A Study to Evaluate XEN1101 as Adjunctive Therapy in Primary Generalized Tonic-Clonic Seizures

Purpose

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).

Condition

  • Primary Generalized Tonic-Clonic Seizures

Eligibility

Eligible Ages
Over 12 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
XEN1101 25 mg/day 		XEN1101 25 mg/day
  • Drug: XEN1101
    XEN1101 capsules
    Other names:
    • Azetukalner
Experimental
XEN1101 15 mg/day 		XEN1101 15 mg/day
  • Drug: XEN1101
    XEN1101 capsules
    Other names:
    • Azetukalner
Placebo Comparator
Placebo 		Placebo
  • Drug: Placebo
    Placebo capsules

Recruiting Locations

University of Alabama - Strada Patient Care Center, Neurology
Mobile 4076598, Alabama 4829764 36604

Xenoscience
Phoenix 5308655, Arizona 5551752 85004

University of Arizona - Health Science Center
Tucson 5318313, Arizona 5551752 85724

University of Arkansas for Medical Sciences
Little Rock 4119403, Arkansas 4099753 72205

Brain Science Research Institute
Los Angeles 5368361, California 5332921 90025

University of California, Irvine - Health Neurology Services
Orange 5379513, California 5332921 92868

University California, Davis Clinical & Translation Science Center Clinical Research (CCRC)
Sacramento 5389489, California 5332921 95817

University of Colorado Anschutz Medical Campus
Aurora 5412347, Colorado 5417618 80045

Serenity Research Center, LLC
Miami 4164138, Florida 4155751 33176

Research Institute of Orlando, LLC
Orlando 4167147, Florida 4155751 32806

Panhandle Research and Medical Clinic
Pensacola 4168228, Florida 4155751 32503

Medsol Clinical Research Center Harbor Professional Centre
Port Charlotte 4169130, Florida 4155751 33952

University of South Florida
Tampa 4174757, Florida 4155751 33606

Encore Medical Research of Weston, LLC
Weston 4178003, Florida 4155751 33331

Emory Brain Health Center
Atlanta 4180439, Georgia 4197000 30329

Children's Healthcare of Atlanta
Atlanta 4180439, Georgia 4197000 30342

Hawaii Pacific Neuroscience, Comprehensive Epilepsy Center
Honolulu 5856195, Hawaii 5855797 96817

Consultants in Epilepsy and Neurology, PLLC
Boise 5586437, Idaho 5596512 83702

Southern Illinois University School of Medicine
Springfield 4250542, Illinois 4896861 62794

Indiana University School of Medicine
Indianapolis 4259418, Indiana 4921868 46202

University of Kansas Medical Center
Kansas City 4273837, Kansas 4273857 66160

Bluegrass Epilepsy Research, LLC
Lexington 4297983, Kentucky 6254925 40504

University of Kentucky Albert B. Chandler Hospital (UK Healthcare)
Lexington 4297983, Kentucky 6254925 40536

University of Maryland Medical Center
Baltimore 4347778, Maryland 4361885 21201

MedStar Franklin Square Medical Center
Baltimore 4347778, Maryland 4361885 21237

Mid-Atlantic Epilepsy and Sleep Center
Bethesda 4348599, Maryland 4361885 20817

Medstar Georgetown University Hospital
Clinton 4351871, Maryland 4361885 20735

Brigham and Women's Hospital
Chestnut Hill 4932957, Massachusetts 6254926 02467

UMass Memorial Medical Center
Worcester 4956184, Massachusetts 6254926 01655

University of Michigan Hospitals
Ann Arbor 4984247, Michigan 5001836 48109

Wayne State University
Detroit 4990729, Michigan 5001836 48201

Michigan State University Department of Neurology
East Lansing 4991640, Michigan 5001836 48824

Spectrum Health
Grand Rapids 4994358, Michigan 5001836 49503

Northeast Regional Epilepsy Group
Hackensack 5098706, New Jersey 5101760 07601

Dent Neurosciences Research Facility
Amherst 5107129, New York 5128638 14226

SUNY Upstate Medical University
Syracuse 5140405, New York 5128638 13201

Onsite Clinical Solutions, LLC
Charlotte 4460243, North Carolina 4482348 28211

Wake Forest Baptist Health
Winston-Salem 4499612, North Carolina 4482348 27104

Summa Health Clinical Research Center
Akron 5145476, Ohio 5165418 44304

Cleveland Clinic Foundation
Cleveland 5150529, Ohio 5165418 44195

The Ohio State University
Columbus 4509177, Ohio 5165418 43210

OhioHealth Riverside Methodist Hospital
Columbus 4509177, Ohio 5165418 43214

University of Pennsylvania
Philadelphia 4560349, Pennsylvania 6254927 19104

Temple University Hospital
Philadelphia 4560349, Pennsylvania 6254927 19140

ANESC Research
El Paso 5520993, Texas 4736286 79912

UTHealth Science Center at Houston
Houston 4699066, Texas 4736286 77030

University of Texas Health Science Center at San Antonio
San Antonio 4726206, Texas 4736286 78229

University of Utah Clinical Neurosciences Center
Salt Lake City 5780993, Utah 5549030 84132

Sentara Neurology Specialists
Virginia Beach 4791259, Virginia 6254928 23456

University of Washington, Regional Epilepsy Center at Harborview Medical Center
Seattle 5809844, Washington 5815135 98104

Advocate Aurora Research institute, St. Luke's Medical Center
Milwaukee 5263045, Wisconsin 5279468 53215

More Details

NCT ID
NCT05667142
Status
Recruiting
Sponsor
Xenon Pharmaceuticals Inc.

Study Contact

Xenon Medical Affairs
1-604-484-3300
XenonCares@xenon-pharma.com

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.