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NCT05667142PHASE3Recruiting

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

Xenon Pharmaceuticals Inc.

Start Date

2/14/2023

Completion Date

6/1/2027

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).

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.

Eligibility Criteria

Age Range: 12 years to No maximum

Key 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 3 months prior to the planned randomization (Visit 2), during screening/baseline, and throughout the DBP. 6. Subject is able to keep accurate seizure diaries. Key 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 within 10 years prior to Visit 1. 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, 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 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. Retrospective seizure data documented up to 4 weeks prior to Visit 1 may be used in combination with a minimum of 4 weeks of prospective seizure data recorded in the study eDiary. 2. Study eDiary was completed a minimum of 80% of all applicable days during the last 28-56 days of the baseline period that preceded randomization as evidence of adequate compliance (eg, \>45 of 56 days, if no retrospective data prior to Visit 1 are used). 3. Subject did not change dose of, stop, or initiate any new ASM(s) during the 3 months that preceded randomization and plans on maintaining a stable dose of ASM(s) during the DBP.

Interventions

DRUG

XEN1101

DRUG

Placebo

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Conditions

Primary Generalized Tonic-Clonic Seizures

Locations

University of Alabama - Strada Patient Care Center, Neurology

Mobile, Alabama 36604

United States

Xenoscience

Phoenix, Arizona 85004

United States

University of Arizona - Health Science Center

Tucson, Arizona 85724

United States

University of Arkansas for Medical Sciences

Little Rock, Arkansas 72205

United States

Brain Science Research Institute

Los Angeles, California 90025

United States

University of California, Irvine - Health Neurology Services

Orange, California 92868

United States

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

Sacramento, California 95817

United States

University of Colorado Anschutz Medical Campus

Aurora, Colorado 80045

United States

Mayo Clinic Florida

Jacksonville, Florida 32224

United States

Serenity Research Center, LLC

Miami, Florida 33176

United States

Research Institute of Orlando, LLC

Orlando, Florida 32806

United States

Panhandle Research and Medical Clinic

Pensacola, Florida 32503

United States

Medsol Clinical Research Center Harbor Professional Centre

Port Charlotte, Florida 33952

United States

University of South Florida

Tampa, Florida 33606

United States

Encore Medical Research of Weston, LLC

Weston, Florida 33331

United States

Emory Brain Health Center

Atlanta, Georgia 30329

United States

Children's Healthcare of Atlanta

Atlanta, Georgia 30342

United States

Georgia Neurology & Sleep Medicine Associates

Suwanee, Georgia 30024

United States

Hawaii Pacific Neuroscience, Comprehensive Epilepsy Center

Honolulu, Hawaii 96817

United States

Consultants in Epilepsy and Neurology, PLLC

Boise, Idaho 83702

United States

Southern Illinois University School of Medicine

Springfield, Illinois 62794

United States

Indiana University School of Medicine

Indianapolis, Indiana 46202

United States

University of Kansas Medical Center

Kansas City, Kansas 66160

United States

Bluegrass Epilepsy Research, LLC

Lexington, Kentucky 40504

United States

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

Lexington, Kentucky 40536

United States

University of Maryland Medical Center

Baltimore, Maryland 21201

United States

MedStar Franklin Square Medical Center

Baltimore, Maryland 21237

United States

Mid-Atlantic Epilepsy and Sleep Center

Bethesda, Maryland 20817

United States

Medstar Georgetown University Hospital

