A Study to Evaluate XEN1101 as Adjunctive Therapy in Focal Epilepsy

Focal Epilepsy Clinical Trial

— X-TOLE  

Official title:

A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Safety, Tolerability and Efficacy of XEN1101 as Adjunctive Therapy in Focal-onset Epilepsy, With an Open-label Extension

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03796962
• Other study ID #: XPF-008-201
• Secondary ID: 2018-003221-29
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 30, 2019
• Est. completion date: October 2028

Study information

• Verified date: April 2024
• Source: Xenon Pharmaceuticals Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The XEN1101 Phase 2 clinical trial is a randomized, double-blind, placebo-controlled study that will evaluate the clinical efficacy, safety and tolerability of increasing doses of XEN1101 administered as adjunctive treatment in adult patients diagnosed with focal epilepsy, followed by an optional open-label extension (OLE).

Description:

The XEN1101 Phase 2 clinical trial is designed as a randomized, double-blind, placebo-controlled, multicenter study with an optional open-label extension (OLE) to evaluate the clinical efficacy, safety and tolerability of XEN1101 administered as adjunctive treatment in adult patients aged 18 to 75 years diagnosed with focal epilepsy. Approximately 300 patients will be randomized in a blinded manner to one of three active treatment groups or placebo in a 2:1:1:2 fashion (XEN1101 25 mg : 20 mg : 10 mg : Placebo). After screening, patients will have 8 weeks of baseline to assess frequency of seizures, followed by 8 weeks of treatment and a 6-week post treatment follow-up period. In order to be included in the study, patients must already be treated with a stable dose of 1 to 3 allowable current anti-epileptic drugs for at least one month prior to screening, during baseline, and throughout the double-blind portion (DBP) of the study. During the treatment period, patients will be given XEN1101 or placebo once daily in the evening. An OLE will be available to eligible patients who complete the DBP. All patients will receive a 20 mg daily dose of XEN1101 during this extension period.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 325
• Est. completion date: October 2028
• Est. primary completion date: September 2, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Key Inclusion Criteria:

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

• BMI =40 kg/m2

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

• Prior neuroimaging within the last 10 years and documentation is available

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

• Must be willing to comply with the contraception requirements

• Males must agree not to donate sperm from the time of the first administration of study drug until 6 months after the last dose. Females must agree not to donate ova from the time of the first administration of study drug until 6 months after the last dose.

• Able to keep accurate seizure diaries

Key Exclusion Criteria:

• History of pseudoseizures, psychogenic seizures, primary generalized seizure, or focal aware non-motor seizures only

• Presence or previous history of Lennox-Gastaut syndrome

• Seizures secondary to other diseases or conditions

• History of repetitive seizures within the last 12 months where the individual seizures cannot be counted

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

• Schizophrenia and other psychotic disorders, or active suicidal plan/intent in the past 6 months, or a history of suicide attempt in the last 2 years, or more than 1 lifetime suicide attempt

• History or presence of any significant medical or surgical condition or uncontrolled medical illness at screening, or history of cancer within the past 2 years, with the exception of appropriately treated basal cell or squamous cell carcinoma

• Any clinically significant abnormalities on pre-study physical examination, vital signs, laboratory values or ECG indicating a medical problem that would preclude study participation including but not limited to:

1. History of presence of long QT syndrome; QTcF > 450 msec at baseline; family history of sudden death of unknown cause

2. History of skin or retinal pigment epithelium abnormalities caused by ezogabine

• Past use of vigabatrin without stable visual fields tested twice over the 12 months after the last dose of vigabatrin (concomitant use of vigabatrin is not allowed)

• If felbamate is used as a concomitant AED, patients must be taking it for at least 2 years, with a stable dose for 2 months (or no less than 49 days) and acceptable hematology and LFT history and values prior to Screening. If received in the past, felbamate must have been discontinued 2 months (or no less than 49 days) prior to Screening.

