Clinical trial NCT05667142: A Study to Evaluate XEN1101 as Adjunctive Therapy in Primary Generalized Tonic-Clonic Seizures
Official title: A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase 3 Study to Evaluate the Safety, Tolerability, and Efficacy of XEN1101 as Adjunctive Therapy in Primary Generalized Tonic-Clonic Seizures
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Primary Generalized Tonic-Clonic Seizures
Keywords: Epilepsy
Lead sponsor: Xenon Pharmaceuticals Inc.
Sponsor class: INDUSTRY
Collaborators: name: Worldwide Clinical Trials
First posted: 2022-12-28
Enrollment: 160
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. 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.
2. Subject is ≥12 years of age with a BMI ≤40 kg/m2 at Visit 1.
3. 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.
4. 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).
5. 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.
6. Subject is able to keep accurate seizure diaries.

Exclusion Criteria:

1. Subject has had status epilepticus within the 12 months prior to Visit 1.
2. Subject has history of repetitive seizures within the 12-month period preceding Visit 1 where the individual seizures cannot be counted.
3. Subject has a history of non-epileptic psychogenic seizures.
4. Subject has a concomitant diagnosis of focal-onset seizures (FOS).
5. Subject has presence or history of a developmental and epileptic encephalopathy, including Lennox-Gastaut syndrome.
6. 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.
7. Subject has history of neurosurgery for seizures \<1 year prior to Visit 1, or radiosurgery \<2 years prior to Visit 1.
8. 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.
9. 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.
10. Any personal circumstance that, in the opinion of the investigator, prevents adherence to the protocol.

The criteria to be eligible for randomization are:

1. 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.
2. 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.
3. 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.

