: XEN1101
- Registration Number
- NCT03796962
- Lead Sponsor
- Xenon Pharmaceuticals Inc.
- Brief Summary
The XEN1101 Phase 2 clinical trial is a randomized, double-blind, placebo-controlled study that will evaluate the clinical efficacy, safety and tolerability of increasing doses of XEN1101 administered as adjunctive treatment in adult patients diagnosed with focal epilepsy, followed by an optional open-label extension (OLE).
- Detailed Description
The XEN1101 Phase 2 clinical trial is designed as a randomized, double-blind, placebo-controlled, multicenter study with an optional open-label extension (OLE) to evaluate the clinical efficacy, safety and tolerability of XEN1101 administered as adjunctive treatment in adult patients aged 18 to 75 years diagnosed with focal epilepsy. Approximately 300 patients will be randomized in a blinded manner to one of three active treatment groups or placebo in a 2:1:1:2 fashion (XEN1101 25 mg : 20 mg : 10 mg : Placebo). After screening, patients will have 8 weeks of baseline to assess frequency of seizures, followed by 8 weeks of treatment and a 6-week post treatment follow-up period. In order to be included in the study, patients must already be treated with a stable dose of 1 to 3 allowable current anti-epileptic drugs for at least one month prior to screening, during baseline, and throughout the double-blind portion (DBP) of the study. During the treatment period, patients will be given XEN1101 or placebo once daily in the evening. An OLE will be available to eligible patients who complete the DBP. All patients will receive a 20 mg daily dose of XEN1101 during this extension period.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 325
- Be properly informed of the nature and risks of the study and give informed consent in writing, prior to entering the study
- BMI ≤40 kg/m2
- Diagnosis (≥2 years) of focal epilepsy according to the International League Against Epilepsy [ILAE] Classification of Epilepsy (2017)
- Prior neuroimaging within the last 10 years and documentation is available
- Treatment with a stable dose of 1 to 3 allowable current AEDs for at least one month prior to screening, during baseline, and throughout the duration of the DBP
- Must be willing to comply with the contraception requirements
- Males must agree not to donate sperm from the time of the first administration of study drug until 6 months after the last dose. Females must agree not to donate ova from the time of the first administration of study drug until 6 months after the last dose.
- Able to keep accurate seizure diaries
Key
-
History of pseudoseizures, psychogenic seizures, primary generalized seizure, or focal aware non-motor seizures only
-
Presence or previous history of Lennox-Gastaut syndrome
-
Seizures secondary to other diseases or conditions
-
History of repetitive seizures within the last 12 months where the individual seizures cannot be counted
-
History of neurosurgery for seizures <1 year prior to enrollment, or radiosurgery <2 years prior to enrollment
-
Schizophrenia and other psychotic disorders, or active suicidal plan/intent in the past 6 months, or a history of suicide attempt in the last 2 years, or more than 1 lifetime suicide attempt
-
History or presence of any significant medical or surgical condition or uncontrolled medical illness at screening, or history of cancer within the past 2 years, with the exception of appropriately treated basal cell or squamous cell carcinoma
-
Any clinically significant abnormalities on pre-study physical examination, vital signs, laboratory values or ECG indicating a medical problem that would preclude study participation including but not limited to:
- History of presence of long QT syndrome; QTcF > 450 msec at baseline; family history of sudden death of unknown cause
- History of skin or retinal pigment epithelium abnormalities caused by ezogabine
-
Past use of vigabatrin without stable visual fields tested twice over the 12 months after the last dose of vigabatrin (concomitant use of vigabatrin is not allowed)
-
If felbamate is used as a concomitant AED, patients must be taking it for at least 2 years, with a stable dose for 2 months (or no less than 49 days) and acceptable hematology and LFT history and values prior to Screening. If received in the past, felbamate must have been discontinued 2 months (or no less than 49 days) prior to Screening.
