A Study to Evaluate XEN1101 as Adjunctive Therapy in Focal Epilepsy

NCT ID: NCT03796962

Last Updated: 2024-09-24

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 325 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-30
• Study Completion Date: 2028-10-31

Brief 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).

Detailed 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.

Conditions

Focal Epilepsy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

25 mg XEN1101

Capsule filled with 25 mg XEN1101

Group Type: EXPERIMENTAL

XEN1101

Intervention Type: DRUG

Oral dose

20 mg XEN1101

Capsule filled with 20 mg XEN1101

Group Type: EXPERIMENTAL

XEN1101

Intervention Type: DRUG

Oral dose

10 mg XEN1101

Capsule filled with 10 mg XEN1101

Group Type: EXPERIMENTAL

XEN1101

Intervention Type: DRUG

Oral dose

Placebo

Placebo capsule

Group Type: PLACEBO_COMPARATOR

XEN1101

Intervention Type: DRUG

Oral dose

Interventions

XEN1101

Oral dose

Intervention Type: DRUG

Eligibility Criteria

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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novotech Health Holdings Pte. Ltd.

INDUSTRY

Sponsor Role: collaborator

Xenon Pharmaceuticals Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Xenon Pharmaceuticals Inc.

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Strada Patient Care Center

Mobile, Alabama, United States

Xenoscience, Inc.

Phoenix, Arizona, United States

Clinical Trials, Inc.

Little Rock, Arkansas, United States

Altman Clinical Translational Research Institute (ACTRI)

La Jolla, California, United States

California Pacific Medical Center (CPMC) - Sutter Pacific Epilepsy Program

San Francisco, California, United States

University of Colorado Hospital Anschutz Outpatient Pavilion

Aurora, Colorado, United States

University of Florida Jacksonville

Jacksonville, Florida, United States

Mayo Clinic Florida

Jacksonville, Florida, United States

Visionary Investigators Network

Miami, Florida, United States

Don Clinical Research Center

Miami, Florida, United States

The Neurology Research Group, LLC.

Miami, Florida, United States

Research Institute of Orlando, LLC

Orlando, Florida, United States

Medsol Clinical Research Center

Port Charlotte, Florida, United States

Tallahassee Neurological Clinic

Tallahassee, Florida, United States

University of South Florida

Tampa, Florida, United States

Georgia Neurology and Sleep Medicine Associate

Suwanee, Georgia, United States

Hawaii Pacific Neuroscience

Honolulu, Hawaii, United States

Consultants in Epilepsy and Neurology, PLLC

Boise, Idaho, United States

Northwestern Medical Group, Department of Neurology

Chicago, Illinois, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Bluegrass Epilepsy Research

Lexington, Kentucky, United States

Maine Medical Partners Neurology

Scarborough, Maine, United States

Mid-Atlantic Epilepsy and Sleep Center

Bethesda, Maryland, United States

Boston Neuro Research Center

South Dartmouth, Massachusetts, United States

Minneapolis Clinic of Neurology, Ltd.

Golden Valley, Minnesota, United States

Minnesota Epilepsy Group, P. A.

Saint Paul, Minnesota, United States

Northeast Regional Epilepsy Group

Hackensack, New Jersey, United States

Institute of Neurology and Neurosurgery at Saint Barnabas

Livingston, New Jersey, United States

Northeast Regional Epilepsy Group

Morristown, New Jersey, United States

Dent Neurosciences Research Center

Amherst, New York, United States

NYU Langone Medical Center/NYU School of Medicine

New York, New York, United States

Northwell Health - Lenox Hill

New York, New York, United States

SUNY Upstate Medical University Institute for Human Performance

Syracuse, New York, United States

Five Towns Neuroscience Research

Woodmere, New York, United States

Asheville Neurology Specialists, PA

Asheville, North Carolina, United States

UC Gardner Neuroscience Institute

Cincinnati, Ohio, United States

Miami Valley Hospital

Dayton, Ohio, United States

University of Toledo Medical Center

Toledo, Ohio, United States

Providence Neurological Specialties East

Portland, Oregon, United States

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Thomas Jefferson University Comprehensive Epilepsy Center

