We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04462770
Recruitment Status : Recruiting
First Posted : July 8, 2020
Last Update Posted : December 19, 2022
Sponsor:
Information provided by (Responsible Party):
Epygenix

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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 : September 15, 2020
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : December 2024


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 Name: Placebo to match EPX-100 solution




Primary Outcome Measures :
  1. The mean percent change in countable convulsive seizure frequency (CCSF1) in the Titration and Maintenance (T+M) periods relative to baseline. [ Time Frame: 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 :
  1. The difference between EPX-100 vs placebo in the number of countable convulsive seizure-free days in the T+M periods relative to baseline. [ Time Frame: 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.

  2. 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. [ Time Frame: 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.

  3. The total change in Seizure Severity using Hague Seizure Severity Scale (HASS). [ Time Frame: 20 weeks ]
    The total change in Seizure Severity using Hague Seizure Severity Scale (HASS).

  4. The improvement in Clinical Global Impression (CGI). [ Time Frame: 20 weeks ]
    The improvement in Clinical Global Impression (CGI).

  5. The total change in Quality of Life in Childhood Epilepsy short form (QOLCE 55). [ Time Frame: 20 weeks ]
    The total change in Quality of Life in Childhood Epilepsy short form (QOLCE 55).

  6. 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. [ Time Frame: 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.

  7. 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. [ Time Frame: 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.

  8. The change in the number of episodes of status epilepticus, in the T+M periods relative to the baseline. [ Time Frame: 20 weeks ]
    The change in the number of episodes of status epilepticus, in the T+M periods relative to the baseline.

  9. 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. [ Time Frame: 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.

  10. The individual item changes in Quality of Life in Childhood Epilepsy short form (QOLCE 55). [ Time Frame: 20 weeks ]
    The individual item changes in Quality of Life in Childhood Epilepsy short form (QOLCE 55).

  11. The individual item changes in Seizure Severity using Hague Seizure Severity Scale (HASS). [ Time Frame: 20 weeks ]
    The individual item changes in Seizure Severity using Hague Seizure Severity Scale (HASS).

  12. The change in the Sleep Disturbance Scale for Children (SDSC) between EPX-100 and placebo by each scheduled visit [ Time Frame: 20 weeks ]
    The change in the Sleep Disturbance Scale for Children (SDSC) between EPX-100 and placebo by each scheduled visit



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   2 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04462770


Contacts
Layout table for location contacts
Contact: Lorianne Masuoka, M.D. (415) 933-0826 lm@epygenix.com
Contact: Rebekah DeVitry Fries rfries@epygenix.com

Locations
Layout table for location information
United States, California
Children's Hospital of Los Angeles Recruiting
Los Angeles, California, United States, 90027
Contact: Martha Arellano-Garcia    323-361-5812    margarcia@chla.usc.edu   
Principal Investigator: Deborah L Holder, MD         
UCSF Medical Center Recruiting
San Francisco, California, United States, 94158
Contact: Lucy Liu    415-353-8440    Lucy.Liu3@UCSF.edu   
Principal Investigator: Ernesto Gonzalez-Giraldo, MD         
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago Recruiting
Chicago, Illinois, United States, 60611
Contact: Maya Stosic    312-227-4525    mstosic@luriechildrens.org   
Principal Investigator: Linda C Laux, MD         
United States, Michigan
University of Michigan- Mott Children's Hospital Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Brittany Nordhaus    734-936-4179    nbrittan@med.umich.edu   
Principal Investigator: Julie Ziobro, MD, PhD         
United States, North Carolina
Wake Forest Baptist Health Sciences Department of Neurology Recruiting
Winston-Salem, North Carolina, United States, 27157
Principal Investigator: Gautam Popli, MD         
United States, Ohio
Cincinnati Children's Hospital Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Samantha Ballard, BSN, RN, CPN    513-803-3177    samantha.ballard@cchmc.org   
Principal Investigator: Gewalin Aungaroon, MD         
United States, Tennessee
Le Bonheur Children's Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact: Kenisha Guy    901-287-7484    Kenisia.Guy@lebonheur.org   
Principal Investigator: James Wheless, MD         
United States, Texas
Child Neurology Consultants of Austin Recruiting
Austin, Texas, United States, 78757
Contact: Victoria Henderson    210-416-4163    Victoria_Henderson@mednax.com   
Principal Investigator: Karen Keough, MD         
United States, Washington
Seattle Children's Recruiting
Seattle, Washington, United States, 98105
Contact: Laurie Guidry    206-987-0058    laurie.guidry@seattlechildrens.org   
Principal Investigator: Russell P Saneto, DO, PhD         
Canada, British Columbia
Children's and Women's Health Centre of British Columbia Recruiting
Vancouver, British Columbia, Canada, V6H 3V4
Contact: Inderpal Gill    604-875-2345 ext 6834    laurie.guidry@seattlechildrens.org   
Principal Investigator: Mary Connolly, MD         
Canada, Ontario
Children's Hospital of Eastern Ontario Recruiting
Ottawa, Ontario, Canada, K1H 8L1
Contact: Sarah Healy    613-738-4297    shealy@cheo.on.ca   
Principal Investigator: Sharon Whiting, MD         
The Hospital for Sick Children Recruiting
Toronto, Ontario, Canada, M5G 1X8
Contact: Laura MacDougall, PhD, CCRP    416-813-7996    laura.macdougall@sickkids.ca   
Contact: Christine Kowal    416-813-7654    christine.kowal@sickkids.ca   
Principal Investigator: Elizabeth Donner, MD         
Toronto Western Hospital, University Health Network Recruiting
Toronto, Ontario, Canada, M5T 2S8
Contact: Quratulain Zulfiqar Ali, MD    4166035800 ext 5906    quratulain.zulfiqar_ali@uhn.ca   
Principal Investigator: Danielle M Andrade, MD         
Sponsors and Collaborators
Epygenix
Layout table for additonal information
Responsible Party: Epygenix
ClinicalTrials.gov Identifier: NCT04462770    
Other Study ID Numbers: EPX-100-001
First Posted: July 8, 2020    Key Record Dates
Last Update Posted: December 19, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Epygenix:
Clemizole Hydrochloride
Convulsive Seizure
Pediatric epilepsy
Dravet
Additional relevant MeSH terms:
Layout table for MeSH terms
Epilepsies, Myoclonic
Syndrome
Disease
Pathologic Processes
Epilepsy, Generalized
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Epileptic Syndromes