Primary outcomes:
measure: Median percent change (MPC) in monthly (28 days) PGTCS frequency
timeFrame: Baseline through DBP (Week 12)
Secondary outcomes:
measure: Proportion of subjects
timeFrame: Baseline through DBP (Week 12)
measure: Proportion of subjects
timeFrame: Baseline through Week 12
Other outcomes:
measure: Incidence of adverse events
timeFrame: From Screening Through to 56 Days Post-Final Dose
Locations:
city: Mobile
country: United States
facility: University of Alabama - Strada Patient Care Center, Neurology
state: Alabama
city: Phoenix
country: United States
facility: Xenoscience
state: Arizona
city: Tucson
country: United States
facility: University of Arizona - Health Science Center
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Los Angeles
country: United States
facility: Brain Science Research Institute
state: California
city: Orange
country: United States
facility: University of California, Irvine - Health Neurology Services
state: California
city: Sacramento
country: United States
facility: University California, Davis Clinical & Translation Science Center Clinical Research (CCRC)
state: California
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
city: Miami
country: United States
facility: Serenity Research Center, LLC
state: Florida
city: Orlando
country: United States
facility: Research Institute of Orlando, LLC
state: Florida
city: Pensacola
country: United States
facility: Panhandle Research and Medical Clinic
state: Florida
city: Port Charlotte
country: United States
facility: Medsol Clinical Research Center Harbor Professional Centre
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Weston
country: United States
facility: Encore Medical Research of Weston, LLC
state: Florida
city: Atlanta
country: United States
facility: Emory Brain Health Center
state: Georgia
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta
state: Georgia
city: Suwanee
country: United States
facility: Georgia Neurology & Sleep Medicine Associates
state: Georgia
city: Honolulu
country: United States
facility: Hawaii Pacific Neuroscience, Comprehensive Epilepsy Center
state: Hawaii
city: Boise
country: United States
facility: Consultants in Epilepsy and Neurology, PLLC
state: Idaho
city: Springfield
country: United States
facility: Southern Illinois University School of Medicine
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: Bluegrass Epilepsy Research, LLC
state: Kentucky
city: Lexington
country: United States
facility: University of Kentucky Albert B. Chandler Hospital (UK Healthcare)
state: Kentucky
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Baltimore
country: United States
facility: MedStar Franklin Square Medical Center
state: Maryland
city: Bethesda
country: United States
facility: Mid-Atlantic Epilepsy and Sleep Center
state: Maryland
city: Clinton
country: United States
facility: Medstar Georgetown University Hospital
state: Maryland
city: Chestnut Hill
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Worcester
country: United States
facility: UMass Memorial Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Hospitals
state: Michigan
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: East Lansing
country: United States
facility: Michigan State University Department of Neurology
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health
state: Michigan
city: Hackensack
country: United States
facility: Northeast Regional Epilepsy Group
state: New Jersey
city: Amherst
country: United States
facility: Dent Neurosciences Research Facility
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Woodmere
country: United States
facility: Five Towns Neurology
state: New York
city: Charlotte
country: United States
facility: Onsite Clinical Solutions, LLC
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Akron
country: United States
facility: Summa Health Clinical Research Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Columbus
country: United States
facility: OhioHealth Riverside Methodist Hospital
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina (MUSC)
state: South Carolina
city: El Paso
country: United States
facility: ANESC Research
state: Texas
city: Houston
country: United States
facility: UTHealth Science Center at Houston
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Clinical Neurosciences Center
state: Utah
city: Virginia Beach
country: United States
facility: Sentara Neurology Specialists
state: Virginia
city: Seattle
country: United States
facility: University of Washington, Regional Epilepsy Center at Harborview Medical Center
state: Washington
city: Milwaukee
country: United States
facility: Advocate Aurora Research institute, St. Luke's Medical Center
state: Wisconsin
city: Buenos Aires
country: Argentina
facility: Hospital General de Agudos J.M. Ramos Mejia
city: Buenos Aires
country: Argentina
facility: STAT Research S.A.
city: Buenos Aires
country: Argentina
facility: Hospital Italiano
city: San Miguel De Tucumán
country: Argentina
facility: Sanatorio del Sur S.A
city: Kogarah
country: Australia
facility: Southern Neurology
state: New South Wales
city: South Brisbane
country: Australia
facility: Mater Misericordiae Ltd
state: Queensland
city: Heidelberg
country: Australia
facility: Austin Health Pharmacy Clinical Trials
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Melbourne
country: Australia
facility: St Vincent's Hospital Melbourne, Clinical Neurosciences
