A Randomized Study of XEN1101 Versus Placebo in Focal-Onset Seizures

Focal Onset Seizures Clinical Trial

— X-TOLE2  

Official title:

A Randomized, Double-blind, Placebo-Controlled, Multicenter Phase 3 Study to Evaluate the Safety, Tolerability, and Efficacy of XEN1101 as Adjunctive Therapy in Focal-Onset Seizures

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05614063
• Other study ID #: XPF-010-301
• Secondary ID: 2022-502000-73-0
• Status: Recruiting
• Phase: Phase 3
• Start date: November 18, 2022
• Est. completion date: June 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
• Study type: Interventional

Clinical Trial Summary

The X-TOLE2 Phase 3 clinical trial is a randomized, double-blind, placebo-controlled study that will evaluate the clinical efficacy, safety and tolerability of XEN1101 administered as adjunctive therapy in focal-onset seizures.

Description:

Approximately 360 subjects will be randomized in a blinded manner to one of two active treatment groups or placebo in a 1:1:1 fashion (XEN1101 25 mg : 15 mg : Placebo). Eligible subjects will have up to 9.5 weeks of baseline to assess frequency of seizures, followed by 12 weeks of blinded treatment. In order to be included in the study, subjects must be treated with a stable dose of 1 to 3 allowable antiseizure medications (ASMs) for at least one month prior to screening, during baseline, and throughout the double-blind treatment period (DBP) of the study. 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 qualify and enroll in a separate open-label extension (OLE) study for continued treatment with XEN1101. Subjects who do not enroll in the OLE will enter a 8-week post treatment follow-up period.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 360
• Est. completion date: June 2025
• Est. primary completion date: April 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Be properly informed of the nature and risks of the study and give informed consent in writing, prior to entering the study

• Diagnosis (=2 years) of focal epilepsy according to the International League Against Epilepsy (ILAE) Classification of Epilepsy (2017). 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.

• Treatment with a stable dose of 1 to 3 allowable current ASMs for at least one month prior to screening, during baseline, and throughout the duration of the DBP

• Able to keep accurate seizure diaries

Exclusion Criteria:

• Previously documented electroencephalogram which shows any pattern not consistent with focal etiology of seizures.

• History of focal aware non-motor seizures only, non-epileptic psychogenic seizure, primary generalized seizure, developmental and epileptic encephalopathy, including Lennox-Gastaut syndrome.

• 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.

• History of status epilepticus or repetitive seizures within the 12-month period preceding Visit 1 where the individual seizures cannot be counted.

• History of neurosurgery for seizures <1 year prior to Visit 1, or radiosurgery <2 years prior to enrollment.

• Any medical condition or personal circumstance that, in the opinion of the investigator, exposes the subject to unacceptable risk by participating in the study or prevents adherence to the protocol.

