EPX-100 (Clemizole Hydrochloride) as Add-on Therapy to Control Convulsive Seizures in Patients With Dravet Syndrome

Dravet Syndrome Clinical Trial

— ARGUS  

Official title:

A 20-Week Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of EPX-100 (Clemizole Hydrochloride) as Adjunctive Therapy in Children and Adult Participants With Dravet Syndrome (ARGUS Trial)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04462770
• Other study ID #: EPX-100-001
• Status: Recruiting
• Phase: Phase 2
• Start date: September 15, 2020
• Est. completion date: December 19, 2024

Study information

• Verified date: January 2024
• Source: Epygenix
• Contact: Lorianne Masuoka, M.D.
• Phone: (415) 933-0826
• Email: lm[@]epygenix.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

This is a global, multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of EPX-100 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 period and a 3-year open label extension.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 19, 2024
• Est. primary completion date: December 19, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years and older

Eligibility

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 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), and
• Genetic mutation of the SCN1A gene must be documented.

4. The participant must be approved to participate by the Independent Reviewer, in collaboration with the PI. Participants will be approved for participation 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 generally in 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. 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. 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 and/or phenytoin, as well as refraining from grapefruits and grapefruit juice during the study period. Refer to Appendix 1 for a list of prohibited drugs.

5. Prior or concurrent use of lorcaserin.

6. Concurrent use of fenfluramine. Participants with prior use of fenfluramine within the previous 3 months, or without proper documentation of an echocardiogram, at minimum 3 months following the last dose of fenfluramine, to ensure that the participant does not meet any criteria for drug-related (fenfluramine) cardiac valvular heart disease and/or drug-related pulmonary arterial hypertension (PAH) as indicated by any of the

following:

• documented mild or greater aortic regurgitation [AR] or moderate or greater mitral regurgitation [MR]
• significant (greater than mild) tricuspid regurgitation
• abnormally thickened cardiac valve and/or has restricted motion of the valve leaflets
• elevated right heart/pulmonary artery pressure >35mmHg

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 have had active suicidal thoughts in the past 6 months or a suicide attempt in the past 3 years.

Related Conditions & MeSH terms

• Dravet Syndrome
• Epilepsies, Myoclonic
• Syndrome

Intervention

Drug:
• EPX-100 (Clemizole HCl)
Daily dose of EPX100
• Placebo
Daily dose of Placebo

Locations

Country	Name	City	State
Canada	Children's Hospital of Eastern Ontario	Ottawa	Ontario
Canada	The Hospital for Sick Children	Toronto	Ontario
Canada	Toronto Western Hospital, University Health Network	Toronto	Ontario
Canada	UBC Children's Hospital Research Institute	Vancouver	British Columbia
Georgia	LEPL Tbilisi State Medical University, Givi Zhvania Academic, Clinic of Pediatry	Tbilisi
Georgia	LTD Institute of Neurology and Neuropsychology	Tbilisi
Georgia	LTD Medi Club Georgia LLC	Tbilisi
Hungary	Semmelweis University First Department of Pediatrics, Division of Child Neurology	Budapest
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona	Catalonia
Spain	Hospital Universitario Infantil Niño Jesús	Madrid	Madrid Provincia
United States	University of Michigan- Mott Children's Hospital	Ann Arbor	Michigan
United States	Child Neurology Consultants of Austin	Austin	Texas
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Cincinnati Children's Hospital	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Northeast Regional Epilepsy Group	Hackensack	New Jersey
United States	Children's Hospital of Los Angeles	Los Angeles	California
United States	Le Bonheur Children's Hospital	Memphis	Tennessee
United States	Weill Cornell Medicine/New York-Presbyterian Hospital	New York	New York
United States	Children's Hospital & Medical Center	Omaha	Nebraska
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	University of Utah	Salt Lake City	Utah
United States	UCSF Medical Center	San Francisco	California
United States	Seattle Children's	Seattle	Washington
United States	Nemours Children's Hospital-DE	Wilmington	Delaware
United States	Wake Forest Baptist Health Sciences Department of Neurology	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Epygenix

Countries where clinical trial is conducted

United States,  Canada,  Georgia,  Hungary,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The mean percent change in countable convulsive seizure frequency (CCSF1) in the Titration and Maintenance (T+M) periods relative to baseline.	The mean percent change in countable convulsive seizure frequency (CCSF1) in the Titration and Maintenance (T+M) periods relative to baseline.	20 weeks
Secondary	The difference between EPX-100 vs placebo in the number of countable convulsive seizure-free days in the T+M periods relative to baseline.	The difference between EPX-100 vs placebo in the number of countable convulsive seizure-free days in the T+M periods relative to baseline.	20 weeks
Secondary	The difference between EPX-100 vs placebo in proportion of participants with >50% reduction in the mean CCSF in the T+M periods relative to baseline.	The difference between EPX-100 vs placebo in proportion of participants with >50% reduction in the mean CCSF in the T+M periods relative to baseline.	20 weeks
Secondary	The total change in Seizure Severity using Hague Seizure Severity Scale (HASS).	The total change in Seizure Severity using Hague Seizure Severity Scale (HASS).	20 weeks
Secondary	The improvement in Clinical Global Impression (CGI).	The improvement in Clinical Global Impression (CGI).	20 weeks
Secondary	The total change in Quality of Life in Childhood Epilepsy short form (QOLCE 55).	The total change in Quality of Life in Childhood Epilepsy short form (QOLCE 55).	20 weeks
Secondary	The difference between EPX-100 vs placebo in proportion of participants with >25% reduction in the mean CCSF in the T+M periods relative to baseline.	The difference between EPX-100 vs placebo in proportion of participants with >25% reduction in the mean CCSF in the T+M periods relative to baseline.	20 weeks
Secondary	The mean difference between EPX-100 vs placebo per 28-days in the percent change of all seizures in the T+M periods relative to the baseline.	The mean difference between EPX-100 vs placebo per 28-days in the percent change of all seizures in the T+M periods relative to the baseline.	20 weeks
Secondary	The change in the number of episodes of status epilepticus, in the T+M periods relative to the baseline.	The change in the number of episodes of status epilepticus, in the T+M periods relative to the baseline.	20 weeks
Secondary	The incidence of rescue anti-epileptic drug (AED) use between EPX-100 and placebo, as measured by the number of days on rescue AEDs in the T+M periods relative to the baseline.	The incidence of rescue anti-epileptic drug (AED) use between EPX-100 and placebo, as measured by the number of days on rescue AEDs in the T+M periods relative to the baseline.	20 weeks
Secondary	The individual item changes in Quality of Life in Childhood Epilepsy short form (QOLCE 55).	The individual item changes in Quality of Life in Childhood Epilepsy short form (QOLCE 55).	20 weeks
Secondary	The individual item changes in Seizure Severity using Hague Seizure Severity Scale (HASS).	The individual item changes in Seizure Severity using Hague Seizure Severity Scale (HASS).	20 weeks
Secondary	The change in the Sleep Disturbance Scale for Children (SDSC) between EPX-100 and placebo by each scheduled visit	The change in the Sleep Disturbance Scale for Children (SDSC) between EPX-100 and placebo by each scheduled visit	20 weeks