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

Primary Generalized Tonic-Clonic Seizures Clinical Trial

— X-ACKT  

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 Primary Generalized Tonic-Clonic Seizures

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05667142
• Other study ID #: XPF-010-303
• Secondary ID: 2022-502286-16-0
• Status: Recruiting
• Phase: Phase 3
• Start date: February 14, 2023
• Est. completion date: October 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

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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 160
• Est. completion date: October 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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 1 month prior to screening (Visit 1), during screening/baseline, and throughout the DBP.

6. Subject is able to keep accurate seizure diaries.

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.

4. Subject has a concomitant diagnosis of 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 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, obsessive-compulsive 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 of the baseline period 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.

2. Seizure diary was completed a minimum of 80% of all days (ie, =45 days) during the last 56 days of the baseline period that preceded randomization as evidence of adequate compliance.

3. Subject did not change dose of, stop, or initiate any new ASM(s) during the baseline period and plans on maintaining a stable dose of ASM(s) during the DBP.

Related Conditions & MeSH terms

• Primary Generalized Tonic-Clonic Seizures
• Seizures

Intervention

Drug:
• XEN1101
XEN1101 capsules
• Placebo
Placebo capsules
• XEN1101
XEN1101 capsules

Locations

Country	Name	City	State
Australia	Melbourne Brain Centre	Heidelberg	Victoria
Australia	Southern Neurology	Kogarah	New South Wales
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	The Royal Melbourne Hospital	Parkville
Australia	Mater Misericordiae Ltd	South Brisbane	Queensland
Bulgaria	Multiprofile hospital for active treatment Puls AD	Blagoevgrad
Bulgaria	First University Multiprofile Hospital for Active Treatment Sofia Sv. Joan Krastitel	Sofia
Canada	Center for Neurologic Research	Lethbridge	Alberta
Canada	London Health Sciences Center	London	Ontario
Croatia	Clinical Hospital Center Osijek	Osijek
Croatia	Clinical Hospital Center Rijeka	Rijeka
Croatia	University Hospital Center Zagreb	Zagreb
Czechia	Motol University Hospital	Prague
Italy	Policlinico Umberto I	Roma
Poland	Centrum Medyczne Neuromed	Bydgoszcz
Poland	COPERNICUS Podmiot Leczniczy Sp. z o.o.	Gdansk
Poland	NZOZ Neuromed M. i M.	Lublin
Poland	Twoja Przychodnia Nowosolskie Centrum Medyczne	Nowa Sól
Portugal	Hospital da Senhora da Oliveira	Guimarães
Portugal	CHULN	Lisboa
Portugal	Hospital Egas Moniz	Lisboa
Spain	Hospital 12 de Octubre	Madrid
Spain	Hospital Regional Universitario de Málaga	Málaga
United Kingdom	University Hospital of Wales	Cardiff	Wales
United States	Summa Health Clinical Research Center	Akron	Ohio
United States	Dent Neurosciences Research Facility	Amherst	New York
United States	University of Michigan Hospitals	Ann Arbor	Michigan
United States	University of Colorado Anschutz Medical Campus	Aurora	Colorado
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	Mid-Atlantic Epilepsy and Sleep Center	Bethesda	Maryland
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Michigan State University Department of Neurology	East Lansing	Michigan
United States	Spectrum Health	Grand Rapids	Michigan
United States	Northeast Regional Epilepsy Group	Hackensack	New Jersey
United States	Hawaii Pacific Neuroscience, Comprehensive Epilepsy Center	Honolulu	Hawaii
United States	Indiana University School of Medicine	Indianapolis	Indiana
United States	Bluegrass Epilepsy Research, LLC	Lexington	Kentucky
United States	Kentucky Clinic	Lexington	Kentucky
United States	Brain Science Research Institute	Los Angeles	California
United States	Advocate Aurora Research institute, St. Luke's Medical Center	Milwaukee	Wisconsin
United States	University of Alabama	Mobile	Alabama
United States	UCI Health Neurology Services	Orange	California
United States	Research Institute of Orlando, LLC	Orlando	Florida
United States	Panhandle Research and Medical Clinic	Pensacola	Florida
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	Xenoscience	Phoenix	Arizona
United States	University of Utah Clinical Neurosciences Center	Salt Lake City	Utah
United States	Regional Epilepsy Center at Harborview	Seattle	Washington
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Georgia Neurology & Sleep	Suwanee	Georgia
United States	SUNY Upstate Medical University	Syracuse	New York
United States	Five Towns Neurology	Woodmere	New York
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,  Croatia,  Czechia,  Italy,  Poland,  Portugal,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incidence of adverse events	To assess the safety and tolerability of XEN1101 in subjects with PGTCS (e.g., adverse events).	From Screening Through to 56 Days Post-Final Dose
Primary	Median percent change (MPC) in monthly (28 days) PGTCS frequency	Median percent change (MPC) in monthly (28 days) PGTCS frequency from baseline through the DBP for XEN1101 versus placebo.	Baseline through DBP (Week 12)
Secondary	Proportion of subjects	Proportion of subjects experiencing =50% reduction in monthly (28 days) PGTCS frequency from baseline through the DBP for XEN1101 versus placebo.	Baseline through DBP (Week 12)
Secondary	Proportion of subjects	Proportion of subjects experiencing PGTCS freedom from baseline through the DBP for XEN1101 versus placebo.	Baseline through Week 12