A Study to Evaluate XEN1101 as Adjunctive Therapy in Primary Generalized Tonic-Clonic Seizures (X-ACKT)
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| ClinicalTrials.gov Identifier: NCT05667142 |
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Recruitment Status :
Recruiting
First Posted : December 28, 2022
Last Update Posted : March 7, 2024
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Primary Generalized Tonic-Clonic Seizures | Drug: XEN1101 Drug: Placebo | Phase 3 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 160 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | February 14, 2023 |
| Estimated Primary Completion Date : | June 2025 |
| Estimated Study Completion Date : | October 2025 |
| Arm | Intervention/treatment |
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Experimental: XEN1101 25 mg/day
XEN1101 25 mg/day
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Drug: XEN1101
XEN1101 capsules |
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Placebo Comparator: Placebo
Placebo
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Drug: Placebo
Placebo capsules |
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Experimental: XEN1101 15 mg/day
XEN1101 15 mg/day
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Drug: XEN1101
XEN1101 capsules |
- Median percent change (MPC) in monthly (28 days) PGTCS frequency [ Time Frame: Baseline through DBP (Week 12) ]Median percent change (MPC) in monthly (28 days) PGTCS frequency from baseline through the DBP for XEN1101 versus placebo.
- Proportion of subjects [ Time Frame: Baseline through DBP (Week 12) ]Proportion of subjects experiencing ≥50% reduction in monthly (28 days) PGTCS frequency from baseline through the DBP for XEN1101 versus placebo.
- Proportion of subjects [ Time Frame: Baseline through Week 12 ]Proportion of subjects experiencing PGTCS freedom from baseline through the DBP for XEN1101 versus placebo.
- Incidence of adverse events [ Time Frame: From Screening Through to 56 Days Post-Final Dose ]To assess the safety and tolerability of XEN1101 in subjects with PGTCS (e.g., adverse events).
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 12 Years and older (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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.
- Subject is ≥12 years of age with a BMI ≤40 kg/m2 at Visit 1.
- 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.
- 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).
- 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.
- Subject is able to keep accurate seizure diaries.
Exclusion Criteria:
- Subject has had status epilepticus within the 12 months prior to Visit 1.
- Subject has history of repetitive seizures within the 12-month period preceding Visit 1 where the individual seizures cannot be counted.
- Subject has a history of non-epileptic psychogenic seizures.
- Subject has a concomitant diagnosis of FOS.
- Subject has presence or history of a developmental and epileptic encephalopathy, including Lennox-Gastaut syndrome.
- 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.
- Subject has history of neurosurgery for seizures <1 year prior to Visit 1, or radiosurgery <2 years prior to Visit 1.
- 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.
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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.
- Any personal circumstance that, in the opinion of the investigator, prevents adherence to the protocol.
The criteria to be eligible for randomization are:
- 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.
- 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.
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05667142
| Contact: Xenon Medical Affairs | 1-604-484-3300 | XenonCares@xenon-pharma.com |
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| Study Director: | Medical Director | Xenon Pharmaceuticals Inc. |
| Responsible Party: | Xenon Pharmaceuticals Inc. |
| ClinicalTrials.gov Identifier: | NCT05667142 |
| Other Study ID Numbers: |
XPF-010-303 |
| First Posted: | December 28, 2022 Key Record Dates |
| Last Update Posted: | March 7, 2024 |
| Last Verified: | March 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Epilepsy |
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Seizures Neurologic Manifestations Nervous System Diseases |