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

Phase 3
Recruiting
Conditions
Dravet Syndrome
Interventions
Drug: Placebo
Registration Number
NCT04462770
Lead Sponsor
Epygenix
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
150
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Double-blind clemizole HClClemizole HClParticipants will receive their first dose of study drug following randomization.
PlaceboPlaceboParticipants will receive their first dose of study drug following randomization.
Open-label clemizole HClClemizole HClEligible participants who complete the DB Period will have the option to continue in the OLE Period, during which they will receive clemizole HCL for up to 3 years.
Open-label clemizole HClPlaceboEligible participants who complete the DB Period will have the option to continue in the OLE Period, during which they will receive clemizole HCL for up to 3 years.
Primary Outcome Measures
NameTimeMethod
Percent Change in CMS-28From Baseline Period up to 16 weeks

Percent change in CMS-28 from the Baseline Period through the end of the DB Period

Secondary Outcome Measures
NameTimeMethod
Number of Countable Motor Seizure-free DaysFrom Baseline Period up to 16 weeks

Number of countable motor seizure-free days from the Baseline Period through the end of the DB Period

Clinical Global Impression of Improvement - Clinician (CGII-C) ScoreWeek 16

CGII-C score at the end of the DB Period

Clinical Global Impression of Improvement - Participant/Caregiver (CGII-P) ScoreWeek 16

CGII-P score at the end of the DB Period

Proportion of Participants with ≥50% Reduction in CMS-28From Baseline Period up to 12 weeks

Proportion of participants with ≥50% reduction in CMS-28 from the Baseline Period through the end of the DB Maintenance Phase only

Percent Change in All SeizuresWeek 16

Percent change in all seizures at the end of the DB Period

Incidence of Rescue Anti-epileptic Drug (AED)From Baseline Period up to 16 weeks

Incidence of rescue AED use as measured by the number of days on rescue AEDs from the Baseline Period through the end of the DB Period

Incidence of Treatment-Emergent Adverse Events (TEAEs)From the first dose administration of study drug up to end of the study, approximately up to 172 weeks

Incidence of TEAEs will be compared among the treatment groups

Proportion of Participants with ≥50% reduction in CMS-28From Baseline Period up to 16 weeks

Proportion of participants with ≥50% reduction in CMS-28 from the Baseline Period through the end of the DB Period

Trial Locations

Locations (44)

University of California Irvine

🇺🇸

Orange, California, United States

UCSF Medical Center

🇺🇸

San Francisco, California, United States

The Nemours Foundation

🇺🇸

Wilmington, Delaware, United States

Rare Disease Research FL

🇺🇸

Kissimmee, Florida, United States

Pediatric Neurology and Epilepsy Specialists

🇺🇸

Winter Park, Florida, United States

Clinical Integrative Research Center of Atlanta (CIRCA)

🇺🇸

Atlanta, Georgia, United States

Ann & Robert H. Lurie Children's Hospital of Chicago

🇺🇸

Chicago, Illinois, United States

Norton Children's Research Institute

🇺🇸

Louisville, Kentucky, United States

University of Michigan- Mott Children's Hospital

🇺🇸

Ann Arbor, Michigan, United States

Children's Nebraska

🇺🇸

Omaha, Nebraska, United States

Northeast Regional Epilepsy Group

🇺🇸

Hackensack, New Jersey, United States

Neurology Center for Epilepsy and Seizures

🇺🇸

Marlboro, New Jersey, United States

Weill Cornell Medical Center

🇺🇸

New York, New York, United States

Duke University Health System

🇺🇸

Durham, North Carolina, United States

Wake Forest Baptist Medical Center

🇺🇸

Winston-Salem, North Carolina, United States

Cincinnati Children's Hospital Medical Center

🇺🇸

Cincinnati, Ohio, United States

Cleveland Clinic

🇺🇸

Cleveland, Ohio, United States

Nationwide Children's Hospital

🇺🇸

Columbus, Ohio, United States

The Children's Hospital of Philadelphia

🇺🇸

Philadelphia, Pennsylvania, United States

Le Bonheur Children's Hospital

🇺🇸

Memphis, Tennessee, United States

Child Neurology Consultants of Austin

🇺🇸

Austin, Texas, United States

UT Southwestern/Children's Health

🇺🇸

Dallas, Texas, United States

University of Utah

🇺🇸

Salt Lake City, Utah, United States

Seattle Children's Hospital

🇺🇸

Seattle, Washington, United States

UBC Children's Hospital Research Institute

🇨🇦

Vancouver, British Columbia, Canada

Children's Hospital of Eastern Ontario Research Institute Inc.

🇨🇦

Ottawa, Ontario, Canada

The Hospital for Sick Children

🇨🇦

Toronto, Ontario, Canada

Toronto Western Hospital, University Health Network

🇨🇦

Toronto, Ontario, Canada

Tbilisi State Medical University, Givi Zhvania Academic, Clinic of Pediatry

🇬🇪

Tbilisi, Georgia

Medi Club Georgia LLC

🇬🇪

Tbilisi, Georgia

Institute of Neurology and Neuropsychology

🇬🇪

Tbilisi, Georgia

Semmelweis University

🇭🇺

Budapest, Hungary

University of Debrecen

🇭🇺

Debrecen, Hungary

University Clinical Center in Gdansk, Division of Developmental Neurology

🇵🇱

Gdańsk, Poland

Medical Centre Plejady

🇵🇱

Kraków, Poland

Institute of Mother and Child

🇵🇱

Warsaw, Poland

"Prof. Dr. Al. Obregia" Psychiatry Clinical Hospital

🇷🇴

Bucharest, Romania

Hospital Infantil Universitario Niño Jesús

🇪🇸

Madrid, Madrid provincia, Spain

Hospital de la Santa Creu i Sant Pau

🇪🇸

Barcelona, Spain

Cardiff and Vale University Health Board

🇬🇧

Cardiff, United Kingdom

Alder Hey Children's NHS Foundation Trust

🇬🇧

Liverpool, United Kingdom

Great Ormond Street Hospital For Children

🇬🇧

London, United Kingdom

Sheffield Children's Hospital

🇬🇧

Sheffield, United Kingdom

Children's Hospital of Los Angeles

🇺🇸

Los Angeles, California, United States

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