Clinton, Maryland 20735

United States

Brigham and Women's Hospital

Chestnut Hill, Massachusetts 02467

United States

UMass Memorial Medical Center

Worcester, Massachusetts 01655

United States

University of Michigan Hospitals

Ann Arbor, Michigan 48109

United States

Wayne State University

Detroit, Michigan 48201

United States

Michigan State University Department of Neurology

East Lansing, Michigan 48824

United States

Spectrum Health

Grand Rapids, Michigan 49503

United States

Saint Louis University Medical School

St Louis, Missouri 14624

United States

Northeast Regional Epilepsy Group

Hackensack, New Jersey 07601

United States

Dent Neurosciences Research Facility

Amherst, New York 14226

United States

SUNY Upstate Medical University

Syracuse, New York 13201

United States

Five Towns Neurology

Woodmere, New York 11598

United States

Atrium Health

Charlotte, North Carolina 28203

United States

Onsite Clinical Solutions, LLC

Charlotte, North Carolina 28211

United States

Duke University Clinical Research

Durham, North Carolina 27710

United States

Wake Forest Baptist Health

Winston-Salem, North Carolina 27104

United States

Summa Health Clinical Research Center

Akron, Ohio 44304

United States

Cleveland Clinic Foundation

Cleveland, Ohio 44195

United States

The Ohio State University

Columbus, Ohio 43210

United States

OhioHealth Riverside Methodist Hospital

Columbus, Ohio 43214

United States

University of Pennsylvania

Philadelphia, Pennsylvania 19104

United States

Temple University Hospital

Philadelphia, Pennsylvania 19140

United States

UPMC Comprehensive Epilepsy Center

Pittsburgh, Pennsylvania 15213

United States

Medical University of South Carolina (MUSC)

Charleston, South Carolina 29425

United States

ANESC Research

El Paso, Texas 79912

United States

UTHealth Science Center at Houston

Houston, Texas 77030

United States

University of Texas Health Science Center at San Antonio

San Antonio, Texas 78229

United States

University of Utah Clinical Neurosciences Center

Salt Lake City, Utah 84132

United States

Sentara Neurology Specialists

Virginia Beach, Virginia 23456

United States

University of Washington, Regional Epilepsy Center at Harborview Medical Center

Seattle, Washington 98104

United States

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

Milwaukee, Wisconsin 53215

United States

Hospital General de Agudos J.M. Ramos Mejia

Buenos Aires, 1221

Argentina

STAT Research S.A.

Buenos Aires, C1023AAB

Argentina

Hospital Italiano

Buenos Aires, C1181ACH

Argentina

Sanatorio del Sur S.A

San Miguel de Tucumán, 4000

Argentina

Southern Neurology

Kogarah, New South Wales 2217

Australia

Mater Misericordiae Ltd

South Brisbane, Queensland 4101

Australia

The Alfred Hospital

Melbourne, VC 3004

Australia

Austin Health Pharmacy Clinical Trials

Heidelberg, Victoria 3084

Australia

St Vincent's Hospital Melbourne, Clinical Neurosciences

Melbourne, Victoria 3065

Australia

The Royal Melbourne Hospital

Parkville, 3050

Australia

University Hospital Innsbruck

Innsbruck, 6020

Austria

Universitaetsklinik fuer Kinder

Linz, 4021

Austria

Universitätsklinik für Neurologie

Salzburg, 5020

Austria

Universitätsklinik für Neurologie, Medizinische Universität Wien

Vienna, 1090

Austria

Cliniques Universitaires Saint-Luc

Brussels, 1200

Belgium

Universitair Ziekenhuis Gent

Ghent, 9000

Belgium

Multiprofile hospital for active treatment Puls AD

Blagoevgrad, 2700

Bulgaria

MHATNP 'Sveti Naum' EAD

Sofia, 1113

Bulgaria

First University Multiprofile Hospital for Active Treatment Sofia Sv. Joan Krastitel

Sofia, 1142

Bulgaria

Center for Neurologic Research

Lethbridge, Alberta T1J 0N9

Canada

Children and Women's Health Centre of BC (BC Children's Hospital)

Vancouver, British Columbia V6H 3V4

Canada

London Health Sciences Center

London, Ontario N6A5A5

Canada

Le Centre Hospitalier de l'Universite' de Montreal (CHUM)