Related Conditions & MeSH terms

• Focal Onset Seizures
• Seizures

Intervention

Drug:
• XEN1101
XEN1101 Capsules
• Placebo
Placebo Capsules

Locations

Country	Name	City	State
Australia	The University of Queensland (UQ)	Brisbane	Queensland
Australia	Royal Prince Alfred Hospital (RAPH)	Camperdown	New South Wales
Australia	St Vincent's Hospital Melbourne	Fitzroy	Melbourne
Australia	Austin Health Pharmacy Clinical Trials	Heidelberg	Victoria
Australia	Southern Neurology	Kogarah
Australia	Alfred Health	Melbourne
Australia	The Royal Melbourne Hospital	Melbourne
Australia	Westmead Hospital	Westmead	New South Wales
Bulgaria	MHAT Puls AD	Blagoevgrad
Bulgaria	First Multiprofile Hospital for Active Treatment	Sofia
Canada	Center For Neurologic Research	Lethbridge	Alberta
Canada	London Health Sciences Centre	London	Ontario
Canada	Le Centre Hospitalier de l'Universite' de Montreal (CHUM)	Montréal	Quebec
Italy	Istituto delle Scienze Neurologiche di Bologna	Bologna
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa
Italy	Universita' La Sapienza di Roma	Rome
Poland	Centrum Medyczne Neuromed	Bydgoszcz
Poland	NZOZ Novo-Med	Katowice
Poland	Clinical Best Solutions	Lublin
Spain	Unitat d'Assaigs Clínics. Servei de Farmàcia	Barcelona
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital Ramón y Cajal	Madrid
Spain	Hospital Ruber Internacional	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Vithas La Milagrosa	Madrid
Spain	IIS-Fundacion Jimenez Diaz/Farmacia	Madrid
Spain	Hospital Regional De Malaga	Málaga
Spain	Hospital Universitario y Politecnico La Fe	Valencia
Spain	Hospital Clínico Universitario Valladolid	Valladolid
United Kingdom	Queen Elizabeth Hospital	Birmingham
United Kingdom	University Hospital of Wales	Cardiff
United Kingdom	Clinical Trials	Dundee
United Kingdom	Northern Care Alliance NHS Foundation Trust	Salford
United States	Summa Health	Akron	Ohio
United States	University of Michigan	Ann Arbor	Michigan
United States	Anschutz Health Sciences	Aurora	Colorado
United States	Austin Epilepsy Care Center (AECC)	Austin	Texas
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	Mid-Atlantic Epilepsy and Sleep Center	Bethesda	Maryland
United States	Consultants in Epilepsy and Neurology	Boise	Idaho
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Dent Neurosciences Research Center	Buffalo	New York
United States	Minneapolis Clinic of Neurology	Burnsville	Minnesota
United States	Rush University Medical Center	Chicago	Illinois
United States	Duke Neurology	Durham	North Carolina
United States	Michigan State University	East Lansing	Michigan
United States	ANESC Research	El Paso	Texas
United States	Cornwell Health	Grand Rapids	Michigan
United States	Northeast Epilepsy Group	Hackensack	New Jersey
United States	Hawaii Pacific Neuroscience	Honolulu	Hawaii
United States	University of Texas Health Science Center	Houston	Texas
United States	Indiana University School of Medicine	Indianapolis	Indiana
United States	Bluegrass Epilepsy Research, LLC	Lexington	Kentucky
United States	UK HealthCare - Kentucky Neuroscience Institute (KNI)	Lexington	Kentucky
United States	Clinical Trials, Inc	Little Rock	Arkansas
United States	Brain Science Research Institute	Los Angeles	California
United States	Aurora St. Luke's Medical Center	Milwaukee	Wisconsin
United States	Strada Patient Care Center	Mobile	Alabama
United States	Mount Sinai Medical Center	New York	New York
United States	NYPH WCMC-Research Pharmacy	New York	New York
United States	NYU Langone	New York	New York
United States	Research Institute of Orlando, LLC	Orlando	Florida
United States	Panhandle Research & Medical Clinic	Pensacola	Florida
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Xenoscience	Phoenix	Arizona
United States	Providence Brain & Spine Institute	Portland	Oregon
United States	Meridian Clinical Research	Raleigh	North Carolina
United States	Carilion Clinic - Neurology	Roanoke	Virginia
United States	UC Davis Medical Center	Sacramento	California
United States	Washington University, St. Louis	Saint Louis	Missouri
United States	CPMC Research Institute	San Francisco	California
United States	MMP Neurology	Scarborough	Maine
United States	University of Washington Main Hospital	Seattle	Washington
United States	Georgia Neurology and Sleep Medicine Associates	Suwanee	Georgia
United States	SUNY Upstate Medical University	Syracuse	New York
United States	University of Toledo Medical Center	Toledo	Ohio
United States	Sentara Neurology Specialists	Virginia Beach	Virginia
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,  Italy,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Median percent change (MPC) in monthly (28 days) focal seizure frequency from baseline to DBP for XEN1101 versus placebo.		From baseline through to the double blind period (week 12)
Secondary	Proportion of subjects experiencing =50% reduction in monthly (28 days) focal seizure frequency from baseline through the DBP for XEN1101 versus placebo.		From baseline through to the double blind period (week 12)
Secondary	MPC in weekly (7 days) focal seizure frequency from baseline to Week 1 for XEN1101 versus placebo.		From baseline through to the week 1
Secondary	Proportion of subjects experiencing "at least much improved" (including "much" and "very much improved") in Patient Global Impression of Change (PGI-C).		From baseline through to the double blind period (week 12)
Secondary	To assess adverse events as criteria for safety and tolerability of XEN1101		From screening through to 56 days post-final dose.