-
Have had multiple drug allergies or a severe drug reaction to an AED(s), including dermatological (e.g., Stevens-Johnson syndrome), hematological, or organ toxicity reactions
-
Current use of a ketogenic diet
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 25 mg XEN1101 XEN1101 Capsule filled with 25 mg XEN1101 20 mg XEN1101 XEN1101 Capsule filled with 20 mg XEN1101 10 mg XEN1101 XEN1101 Capsule filled with 10 mg XEN1101 Placebo XEN1101 Placebo capsule
- Primary Outcome Measures
Name Time Method Median Percent Change in Focal Seizure Frequency From baseline (8 weeks prior to Day 0) through to the final dose (up to Day 56) Median percent change in monthly (28 days) focal seizure frequency from baseline to DBP for XEN1101 versus placebo
- Secondary Outcome Measures
Name Time Method 50% XEN1101 Response Rate From baseline (8 weeks prior to Day 0) through to the final dose (up to Day 56) Responders are defined as patients experiencing ≥50% reduction in monthly (28 days) focal seizure frequency from baseline to DBP
Percent Change in Focal Seizure Frequency Over Time From baseline (8 weeks prior to Day 0) through to the final dose (up to Day 56) Percent change from baseline in focal seizure frequency at Month 1 and Month 2 in the DBP
Trial Locations
- Locations (94)
James W. Aston Ambulatory Care Center
🇺🇸Dallas, Texas, United States
Don Clinical Research Center
🇺🇸Miami, Florida, United States
The Neurology Research Group, LLC.
🇺🇸Miami, Florida, United States
Allegheny Neurological Associates
🇺🇸Pittsburgh, Pennsylvania, United States
UC Gardner Neuroscience Institute
🇺🇸Cincinnati, Ohio, United States
Altman Clinical Translational Research Institute (ACTRI)
🇺🇸La Jolla, California, United States
University of Florida Jacksonville
🇺🇸Jacksonville, Florida, United States
Mayo Clinic Florida
🇺🇸Jacksonville, Florida, United States
Tallahassee Neurological Clinic
🇺🇸Tallahassee, Florida, United States
Consultants in Epilepsy and Neurology, PLLC
🇺🇸Boise, Idaho, United States
Maine Medical Partners Neurology
🇺🇸Scarborough, Maine, United States
Minnesota Epilepsy Group, P. A.
🇺🇸Saint Paul, Minnesota, United States
Northeast Regional Epilepsy Group
🇺🇸Morristown, New Jersey, United States
Five Towns Neuroscience Research
🇺🇸Woodmere, New York, United States
University of Toledo Medical Center
🇺🇸Toledo, Ohio, United States
UW Medicine Valle Medical Center
🇺🇸Renton, Washington, United States
University of Washington School of Medicine, Regional Epilepsy Center at Harborview Medical Center
🇺🇸Seattle, Washington, United States
Epilepsiezentrum Berlin-Brandenburg
🇩🇪Berlin, Germany
London Health Sciences Center
🇨🇦London, Ontario, Canada
Univ.-Klinik Bonn, Klinik und Poliklinik fur Epileptologie
🇩🇪Bonn, Germany
University Hospital Munster (UKM)
🇩🇪Muenster, Germany
Universitatsklinikym Frankfurt
🇩🇪Frankfurt, Germany
Klinikum Osnabruck
🇩🇪Osnabrück, Germany
IRCCS- Istituto delle Scienze Neurologiche, Bellaria Hospital
🇮🇹Bologna, Italy
Dipartimento Scienze Mediche e Chirurgiche, Universita Magna Graecia di Catanzaro
🇮🇹Catanzaro, Italy
Azienda Ospedaliera Universita' Pisana
🇮🇹Pisa, Italy
IRCCS Istituto Neurologico Nazionale C. Mondino
🇮🇹Pavia, Italy
Policlinico di Roma Umberto I
🇮🇹Roma, Italy
PMSI Republican Clinical Hospital, ARENSIA Exploratory Medicine
🇲🇩Chisinau, Moldova, Republic of
Hospital Germans Trias I Pujol
🇪🇸Badalona, Barcelona, Spain
Centro de Neurologia Avanzada
🇪🇸Sevilla, Andalusia, Spain
Hospital Virgen Macarena
🇪🇸Sevilla, Andalusia, Spain
Hospital Ruber Internacional
🇪🇸Madrid, Spain
Clínica Universidad Navarra
🇪🇸Pamplona, Navarra, Spain
Hospital del Mar
🇪🇸Barcelona, Spain
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital U. Ramón y Cajal
🇪🇸Madrid, Spain
Hospital Vithas La Salud
🇪🇸Granada, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Hospital Universitario y Politécnico La Fe
🇪🇸Valencia, Spain
Medical Center of Limited Liability Company "Harmoniya Krasy"
🇺🇦Kyiv, Ukraine
Hospital Regional Universitario de Málaga
🇪🇸Málaga, Spain
Hospital Clínico Universitario Valladolid
🇪🇸Valladolid, Spain
University Hospital of Wales
🇬🇧Cardiff, Wales, United Kingdom
Institute of Neurological Sciences
🇬🇧Glasgow, Scotland, United Kingdom
King's College Hospital NHS Foundation Trust
🇬🇧London, United Kingdom
St. George's University Hospitals NHS Foundation Trust
🇬🇧London, United Kingdom
Minneapolis Clinic of Neurology, Ltd.
