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

Официальное название

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

Обзор

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).

Подробное описание

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.

Вмешательства

• Препарат XEN1101
  XEN1101 capsules
• Препарат Placebo
  Placebo capsules

Первичные конечные точки

• Median percent change (MPC) in monthly (28 days) PGTCS frequency [Срок оценки: Baseline through DBP (Week 12)]

Вторичные конечные точки (2)

• Proportion of subjects [Срок оценки: Baseline through DBP (Week 12)]
• Proportion of subjects [Срок оценки: Baseline through Week 12]

Критерии участия

Критерии включения

• 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 3 months prior to the planned randomization (Visit 2), during screening/baseline, and throughout the DBP.
• Subject is able to keep accurate seizure diaries.

Критерии исключения

• 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 within 10 years prior to Visit 1.
• Subject has a concomitant diagnosis of focal-onset seizures (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 central nervous system (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, or another serious mental health disorder. Subject has uncontrolled unipolar major depression where changes in pharmacotherapy are needed or anticipated during the study.
• 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 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. Retrospective seizure data documented up to 4 weeks prior to Visit 1 may be used in combination with a minimum of 4 weeks of prospective seizure data recorded in the study eDiary.
• Study eDiary was completed a minimum of 80% of all applicable days during the last 28-56 days of the baseline period that preceded randomization as evidence of adequate compliance (eg, >45 of 56 days, if no retrospective data prior to Visit 1 are used).
• Subject did not change dose of, stop, or initiate any new ASM(s) during the 3 months that preceded randomization and plans on maintaining a stable dose of ASM(s) during the DBP.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

США · 59 центров

• University of Alabama - Strada Patient Care Center, Neurology — Mobile
• Xenoscience — Phoenix
• University of Arizona - Health Science Center — Tucson
• University of Arkansas for Medical Sciences — Little Rock
• Brain Science Research Institute — Los Angeles
• University of California, Irvine - Health Neurology Services — Orange
• University California, Davis Clinical & Translation Science Center Clinical Research (CCRC — Sacramento
• University of Colorado Anschutz Medical Campus — Aurora
• … и ещё 51 центр

Германия · 10 центров

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Португалия · 7 центров

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Австралия · 6 центров

• Southern Neurology — Kogarah
• Mater Misericordiae Ltd — South Brisbane
• The Alfred Hospital — Melbourne
• Austin Health Pharmacy Clinical Trials — Heidelberg
• St Vincent's Hospital Melbourne, Clinical Neurosciences — Melbourne
• The Royal Melbourne Hospital — Parkville

Великобритания · 6 центров

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Франция · 5 центров

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Италия · 5 центров

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Польша · 5 центров

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Испания · 5 центров

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Аргентина · 4 центра

• Hospital General de Agudos J.M. Ramos Mejia — Buenos Aires
• STAT Research S.A. — Buenos Aires
• Hospital Italiano — Buenos Aires
• Sanatorio del Sur S.A — San Miguel de Tucumán

Австрия · 4 центра

• University Hospital Innsbruck — Innsbruck
• Universitaetsklinik fuer Kinder — Linz
• Universitätsklinik für Neurologie — Salzburg
• Universitätsklinik für Neurologie, Medizinische Universität Wien — Vienna

Канада · 4 центра

• Center for Neurologic Research — Lethbridge
• Children and Women's Health Centre of BC (BC Children's Hospital) — Vancouver
• … и ещё 2 центра

Израиль · 4 центра

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Болгария · 3 центра

• Multiprofile hospital for active treatment Puls AD — Blagoevgrad
• MHATNP 'Sveti Naum' EAD — Sofia
• First University Multiprofile Hospital for Active Treatment Sofia Sv. Joan Krastitel — Sofia

Хорватия · 3 центра

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Мексика · 3 центра

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Бельгия · 2 центра

• Cliniques Universitaires Saint-Luc — Brussels
• Universitair Ziekenhuis Gent — Ghent

Чили · 1 центр

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Чехия · 1 центр

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Нидерланды · 1 центр

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Идентификаторы

NCT: NCT05667142 · XPF-010-303 · 2022-502286-16-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