Dravet Syndrome
Conditions
Keywords
Clemizole hydrochloride, Convulsive seizure, Pediatric epilepsy, Dravet syndrome
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.
Interventions
DRUGClemizole HCl
Clemizole HCl will be administered as an oral solution.
DRUGPlacebo
Placebo will be administered as an oral solution.
Sponsors
Epygenix
Harmony Biosciences Management, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
Patients are randomized 1:1 to clemizole HCl (EPX-100) or placebo.
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
No
Inclusion 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 and assent (if applicable) prior to initiation of any study related procedures. 3. 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
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 disease deemed progressive, metabolic illness, or progressive degenerative disease. 4. Concurrent use of lorcaserin. Note: Prior use of lorcaserin is permitted if at least 30 days have passed since the last dose. 5. Concurrent use of fenfluramine. 6. Epilepsy surgery planned during the study or epilepsy surgery within 6 months prior to Screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Argentina, Brazil, Canada, Georgia, Hungary, India, Poland, Spain, United Kingdom, United States
Contacts
CONTACTKrystle Rapchak
CONTACTEric Bauer
STUDY_DIRECTORAmit Ray, MD
Harmony Biosciences Management, Inc.
Outcome results
None listed