Philadelphia, Pennsylvania, United States

Allegheny Neurological Associates

Pittsburgh, Pennsylvania, United States

Vanderbilt Epilepsy Clinic

Nashville, Tennessee, United States

Austin Epilepsy Care Center

Austin, Texas, United States

James W. Aston Ambulatory Care Center

Dallas, Texas, United States

The University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

University of Utah Health Clinical Neurosciences Center

Salt Lake City, Utah, United States

University of Virginia

Charlottesville, Virginia, United States

Virginia Commonwealth University

Richmond, Virginia, United States

Carilion Neurology Clinic

Roanoke, Virginia, United States

Winchester Neurological Consultants

Winchester, Virginia, United States

UW Medicine Valle Medical Center

Renton, Washington, United States

University of Washington School of Medicine, Regional Epilepsy Center at Harborview Medical Center

Seattle, Washington, United States

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

Vancouver, British Columbia, Canada

London Health Sciences Center

London, Ontario, Canada

University Health Network-Toronto Western Hospital

Toronto, Ontario, Canada

LLC Arensia Exploratory Medicine

Tbilisi, , Georgia

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 im Breisgau, , Germany

University Hospital Munster (UKM)

Münster, , Germany

Klinikum Osnabruck

Osnabrück, , Germany

Krankenhaus Barmherzige Brueder Regensburg

Regensburg, , Germany

University of Tubingen-Dept. of Neurology and Epileptology

Tübingen, , Germany

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

Milan, , 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, , Italy

PMSI Republican Clinical Hospital, ARENSIA Exploratory Medicine

Chisinau, , Moldova

Hospital Virgen Macarena

Seville, Andalusia, Spain

Centro de Neurologia Avanzada

Seville, Andalusia, Spain

Hospital Germans Trias I Pujol

Badalona, Barcelona, Spain

Clínica Universidad Navarra

Pamplona, Navarre, Spain

Hospital del Mar

Barcelona, , Spain

Hospital Universitario Vall d'Hebron

Barcelona, , Spain

Hospital Vithas La Salud

Granada, , Spain

Hospital U. Ramón y Cajal

Madrid, , Spain

Hospital Ruber Internacional

Madrid, , Spain

Hospital U. Clínico San Carlos

Madrid, , Spain

Hospital Universitario Fundacion Jimenez Diaz

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Regional Universitario de Málaga

Málaga, , Spain

Hospital Universitario y Politécnico La Fe

Valencia, , Spain

Hospital Clínico Universitario Valladolid

Valladolid, , Spain

Medical Center of Limited Liability Company "Harmoniya Krasy"

Kyiv, , Ukraine

Institute of Neurological Sciences

Glasgow, Scotland, United Kingdom

University Hospital of Wales

Cardiff, Wales, United Kingdom

King's College Hospital NHS Foundation Trust

London, , United Kingdom

St. George's University Hospitals NHS Foundation Trust

London, , United Kingdom

Countries

United States; Canada; Georgia; Germany; Italy; Moldova; Spain; Ukraine; United Kingdom

References

French JA, Porter RJ, Perucca E, Brodie MJ, Rogawski MA, Pimstone S, Aycardi E, Harden C, Qian J, Rosenblut CL, Kenney C, Beatch GN; X-TOLE Study Group. Efficacy and Safety of XEN1101, a Novel Potassium Channel Opener, in Adults With Focal Epilepsy: A Phase 2b Randomized Clinical Trial. JAMA Neurol. 2023 Nov 1;80(11):1145-1154. doi: 10.1001/jamaneurol.2023.3542.

Reference Type: RESULT

PMID: 37812429 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2018-003221-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

XPF-008-201

Identifier Type: -

Identifier Source: org_study_id