A Study of EPX-100 (Clemizole Hydrochloride) in Participants With Dravet Syndrome

Официальное название

A 20-Week Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of EPX-100 (Clemizole Hydrochloride) as Adjunctive Therapy in Children and Adult Participants With Dravet Syndrome (ARGUS Trial)

Обзор

This is a multicenter, Phase 3, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of clemizole hydrochloride (EPX-100) as adjunctive therapy in children and adult participants with Dravet syndrome (DS).

Подробное описание

This is a global, multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of clemizole hydrochloride as adjunctive therapy in children and adult participants with DS. The study consists of a 4-week Observational Period, a 16-week Double-Blind (DB) Period and an Open-Label Extension (OLE) Period.

Вмешательства

• Препарат Clemizole HCl
  Clemizole HCl will be administered as an oral solution.
• Препарат Placebo
  Placebo will be administered as an oral solution.

Первичные конечные точки

• Percent Change in Countable Motor Seizures Per 28 Days (CMS-28) in the Titration Plus Maintenance Periods Relative to Baseline [Срок оценки: From Baseline Period (Day 1) up to 16 weeks]
• European Union: Percent Change in Countable Motor Seizures Per 28 Days in the Maintenance Period Relative to Baseline [Срок оценки: From maintenance period Baseline (Day 29) up to Day 85]

Вторичные конечные точки (12)

• Proportion of Participants with >=50% reduction in Countable Motor Seizures Per 28 Days in the Titration Plus Maintenance Periods Relative to Baseline [Срок оценки: From Baseline Period (Day 1) up to 16 weeks]
• European Union: Proportion of Participants with >=50% reduction in Countable Motor Seizures Per 28 Days in the Maintenance Period Relative to Baseline [Срок оценки: From maintenance period Baseline (Day 29) up to Day 85]
• Number of Countable Motor Seizure-free Days in the Titration Plus Maintenance Periods Relative to Baseline [Срок оценки: From Baseline Period (Day 1) up to 16 weeks]
• European Union: Number of Countable Motor Seizure-free Days in the Maintenance Period Relative to Baseline [Срок оценки: From maintenance period Baseline (Day 29) up to Day 85]
• Clinical Global Impression of Improvement - Clinician (CGII-C) Score [Срок оценки: Day 85]
• Clinical Global Impression of Improvement - Participant/Caregiver (CGII-P) Score [Срок оценки: Day 85]
• Percent Change in All Seizures in the Titration Plus Maintenance Periods Relative to Baseline [Срок оценки: From Baseline Period (Day 1) up to 16 weeks]
• Percent Change in All Seizures in the Maintenance Period Relative to Baseline [Срок оценки: From maintenance period Baseline (Day 29) up to Day 85]
• Incidence of Rescue Anti-epileptic Drug (AED) Use in the Titration Plus Maintenance Periods Relative to Baseline [Срок оценки: From Baseline Period (Day 1) up to 16 weeks]
• Incidence of Rescue Anti-epileptic Drug Use in the Maintenance Period Relative to Baseline [Срок оценки: From maintenance period Baseline (Day 29) up to Day 85]
• United States FDA: Proportion of Participants with >=50% Reduction in the Countable Motor Seizures Per 28 Days in the Maintenance Period Relative to Baseline [Срок оценки: From maintenance period Baseline (Day 29) up to Day 85]
• Incidence of Treatment-Emergent Adverse Events (TEAEs) [Срок оценки: From the first dose administration of study drug up to end of the study, approximately up to 172 weeks]

Критерии участия

Критерии включения

• Male and female participants 2 years and older at time of consent.
• Participant or parent/legally authorized representative (LAR) willing and able to provide written informed consent and assent (if applicable) prior to initiation of any study related procedures.
• Clinical diagnosis of DS. Participants must have seizures which are not completely controlled by AEDs with the following criteria:

• Onset of seizures prior to 18 months of age,
• Normal development at onset,
• History of at least one type of countable motor seizure (CMS),
• Brain MRI without cortical malformation (not including mild atrophy associated with the natural progression of DS),
• Genetic mutation of the SCN1A gene must be documented.

Критерии исключения

• Known sensitivity, allergy, or previous exposure to clemizole HCl.
• Exposure to any investigational drug or device <90 days prior to screening or plans to participate in another drug or device trial at any time during the study.
• Seizures secondary to illicit drug (this includes concomitant use of tetrahydrocannabinol \[THC\] and nonprescription cannabidiol preparations) or alcohol use, infection, neoplasm, demyelinating disease, degenerative neurological disease, or central nervous system disease deemed progressive, metabolic illness, or progressive degenerative disease.
• Concurrent use of lorcaserin. Note: Prior use of lorcaserin is permitted if at least 30 days have passed since the last dose.
• Concurrent use of fenfluramine.
• Epilepsy surgery planned during the study or epilepsy surgery within 6 months prior to Screening.

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

Тройное слепое

Основная цель

Лечение

Центры проведения

США · 32 центра

• University of Alabama at Birmingham — Birmingham
• Arkansas Children's Hospital — Little Rock
• Children's Hospital of Los Angeles — Los Angeles
• University of California Irvine — Orange
• UCSF Medical Center — San Francisco
• Yale University School of Medicine — New Haven
• Yale School of Medicine - Yale-New Haven Hospital — New Haven
• The Nemours Foundation — Wilmington
• … и ещё 24 центра

Индия · 10 центров

• Saachi Children's Hospital — Surat
• National Institute of Mental Health and Neurosciences (NIMHANS) — Adugodi
• Central India Cardiology Hospital and Research Institute — Nagpur
• All India Institute of Medical Sciences (AIIMS) — New Delhi
• Christian Medical College — Vellore
• Rainbow Children's Hospital — Hyderabad
• Amrita Institute of Medical Sciences & Research Center — Kochi
• Jaslok Hospital & Research Centre — Mumbai
• … и ещё 2 центра

Канада · 4 центра

• UBC Children's Hospital Research Institute — Vancouver
• Children's Hospital of Eastern Ontario Research Institute Inc. — Ottawa
• The Hospital for Sick Children — Toronto
• Toronto Western Hospital, University Health Network — Toronto

Грузия · 3 центра

• Tbilisi State Medical University, Givi Zhvania Academic, Clinic of Pediatry — Tbilisi
• Medi Club Georgia LLC — Tbilisi
• Institute of Neurology and Neuropsychology LTD — Tbilisi

Польша · 3 центра

• University Clinical Center in Gdansk, Division of Developmental Neurology — Gdansk
• Medical Centre Plejady — Krakow
• Institute of Mother and Child — Warsaw

Великобритания · 3 центра

• Cardiff and Vale University Health Board — Cardiff
• Great Ormond Street Hospital For Children — London
• Sheffield Children's Hospital — Sheffield

Венгрия · 2 центра

• Semmelweis University — Budapest
• University of Debrecen — Debrecen

Испания · 2 центра

• Hospital Infantil Universitario Niño Jesús — Madrid
• Hospital de la Santa Creu i Sant Pau — Barcelona

Румыния · 1 центр

• "Prof. Dr. Al. Obregia" Psychiatry Clinical Hospital — Bucharest

Идентификаторы

NCT: NCT04462770 · EPX-100-001 · 2024-518628-57-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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