A Trial of EPX-100 (Clemizole Hydrochloride) as an Add-on Therapy in Children With Dravet Syndrome
A Trial of EPX-100 (Clemizole Hydrochloride) as an Add-on Therapy in Children With Dravet Syndrome
The purpose of this study is to compare the efficacy of EPX-100 against placebo as adjunctive
 therapy in patients with Dravet Syndrome.
This is a multicenter, randomized, double-blind, placebo-controlled, proof of concept trial
 to evaluate the efficacy of EPX-100 (clemizole hydrochloride) in children with Dravet
 Syndrome. The 20-week study begins with a 4-week Observational Phase which will establish
 seizure frequency and eligibility for treatment, followed by a 4-week Titration Phase to
 identify the maximum tolerated dose in each patient. Thereafter, the patient will enter into
 a 12-week Maintenance Phase. A battery of chemistries, hematology, urinalysis,
 pharmacokinetics, and ECG's will be monitored throughout the 20-week study. The patient will
 have the opportunity to enter a 52-week Open-Label Extension phase at the end of the
 Maintenance Phase. The primary endpoint is the percent change in the 28-day seizure frequency
 in the final 4-weeks of the 12-week Maintenance Phase relative to the 4-week Observational
 Phase in the modified intent-to-treat (mITT) population between active and placebo (3:1)
 therapy.
Inclusion Criteria:

 1. Clinical diagnosis of Dravet Syndrome. Participants must have seizures which are not
 completely controlled by anti-epileptic drugs (AEDs) with the following criteria:

 -  Onset of frequent seizures prior to 18 months of age,

 -  Normal development at onset,

 -  History of seizures that are generalized, unilateral clonic, and/or hemi-clonic,
 namely:

 -  Hemi-clonic (Note: Lateralization - right body, left body, or independent R
 and L)

 -  Focal with clear, observable motor signs (i.e., automatisms, dystonic
 posturing, focal tonic stiffening)

 -  Secondarily generalized tonic clonic (evolving to bilateral convulsive
 seizure from focal seizure)

 -  Generalized tonic clonic convulsion

 -  Tonic

 -  Clonic (note bilateral: symmetric R and L)

 -  Tonic/Atonic - aka 'drop attacks'

 -  Brain MRI without cortical malformation, and

 -  Genetic mutation of the sodium voltage-gated channel alpha subunit 1 (SCN1A) gene
 must be documented.

 2. The participant must be approved to participate by the PI after a review of the
 medical history, baseline seizure calendars and inclusion/exclusion criteria. The
 Independent Reviewer will confirm Dravet Syndrome diagnosis for each participant
 enrolled in the study.

 3. Seizure criteria of ≥4 countable convulsive seizures (tonic-clonic, tonic, clonic,
 atonic, focal with observable motor signs) per 4-week baseline period (Observational
 Phase).

 4. Participants should be on a stable regimen of AEDs≥30days prior to Visit 1 and
 generally in good health.

 5. Parent or Legal Authorised Representative (LAR) is willing and able to maintain an
 accurate and complete daily seizure calendar.

 6. Sexually active women of child-bearing potential (WCBP) must be using a medically
 acceptable method of birth control and have a negative urine pregnancy test at the
 screening visit. A WCBP is defined as a female who is biologically capable of becoming
 pregnant. A medically acceptable method of birth control includes intrauterine devices
 in place for at least 3 months, surgical sterilization, or adequate barrier methods
 (e.g., diaphragm and foam). Use of oral contraceptives in combination with another
 method (e.g., a spermicidal cream) is acceptable. In participants who are not sexually
 active, abstinence is an acceptable form of birth control and urine will be tested per
 protocol. Women who are of non-child-bearing potential, i.e., post-menopause, must
 have this condition captured in their medical history. Pregnant women are excluded
 from this study.

 7. Have parent or LAR available and willing to give written informed consent, after being
 properly informed of the nature and risks of the study and prior to engaging in any
 study-related procedures.

 Exclusion Criteria:

 The presence of any of the following excludes a participant from study enrollment:

 1. Known sensitivity, allergy, or previous exposure to EPX-100 (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 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. Concurrent use of drugs known to interfere with EPX-100, including moderate or severe
 inducers or inhibitors of CYP3A4/5/7. Specifically, concurrent use of carbamazepine,
 oxcarbazepine, phenytoin, and/or phenobarbital, or fenfluramine as an investigational
 drug, are excluded, as well as refraining from grapefruits and grapefruit juice during
 the study period.

 5. Has any medical condition that, in the PI's judgement, is considered to be clinically
 significant and could potentially affect participant safety or study outcome,
 including but not limited to: clinically significant cardiac disease (including
 angina, congestive heart failure, uncontrolled hypertension, and history of
 arrhythmias), renal, pulmonary, gastrointestinal, hematologic or hepatic conditions;
 or a condition that affects the absorption, distribution, metabolism, or excretion of
 drugs.

 6. Has an active suicidal plan/intent or have had active suicidal thoughts in the past 6
 months or a suicide attempt in the past 3 years.