Clinical trial NCT05718817: An Open-label Study of XEN1101 in Epilepsy
Official title: A Multicenter, Open-label, Long-term, Safety, Tolerability, and Efficacy Study of XEN1101 in Subjects Diagnosed With Epilepsy
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE3
Conditions: Focal Epilepsy
Tonic-Clonic Seizures
Keywords: Epilepsy
Seizures
Lead sponsor: Xenon Pharmaceuticals Inc.
Sponsor class: INDUSTRY
Collaborators: name: Worldwide Clinical Trials
First posted: 2023-02-08
Enrollment: 880
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. 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.
2. 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.
3. 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.
4. Subject is able to keep accurate seizure diaries.

Exclusion Criteria:

1. Subject met any of the withdrawal criteria while in Study X-TOLE2, X-TOLE3, or X-ACKT.
2. 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.
3. 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.

Primary outcomes:
measure: The adverse events
timeFrame: From the start of treatment in the open-label extension (OLE) study through 8 weeks after the last dose.
Secondary outcomes:
measure: Change in monthly seizure rate
timeFrame: From baseline through the active extension treatment (Week 156).
measure: Proportion of responders
timeFrame: From baseline through the active extension treatment (Week 156).
measure: Change in Clinical Global Impression of Severity (CGI-S)
timeFrame: From baseline through the active extension treatment (Week 156).
measure: Change in Patient Global Impression of Severity (PGI-S)
timeFrame: From baseline through the active extension treatment (Week 156).
measure: Change in Quality of Life in Epilepsy Inventory (QOLIE-31)
timeFrame: From baseline through the active extension treatment (Week 156).
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Xenoscience
state: Arizona
city: Little Rock
country: United States
facility: Clinical Trials, Inc
state: Arkansas
city: Los Angeles
country: United States
facility: Brain Science Research Institute
state: California
city: Orange
country: United States
facility: UC Irvine Health
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital Anschutz Outpatient Pavilion
state: Colorado
city: Orlando
country: United States
facility: Research Institute of Orlando, LLC
state: Florida
city: Pensacola
country: United States
facility: Panhandle Research & Medical Clinic
state: Florida
city: Weston
country: United States
facility: Encore Medical Research of Weston, LLC
state: Florida
city: Honolulu
country: United States
facility: Hawaii Pacific Neuroscience
state: Hawaii
city: Boise
country: United States
facility: Consultants in Epilepsy and Neurology
state: Idaho
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: Kansas City
country: United States
facility: The 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: Kentucky Clinic
state: Kentucky
city: Scarborough
country: United States
facility: MMP Neurology
state: Maine
city: Bethesda
country: United States
facility: Mid-Atlantic Epilepsy and Sleep Center
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan Hospitals
state: Michigan
city: East Lansing
country: United States
facility: Michigan State University
state: Michigan
city: Grand Rapids
country: United States
facility: Cornwell Health (Spectrum Health Hospitals)
state: Michigan
city: Hackensack
country: United States
facility: Northeast Epilepsy Group
state: New Jersey
city: Bronx
country: United States
facility: Montefiiore Medical Center
state: New York
city: Buffalo
country: United States
facility: Dent Neurosciences Research Center
state: New York
city: New York
country: United States
facility: New York University Comprehensive Epilepsy Center
state: New York
city: New York
country: United States
facility: Mount Sinai Health
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Raleigh
country: United States
facility: Meridian Clinical Research, LLC
state: North Carolina
city: Akron
country: United States
facility: Summa Health
state: Ohio
city: Portland
country: United States
facility: Providence Neurological Specialities
state: Oregon
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Austin
country: United States
facility: Austin Epilepsy Care Center
state: Texas
city: El Paso
country: United States
facility: ANESC Research
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Clinical Neurosciences Center
state: Utah
city: Roanoke
country: United States
facility: Carilion Clinic
state: Virginia
city: Virginia Beach
country: United States
facility: Sentara Neurology Specialists
state: Virginia
city: Seattle
country: United States
facility: University of Washington Main Hospital
state: Washington
city: Milwaukee
country: United States
facility: Aurora St. Luke's Medical Center
state: Wisconsin
city: Buenos Aires
country: Argentina
facility: Hospital General de Agudos "José M. Ramos Mejía"
city: Buenos Aires
country: Argentina
facility: STAT Research S.A.
city: Buenos Aires
country: Argentina
facility: FLENI (Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia)
city: Florencio Varela
country: Argentina
facility: Hospital De Alta Complejidad en Red El Cruce - Dr Nester Carlos Kirchner Servicio de Atencion Medica Integral Para la Communidad
city: Tucumán
country: Argentina
facility: Sanatorio del SUR S.A.
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
city: Fitzroy
country: Australia
facility: St Vincent's Hospital Melbourne
city: Heidelberg
country: Australia
facility: Austin Health Pharmacy Clinical Trials
city: Kogarah
country: Australia
facility: Southern Neurology
city: Melbourne
country: Australia
facility: Alfred Hospital Neurology CT Dept of Neuroscience
city: Parkville
country: Australia
facility: The Royal Melbourne Hospital
city: South Brisbane
country: Australia
facility: Mater Misericordiae Ltd South Brisbane
city: Westmead
country: Australia
facility: Westmead Hospital Dept. of Neurology Epilepsy Unit
city: Innsbruck
country: Austria
facility: University Hospital Innsbruck
city: Blagoevgrad
country: Bulgaria
facility: Hospital for active treatmnt Puls AD Neurology Dpt
city: Sofia
country: Bulgaria
facility: MHATNP St. Naum
city: Lethbridge
country: Canada
facility: Center for Neurologic Research
state: Alberta
city: Santiago
country: Chile
facility: Centro de investigación Clinica UC
city: Viña Del Mar
country: Chile
facility: Hospital Clinico Viña del Mar
city: Zagreb
country: Croatia
facility: Altavita Centar j.d.o.o.
city: Zagreb
country: Croatia
facility: University Hospital Centre Zagreb
city: Prague
country: Czechia
facility: Motol University Hospital
city: Prague
country: Czechia
facility: Forbeli s.r.o.
city: Lyon
country: France
facility: Hopital Neurologique Pierre Wertheimer, Hospices Civils de Lyon
city: Paris
country: France
facility: Hôpital Fondation Adolphe de Rothschild
city: Rennes
country: France
facility: CHU De Rennes - Hôpital Pontchaillou
city: Tbilisi
country: Georgia
facility: American Hospital Network LLC
city: Bielefeld
country: Germany
facility: Krankenhaus Mara gGmbH
city: Frankfurt
country: Germany
facility: Universitätsklinikum, ZNN - Epilepsiezentrum Frankfurt Rhein-Main
city: München
country: Germany
facility: Klinikum der Universität München
city: Ulm
country: Germany
facility: Universitaets-Und Rehabilitations Ulm (RKU)
city: Budapest
country: Hungary
facility: Semmelweis Egyetem, Idegsebeszeti es Neurointervencios Klinika
city: Jerusalem
country: Israel
facility: Hadassah Medical Center (HMC)
city: Reẖovot
country: Israel
facility: Kaplan Medical Center (KMC)
city: Tel Aviv
country: Israel
facility: The Tel Aviv Sourasky Medical Center
city: Bologna
country: Italy
facility: IRCCS Istituto delle Scienze Neurologiche Bologna
city: Chieti
country: Italy
facility: Universita' Degli Studi Gabriele d'Annunzio Di Chieti
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
city: Roma
country: Italy
facility: Azienda Ospedaliero Universitaria Policlinico Umberto I
city: Ciudad de México
country: Mexico
facility: Grupo Medico Camino SC
city: Mexico City
country: Mexico
facility: Human Science Research Trials
city: Bydgoszcz
country: Poland
facility: Centrum Medyczne Neuromed
city: Gdańsk
country: Poland
facility: COPERNICUS Podmiot Leczniczy Sp. z o.o.
city: Lublin
country: Poland
facility: NZOZ Neuromed M. i M.
city: Nowa Sól
country: Poland
facility: Twoja Przychodnia Nowosolskie Centrum Medyczne
city: Warsaw
country: Poland
facility: MTZ Clinical Research Powered by Pratia
city: Warszawa
country: Poland
facility: Neurosphera Sp z o.o.
city: Coimbra
country: Portugal
facility: Centro Hospitalar Universitário de Coimbra (CHUC)
city: Guimarães
country: Portugal
facility: Hospital Senhora da Oliviera de Guimaraes
city: Lisboa
country: Portugal
facility: Centro Hospitalar Lisboa Ocidental, EPE - Hospital Egas Moniz
city: Porto
country: Portugal
facility: Centro Hospitalar Universitario de Santo António, E.P.E
city: Porto
country: Portugal
facility: Unidade Local Saúde Matosinhos
city: Santa Maria Da Feira
country: Portugal
facility: Centro Hospitalar de Entre o Douro e Vouga
city: Baracaldo
country: Spain
facility: Hospital Universitario Cruces
city: Barcelona
country: Spain
facility: Vall d'Hebron Hospital
city: Madrid
country: Spain
facility: Hospital Vithas La Milagrosa
city: Madrid
country: Spain
facility: Hospital Ramón Y Cajal
city: Madrid
country: Spain
facility: Hospital Ruber Internacional
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz
city: Málaga
country: Spain
facility: Hospital Regional De Malaga
city: Valencia
country: Spain
facility: Hospital La Fe
city: Valladolid
country: Spain
facility: Hospital Clinico Universitario de Valladolid
city: Cardiff
country: United Kingdom
facility: Cardiff and Vale UHB
state: Wales
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital Birmingham
city: London
country: United Kingdom
facility: St George's Hospital NHS Foundation Trust
city: London
country: United Kingdom
facility: University College London
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: