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 Genders
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 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

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
Placebo Comparator
Placebo 		Placebo
  • Drug: Placebo
    Placebo capsules
Experimental
XEN1101 15 mg/day 		XEN1101 15 mg/day
  • Drug: XEN1101
    XEN1101 capsules

Recruiting Locations

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

Xenoscience
Phoenix, Arizona 85004

University of Arkansas for Medical Sciences
Little Rock, Arkansas 72205

Brain Science Research Institute
Los Angeles, California 90025

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

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

University of Colorado Anschutz Medical Campus
Aurora, Colorado 80045

Serenity Research Center, LLC
Miami, Florida 33176

Research Institute of Orlando, LLC
Orlando, Florida 32806

Panhandle Research and Medical Clinic
Pensacola, Florida 32503

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

University of South Florida
Tampa, Florida 33606

Encore Medical Research of Weston, LLC
Weston, Florida 33331

Emory Brain Health Center
Atlanta, Georgia 30329

Georgia Neurology & Sleep Medicine Associates
Suwanee, Georgia 30024

Hawaii Pacific Neuroscience, Comprehensive Epilepsy Center
Honolulu, Hawaii 96817

Consultants in Epilepsy and Neurology, PLLC
Boise, Idaho 83702

Southern Illinois University School of Medicine
Springfield, Illinois 62794

Indiana University School of Medicine
Indianapolis, Indiana 46202

University of Kansas Medical Center
Kansas City, Kansas 66160

Bluegrass Epilepsy Research, LLC
Lexington, Kentucky 40504

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

University of Maryland Medical Center
Baltimore, Maryland 21201

Mid-Atlantic Epilepsy and Sleep Center
Bethesda, Maryland 20817

Brigham and Women's Hospital
Chestnut Hill, Massachusetts 02467

UMass Memorial Medical Center
Worcester, Massachusetts 01655

University of Michigan Hospitals
Ann Arbor, Michigan 48109

Wayne State University
Detroit, Michigan 48201

Michigan State University Department of Neurology
East Lansing, Michigan 48824

Spectrum Health
Grand Rapids, Michigan 49503

Northeast Regional Epilepsy Group
Hackensack, New Jersey 07601

Dent Neurosciences Research Facility
Amherst, New York 14226

SUNY Upstate Medical University
Syracuse, New York 13201

Five Towns Neurology
Woodmere, New York 11598

Wake Forest Baptist Health
Winston-Salem, North Carolina 27104

Summa Health Clinical Research Center
Akron, Ohio 44304

Cleveland Clinic Foundation
Cleveland, Ohio 44195

The Ohio State University
Columbus, Ohio 43210

OhioHealth Riverside Methodist Hospital
Columbus, Ohio 43214

University of Pennsylvania
Philadelphia, Pennsylvania 19104

Temple University Hospital
Philadelphia, Pennsylvania 19140

Medical University of South Carolina (MUSC)
Charleston, South Carolina 29425

ANESC Research
El Paso, Texas 79912

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

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

Sentara Neurology Specialists
Virginia Beach, Virginia 23456

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

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