A Study to Evaluate XEN1101 as Adjunctive Therapy in Primary Generalized Tonic-Clonic Seizures (X-ACKT)

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

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).

Study Overview

• Status: Recruiting
• Conditions: Primary Generalized Tonic-Clonic Seizures
• Intervention / Treatment: Drug: Placebo; Drug: XEN1101

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.

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Xenon Medical Affairs; Phone Number: 1-604-484-3300; Email: XenonCares@xenon-pharma.com

Study Locations

• Australia
  • Parkville, Australia, 3050
    • Recruiting
    • The Royal Melbourne Hospital
  • New South Wales
    • Kogarah, New South Wales, Australia, 2217
      • Recruiting
      • Southern Neurology
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Recruiting
      • Mater Misericordiae Ltd
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Recruiting
      • Melbourne Brain Centre
    • Melbourne, Victoria, Australia, 3004
      • Recruiting
      • The Alfred Hospital
• Bulgaria
  • Blagoevgrad, Bulgaria, 2700
    • Recruiting
    • Multiprofile Hospital for Active Treatment Puls AD
  • Sofia, Bulgaria, 1142
    • Recruiting
    • First University Multiprofile Hospital for Active Treatment Sofia Sv. Joan Krastitel
• Canada
  • Alberta
    • Lethbridge, Alberta, Canada, T1J 0N9
      • Recruiting
      • Center For Neurologic Research
  • Ontario
    • London, Ontario, Canada, N6A5A5
      • Recruiting
      • London Health Sciences Center
• Croatia
  • Osijek, Croatia, 310 00
    • Recruiting
    • Clinical Hospital Center Osijek
  • Rijeka, Croatia, 510 00
    • Recruiting
    • Clinical Hospital Center Rijeka
  • Zagreb, Croatia, 100 00
    • Recruiting
    • University Hospital Center Zagreb
• Czechia
  • Prague, Czechia, 150 06
    • Recruiting
    • Motol University Hospital
• Italy
  • Roma, Italy, 185
    • Recruiting
    • Policlinico Umberto I
• Poland
  • Bydgoszcz, Poland, 85-163
    • Recruiting
    • Centrum Medyczne Neuromed
  • Gdańsk, Poland, 80-803
    • Recruiting
    • Copernicus Podmiot Leczniczy Sp. z o.o.
  • Lublin, Poland, 20-064
    • Recruiting
    • NZOZ Neuromed M. i M.
  • Nowa Sól, Poland, 67-100
    • Recruiting
    • Twoja Przychodnia Nowosolskie Centrum Medyczne
• Portugal
  • Guimarães, Portugal, 4835-044
    • Recruiting
    • Hospital da Senhora da Oliveira
• Spain
  • Madrid, Spain, 280 41
    • Recruiting
    • Hospital 12 de Octubre
• United States
  • Alabama
    • Mobile, Alabama, United States, 36604
      • Recruiting
      • University of Alabama
  • Arizona
    • Phoenix, Arizona, United States, 85004
      • Recruiting
      • Xenoscience
  • California
    • Los Angeles, California, United States, 90025
      • Recruiting
      • Brain Science Research Institute
    • Orange, California, United States, 92868
      • Recruiting
      • UCI Health Neurology Services
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Anschutz Medical Campus
  • Florida
    • Orlando, Florida, United States, 32806
      • Recruiting
      • Research Institute of Orlando, LLC
      • Contact: Ahmed Sadek, M.D.
    • Pensacola, Florida, United States, 32503
      • Recruiting
      • Panhandle Research and Medical Clinic
  • Georgia
    • Suwanee, Georgia, United States, 30024
      • Recruiting
      • Georgia Neurology & Sleep
  • Hawaii
    • Honolulu, Hawaii, United States, 96817
      • Recruiting
      • Hawaii Pacific Neuroscience, Comprehensive Epilepsy Center
  • Illinois
    • Springfield, Illinois, United States, 62794
      • Recruiting
      • Southern Illinois University School of Medicine
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Indiana University School of Medicine
  • Kentucky
    • Lexington, Kentucky, United States, 40504
      • Recruiting
      • Bluegrass Epilepsy Research, LLC
    • Lexington, Kentucky, United States, 40536
      • Recruiting
      • Kentucky Clinic
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Recruiting
      • Mid-Atlantic Epilepsy and Sleep Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University Of Michigan Hospitals
    • East Lansing, Michigan, United States, 48824
      • Recruiting
      • Michigan State University Department of Neurology
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Recruiting
      • Northeast Regional Epilepsy Group
  • New York
    • Amherst, New York, United States, 14226
      • Recruiting
      • Dent Neurosciences Research Facility
    • Syracuse, New York, United States, 13201
      • Recruiting
      • SUNY Upstate Medical University
    • Woodmere, New York, United States, 11598
      • Recruiting
      • Five Towns Neurology
  • Ohio
    • Akron, Ohio, United States, 44304
      • Recruiting
      • Summa Health Clinical Research Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Recruiting
      • Temple University Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Recruiting
      • University of Utah Clinical Neurosciences Center
  • Washington
    • Seattle, Washington, United States, 98104
      • Recruiting
      • Regional Epilepsy Center at Harborview
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Recruiting
      • Advocate Aurora Research institute, St. Luke's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo capsules
Experimental: XEN1101 25 mg/day	Drug: XEN1101; XEN1101 capsules
Experimental: XEN1101 15 mg/day	Drug: XEN1101; XEN1101 capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
Proportion of subjects	Proportion of subjects experiencing PGTCS freedom from baseline through the DBP for XEN1101 versus placebo.	Baseline through Week 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Xenon Pharmaceuticals Inc.
• Collaborators: Worldwide Clinical Trials
• Investigators: Study Director: Medical Director, Xenon Pharmaceuticals Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2023
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: December 19, 2022
• First Submitted That Met QC Criteria: December 27, 2022
• First Posted (Actual): December 28, 2022

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 5, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Epilepsy
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Seizures
• Other Study ID Numbers: XPF-010-303

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No