Clinical trial NCT03796962: A Study to Evaluate XEN1101 as Adjunctive Therapy in Focal Epilepsy
Official title: A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Safety, Tolerability and Efficacy of XEN1101 as Adjunctive Therapy in Focal-onset Epilepsy, With an Open-label Extension
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Focal Epilepsy
Keywords: Epilepsy
Lead sponsor: Xenon Pharmaceuticals Inc.
Sponsor class: INDUSTRY
Collaborators: name: Novotech Health Holdings Pte. Ltd.
First posted: 2019-01-08
Enrollment: 325
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Key Inclusion Criteria:

* 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 Exclusion Criteria:

* 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:

  1. History of presence of long QT syndrome; QTcF \> 450 msec at baseline; family history of sudden death of unknown cause
  2. 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

Primary outcomes:
measure: Median Percent Change in Focal Seizure Frequency
timeFrame: From baseline (8 weeks prior to Day 0) through to the final dose (up to Day 56)
Secondary outcomes:
measure: 50% XEN1101 Response Rate
timeFrame: From baseline (8 weeks prior to Day 0) through to the final dose (up to Day 56)
measure: Percent Change in Focal Seizure Frequency Over Time
timeFrame: From baseline (8 weeks prior to Day 0) through to the final dose (up to Day 56)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Mobile
country: United States
facility: Strada Patient Care Center
state: Alabama
city: Phoenix
country: United States
facility: Xenoscience, Inc.
state: Arizona
city: Little Rock
country: United States
facility: Clinical Trials, Inc.
state: Arkansas
city: La Jolla
country: United States
facility: Altman Clinical Translational Research Institute (ACTRI)
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center (CPMC) - Sutter Pacific Epilepsy Program
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital Anschutz Outpatient Pavilion
state: Colorado
city: Jacksonville
country: United States
facility: University of Florida Jacksonville
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Miami
country: United States
facility: Visionary Investigators Network
state: Florida
city: Miami
country: United States
facility: Don Clinical Research Center
state: Florida
city: Miami
country: United States
facility: The Neurology Research Group, LLC.
state: Florida
city: Orlando
country: United States
facility: Research Institute of Orlando, LLC
state: Florida
city: Port Charlotte
country: United States
facility: Medsol Clinical Research Center
state: Florida
city: Tallahassee
country: United States
facility: Tallahassee Neurological Clinic
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Suwanee
country: United States
facility: Georgia Neurology and Sleep Medicine Associate
state: Georgia
city: Honolulu
country: United States
facility: Hawaii Pacific Neuroscience
state: Hawaii
city: Boise
country: United States
facility: Consultants in Epilepsy and Neurology, PLLC
state: Idaho
city: Chicago
country: United States
facility: Northwestern Medical Group, Department of Neurology
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: Bluegrass Epilepsy Research
state: Kentucky
city: Scarborough
country: United States
facility: Maine Medical Partners Neurology
state: Maine
city: Bethesda
country: United States
facility: Mid-Atlantic Epilepsy and Sleep Center
state: Maryland
city: South Dartmouth
country: United States
facility: Boston Neuro Research Center
state: Massachusetts
city: Golden Valley
country: United States
facility: Minneapolis Clinic of Neurology, Ltd.
state: Minnesota
city: Saint Paul
country: United States
facility: Minnesota Epilepsy Group, P. A.
state: Minnesota
city: Hackensack
country: United States
facility: Northeast Regional Epilepsy Group
state: New Jersey
city: Livingston
country: United States
facility: Institute of Neurology and Neurosurgery at Saint Barnabas
state: New Jersey
city: Morristown
country: United States
facility: Northeast Regional Epilepsy Group
state: New Jersey
city: Amherst
country: United States
facility: Dent Neurosciences Research Center
state: New York
city: New York
country: United States
facility: NYU Langone Medical Center/NYU School of Medicine
state: New York
city: New York
country: United States
facility: Northwell Health - Lenox Hill
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University Institute for Human Performance
state: New York
city: Woodmere
country: United States
facility: Five Towns Neuroscience Research
state: New York
city: Asheville
country: United States
facility: Asheville Neurology Specialists, PA
state: North Carolina
city: Cincinnati
country: United States
facility: UC Gardner Neuroscience Institute
state: Ohio
city: Dayton
country: United States
facility: Miami Valley Hospital
state: Ohio
city: Toledo
country: United States
facility: University of Toledo Medical Center
