A Randomized Study of XEN1101 Versus Placebo in Focal-Onset Seizures (X-TOLE3)

Focal Onset Seizures Clinical Trial

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: NCT05716100
• Other study ID #: XPF-010-302
• Status: Recruiting
• Phase: Phase 3
• Start date: May 9, 2023
• Est. completion date: December 2025

Study information

• Verified date: April 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-TOLE3 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: December 2025
• Est. primary completion date: August 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
Argentina	STAT Resarch S.A.	Buenos Aires
Austria	University Hospital Innsbruck	Innsbruck
Chile	Centro de Investigacion Clinica UC	Santiago
Chile	Clinica Universidad de Los Andes	Santiago
Chile	Hospital Clínico Viña del Mar	Viña Del Mar
Croatia	University Hospital Center Osijek	Osijek
Croatia	Poliklinika Bonifarm	Zagreb
Croatia	University Hospital Center Zagreb	Zagreb
Czechia	EUC Hradec Kralove Clinic	Hradec Králové
Czechia	Forbeli s.r.o.	Prague
Czechia	Nemocnicni lekarna FN Motol / Motol University Hospital	Prague
Italy	Ospedali Riuniti di Ancona	Ancona
Poland	COPERNICUS Podmiot Leczniczy	Gdansk
Poland	NZOZ Neuromed M. i M. Nastaj Sp. P.	Lublin
Poland	Twoja Przychodnia Nowosolskie Centrum Medyczne	Nowa Sól
Poland	MTZ Clinical Research Powered by Pratia	Warsaw
Portugal	Centro Hospitalar Universitário de Coimbra - CHUC	Coimbra
Portugal	Hospital da Senhora da Oliveira	Guimarães
Portugal	Centro Hospitalar de Lisboa Norte	Lisbon
Portugal	Centro Hospitalar Lisboa Ocidental	Lisbon
Portugal	Centro Hospitalar Universitário de Santo António	Porto
Portugal	Hospital Pedro Hispano	Porto
Portugal	Centro Hospitalar de Entre o Douro e Vouga	Santa Maria Da Feira
Spain	Hospital Universitario Cruces	Barakaldo
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	University of California Irvine Health	Orange	California
United States	University of Utah Clinical Neurosciences Center	Salt Lake City	Utah
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Five Towns Neuroscience Research	Woodmere	New York

Sponsors (2)

Lead Sponsor	Collaborator
Xenon Pharmaceuticals Inc.	Worldwide Clinical Trials

Countries where clinical trial is conducted

United States,  Argentina,  Austria,  Chile,  Croatia,  Czechia,  Italy,  Poland,  Portugal,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Median percent change (MPC) in 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 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