• Have had multiple drug allergies or a severe drug reaction to an AED(s), including dermatological (e.g., Stevens-Johnson syndrome), hematological, or organ toxicity reactions

• Current use of a ketogenic diet

Related Conditions & MeSH terms

• Epilepsies, Partial
• Epilepsy
• Focal Epilepsy

Intervention

Drug:
• XEN1101
Oral dose

Locations

Country	Name	City	State
Canada	London Health Sciences Center	London	Ontario
Canada	University Health Network-Toronto Western Hospital	Toronto	Ontario
Canada	Children's and Women's Health Centre of British Columbia (BC Children's Hospital)	Vancouver	British Columbia
Georgia	LLC Arensia Exploratory Medicine	Tbilisi
Germany	Epilepsiezentrum Berlin-Brandenburg	Berlin
Germany	Bethel Epilepsy Centre	Bielefeld
Germany	Univ.-Klinik Bonn, Klinik und Poliklinik fur Epileptologie	Bonn
Germany	Universitatsklinikym Frankfurt	Frankfurt
Germany	Universitatsklinikum Freiburg, Neurozentrum/Epilepsiezentrum	Freiburg
Germany	University Hospital Munster (UKM)	Muenster
Germany	Klinikum Osnabruck	Osnabrück
Germany	Krankenhaus Barmherzige Brueder Regensburg	Regensburg
Germany	University of Tubingen-Dept. of Neurology and Epileptology	Tübingen
Italy	IRCCS- Istituto delle Scienze Neurologiche, Bellaria Hospital	Bologna
Italy	Dipartimento Scienze Mediche e Chirurgiche, Universita Magna Graecia di Catanzaro	Catanzaro
Italy	Fondazione IRCCS Istituto Neurologico C. Besta	Milano
Italy	IRCCS Istituto Neurologico Nazionale C. Mondino	Pavia
Italy	Azienda Ospedaliera Universita' Pisana	Pisa
Italy	Azienda Ospedaliera "Bianchi-Melacrino-Morelle"di Reggio Calabria	Reggio Calabria
Italy	Policlinico di Roma Umberto I	Roma
Moldova, Republic of	PMSI Republican Clinical Hospital, ARENSIA Exploratory Medicine	Chisinau
Spain	Hospital Germans Trias I Pujol	Badalona	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Hospital Vithas La Salud	Granada
Spain	Hospital Ruber Internacional	Madrid
Spain	Hospital U. Clínico San Carlos	Madrid
Spain	Hospital U. Ramón y Cajal	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	Hospital Regional Universitario de Málaga	Málaga
Spain	Clínica Universidad Navarra	Pamplona	Navarra
Spain	Centro de Neurologia Avanzada	Sevilla	Andalusia
Spain	Hospital Virgen Macarena	Sevilla	Andalusia
Spain	Hospital Universitario y Politécnico La Fe	Valencia
Spain	Hospital Clínico Universitario Valladolid	Valladolid
Ukraine	Medical Center of Limited Liability Company "Harmoniya Krasy"	Kyiv
United Kingdom	University Hospital of Wales	Cardiff	Wales
United Kingdom	Institute of Neurological Sciences	Glasgow	Scotland
United Kingdom	King's College Hospital NHS Foundation Trust	London
United Kingdom	St. George's University Hospitals NHS Foundation Trust	London
United States	Dent Neurosciences Research Center	Amherst	New York
United States	Asheville Neurology Specialists, PA	Asheville	North Carolina
United States	University of Colorado Hospital Anschutz Outpatient Pavilion	Aurora	Colorado
United States	Austin Epilepsy Care Center	Austin	Texas
United States	Mid-Atlantic Epilepsy and Sleep Center	Bethesda	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Consultants in Epilepsy and Neurology, PLLC	Boise	Idaho
United States	University of Virginia	Charlottesville	Virginia
United States	Northwestern Medical Group, Department of Neurology	Chicago	Illinois
United States	UC Gardner Neuroscience Institute	Cincinnati	Ohio
United States	James W. Aston Ambulatory Care Center	Dallas	Texas
United States	Miami Valley Hospital	Dayton	Ohio
United States	Minneapolis Clinic of Neurology, Ltd.	Golden Valley	Minnesota
United States	Northeast Regional Epilepsy Group	Hackensack	New Jersey
United States	Hawaii Pacific Neuroscience	Honolulu	Hawaii
United States	Mayo Clinic Florida	Jacksonville	Florida
United States	University of Florida Jacksonville	Jacksonville	Florida
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Altman Clinical Translational Research Institute (ACTRI)	La Jolla	California
United States	Bluegrass Epilepsy Research	Lexington	Kentucky
United States	Clinical Trials, Inc.	Little Rock	Arkansas
United States	Institute of Neurology and Neurosurgery at Saint Barnabas	Livingston	New Jersey
United States	Don Clinical Research Center	Miami	Florida
United States	The Neurology Research Group, LLC.	Miami	Florida
United States	Visionary Investigators Network	Miami	Florida
United States	Strada Patient Care Center	Mobile	Alabama
United States	Northeast Regional Epilepsy Group	Morristown	New Jersey
United States	Vanderbilt Epilepsy Clinic	Nashville	Tennessee
United States	Northwell Health - Lenox Hill	New York	New York
United States	NYU Langone Medical Center/NYU School of Medicine	New York	New York
United States	Research Institute of Orlando, LLC	Orlando	Florida
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Comprehensive Epilepsy Center	Philadelphia	Pennsylvania
United States	Xenoscience, Inc.	Phoenix	Arizona
United States	Allegheny Neurological Associates	Pittsburgh	Pennsylvania
United States	Medsol Clinical Research Center	Port Charlotte	Florida
United States	Providence Neurological Specialties East	Portland	Oregon
United States	UW Medicine Valle Medical Center	Renton	Washington
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Carilion Neurology Clinic	Roanoke	Virginia
United States	Minnesota Epilepsy Group, P. A.	Saint Paul	Minnesota
United States	University of Utah Health Clinical Neurosciences Center	Salt Lake City	Utah
United States	The University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	California Pacific Medical Center (CPMC) - Sutter Pacific Epilepsy Program	San Francisco	California
United States	Maine Medical Partners Neurology	Scarborough	Maine
United States	University of Washington School of Medicine, Regional Epilepsy Center at Harborview Medical Center	Seattle	Washington
United States	Boston Neuro Research Center	South Dartmouth	Massachusetts
United States	Georgia Neurology and Sleep Medicine Associate	Suwanee	Georgia
United States	SUNY Upstate Medical University Institute for Human Performance	Syracuse	New York
United States	Tallahassee Neurological Clinic	Tallahassee	Florida
United States	University of South Florida	Tampa	Florida
United States	University of Toledo Medical Center	Toledo	Ohio
United States	Winchester Neurological Consultants	Winchester	Virginia
United States	Five Towns Neuroscience Research	Woodmere	New York