🇺🇸Golden Valley, Minnesota, United States
Clinical Trials, Inc.
🇺🇸Little Rock, Arkansas, United States
Visionary Investigators Network
🇺🇸Miami, Florida, United States
Medsol Clinical Research Center
🇺🇸Port Charlotte, Florida, United States
University Health Network-Toronto Western Hospital
🇨🇦Toronto, Ontario, Canada
Boston Neuro Research Center
🇺🇸South Dartmouth, Massachusetts, United States
LLC Arensia Exploratory Medicine
🇬🇪Tbilisi, Georgia
Universitatsklinikum Freiburg, Neurozentrum/Epilepsiezentrum
🇩🇪Freiburg, Germany
Krankenhaus Barmherzige Brueder Regensburg
🇩🇪Regensburg, Germany
Azienda Ospedaliera "Bianchi-Melacrino-Morelle"di Reggio Calabria
🇮🇹Reggio Calabria, Italy
Bethel Epilepsy Centre
🇩🇪Bielefeld, Germany
University of Tubingen-Dept. of Neurology and Epileptology
🇩🇪Tübingen, Germany
Fondazione IRCCS Istituto Neurologico C. Besta
🇮🇹Milano, Italy
Institute of Neurology and Neurosurgery at Saint Barnabas
🇺🇸Livingston, New Jersey, United States
Children's and Women's Health Centre of British Columbia (BC Children's Hospital)
🇨🇦Vancouver, British Columbia, Canada
Strada Patient Care Center
🇺🇸Mobile, Alabama, United States
Northwestern Medical Group, Department of Neurology
🇺🇸Chicago, Illinois, United States
Georgia Neurology and Sleep Medicine Associate
🇺🇸Suwanee, Georgia, United States
Bluegrass Epilepsy Research
🇺🇸Lexington, Kentucky, United States
NYU Langone Medical Center/NYU School of Medicine
🇺🇸New York, New York, United States
Dent Neurosciences Research Center
🇺🇸Amherst, New York, United States
Northwell Health - Lenox Hill
🇺🇸New York, New York, United States
SUNY Upstate Medical University Institute for Human Performance
🇺🇸Syracuse, New York, United States
Asheville Neurology Specialists, PA
🇺🇸Asheville, North Carolina, United States
Hospital of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Miami Valley Hospital
🇺🇸Dayton, Ohio, United States
Thomas Jefferson University Comprehensive Epilepsy Center
🇺🇸Philadelphia, Pennsylvania, United States
Carilion Neurology Clinic
🇺🇸Roanoke, Virginia, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
Winchester Neurological Consultants
🇺🇸Winchester, Virginia, United States
Hospital U. Clínico San Carlos
🇪🇸Madrid, Spain
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
California Pacific Medical Center (CPMC) - Sutter Pacific Epilepsy Program
🇺🇸San Francisco, California, United States
Xenoscience, Inc.
🇺🇸Phoenix, Arizona, United States
University of South Florida
🇺🇸Tampa, Florida, United States
Mid-Atlantic Epilepsy and Sleep Center
🇺🇸Bethesda, Maryland, United States
University of Colorado Hospital Anschutz Outpatient Pavilion
🇺🇸Aurora, Colorado, United States
Providence Neurological Specialties East
🇺🇸Portland, Oregon, United States
Vanderbilt Epilepsy Clinic
🇺🇸Nashville, Tennessee, United States
The University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
University of Utah Health Clinical Neurosciences Center
🇺🇸Salt Lake City, Utah, United States
Research Institute of Orlando, LLC
🇺🇸Orlando, Florida, United States
Hawaii Pacific Neuroscience
🇺🇸Honolulu, Hawaii, United States
Austin Epilepsy Care Center
🇺🇸Austin, Texas, United States
Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
Related News
Interim Analysis Highlights Long-Term Safety of Azetukalner for Focal Epilepsy
- Prev
- 1
- Next