Montreal, Quebec H2X 0C1

Canada

Centro de investigación Clinica UC-CICUC

Santiago,

Chile

Clinical Hospital Center Osijek

Osijek, 310 00

Croatia

Clinical Hospital Center Rijeka

Rijeka, 510 00

Croatia

University Hospital Center Zagreb

Zagreb, 100 00

Croatia

Fakultni nemocnice v Motole Neurologicka klinika 2. LF UK a FN Motol

Prague, 150 06

Czechia

CHU de Lille, Hôpital Roger Salengro - Neurophysiologie clinique

Lille, 59037

France

Hopital Neurologique Pierre Wertheimer, Hospices Civils de Lyon

Lyon, 9003

France

Hôpital Fondation A. de Rothschild

Paris, 75019

France

CHU de Rennes - Hôpital Pontchaillou

Rennes, 35033

France

CHU de Strasbourg - Hôpital de Hautepierre

Strasbourg, 67098

France

Universitätsklinikum Aachen

Aachen, D-52074

Germany

Vivantes Humboldt Klinikum

Berlin, 13509

Germany

Bethel Epilepsy Centre

Bielefeld, 33617

Germany

Universitätsklinikum Frankfurt

Frankfurt, 60528

Germany

Epilepsiezentrum im Neuozentrum

Freiburg im Breisgau, 79106

Germany

Philipps-Universität Marburg

Marburg, 35043

Germany

Klinikum der Universität München

München, 81377

Germany

Epilepsiezentrum Kleinwachau gemeinnützige GmbH

Radeberg, 01454

Germany

Universitätsklinikum Tübingen

Tübingen, 72076

Germany

Universitätsklinikum Ulm

Ulm, 89081

Germany

Hadassah University Medical Center

Jerusalem, 9112001

Israel

The Chaim Sheba Medical Center

Ramat Gan, 6265601

Israel

Kaplan Medical Center

Rehovot, 7661041

Israel

The Tel Aviv Sourasky Medical Center

Tel Aviv, 64239

Israel

Azienda Ospedaliero Universitaria Ospedali Riuniti Ancona

Ancona, 60126

Italy

Università Degli Studi Gabriele d'Annunzio Di Chieti

Chieti, 66100

Italy

Azienda Ospedaliero Universitaria Pisana

Pisa, 56126

Italy

Ospedalo Pediatrico Bambino Gesu

Roma, 00165

Italy

Policlinico Umberto I

Roma, 185

Italy

Grupo Medico Camino SC

Mexico City, 03310

Mexico

Human Science Research Trials S. de R.L. de C.V.

Mexico City, 14050

Mexico

Neurociencias Estudios Clínicos S.C

Sinaloa, 80020

Mexico

Kempenhaeghe

Heeze, 5591BL VE

Netherlands

Centrum Medyczne Neuromed

Bydgoszcz, 85-163

Poland

COPERNICUS Podmiot Leczniczy Sp. z o.o.

Gdansk, 80-803

Poland

Novo-Med Zielinski I Wspolnicy Sp. J.

Katowice, 40-584

Poland

NZOZ Neuromed M. i M.

Lublin, 20-064

Poland

Twoja Przychodnia Nowosolskie Centrum Medyczne

Nowa Sól, 67-100

Poland

Centro Hospitalar Universitário de Coimbra (CHUC)

Coimbra, 3000-075

Portugal

Hospital da Senhora da Oliveira

Guimarães, 4835-044

Portugal

Centro Hospitalar Lisboa Ocidental, Hospital Egas Moniz

Lisbon, 1349-019

Portugal

Centre Hospitalar Universitario de Lisboa Norte (CHULN)

Lisbon, 1649-035

Portugal

Unidade Local de Saúde de Matosinhos

Matosinhos Municipality, 4450-024

Portugal

Centro Hospitalar Universitário de Santo António

Porto, 4050-342

Portugal

Centro Hospitalar de Entre o Douro e Vouga

Santa Maria da Feira, 4520-211

Portugal

Hospital Universitario 12 de Octubre

Madrid, 280 41

Spain

Hospital Universitario Vithas Madrid La Milagrosa

Madrid, 28010

Spain

Hospital Regional Universitario de Málaga

Málaga, 29010

Spain

Hospital Clinico Universitario de Valladolid

Valladolid, 47003

Spain

Hospital Clinico Viña del Mar

Valparaíso, 2520612

Spain

University Hospital of Wales

Cardiff, Wales CF14 4XW

United Kingdom

Mid Yorkshire Hospitals NHS Trust

Wakefield, West Yorkshire WF1 4DG

United Kingdom

St George's University Hospitals NHS Foundation Trust

London, SW17 0QT

United Kingdom

University College London Hospitals NHS Foundation Trust

London, WC1N 3BG

United Kingdom

John Radcliffe Hospital

Oxford, OX3 9DU

United Kingdom

Salford Royal NHS Foundation Trust - Greater Manchester Neuroscience Centre (GMNC)

Salford, M6 8HD

United Kingdom