Clinical trial NCT04462770: A Study of EPX-100 (Clemizole Hydrochloride) in Participants With Dravet Syndrome
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Dravet Syndrome
Keywords: Clemizole hydrochloride
Convulsive seizure
Pediatric epilepsy
Dravet syndrome
Lead sponsor: Epygenix
Sponsor class: INDUSTRY
Collaborators: name: Harmony Biosciences Management, Inc.
First posted: 2020-07-08
Enrollment: 150
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients are randomized 1:1 to clemizole HCl (EPX-100) or placebo.
Primary purpose: TREATMENT

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

Detailed description: This is a global multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of clemizole HCl as adjunctive therapy in children and adult participants with Dravet syndrome. The study consists of a 4-week Observational Period, a 16-week Double-Blind (DB) Period and an Open-Label Extension (OLE) Period for up to 156 weeks.

Eligibility criteria: Key Inclusion Criteria:

1. Male and female participants 2 years and older at time of consent.
2. Participant or parent/legally authorized representative (LAR) willing and able to provide written informed consent, assent (if applicable) prior to initiation of any study related procedures.
3. Clinical diagnosis of Dravet syndrome. 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 Dravet syndrome),
   * Genetic mutation of the SCN1A gene must be documented.

Key Exclusion Criteria:

1. Known sensitivity, allergy, or previous exposure to clemizole HCl.
2. 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.
3. 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 (CNS) disease deemed progressive, metabolic illness, or progressive degenerative disease.
4. Prior or concurrent use of lorcaserin.
5. Concurrent use of fenfluramine.
6. Epilepsy surgery planned during the study or epilepsy surgery within 6 months prior to Screening.

Primary outcomes:
measure: Percent Change in CMS-28
timeFrame: From Baseline Period up to 16 weeks
Secondary outcomes:
measure: Proportion of Participants with ≥50% reduction in CMS-28
timeFrame: From Baseline Period up to 16 weeks
measure: Number of Countable Motor Seizure-free Days
timeFrame: From Baseline Period up to 16 weeks
measure: Clinical Global Impression of Improvement - Clinician (CGII-C) Score
timeFrame: Week 16
measure: Clinical Global Impression of Improvement - Participant/Caregiver (CGII-P) Score
timeFrame: Week 16
measure: Proportion of Participants with ≥50% Reduction in CMS-28
timeFrame: From Baseline Period up to 12 weeks
measure: Percent Change in All Seizures
timeFrame: Week 16
measure: Incidence of Rescue Anti-epileptic Drug (AED)
timeFrame: From Baseline Period up to 16 weeks
measure: Incidence of Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From the first dose administration of study drug up to end of the study, approximately up to 172 weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: Orange
country: United States
facility: University of California Irvine
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center
state: California
city: Wilmington
country: United States
facility: The Nemours Foundation
state: Delaware
city: Kissimmee
country: United States
facility: Rare Disease Research FL
state: Florida
city: Winter Park
country: United States
facility: Pediatric Neurology and Epilepsy Specialists
state: Florida
city: Atlanta
country: United States
facility: Clinical Integrative Research Center of Atlanta (CIRCA)
state: Georgia
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Louisville
country: United States
facility: Norton Children's Research Institute
state: Kentucky
city: Ann Arbor
country: United States
facility: University of Michigan- Mott Children's Hospital
state: Michigan
city: Omaha
country: United States
facility: Children's Nebraska
state: Nebraska
city: Hackensack
country: United States
facility: Northeast Regional Epilepsy Group
state: New Jersey
city: Marlboro
country: United States
facility: Neurology Center for Epilepsy and Seizures
state: New Jersey
city: New York
country: United States
facility: Weill Cornell Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Health System
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Memphis
country: United States
facility: Le Bonheur Children's Hospital
state: Tennessee
city: Austin
country: United States
facility: Child Neurology Consultants of Austin
state: Texas
city: Dallas
country: United States
facility: UT Southwestern/Children's Health
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Vancouver
country: Canada
facility: UBC Children's Hospital Research Institute
state: British Columbia
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario Research Institute Inc.
state: Ontario
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Toronto
country: Canada
facility: Toronto Western Hospital, University Health Network
state: Ontario
city: Tbilisi
country: Georgia
facility: Tbilisi State Medical University, Givi Zhvania Academic, Clinic of Pediatry
city: Tbilisi
country: Georgia
facility: Medi Club Georgia LLC
city: Tbilisi
country: Georgia
facility: Institute of Neurology and Neuropsychology
city: Budapest
country: Hungary
facility: Semmelweis University
city: Debrecen
country: Hungary
facility: University of Debrecen
city: Gdańsk
country: Poland
facility: University Clinical Center in Gdansk, Division of Developmental Neurology
city: Kraków
country: Poland
facility: Medical Centre Plejady
city: Warsaw
country: Poland
facility: Institute of Mother and Child
city: Bucharest
country: Romania
facility: "Prof. Dr. Al. Obregia" Psychiatry Clinical Hospital
city: Madrid
country: Spain
facility: Hospital Infantil Universitario Niño Jesús
state: Madrid provincia
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Cardiff
country: United Kingdom
facility: Cardiff and Vale University Health Board
city: Liverpool
country: United Kingdom
facility: Alder Hey Children's NHS Foundation Trust
city: London
country: United Kingdom
facility: Great Ormond Street Hospital For Children
city: Sheffield
country: United Kingdom
facility: Sheffield Children's Hospital
Study officials:
affiliation: Harmony Biosciences Management, Inc.
name: Amit Ray, MD
role: STUDY_DIRECTOR
References: