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

Sponsor

Epygenix (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04462770

Collaborator

(none)

100

Enrollment

Locations

Arms

35.5

Anticipated Duration (Months)

11.1

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Dravet Syndrome	Drug: EPX-100 (Clemizole HCl) Drug: Placebo	Phase 2

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Patients are randomized 1:1 to EPX-100 or placebo.Patients are randomized 1:1 to EPX-100 or placebo.

Masking:

Triple (Participant, Care Provider, Investigator)

Masking Description:

Matching active vs placebo solutions have been prepared including color and taste.

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Sep 15, 2020

Anticipated Primary Completion Date :

Sep 1, 2022

Anticipated Study Completion Date :

Sep 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Active arm with EPX-100 (Clemizole HCl) EPX-100 oral solution	Drug: EPX-100 (Clemizole HCl) Daily dose of EPX100 Other Names: Clemizole Hydrochloride Clemizole HCl Clemizole
Placebo Comparator: Placebo arm Color- and taste-matched placebo oral solution dosed to match the active arm.	Drug: Placebo Daily dose of Placebo Other Names: Placebo to match EPX-100 solution

Arm

Intervention/Treatment

Experimental: Active arm with EPX-100 (Clemizole HCl)

EPX-100 oral solution

Drug: EPX-100 (Clemizole HCl)

Daily dose of EPX100

Other Names:

Clemizole Hydrochloride

Clemizole HCl

Clemizole

Placebo Comparator: Placebo arm

Color- and taste-matched placebo oral solution dosed to match the active arm.

Drug: Placebo

Daily dose of Placebo

Other Names:

Placebo to match EPX-100 solution

Outcome Measures

Primary Outcome Measures

The mean percent change in countable convulsive seizure frequency (CCSF1) in the Titration and Maintenance (T+M) periods relative to baseline. [20 weeks]
The mean percent change in countable convulsive seizure frequency (CCSF1) in the Titration and Maintenance (T+M) periods relative to baseline.

Secondary Outcome Measures

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]
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 proportion of participants with >50% reduction in the mean CCSF in the T+M periods relative to baseline. [20 weeks]
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 total change in Seizure Severity using Hague Seizure Severity Scale (HASS). [20 weeks]
The total change in Seizure Severity using Hague Seizure Severity Scale (HASS).
The improvement in Clinical Global Impression (CGI). [20 weeks]
The improvement in Clinical Global Impression (CGI).
The total change in Quality of Life in Childhood Epilepsy short form (QOLCE 55). [20 weeks]
The total change in Quality of Life in Childhood Epilepsy short form (QOLCE 55).
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]
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 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]
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 change in the number of episodes of status epilepticus, in the T+M periods relative to the baseline. [20 weeks]
The change in the number of episodes of status epilepticus, 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]
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 individual item changes in Quality of Life in Childhood Epilepsy short form (QOLCE 55). [20 weeks]
The individual item changes in Quality of Life in Childhood Epilepsy short form (QOLCE 55).
The individual item changes in Seizure Severity using Hague Seizure Severity Scale (HASS). [20 weeks]
The individual item changes in Seizure Severity using Hague Seizure Severity Scale (HASS).
The change in the Sleep Disturbance Scale for Children (SDSC) between EPX-100 and placebo by each scheduled visit [20 weeks]
The change in the Sleep Disturbance Scale for Children (SDSC) between EPX-100 and placebo by each scheduled visit

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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 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.

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

Known sensitivity, allergy, or previous exposure to EPX-100 (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 or alcohol use, infection, neoplasm, demyelinating disease, degenerative neurological disease, or central nervous system (CNS) disease deemed progressive, metabolic illness, or progressive degenerative disease.
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.
Prior or concurrent use of lorcaserin.
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

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.
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital of Los Angeles	Los Angeles	California	United States	90027
2	UCSF Medical Center	San Francisco	California	United States	94158
3	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois	United States	60611
4	University of Michigan- Mott Children's Hospital	Ann Arbor	Michigan	United States	48109
5	Wake Forest Baptist Health Sciences Department of Neurology	Winston-Salem	North Carolina	United States	27157
6	Le Bonheur Children's Hospital	Memphis	Tennessee	United States	38105
7	Child Neurology Consultants of Austin	Austin	Texas	United States	78757
8	Children's Hospital of Eastern Ontario	Ottawa	Ontario	Canada	K1H 8L1
9	Toronto Western Hospital, University Health Network	Toronto	Ontario	Canada	M5T 2S8