state: Victoria
city: Parkville
country: Australia
facility: The Royal Melbourne Hospital
city: Innsbruck
country: Austria
facility: University Hospital Innsbruck
city: Linz
country: Austria
facility: Universitaetsklinik fuer Kinder
city: Salzburg
country: Austria
facility: Universitätsklinik für Neurologie
city: Vienna
country: Austria
facility: Universitätsklinik für Neurologie, Medizinische Universität Wien
city: Brussel
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Blagoevgrad
country: Bulgaria
facility: Multiprofile hospital for active treatment Puls AD
city: Sofia
country: Bulgaria
facility: MHATNP 'Sveti Naum' EAD
city: Sofia
country: Bulgaria
facility: First University Multiprofile Hospital for Active Treatment Sofia Sv. Joan Krastitel
city: Lethbridge
country: Canada
facility: Center for Neurologic Research
state: Alberta
city: Vancouver
country: Canada
facility: Children and Women's Health Centre of BC (BC Children's Hospital)
state: British Columbia
city: London
country: Canada
facility: London Health Sciences Center
state: Ontario
city: Montréal
country: Canada
facility: Le Centre Hospitalier de l'Universite' de Montreal (CHUM)
state: Quebec
city: Osijek
country: Croatia
facility: Clinical Hospital Center Osijek
city: Rijeka
country: Croatia
facility: Clinical Hospital Center Rijeka
city: Zagreb
country: Croatia
facility: University Hospital Center Zagreb
city: Prague
country: Czechia
facility: Fakultni nemocnice v Motole Neurologicka klinika 2. LF UK a FN Motol
city: Lille
country: France
facility: CHU de Lille, Hôpital Roger Salengro - Neurophysiologie clinique
city: Lyon
country: France
facility: Hopital Neurologique Pierre Wertheimer, Hospices Civils de Lyon
city: Paris
country: France
facility: Hôpital Fondation A. de Rothschild
city: Rennes
country: France
facility: CHU de Rennes - Hôpital Pontchaillou
city: Strasbourg
country: France
facility: CHU de Strasbourg - Hôpital de Hautepierre
city: Aachen
country: Germany
facility: Universitätsklinikum Aachen
city: Berlin
country: Germany
facility: Vivantes Humboldt Klinikum
city: Bielefeld
country: Germany
facility: Bethel Epilepsy Centre
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt
city: Marburg
country: Germany
facility: Philipps-Universität Marburg
city: München
country: Germany
facility: Klinikum der Universität München
city: Radeberg
country: Germany
facility: Epilepsiezentrum Kleinwachau gemeinnützige GmbH
city: Tuebingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Jerusalem
country: Israel
facility: Hadassah University Medical Center
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center
city: Reẖovot
country: Israel
facility: Kaplan Medical Center
city: Tel Aviv
country: Israel
facility: The Tel Aviv Sourasky Medical Center
city: Ancona
country: Italy
facility: Azienda Ospedaliero Universitaria Ospedali Riuniti Ancona
city: Chieti
country: Italy
facility: Università Degli Studi Gabriele d'Annunzio Di Chieti
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
city: Roma
country: Italy
facility: Ospedalo Pediatrico Bambino Gesu
city: Roma
country: Italy
facility: Policlinico Umberto I
city: Ciudad de México
country: Mexico
facility: Grupo Medico Camino SC
city: Mexico City
country: Mexico
facility: Human Science Research Trials S. de R.L. de C.V.
city: Sinaloa
country: Mexico
facility: Neurociencias Estudios Clínicos S.C
city: Heeze
country: Netherlands
facility: Kempenhaeghe
city: Bydgoszcz
country: Poland
facility: Centrum Medyczne Neuromed
city: Gdańsk
country: Poland
facility: COPERNICUS Podmiot Leczniczy Sp. z o.o.
city: Katowice
country: Poland
facility: Novo-Med Zielinski I Wspolnicy Sp. J.
city: Lublin
country: Poland
facility: NZOZ Neuromed M. i M.
city: Nowa Sól
country: Poland
facility: Twoja Przychodnia Nowosolskie Centrum Medyczne
city: Coimbra
country: Portugal
facility: Centro Hospitalar Universitário de Coimbra (CHUC)
city: Guimarães
country: Portugal
facility: Hospital da Senhora da Oliveira
city: Lisboa
country: Portugal
facility: Centro Hospitalar Lisboa Ocidental, Hospital Egas Moniz
city: Lisboa
country: Portugal
facility: Centre Hospitalar Universitario de Lisboa Norte (CHULN)
city: Matosinhos
country: Portugal
facility: Unidade Local de Saúde de Matosinhos
city: Porto
country: Portugal
facility: Centro Hospitalar Universitário de Santo António
city: Santa Maria Da Feira
country: Portugal
facility: Centro Hospitalar de Entre o Douro e Vouga
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario Vithas Madrid La Milagrosa
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Málaga
city: Valladolid
country: Spain
facility: Hospital Clinico Universitario de Valladolid
city: Valparaiso
country: Spain
facility: Hospital Clinico Viña del Mar
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
state: Wales
city: Wakefield
country: United Kingdom
facility: Mid Yorkshire Hospitals NHS Trust
state: West Yorkshire
city: London
country: United Kingdom
facility: St George's University Hospitals NHS Foundation Trust
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust
city: Oxford
country: United Kingdom
facility: John Radcliffe Hospital
city: Salford
country: United Kingdom
facility: Salford Royal NHS Foundation Trust - Greater Manchester Neuroscience Centre (GMNC)
Study officials:
affiliation: Xenon Pharmaceuticals Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: