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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05667142
Other study ID # XPF-010-303
Secondary ID 2022-502286-16-0
Status Recruiting
Phase Phase 3
First received
Last updated
Start date February 14, 2023
Est. completion date October 2025

Study information

Verified date May 2024
Source Xenon Pharmaceuticals Inc.
Contact Xenon Medical Affairs
Phone 1-604-484-3300
Email XenonCares@xenon-pharma.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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).


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 160
Est. completion date October 2025
Est. primary completion date June 2025
Accepts healthy volunteers No
Gender All
Age group 12 Years and older
Eligibility 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 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 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.

Study Design


Related Conditions & MeSH terms

  • Primary Generalized Tonic-Clonic Seizures
  • Seizures

Intervention

Drug:
XEN1101
XEN1101 capsules
Placebo
Placebo capsules
XEN1101
XEN1101 capsules

Locations

Country Name City State
Australia Melbourne Brain Centre Heidelberg Victoria
Australia Southern Neurology Kogarah New South Wales
Australia The Alfred Hospital Melbourne Victoria
Australia The Royal Melbourne Hospital Parkville
Australia Mater Misericordiae Ltd South Brisbane Queensland
Bulgaria Multiprofile hospital for active treatment Puls AD Blagoevgrad
Bulgaria First University Multiprofile Hospital for Active Treatment Sofia Sv. Joan Krastitel Sofia
Canada Center for Neurologic Research Lethbridge Alberta
Canada London Health Sciences Center London Ontario
Croatia Clinical Hospital Center Osijek Osijek
Croatia Clinical Hospital Center Rijeka Rijeka
Croatia University Hospital Center Zagreb Zagreb
Czechia Motol University Hospital Prague
Italy Policlinico Umberto I Roma
Poland Centrum Medyczne Neuromed Bydgoszcz
Poland COPERNICUS Podmiot Leczniczy Sp. z o.o. Gdansk
Poland NZOZ Neuromed M. i M. Lublin
Poland Twoja Przychodnia Nowosolskie Centrum Medyczne Nowa Sól
Portugal Hospital da Senhora da Oliveira Guimarães
Portugal CHULN Lisboa
Portugal Hospital Egas Moniz Lisboa
Spain Hospital 12 de Octubre Madrid
Spain Hospital Regional Universitario de Málaga Málaga
United Kingdom University Hospital of Wales Cardiff Wales
United States Summa Health Clinical Research Center Akron Ohio
United States Dent Neurosciences Research Facility Amherst New York
United States University of Michigan Hospitals Ann Arbor Michigan
United States University of Colorado Anschutz Medical Campus Aurora Colorado
United States University of Maryland Medical Center Baltimore Maryland
United States Mid-Atlantic Epilepsy and Sleep Center Bethesda Maryland
United States Medical University of South Carolina Charleston South Carolina
United States Michigan State University Department of Neurology East Lansing Michigan
United States Spectrum Health Grand Rapids Michigan
United States Northeast Regional Epilepsy Group Hackensack New Jersey
United States Hawaii Pacific Neuroscience, Comprehensive Epilepsy Center Honolulu Hawaii
United States Indiana University School of Medicine Indianapolis Indiana
United States Bluegrass Epilepsy Research, LLC Lexington Kentucky
United States Kentucky Clinic Lexington Kentucky
United States Brain Science Research Institute Los Angeles California
United States Advocate Aurora Research institute, St. Luke's Medical Center Milwaukee Wisconsin
United States University of Alabama Mobile Alabama
United States UCI Health Neurology Services Orange California
United States Research Institute of Orlando, LLC Orlando Florida
United States Panhandle Research and Medical Clinic Pensacola Florida
United States Temple University Hospital Philadelphia Pennsylvania
United States Xenoscience Phoenix Arizona
United States University of Utah Clinical Neurosciences Center Salt Lake City Utah
United States Regional Epilepsy Center at Harborview Seattle Washington
United States Southern Illinois University School of Medicine Springfield Illinois
United States Georgia Neurology & Sleep Suwanee Georgia
United States SUNY Upstate Medical University Syracuse New York
United States Five Towns Neurology Woodmere New York
United States UMass Memorial Medical Center Worcester Massachusetts

Sponsors (2)

Lead Sponsor Collaborator
Xenon Pharmaceuticals Inc. Worldwide Clinical Trials

Countries where clinical trial is conducted

United States,  Australia,  Bulgaria,  Canada,  Croatia,  Czechia,  Italy,  Poland,  Portugal,  Spain,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Other Incidence of adverse events To assess the safety and tolerability of XEN1101 in subjects with PGTCS (e.g., adverse events). From Screening Through to 56 Days Post-Final Dose
Primary Median percent change (MPC) in monthly (28 days) PGTCS frequency Median percent change (MPC) in monthly (28 days) PGTCS frequency from baseline through the DBP for XEN1101 versus placebo. Baseline through DBP (Week 12)
Secondary Proportion of subjects Proportion of subjects experiencing =50% reduction in monthly (28 days) PGTCS frequency from baseline through the DBP for XEN1101 versus placebo. Baseline through DBP (Week 12)
Secondary Proportion of subjects Proportion of subjects experiencing PGTCS freedom from baseline through the DBP for XEN1101 versus placebo. Baseline through Week 12
See also
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Completed NCT03059381 - Investigation of the Clinical Safety and Efficacy of Long-term Treatment With Fycompa Tablets in Adolescence Epilepsy Patients With Partial-onset Seizures (With or Without Secondary Generalized Seizures) or Primary Generalized Tonic-clonic Seizures
Completed NCT03059329 - Investigation of the Clinical Safety and Efficacy of Long-term Treatment With Fycompa Tablets in Adult Epilepsy Patients With Partial-onset Seizures (With or Without Secondary Generalized Seizures) or Primary Generalized Tonic-clonic Seizures
Completed NCT02736162 - Study to Investigate Dosage, Efficacy, and Safety of Perampanel Given as Monotherapy in Patients With Epilepsy N/A