A Study of EPX-100 (Clemizole Hydrochloride) in Participants With Dravet Syndrome
- 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 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 for up to 156 weeks.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 150
-
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, 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.
Key
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Double-blind clemizole HCl Clemizole HCl Participants will receive their first dose of study drug following randomization. Placebo Placebo Participants will receive their first dose of study drug following randomization. Open-label clemizole HCl Clemizole HCl Eligible 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 HCl Placebo Eligible 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
Name Time Method Percent Change in Countable Motor Seizures Per 28 Days (CMS-28) in the Titration Plus Maintenance Periods Relative to Baseline From Baseline Period (Day 1) up to 16 weeks Percent change in CMS-28 from the Baseline Period through the end of the DB period.
European Union: Percent Change in Countable Motor Seizures Per 28 Days in the Maintenance Period Relative to Baseline From maintenance period Baseline (Day 29) up to Day 85 Percent change in CMS-28 from the Baseline Period through the end of the maintenance period.
- Secondary Outcome Measures
Name Time Method Proportion of Participants with >=50% reduction in Countable Motor Seizures Per 28 Days in the Titration Plus Maintenance Periods Relative to Baseline From Baseline Period (Day 1) up to 16 weeks Proportion of participants with \>=50% reduction in CMS-28 from the Baseline Period through the end of the DB Period.
European Union: Proportion of Participants with >=50% reduction in Countable Motor Seizures Per 28 Days in the Maintenance Period Relative to Baseline From maintenance period Baseline (Day 29) up to Day 85 Proportion of participants with \>=50% reduction in CMS-28 from the Baseline Period through the end of the maintenance period.
Number of Countable Motor Seizure-free Days in the Titration Plus Maintenance Periods Relative to Baseline From Baseline Period (Day 1) up to 16 weeks Number of countable motor seizure-free days from the Baseline Period through the end of the DB Period.
European Union: Number of Countable Motor Seizure-free Days in the Maintenance Period Relative to Baseline From maintenance period Baseline (Day 29) up to Day 85 Number of countable motor seizure-free days from the Baseline Period through the end of the maintenance period.
Clinical Global Impression of Improvement - Clinician (CGII-C) Score Day 85 CGII-C score at the end of the maintenance Period. This 1-item scale asks the clinician to rate how the participant's symptoms have improved or worsened relative to baseline.
Clinical Global Impression of Improvement - Participant/Caregiver (CGII-P) Score Day 85 CGII-C score at the end of the maintenance Period. This 1-item scale asks the clinician to rate how the participant's symptoms have improved or worsened relative to baseline.
Percent Change in All Seizures in the Titration Plus Maintenance Periods Relative to Baseline From Baseline Period (Day 1) up to 16 weeks Percent change in all seizures at the end of the DB Period.
Percent Change in All Seizures in the Maintenance Period Relative to Baseline From maintenance period Baseline (Day 29) up to Day 85 Percent change in all seizures at the end of the maintenance period.
Incidence of Rescue Anti-epileptic Drug (AED) Use in the Titration Plus Maintenance Periods Relative to Baseline From Baseline Period (Day 1) 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 Rescue Anti-epileptic Drug Use in the Maintenance Period Relative to Baseline From maintenance period Baseline (Day 29) up to Day 85 Incidence of rescue AED use as measured by the number of days on rescue AEDs from the Baseline Period through the end of the maintenance period.
United States FDA: Proportion of Participants with >=50% Reduction in the Countable Motor Seizures Per 28 Days in the Maintenance Period Relative to Baseline From maintenance period Baseline (Day 29) up to Day 85 Proportion of participants with ≥50% reduction in CMS-28 from the Baseline Period through the end of the DB Maintenance Phase only.
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.
Trial Locations
- Locations (46)
Children's Hospital of Los Angeles
🇺🇸Los Angeles, California, United States
University of California Irvine
🇺🇸Orange, California, United States
UCSF Medical Center
🇺🇸San Francisco, California, United States
Yale University School of Medicine
🇺🇸New Haven, Connecticut, 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
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