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)

Overview

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).

Detailed description

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.

Interventions

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

Primary outcome measures

• Percent Change in Countable Motor Seizures Per 28 Days (CMS-28) in the Titration Plus Maintenance Periods Relative to Baseline [Time frame: 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 [Time frame: From maintenance period Baseline (Day 29) up to Day 85]

Secondary outcome measures (12)

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

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

United States · 32 centers

• 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
• … and 24 more centers

India · 10 centers

• 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
• … and 2 more centers

Canada · 4 centers

• 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

Georgia · 3 centers

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

Poland · 3 centers

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

United Kingdom · 3 centers

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

Hungary · 2 centers

• Semmelweis University — Budapest
• University of Debrecen — Debrecen

Spain · 2 centers

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

Romania · 1 center

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

Identifiers

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

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