An Efficacy and Safety Study of Clemizole HCl in Patients With Lennox-Gastaut Syndrome (LGS)

Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Clemizole HCl as Adjunctive Therapy in Patients With Lennox-Gastaut Syndrome

This is a multicenter, Phase 3, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of clemizole HCL (EPX-100) as adjunctive therapy in children and adult participants with Lennox-Gastaut syndrome (LGS).

Study Overview

• Status: Recruiting
• Conditions: Lennox Gastaut Syndrome
• Intervention / Treatment: Drug: Placebo; Drug: Clemizole HCl

Detailed Description

This is a multicenter, Phase 3, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of clemizole HCl as adjunctive therapy in children and adult participants with LGS.

The study will consist of an Observational Period, a Double-Blind (DB) Period, and an optional Open-Label Extension (OLE) Period.

• Study Type: Interventional
• Enrollment (Estimated): 260
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Juby Philip; Phone Number: (302) 559-4320; Email: clinicaltrials@harmonybiosciences.com
• Study Contact Backup: Name: Cindy Sandy; Phone Number: (317) 258-7262; Email: clinicaltrials@harmonybiosciences.com

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Active, not recruiting
      • Arkansas Children's Hospital
  • California
    • Orange, California, United States, 92868
      • Active, not recruiting
      • UC Irvine Medical Center
    • Orange, California, United States, 92868
      • Recruiting
      • UCI Center for Innovative Health Therapies
      • Contact: David King-Stephens, MD; Phone Number: 714-456-7720
      • Principal Investigator: David King-Stephens
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Not yet recruiting
      • Nemours Children's Health
      • Contact: Cecelia Krienen, MD; Email: Cecilia.Krienen@nemours.org
      • Principal Investigator: Lily Tran, MD
  • Florida
    • Kissimmee, Florida, United States, 34746
      • Suspended
      • Rare Disease Research
    • Miami, Florida, United States, 33136
      • Recruiting
      • University of Miami Miller School of Medicine
      • Contact: Brett Alonso Cardenas; Phone Number: 305-243-3100; Email: bac301@med.miami.edu
      • Principal Investigator: Kamil Detyniecki, MD
    • Winter Park, Florida, United States, 32789
      • Active, not recruiting
      • Pediatric Neurology and Epilepsy Specialists
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Re:Cognition Health
      • Contact: Antonio Iglesias, MD; Phone Number: 312-971-3318; Email: aiglesias@re-cognitionhealth.com
      • Principal Investigator: Antonio Iglesias, MD
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Active, not recruiting
      • Norton Children's Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Active, not recruiting
      • Henry Ford Hospital
  • Minnesota
    • Roseville, Minnesota, United States, 55102
      • Active, not recruiting
      • Minnesota Epilepsy Group, P.A.
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Active, not recruiting
      • Children's Nebraska
  • New Jersey
    • Marlboro, New Jersey, United States, 07746
      • Recruiting
      • Neurology Center for Epilepsy and Seizures
      • Contact: Phone Number: 732-433-3431
    • Marlboro, New Jersey, United States, 07746
      • Recruiting
      • Tekton Research
      • Principal Investigator: Amor Mehta, MD
      • Contact: Aimee Kinlan; Phone Number: 626-218-8294; Email: aimee.kinlan@tektonresearch.com
  • New York
    • New York, New York, United States, 10021
      • Recruiting
      • Weill Cornell Medicine/New York Presbyterian Hospital
      • Contact: Lundy Santil; Phone Number: Ext. 198 800-785-3150; Email: ludny.saintil@thermofisher.com
      • Contact: Asim Shahid; Email: los9075@med.cornell.edu
      • Principal Investigator: Asim Shahid, MD
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Active, not recruiting
      • Atrium Health STRIVE Research
    • Charlotte, North Carolina, United States, 28211
      • Active, not recruiting
      • On-Site Clinical Solution
    • Durham, North Carolina, United States, 27705
      • Recruiting
      • Duke University Medical Center
      • Contact: Muhammad Zafar, MD; Email: muhammad.zafar@duke.edu
      • Principal Investigator: Muhammad Zafar, MD
    • Morrisville, North Carolina, United States, 27560
      • Active, not recruiting
      • PPD Virtual-Science 37, Inc.
  • Texas
    • Houston, Texas, United States, 77030
      • Active, not recruiting
      • UTHealth Houston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Males or females, ages ≥2 to ≤55 years, at the time of Screening.
2. Participant/parent/legal authorized representative (LAR) willing and able to give written informed consent/assent.

3. Diagnosis of LGS, including:

   • Evidence of at least one type of countable major motor seizure.
   • History of electroencephalogram (EEG) consistent with LGS (abnormal background activity, and one of the following: 1) slow spike-wave discharges [<2.5 Hz], or 2) paroxysmal fast activity during sleep).
   • Abnormal cognitive development.
   • Onset of seizures at 11 years of age or younger.

Key Exclusion Criteria:

1. Known sensitivity, allergy, or previous exposure to clemizole HCl.
2. Known history of long QT syndrome or any significant history of a serious abnormality of the electrocardiogram (ECG) (e.g., recent myocardial infarction, clinically significant arrhythmia).
3. Family history of sudden cardiac death, unexplained death, or death from a primary dysrhythmia potentially associated with QT prolongation in any family member.
4. Seizures secondary to illicit drug or alcohol use, infection, neoplasm, demyelinating disease, degenerative neurological disease, or progressive central nervous system disease, metabolic illness, recent anoxic episode within the last 6 months requiring resuscitation, or progressive degenerative disease or any other condition, which in the opinion of the investigator, could affect seizure control.
5. Epilepsy surgery planned during the study or epilepsy surgery within 6 months prior to Screening.
6. Concomitant use of fenfluramine.
7. Prior or concomitant use of lorcaserin.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants will receive their first dose of study drug following randomization.	Drug: Placebo; Placebo will be administered as an oral solution.
Experimental: Double-blind clemizole HCl; Participants will receive their first dose of study drug following randomization.	Drug: Clemizole HCl; Clemizole HCl will be administered as an oral solution.; Other Names: EPX-100
Experimental: Open-label clemizole HCl; Eligible participants who complete the DB Period will have the option to continue in the OLE Period, during which they will receive clemizole HCl for up to 3 years.	Drug: Placebo; Placebo will be administered as an oral solution.; Drug: Clemizole HCl; Clemizole HCl will be administered as an oral solution.; Other Names: EPX-100

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in CMMS-28	Percent change in CMMS-28 from the Baseline Period through the end of the DB Period	From Baseline Period up to 16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants with ≥50% Reduction in CMMS-28	Proportion of participants with ≥50% reduction in CMMS-28 from the Baseline Period through the end of the DB Period	From Baseline Period up to 16 weeks
Percent Change in CMMS-28 Seizure-free Days	Percent change in CMMS-28 seizure-free days from the Baseline Period through the end of the DB Period	From Baseline Period up to 16 weeks
Clinical Global Impression of Change (CGI-C) Score	CGI-C score at the end of the DB Period	Week 16
Caregiver Global Impression of Change (CaGI-C) Score	CaGI-C score at the end of the DB Period	Week 16
Caregiver Global Impression of Change in Seizure Intensity/Duration (CaGI-CSID) Score	CaGI-CSID score at the end of the DB Period	Week 16
Change in Quality of Life Inventory (QI)-Disability Score	Change in QI-disability score from Baseline to the end of the DB Period	From Baseline Period up to 16 weeks
Percent Change per 28 Days in the Number of Seizure Free Days	Percent change per 28 days in the number of seizure-free days (based on all seizure types) from the Baseline Period through the end of the DB Period	From Baseline Period up to 16 weeks
Percent Change in CMMS-28	Percent change in CMMS-28 from the Baseline Period through the end of the DB Maintenance Phase only	From Baseline Period up to 12 weeks
Proportion of Participants with ≥50% Reduction in CMMS-28	Proportion of participants with ≥50% reduction in CMMS-28 from the Baseline Period through the end of the DB Maintenance Phase only	From Baseline Period up to 12 weeks
Incidence of Treatment-Emergent Adverse Events (TEAEs)	Incidence of TEAEs will be compared among the treatment groups	From the first dose administration of study drug up to end of the study, approximately up to 172 weeks

Collaborators and Investigators

• Sponsor: Epygenix
• Collaborators: Harmony Biosciences Management, Inc.
• Investigators: Study Director: Amit Ray, MD, Harmony Biosciences Management, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2025
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2029

Study Registration Dates

• First Submitted: September 23, 2021
• First Submitted That Met QC Criteria: September 23, 2021
• First Posted (Actual): October 4, 2021

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: LGS; Seizure; Lennox Gastaut Syndrome; Lennox-Gastaut Syndrome; Clemizole HCl
• Additional Relevant MeSH Terms: Epileptic Syndromes; Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Epilepsy; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Seizures; Lennox Gastaut Syndrome
• Other Study ID Numbers: EPX-100-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No