Sponsors (2)

Lead Sponsor	Collaborator
Xenon Pharmaceuticals Inc.	Novotech Health Holdings Pte. Ltd.

Countries where clinical trial is conducted

United States,  Canada,  Georgia,  Germany,  Italy,  Moldova, Republic of,  Spain,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To assess the efficacy of XEN1101 compared to placebo on focal seizure frequency (e.g., median percent change in focal seizure frequency) in adults with focal epilepsy taking 1-3 antiepileptic drugs (AEDs) in the double-blind treatment period (DBP)	Median percent change in monthly (28 days) focal seizure frequency from baseline to DBP for XEN1101 versus placebo	From baseline (8 weeks prior to Day 0) through to the final dose (up to Day 56)
Primary	To assess the safety and tolerability of XEN1101 (e.g., adverse events) in adults with focal epilepsy taking 1-3 AEDs	To assess adverse events as criteria for safety and tolerability	From screening (up to 28 days prior to baseline) through to 42 days post-final dose
Secondary	To evaluate the 50% XEN1101 response rates in comparison to placebo in the DBP	Responders are defined as patients experiencing =50% reduction in monthly (28 days) focal seizure frequency from baseline to DBP	From baseline (8 weeks prior to Day 0) through to the final dose (up to Day 56)
Secondary	To evaluate trends in focal seizure frequency over time in the DBP	Percent change from baseline in weekly focal seizure frequency for each week in the DBP	From baseline (8 weeks prior to Day 0) through to the final dose (up to Day 56)