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

The purpose of this study is to evaluate the safety and efficacy of EPX-100 as adjunctive therapy in participants with Dravet syndrome.

This is a global, multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of EPX-100 as adjunctive therapy in participants with Dravet syndrome. The study consists of a 4-week observational period, a 16-week double blind period and a 3-year open label extension.

Eligibility Criteria:
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 that 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 seizures that are generalized, unilateral clonic, and/or hemiclonic
   * Brain MRI without cortical malformation (not including mild atrophy associated with the natural progression of Dravet Syndrome)
   * Documented mutation of the SCN1A gene.
4. Must be approved to participate by the Independent Reviewer, in collaboration with the Principal Investigator (PI). Participants will be approved following review of the participant's medical and seizure history, historical neuroimaging, historical EEGs, genetic report confirming SCN1A mutation, and review and classification of at least 28 days of baseline seizures.
5. ≥4 countable convulsive seizures within minimum 28-day screening/baseline period (e.g., hemiclonic, secondarily generalized tonic-clonic, generalized tonic-clonic, tonic, clonic, tonic/atonic \[resulting in a drop\], and focal with clear observable motor signs).
6. Participants should be on a stable regimen of AEDs ≥30 days prior to Visit 1 and in generally good health.
7. Participant or parent/ LAR is able and willing to maintain an accurate and complete daily seizure and medication diary for the duration of the trial.
8. Sexually active women of child-bearing potential (WCBP) must be using a medically acceptable method of birth control and have a negative serum or urine pregnancy test at the screening (Visit 1) and Randomization (Visit 2). A WCBP is defined as a female who is biologically capable of becoming pregnant. Medically acceptable methods of birth control include 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.

Exclusion Criteria:

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

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 and/or phenytoin, as well ingestion of grapefruits and grapefruit juice, are prohibited.
5. Prior or concurrent use of lorcaserin.
6. Concurrent use of fenfluramine.
7. Has any medical condition that, in the PI's judgment, 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.
8. Has an active suicidal plan/intent or has had active suicidal thoughts in the past 6 months or a suicide attempt in the past 3 years.