state: Ohio
city: Portland
country: United States
facility: Providence Neurological Specialties East
state: Oregon
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Comprehensive Epilepsy Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny Neurological Associates
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt Epilepsy Clinic
state: Tennessee
city: Austin
country: United States
facility: Austin Epilepsy Care Center
state: Texas
city: Dallas
country: United States
facility: James W. Aston Ambulatory Care Center
state: Texas
city: San Antonio
country: United States
facility: The University of Texas Health Science Center at San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Health Clinical Neurosciences Center
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Roanoke
country: United States
facility: Carilion Neurology Clinic
state: Virginia
city: Winchester
country: United States
facility: Winchester Neurological Consultants
state: Virginia
city: Renton
country: United States
facility: UW Medicine Valle Medical Center
state: Washington
city: Seattle
country: United States
facility: University of Washington School of Medicine, Regional Epilepsy Center at Harborview Medical Center
state: Washington
city: Vancouver
country: Canada
facility: Children's and Women's Health Centre of British Columbia (BC Children's Hospital)
state: British Columbia
city: London
country: Canada
facility: London Health Sciences Center
state: Ontario
city: Toronto
country: Canada
facility: University Health Network-Toronto Western Hospital
state: Ontario
city: Tbilisi
country: Georgia
facility: LLC Arensia Exploratory Medicine
city: Berlin
country: Germany
facility: Epilepsiezentrum Berlin-Brandenburg
city: Bielefeld
country: Germany
facility: Bethel Epilepsy Centre
city: Bonn
country: Germany
facility: Univ.-Klinik Bonn, Klinik und Poliklinik fur Epileptologie
city: Frankfurt
country: Germany
facility: Universitatsklinikym Frankfurt
city: Freiburg
country: Germany
facility: Universitatsklinikum Freiburg, Neurozentrum/Epilepsiezentrum
city: Muenster
country: Germany
facility: University Hospital Munster (UKM)
city: Osnabrück
country: Germany
facility: Klinikum Osnabruck
city: Regensburg
country: Germany
facility: Krankenhaus Barmherzige Brueder Regensburg
city: Tübingen
country: Germany
facility: University of Tubingen-Dept. of Neurology and Epileptology
city: Bologna
country: Italy
facility: IRCCS- Istituto delle Scienze Neurologiche, Bellaria Hospital
city: Catanzaro
country: Italy
facility: Dipartimento Scienze Mediche e Chirurgiche, Universita Magna Graecia di Catanzaro
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Neurologico C. Besta
city: Pavia
country: Italy
facility: IRCCS Istituto Neurologico Nazionale C. Mondino
city: Pisa
country: Italy
facility: Azienda Ospedaliera Universita' Pisana
city: Reggio Calabria
country: Italy
facility: Azienda Ospedaliera "Bianchi-Melacrino-Morelle"di Reggio Calabria
city: Roma
country: Italy
facility: Policlinico di Roma Umberto I
city: Chisinau
country: Moldova, Republic of
facility: PMSI Republican Clinical Hospital, ARENSIA Exploratory Medicine
city: Sevilla
country: Spain
facility: Hospital Virgen Macarena
state: Andalusia
city: Sevilla
country: Spain
facility: Centro de Neurologia Avanzada
state: Andalusia
city: Badalona
country: Spain
facility: Hospital Germans Trias I Pujol
state: Barcelona
city: Pamplona
country: Spain
facility: Clínica Universidad Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Granada
country: Spain
facility: Hospital Vithas La Salud
city: Madrid
country: Spain
facility: Hospital U. Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Ruber Internacional
city: Madrid
country: Spain
facility: Hospital U. Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Málaga
city: Valencia
country: Spain
facility: Hospital Universitario y Politécnico La Fe
city: Valladolid
country: Spain
facility: Hospital Clínico Universitario Valladolid
city: Kyiv
country: Ukraine
facility: Medical Center of Limited Liability Company "Harmoniya Krasy"
city: Glasgow
country: United Kingdom
facility: Institute of Neurological Sciences
state: Scotland
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
state: Wales
city: London
country: United Kingdom
facility: King's College Hospital NHS Foundation Trust
city: London
country: United Kingdom
facility: St. George's University Hospitals NHS Foundation Trust
Study officials:
affiliation: Xenon Pharmaceuticals Inc.
name: Study Director
role: STUDY_DIRECTOR
References:
citation: French JA, Porter RJ, Perucca E, Brodie MJ, Rogawski MA, Pimstone S, Aycardi E, Harden C, Qian J, Rosenblut CL, Kenney C, Beatch GN; X-TOLE Study Group. Efficacy and Safety of XEN1101, a Novel Potassium Channel Opener, in Adults With Focal Epilepsy: A Phase 2b Randomized Clinical Trial. JAMA Neurol. 2023 Nov 1;80(11):1145-1154. doi: 10.1001/jamaneurol.2023.3542.